CN116569018A - Systems and methods for sample collection - Google Patents

Abstract

Disclosed herein are systems, methods, and kits for collecting and storing samples from a subject. The system may include a cartridge assembly for separating blood. The cartridge assembly may include a cartridge port configured to be coupled to a sample collection device that is operable to collect blood from a subject. The cartridge assembly may include at least one blood separation membrane configured to separate plasma or serum from blood. In some cases, the cartridge port may include a path configured to direct blood from the sample acquisition device to flow through the path and to the cartridge assembly. In some cases, the direction of blood flow through the at least one blood separation membrane may be different from the direction of blood flow through the path and toward the interior portion of the cartridge assembly.

Description

Systems and methods for sample collection

Cross References to Related Applications

This application claims U.S. Provisional Application No. 62/991,261, filed March 18, 2020, entitled "SYSTEMS AND METHODS FOR SAMPLE COLLECTION" and U.S. Provisional Application No. Benefit of Application No. 63/117,188, each of which is hereby incorporated by reference in its entirety.

Background technique

Collection of bodily fluids, such as collection of blood samples for diagnostic testing, can be used to assess and inform an individual's health. Early detection and reliable diagnosis can play a central role in making effective treatment decisions for treating disease or managing certain physiological conditions. Detection can involve identifying disease-specific biomarkers in human body fluids that can indicate irregularities in cellular regulatory function, pathological response, or therapeutic drug intervention.

However, many people may dislike the process of having blood drawn from their body, possibly due to the associations with pain, cuts, bleeding, sharp objects, seeing blood, fear of infection, etc. Typically, phlebotomy from subjects is performed at outside facilities such as hospitals, skilled nursing facilities, and outpatient settings such as primary care physicians (PCPs) and specialty hospital clinics, surgery centers, occupational health clinics, or physician offices. The blood collection process can be tedious and time-consuming for individuals who must visit these facilities for blood draws, as well as healthcare workers who may have to deal with multiple patient appointments in a single day.

Accordingly, there is a need for improved devices and methods that allow users to easily and conveniently perform blood draws and that can reduce the user's reliance on traditional healthcare facilities for blood draws.

Contents of the invention

The present disclosure addresses at least the above needs. Various embodiments of the present disclosure address the need for devices and methods that enable individuals to easily, conveniently, and reliably collect and store blood samples. Individuals with minimal or no medical training can use the disclosed devices and methods to efficiently collect and store blood, on their own or with the assistance of others, without the need for trained healthcare personnel. Embodiments described herein may obviate the need for an individual to schedule or make special or frequent trips to a medical facility to collect blood samples, which helps free up the individual's time and reduces the patient's burden on medical resources. Nonetheless, it should be understood that the disclosed devices and methods are also suitable for use by healthcare personnel or non-healthcare personnel in a variety of settings or applications, such as at the point of care (POC), emergency medical services (EMS), ambulatory Nursing, hospitals, clinics, emergency rooms, patient examination rooms, acute care wards, field settings, nurses' offices in educational settings, occupational health clinics, surgery or operating rooms, etc.

Blood samples collected using the devices and methods described herein can be analyzed to determine the physiological state of a person, for detecting disease, and also for monitoring the health of an individual or subject. In some cases, individuals can rapidly assess their physiological status because blood samples can be rapidly collected using the devices and methods described herein and can be (1) analyzed on-site using, for example, an immunoassay or (2) rapidly shipped to testing facility. Reducing lead times for blood collection, analysis, and quantification may benefit many users, especially subjects with certain physiological conditions/diseases that require continuous and frequent collection/monitoring of blood samples. Taking diabetes as an example, hemoglobin A1c (HbA1c) can account for 60% of all glycosylated hemoglobin and can be used to monitor blood sugar control. The content of HbA1c (percentage of total hemoglobin) can reflect the average blood sugar concentration in the patient's blood in the past 120 days. It is generally recommended that people with diabetes have their HbA1c levels tested every three to six months. Glycemic recommendations for nonpregnant adults with diabetes may be <7.0%, whereas HbA1c levels ≥8% may indicate the possible need for medical action to manage diabetic complications, including cognitive impairment and susceptibility to hypoglycemia.

Various embodiments described herein enable blood to be drawn at increased flow rates and higher sample volumes from the time of skin incision as compared to conventional non-venous blood collection devices and methods. The disclosed devices and methods can be used to collect a predetermined volume of blood samples, for example, by using custom matrices for sample collection and absorbent pads for containing and metering excess blood. Furthermore, the blood collection devices and methods described herein are minimally invasive and allow for a lower level of pain (or pain perception) in the subject, which can help improve the subject's overall blood collection experience.

One aspect of the present disclosure provides a cartridge assembly for separating blood collected from a subject, the cartridge assembly comprising: a cartridge port configured to couple to a sample collection device operable to collect blood from the subject; at least one blood separation membrane configured to separate plasma or serum from the sample; and a slot configured to support the at least one blood separation membrane, wherein the cartridge port includes a pathway configured to direct blood from the sample collection device Flow into the proximal end of the pathway in a first direction, pass through the pathway, and flow out from the distal end of the pathway in a second direction different from the first direction to at least one blood separation membrane.

Paths may include grooves or channels. The angle between the first direction and the longitudinal axis of the cartridge assembly may be greater than 0 degrees and less than 180 degrees. The angle between the second direction and the longitudinal axis of the cartridge assembly may be greater than 0 degrees and less than 180 degrees. The intersection angle between the first direction and the second direction may be greater than 0 degrees and less than 180 degrees.

The slot may also be configured to support a collection medium for collecting separated plasma or serum. The slot may also be configured to support a pre-filter for filtering blood prior to separating plasma or serum from the blood. At least one blood separation membrane, collection medium and prefilter may be arranged in a stack within the slot. The stack may be positioned in a configuration that allows blood to flow transversely through the thickness of the stack in a third direction, and across a planar region of the stack in at least one other direction than the third direction. The third direction may be different from the first direction or the second direction. The third direction may be substantially normal to the longitudinal axis of the cartridge. The third direction and the at least one other direction may be substantially orthogonal to each other. The distal end of the path may be configured to direct blood to the planar surface of the pre-filter before the blood flows onto the at least one blood separation membrane.

The proximal end of the pathway can be configured to receive blood from a recessed opening in the housing of the sample acquisition device. The proximal and distal ends of the path may not lie along the longitudinal axis of the cartridge assembly. The proximal and distal ends of the path may not lie along a straight line extending between the proximal and distal ends. The distal end of the path may be offset from a linear axis extending between (1) the proximal end of the path and (2) the edge thickness portion of the stack between the proximal and distal ends of the path. The distal end of the path may be adjacent to but not in contact with the flat surface of the pre-filter.

Paths may include curved, bent or angled sections.

The path may include a cutout exposing a portion along the length of the inlet port. The cartridge can withstand vacuum pressure when the vacuum in the sample acquisition device is activated. The vacuum may be configured to assist blood flow laterally and/or across the stack.

The slot may also include an accumulation region, wherein the accumulation region may be configured to hold a volume of blood to contain the blood as it is absorbed into at least a portion of the at least one blood separation membrane. The accumulation area may be positioned adjacent to the pre-filter. The pooling area may be configured to hold a predetermined volume of blood.

The cartridge is configured to be released and uncoupled from the sample collection device after the plasma or serum has been separated and collected onto the collection medium. The collection medium may be configured to be released and uncoupled from the cartridge assembly after plasma or serum has been separated and collected onto the collection medium. The cartridge assembly can be configured to remain coupled to the sample acquisition device after the acquisition medium has been released and decoupled from the cartridge assembly.

The at least one blood separation membrane may include a plurality of blood separation membranes, and wherein the collection medium may be disposed between the plurality of blood separation membranes.

The cartridge assembly may also include a window that allows the user to observe the progress of the blood separation. The window may be located adjacent to at least one blood separation membrane, collection medium, or prefilter.

At least one blood separation membrane may include an anticoagulant. The cartridge assembly can also include an anticoagulant coupled to the pathway surface.

Another aspect of the present disclosure provides a cartridge assembly for separating blood collected from a subject, the cartridge assembly comprising: a cartridge port configured to couple to a sample collection device operable to collect blood from the subject at least one blood separation membrane configured to separate plasma or serum from blood; and a slot configured to support at least one blood separation membrane, wherein the cartridge port includes a path configured to guide blood from sample collection The device flows through the path and toward the inner portion of the cartridge assembly comprising the slot, and wherein (i) the blood flows through the at least one blood separation membrane in a direction different from (ii) the blood flows through the path and toward the inner portion of the cartridge assembly direction.

The direction of blood flow through the at least one blood separation membrane may be substantially orthogonal to the direction of blood flow through the pathway.

The slot may also be configured to support one or both of: (1) a collection medium for collecting separated plasma or serum and (2) a pre-filter for filtering the blood prior to separating the plasma or serum from the blood. At least one blood separation membrane may be disposed between the collection medium and the prefilter.

Another aspect of the present disclosure provides a cartridge assembly for separating blood collected from a subject, the cartridge assembly comprising: a cartridge port configured to couple to a sample collection device operable to collect blood from the subject ; at least one blood separation membrane, which is configured to separate plasma or serum from blood; a slot, which is configured to support at least one blood separation membrane; and a collection container, which is configured to contain Blood collected from a sample collection device prior to or during separation of plasma or serum, wherein the cartridge port includes a pathway configured to direct blood from the sample collection device to flow through the pathway and to the collection container.

The direction of blood flow through the at least one blood separation membrane may be different from the direction of blood flow through the path and toward the collection container. The direction of blood flow through the at least one blood separation membrane may be substantially orthogonal to the direction of blood flow through the pathway and toward the collection container. The collection container may be positioned adjacent to the planar surface of the at least one blood separation membrane.

The slot may also be configured to support one or both of: (1) a collection medium for collecting separated plasma or serum and (2) a pre-filter for filtering the blood prior to separating the plasma or serum from the blood. At least one blood separation membrane may be disposed between the collection medium and the prefilter. A collection container may be positioned adjacent to the flat surface of the pre-filter.

Another aspect of the present disclosure provides a system for blood collection and blood separation, comprising: any subject sample collection device and cartridge assembly of the present disclosure.

The sample collection device may include a built-in vacuum.

Another aspect of the present disclosure provides a method comprising: collecting blood from a subject using any of the subject sample collection devices of the present disclosure; and isolating plasma or serum from the blood using any of the subject cartridge assemblies of the present disclosure .

Another aspect of the present disclosure provides a cartridge assembly for storing liquid blood collected from a subject, the cartridge assembly comprising: a coupling unit configured to be coupled to a cartridge chamber of a sample collection device, wherein the sample collection device a container configured to store liquid blood; and a cartridge holder configured to support the container, wherein the proximal end of the container is configured to be coupled to the coupling unit and the distal end of the container is configured to be coupled to the coupling unit. configured to couple to a cartridge holder.

The container may include a cap coupled to a proximal end of the container, and wherein the proximal end of the container may be configured to be coupled to the coupling unit using the cap. The lid may include one or more openings configured to open and allow liquid to enter the container when the lid is coupled to the coupling unit. The one or more openings may also be configured to close and prevent liquid from entering the container when the lid is decoupled from the coupling unit. The coupling unit may include one or more fluid paths that allow air to exit the container and enter the cartridge chamber when blood is collected into the container. One or more fluid paths may include one or more ventilation slots or channels. The one or more fluid paths may be configured to allow equalization of vacuum pressure within the cartridge chamber as blood is collected into the container. The container may be configured to receive blood flowing into the container in a first direction, and wherein the one or more fluid paths may be configured to direct air to and out of the container in a second direction different from the first direction. The first direction and the second direction may be substantially opposite to each other. The first direction and the second direction may be substantially orthogonal to each other.

A portion of the cartridge holder may be configured to extend outside of the cartridge when the cartridge assembly is coupled to the cartridge. A portion of the holder may include a box tab.

The cartridge holder may include a gasket configured to hermetically seal the cartridge chamber when the cartridge assembly is coupled to the cartridge chamber.

The container and cartridge holder may include a set of interlocking mating features that allow the container to be secured to the holder.

The cartridge chamber may be under vacuum pressure due to activation of the vacuum in the sample acquisition device. The vacuum may be configured to assist blood flow into the container from a recessed opening in the housing of the sample acquisition device.

At least a portion of the cartridge assembly may be configured to be released and uncoupled from the cartridge chamber of the sample collection device after blood has been collected into the container.

The container may be configured to be released and uncoupled from the coupling unit after blood has been collected into the container.

The container may include a window that allows the user to observe the progress of the liquid blood collection.

The cartridge assembly may also include one or more sensors configured to detect the amount of blood collected in the container. The one or more sensors may include optical sensors. The one or more sensors may be in communication with the electronic fill indicator, and wherein the electronic fill indicator is configured to provide information to the user regarding the amount of blood collected in the container. Electronic fill indicators may be configured to generate one or more visual, audible or tactile signals. The electronic fill indicator can be located on or at the box. The electronic fill indicator can be located on or at the sample acquisition device.

The coupling unit may include a luer type fitting.

The container may include one or more indicator lines for monitoring the progress of the liquid blood collection.

One or more indicator lines can be used to estimate the volume of blood collected in the container.

Containers can include tubes.

Another aspect of the present disclosure provides a system for collecting and storing blood from a subject comprising: any of the subject sample collection devices and cartridge assemblies of the present disclosure. The sample collection device includes built-in vacuum.

Another aspect of the present disclosure provides a method comprising: collecting blood from a subject using any of the subject sample collection devices of the present disclosure; and storing the blood as liquid blood using any of the subject cartridge assemblies of the present disclosure.

Another aspect of the present disclosure provides a modular chamber assembly for storing blood collected from a subject, the modular assembly comprising: an inlet port configured to be coupled to a sample collection device, wherein the sample collection device is configured to collect blood from a subject; and a chamber configured to be coupled to the inlet port, wherein the chamber when coupled to the inlet port forms a housing, wherein the housing is configured to support a plurality of different cartridge assembly types of cartridge assemblies therein , and wherein the plurality of different cartridge assembly types allows collection, processing or storage of blood in a variety of different forms including plasma, serum, dried blood, liquid blood, or clotted blood.

A portion of the sample acquisition device may be configured to extend out of the sample acquisition device when the inlet port is coupled to a mating port of the sample acquisition device. A portion of the sample acquisition device may include a protrusion.

The inlet port may comprise a pierceable self-sealing port configured to hermetically seal the housing.

The cartridge assembly can be configured to be coupled to (1) at least a portion of the inlet port and/or (2) at least a portion of the chamber.

A plurality of different cartridge assembly types may include two or more of: (1) a first cartridge assembly type configured to separate plasma or serum from collected blood, (2) a second cartridge assembly type , which is configured to collect and store liquid blood, (3) a third cartridge assembly type configured to house one or more matrices for collecting and storing blood as dried blood, or (4) a fourth cartridge assembly type, which is configured to store clotted blood.

The first cartridge assembly type can be configured to separate plasma from collected blood. The first cartridge assembly type can be configured to separate serum from collected blood.

The modular chamber assembly can be configured to be released and disengaged from the sample acquisition device when the inlet port is decoupled from the sample acquisition device.

The modular chamber assembly can be configured to be released and disengaged from the sample collection device after blood has been collected, processed, or stored on the cartridge assembly.

The chamber may be configured to protect the cartridge assembly from the external environment after blood is collected, processed, or stored on the cartridge assembly and after the modular chamber assembly is released and disengaged from the sample collection device.

The chamber may be tubular.

The modular chamber assembly may be configured to be used as a transport container for transporting or transporting blood after it has been collected, processed, or stored on the cassette assembly.

The chamber may include a desiccant.

The chamber may include transparent or translucent windows to allow visualization of interior portions of the chamber.

Another aspect of the present disclosure provides a system for collecting and storing blood from a subject, comprising: any of the subject sample collection devices and modular chamber assemblies of the present disclosure.

The sample collection device may include a built-in vacuum.

Modular chamber assemblies can include built-in vacuum.

The complete coupling of the sample collection device and the modular chamber assembly can be configured to activate sufficient vacuum to collect and store blood from the subject.

Another aspect of the present disclosure provides a method comprising: collecting blood from a subject using any of the subject sample collection devices of the present disclosure; and using any of the subject modular chamber assemblies of the present disclosure in a plurality of different formats 1. Store blood.

Another aspect of the present disclosure provides a kit comprising: any of the subject sample collection devices of the present disclosure, a modular chamber assembly, and/or a plurality of different cartridge assembly types.

Another aspect of the present disclosure provides a sample collection device for collecting blood from a subject, the sample collection device comprising: a body including a groove having an opening; and one or more piercing elements extendable through the opening to pierce the subject's skin so that blood can be collected into the sample collection device while the skin is drawn into the groove; and a sample chamber including a connection port sized and shaped to allow Interchangeably and releasably coupled to a cartridge assembly of a plurality of different cartridge assembly types, wherein the plurality of different cartridge assembly types allows for multiple Collect, process or store blood in different ways.

The body is operably coupled to the vacuum chamber. The vacuum chamber may be configured such that activation of the vacuum causes fluid communication to be established between the vacuum chamber and the recess to draw the subject's skin into the recess, and the recess may serve as a suction chamber for suctioning the skin.

Modular chamber assemblies can include built-in vacuum. The modular chamber assembly can be configured such that the coupling of the modular chamber assembly to the body can result in fluid communication between the modular chamber assembly and the recess to draw the subject's skin into the recess, and the recess can act as a Suction chamber for suctioning the skin.

The cartridge assembly can be configured to be releasably coupled to the body.

When the cartridge assembly is coupled to the connection port of the sample chamber, the sample chamber can be hermetically sealed.

A plurality of different cartridge assembly types may include two or more of: (1) a first cartridge assembly type configured to separate plasma or serum from collected blood, (2) a second cartridge assembly type , which is configured to collect and store liquid blood, (3) a third cartridge assembly type configured to house one or more matrices for collecting and storing blood as dried blood, or (4) a fourth cartridge assembly type, which is configured to store clotted blood.

Another aspect of the present disclosure provides a kit comprising: a sample collection device configured to collect blood from a subject, wherein the sample collection device includes a port sized and shaped to be interchangeable and releasable A cartridge assembly coupled to a plurality of different cartridge assembly types; and a plurality of different cartridge assembly types, wherein the plurality of different cartridge assembly types includes two or more of: (1) a first cartridge assembly type, which is Configured to separate plasma or serum from collected blood, (2) a second cartridge assembly type configured to store blood in liquid form, (3) a third cartridge assembly type configured to accommodate one or more A matrix for storing blood in a substantially dry state, or (4) a fourth cartridge assembly type configured to store clotted blood.

The kit may also include a sample chamber, wherein a plurality of cartridge assemblies of different cartridge assembly types are contained within the sample chamber, and wherein the sample chamber is sized and shaped to be interchangeably and releasably coupled to the cartridge assembly. The sample chamber can include a built-in vacuum.

The sample collection device may include a built-in vacuum.

Provided herein are medical systems, devices, and methods for sample collection and storage. The disclosed systems, devices, and methods include structural features that facilitate sample collection (eg, blood collection devices) and components for collecting blood samples onto substrates (eg, matrices) for storage and transport.

Any of the devices disclosed herein may utilize vacuum generation to apply negative pressure to deform the subject's skin and apply localized suction directly to the sample collection site, thereby facilitating sample flow and collection. Any of the devices disclosed herein can include an indentation (eg, a cavity) that can be placed on the surface of the skin of a subject. The grooves may be configured to deliver a vacuum (eg, negative pressure, suction, etc.) to the subject's skin. Any of the devices disclosed herein may include openings disposed at the apices or other surfaces of the grooves. The opening can be tailored to allow the piercing element to pierce the subject's skin. The piercing element may be configured to pass through the inner diameter of the opening. Localized suction can be applied to the sample collection site through the openings and using grooves.

The vacuum can be configured to deform the subject's skin using different mechanisms, for example, the vacuum can be configured to draw the subject's skin into a groove (eg, cavity). The concave cavity may be configured to constrain the skin surface over its entire concave surface (or a portion thereof), at which point the piercing element may be used to pierce the subject's skin. When a vacuum is applied to the subject's skin, and after an incision is made on the subject's skin, the opening adjacent to the fluid path (e.g., a flow channel in fluid communication with the cartridge) can draw blood from the subject to the device.

The vacuum pressure may be generated using an evacuation chamber configured such that activation of the evacuation chamber creates a negative pressure that draws blood from the subject through the openings and channels of the device, and into the subject sample of the sample room. The sample chamber can collect a fluid sample (eg, fluid blood) from the subject. The sample chamber may include one or more cartridges to collect other types or forms of subject samples (eg, plasma or serum). In some cases, a cartridge may include a solid matrix for sample collection and/or storage. The vacuum pressure may be below ambient pressure (ie, under vacuum conditions), for example, in the range of 1-20 psi below ambient pressure. Vacuum pressure can be about 5 psi lower than ambient pressure. The vacuum chamber volume may be within a 10%-100% margin of twice the total volume of a plurality of factors including two or more of: the cavity, the opening, the channel, and at least a portion of the sample chamber. Any of the devices disclosed herein may include a vacuum-activated actuator that may be configured to activate a vacuum upon actuation of the vacuum-activated actuator. The vacuum activated actuator may comprise a button located on the device or on the cassette. As an alternative or in addition to the embodiments described above, the vacuum pressure may be generated by inserting a sample chamber comprising an evacuated chamber. Inserting (or coupling) the sample chamber into the sample acquisition device can initiate vacuum evacuation from the vacuum chamber into the device, creating a negative pressure (eg, less than ambient pressure) within the device and within at least a portion of the sample chamber. The negative pressure can be configured to be sufficient to draw the subject's skin into the recess (eg, cavity) of the device. The piercing element of the device can be activated to pierce the skin of the subject, after which the pressure differential can draw blood from the subject through the device and into at least a portion of the sample chamber.

Another aspect of the present disclosure provides a cartridge assembly for separating blood collected from a subject, the cartridge assembly comprising: a cartridge including a cartridge port, wherein the cartridge is configured to be coupled to a sample collection device through the cartridge port, The sample collection device can be used to collect a blood sample from a subject; a cartridge tab, which includes a base; and a processing/stabilization unit, supported between the cartridge and the base of the cartridge tab, wherein the processing/stabilization unit includes a multi-component collection A matrix configured to separate plasma or serum from a blood sample, wherein the multicomponent collection matrix includes at least one submatrix having a different size or shape than one or more other submatrixes of the multicomponent collection matrix.

A multi-component acquisition matrix can include at least three sub-matrices. The multicomponent collection matrix can also be configured to store plasma or serum separated from a blood sample. The multi-component collection matrix can also be configured to stabilize plasma or serum separated from a blood sample. A portion of at least one submatrix of the multicomponent acquisition matrix may be exposed to the surrounding environment. A portion of at least one submatrix of the multicomponent acquisition matrix is located at a portion of the processing/stabilization unit remote from the cartridge port. A portion of at least one submatrix of the multicomponent acquisition matrix may be in contact with the substrate. A portion of at least one submatrix of the multicomponent acquisition matrix may not be in contact with the cartridge. The surface area of a portion of at least one submatrix of the multicomponent acquisition matrix may be from about 100 mm ² to about 150 mm ² . A portion of at least one submatrix is detachable from the multicomponent acquisition matrix. The base of the cartridge and cartridge tab may be configured to support the handling/stabilizing unit in a configuration that enables the cartridge assembly to be used or operated in a substantially vertical orientation. The cartridge assembly may be configured for use or operation at an angle from about 40 degrees to about 140 degrees relative to horizontal. The cartridge assembly may be configured to be used or operated at an angle from about 60 degrees to about 120 degrees relative to horizontal. The cartridge also includes a compression region that may be configured to apply a compressive force to a portion of the multi-component acquisition matrix. The compressive force can be from about 1 pound to about 10 pounds. The compressive force can be used to improve or control the passage or flow of the blood sample through the multicomponent collection matrix. The compressive force may be configured to retain or maintain the portion of the multicomponent acquisition matrix at a compressed thickness that is about 30% to about 90% of the uncompressed thickness of the portion of the multicomponent acquisition matrix. The compressive force is configured to retain or maintain a portion of the multicomponent acquisition matrix at a thickness of about 0.75 mm to about 1.0 mm. The cartridge may also include a compression stop configured to limit (a) the compressive force to be less than or equal to a predetermined value and/or limit (b) the compressed thickness of a portion of the multicomponent acquisition matrix to be less than or equal to equal to the predetermined thickness. The cartridge also includes one or more vents configured to allow fluid communication between the multi-component acquisition matrix and the external ambient environment. The one or more vents are configured to control plasma concentration during collection of the matrix-separated blood sample through the multi-component. The one or more vents are configured to control a drying rate during separation of a blood sample by the multi-component collection matrix. A portion of at least one submatrix of the multicomponent acquisition matrix is not subjected to compressive forces. At least one other portion of the multicomponent acquisition matrix is subjected to a compressive force.

Other aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description of illustrative embodiments of the present disclosure, shown and described. As will be realized, the disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and descriptions are to be regarded as illustrative in nature and not restrictive.

Incorporate by reference

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

Description of drawings

The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description and accompanying drawings which set forth illustrative embodiments in which the principles of the invention are utilized:

Figure 1A is a perspective view of a sample acquisition device, according to some embodiments.

Figure IB illustrates a perspective view of various components of a sample acquisition device, according to some embodiments.

Figure 2A shows a perspective view of a shipping sleeve, according to some embodiments.

Figure 2B illustrates a cassette assembly inserted into a shipping sleeve, according to some embodiments.

Figure 3A shows a different perspective view of a cartridge assembly, according to some embodiments.

Figure 3B illustrates a side cross-sectional view of a cartridge assembly, according to some embodiments.

3C illustrates a side cross-sectional view of a cartridge assembly with an indication of sample flow direction, according to some embodiments.

3D illustrates a side cross-sectional view of a sample acquisition device operably coupled to a cartridge assembly, according to some embodiments.

3E and 3F schematically illustrate cross-sectional views of another cartridge assembly and exemplary uses thereof, according to some embodiments.

4 shows a side cross-sectional view of a different cartridge assembly with an indication of sample flow direction, according to some embodiments.

5A shows a side cross-sectional view (left) and a perspective view (right) of a sample chamber configured to collect a liquid or liquid-like sample, according to some embodiments.

5B illustrates a side cross-sectional view of a sample acquisition device operably coupled to a cartridge assembly, according to some embodiments.

5C illustrates a perspective view of a viewable metering window of a sample acquisition device operably coupled to a cartridge assembly, according to some embodiments.

Figure 6 illustrates a box assembly inserted into a shipping sleeve, according to some embodiments.

7A shows a perspective view (left two views) and a side cross-sectional view of a modular sample chamber assembly for sample acquisition and storage, according to some embodiments.

Figure 7B illustrates principles of operation and use of a sample acquisition device operably coupled to a modular sample chamber assembly, according to some embodiments.

7C illustrates a perspective view of a sample acquisition device operably coupled to a modular sample chamber assembly, according to some embodiments.

Figure 7D illustrates different types of modular sample chamber assemblies for sample collection and storage, according to some embodiments.

8A-8C illustrate various perspective views of a modular sample acquisition device and modular sample chamber assembly, according to some embodiments.

8D and 8E illustrate principles of operation and use of a modular sample acquisition device and modular sample chamber assembly, according to some embodiments.

Figure 9 illustrates an example of a modular sample acquisition device operably coupled to different types of modular sample chamber assemblies according to some embodiments; and

Figure 10 illustrates example dimensions and pressure parameters of a device used in a sample collection process, according to some embodiments.

Figure 11 shows a perspective view of a sample acquisition device and cartridge assembly, according to some embodiments.

Figure 12 illustrates a perspective view of various components of a cartridge assembly, according to some embodiments.

Figure 13A shows a perspective view of various components of a blood filtration assembly, according to some embodiments.

13B and 13C illustrate perspective views of various components of a blood filtration assembly, according to some embodiments.

Figure 14 illustrates data analysis performed on a sample collected from a sample collection device, according to some embodiments.

Figure 15 illustrates a perspective view of various components of a blood separation assembly, according to some embodiments.

Figure 16A shows a perspective view of a first assembly structure of a blood separation assembly, according to some embodiments.

Figure 16B shows a perspective view and a side cross-sectional view of a blood separation assembly, according to some embodiments.

Figure 17A shows perspective and cross-sectional views of a blood separation assembly, according to some embodiments.

17B-17D illustrate side cross-sectional views of a blood separation assembly incorporating an absorbent pad, according to some embodiments.

17E-17G illustrate perspective views of various components of a blood separation assembly, according to some embodiments.

Figure 18 shows a perspective view of a processing/stabilization unit for use according to some embodiments.

Figure 19 illustrates a perspective view of a cartridge according to some embodiments.

20 illustrates perspective and side cross-sectional views of a cartridge assembly that can provide a visual cue to a user, according to some embodiments.

21A-21C illustrate cross-sectional views of a blood separation assembly incorporating a release mechanism, according to some embodiments.

Detailed ways

Reference will now be made in detail to the exemplary embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings and disclosure to refer to the same or like parts.

I. Overview

Provided herein are devices, methods, and kits for collecting a fluid sample (eg, from the body of a subject). The liquid sample may be, for example, blood, such as capillary blood taken from a subject penetrating the skin. The devices disclosed herein may be hand-held and user-activatable (e.g., by a subject to draw a fluid sample or a third-party user assisting the subject in drawing a fluid sample from the subject), and are suitable for use in traditional medical Use outside the institution, such as at home, in remote areas, when subjects are traveling, etc. These devices are portable and easy to use, and allow individuals to efficiently and reliably collect their own blood samples without relying on trained healthcare personnel and without requiring the individual to have any prior training in blood drawing. The devices, methods, and kits described herein can be minimally invasive and allow for lower levels of pain (or pain perception) in the subject, which can improve the subject's pain compared to using other devices, methods, and kits. Overall blood draw experience. The kit can be provided with the device and instructions instructing the user on how the device can be used for blood sample collection and storage. Kits may include shipping sleeves and bags for shipping/transporting one or more samples to one or more testing facilities. One or more samples may be collected within one or more sample chambers or a portion thereof (eg, one or more cartridges) during shipping/transportation. Alternatively, the sample chamber or a portion thereof may not require any shipping sleeve/bag to carry/transport the cassette. In some examples, the cartridge may be enclosed in a housing (eg, a sample chamber) configured to protect the cartridge during shipping/transportation. For example, the housing may be a tube, as described and illustrated in some embodiments herein. The enclosure may allow for processing and/or stabilization of the sample prior to or during shipping/transport (eg, the enclosure may include a desiccant). The cartridge may allow for processing and/or stabilization of the sample prior to or during shipping/transportation. The enclosure can protect collected samples from the external environment (eg, control temperature, pressure, humidity, motion (eg, vibration), etc.). In some cases, the housing may include a seal (e.g., a cover or seal) to prevent tampering with the collected sample stored within the housing until the collected sample is retrieved by a technician or medical professional for testing of the collected sample . In some examples, the housing (or sample chamber) can be secured by a physical lock that can be opened by a physical key or a digital key (eg, by providing a digital key code).

Further provided herein is a harvested product for handling (or processing) and/or storing in one or more of a number of different states including a liquid state, a semi-solid state, or a solid state (e.g., a dry state or a solidified state). Systems (eg, devices), methods, and kits for samples (eg, liquid samples) of the present invention. In some embodiments, blood, such as capillary blood, may be collected from a subject, and the collected blood may be processed and/or stored in a number of different forms including plasma, serum, dried blood, liquid blood, or clotted blood one or more.

The cartridge may be configured to support one or more matrices configured to hold at least a portion (eg, at least a predetermined volume) of collected blood. The cartridge can be configured to separate (e.g., isolate or filter) one or more components of blood, including plasma, serum, cells (e.g., white blood cells (or white blood cells) and/or red blood cells (or red blood cells)), polypeptide molecules ( For example proteins, such as growth factors), polynucleotide molecules (eg, DNA, RNA, cell-free DNA (cfDNA), cell-free RNA (cfRNA), etc.), ions and/or small molecules (eg, nutrients). The systems (e.g., devices), methods, and kits disclosed herein can selectively isolate any number of sample components, including cells, plasma, serum, platelets, specific cell types, DNA (e.g., tumor cfDNA), RNA, proteins , inorganic materials, pharmaceuticals or any other components. The systems, methods and kits disclosed herein can also be configured to store any separated component of blood (eg, plasma, serum, etc.).

Samples (e.g., blood samples) collected using the systems (e.g., sample collection devices), methods, and kits described herein can be analyzed to determine the physiological state of a subject, to detect disease, and to monitor a subject health status. An individual can quickly assess his or her physiological state because a sample (e.g., a blood sample) can be rapidly collected using the disclosed devices, methods, and kits, and the sample (e.g., a blood sample) can be (1) used on-site, e.g. Assay for analysis or (2) transport (eg, expedited transport) to a testing facility. Reduced lead times for blood collection, analysis and quantification may be beneficial to many users, for example, subjects with certain physiological conditions/diseases requiring continuous and frequent blood sample collection/monitoring.

The various systems (e.g., devices), methods, and kits of the present disclosure can be combined or modified with other systems, methods, and kits, such as U.S. Patent Publication No. 2019/ 0000365 and those described in US Patent Publication No. 2017/0067803, entitled "SYSTEMS, METHODS, AND DEVICES FOR SAMPLE COLLECTION, STABILIZATION AND PRESERVATION," each of which is incorporated herein by reference in its entirety.

Aspects of the devices, methods and kits described herein may be applied to any particular application described herein as well as to any other type of liquid sample device other than a blood collection device. These devices, methods and kits can be used in any system that requires drawing a fluid sample from a subject. It should be understood that the different aspects of the devices, methods and kits described herein may be taken individually, collectively or in combination with each other.

II. Sample collection device

A sample collection device provided herein can be designed, configured, or used to collect, process (eg, separate), store and/or stabilize at least a portion of a sample, such as a fluid sample, eg, a fluid sample drawn from a subject. A sample can be a biological sample. The biological sample or liquid sample can be whole blood, serum, plasma, etc. The sample acquisition device may be configured to be held and operated by a user's hand. A user can be a subject or a third party, such as a doctor. A sample acquisition device may be hand-held (eg, by one or both hands of a user, by multiple hands from multiple users (eg, subject and medical professional, etc.)) during use. Accordingly, any sample acquisition device of the present disclosure may be a handheld device.

The sample collection devices provided herein can be used in a variety of locations or settings or applications, including, for example, in the subject's own home, at a remote location, on-site, or while the subject is traveling, for personalized healthcare, at the point of care ( POC) environment, in a hospital, in a clinic, in an emergency room, in a patient examination room, in an emergency department, in ambulatory care, in the pediatric field, in a field setting, in a nurse's office in an educational setting, in an occupational health clinic, During surgery or in the operating room.

Sample collection devices can be used to collect and store samples (eg, blood) drawn from a subject. A subject can be a patient. A subject can be an animal, such as a primate or non-primate. Subjects can be male or female. Subjects may be pregnant, suspected of being pregnant, or planning to become pregnant. Subject may be ovulating. A subject may have or be suspected of having a condition, such as cancer, autoimmune disease, or diabetes. The subject can be a human, and the human can be an infant, child, adolescent, adult or elderly.

A sample collection device is a device that a subject can easily and conveniently use to withdraw a sample, such as a blood sample, from a subject without the help or assistance of a third party. In some cases, the device can be operated by a third party to collect blood from a subject. Third parties can include, for example, family members of the subject, medical professionals such as physicians, nurses, or emergency medical technicians (EMTs), clinicians, or laboratory technicians. Third parties can be non-biological entities such as robots.

The sample collection device can be designed such that it is minimally invasive and produces low levels of pain (or reduced pain perception) in the subject. For example, a sample acquisition device may include a small number (e.g., one or two) of piercing elements rather than multiple (three, four, five, or more) needles or arrays of microneedles for piercing the skin . The device need not be prepackaged with one or more piercing elements. For example, various piercing elements may be operably and releasably coupled to the device, and/or interchanged onto the device, eg, after each use. In some alternative cases, the device may be operated without the use of a piercing element. For example, the subject may have one or more pre-existing incisions in the skin, and the device may be placed over the one or more pre-existing incisions to draw blood using skin suction and vacuum pressure.

The device may be portable, disposable and designed for use in a single subject session. In any of the embodiments disclosed herein, the device may be reusable. For example, the device may be used more than once, such as two, three, four, five, five, six, seven, eight, nine, ten or more times. In any of the embodiments disclosed herein, a single device may be used in multiple subject sessions with the same subject or with multiple different subjects. The device may have a certain form factor and be ergonomically designed to facilitate the sample collection process. Sample collection, processing and storage can be performed on a single device. In some cases, sample collection, processing, and storage may be performed using multiple components or devices (for example, a piercing module and a vacuum module may be provided as separate devices that are operably connected or coupled together by one or more channels ).

1A and 1B illustrate an exemplary device 100 according to some implementations. Specifically, Figure 1A shows an overall perspective view of the device. The device may include a housing 102 . The housing may include a housing base 110 and a housing cover 152 operatively coupled to each other. In some embodiments, housing base 110 may include a vacuum chamber and a deposition chamber as further described herein.

In any of the embodiments disclosed herein, the housing may be provided separately from the components of the device, and the housing need not be part of or integral with the components. For example, a vacuum chamber, deposition chamber, cassette chamber, and/or cassette assembly (or cassette module) as described elsewhere herein may be operably coupled to a separately provided housing. A groove as described herein may be disposed on a portion of the housing. Enclosures may include boxes, casings, shells, boxes, and the like. The housing may include one or more hollow chambers, cavities or grooves. The housing can be formed to have any shape and/or size. The housing may be configured to support one or more components as described elsewhere herein. Additionally, one or more components may serve as or function as an enclosure. The housing may be integrated with one or more components herein, or one or more components may be integrated with or into the housing. The housing can be configured to be mounted on a surface, such as the skin of a subject. In any of the embodiments disclosed herein, brackets or straps may be provided which allow the housing to be mounted to a surface.

The device may include a vacuum activator 114 . The vacuum activator may include a button 115 located on the base of the housing. In some cases, the device has no vacuum activator or does not require a vacuum activator. In one example, installing the sample chamber into the device can automatically provide a vacuum in the vacuum chamber of the device. The device may also include a piercing activator 166 . The piercing activator may include a button 167 . In some cases, button 167 may be exposed adjacent to the housing cover. In some cases, the device does not have or need not have a piercing activator. In one example, the device may be used to draw blood from skin that has been pierced or pre-cut by other discrete individual piercing elements. In another example, installation of the sample chamber into the device may automatically activate the device to pierce the subject's skin. Preferably, piercing may be activated (eg, by a piercing activator) after activation of the vacuum activator. In some cases, the piercing can be activated independently of the vacuum activator or the vacuum state of the device. In some embodiments, the piercing activator can be locked prior to use of the device, and the piercing activator can only be activated after the vacuum activator is activated. In some cases, the vacuum activator is locked prior to use of the device, and the vacuum activator may only be activated after the piercing activator is activated. As noted above, device 100, or any device herein, is operably coupled to a sample chamber, eg, cartridge assembly 180 as shown in FIG. 1A. Such a cartridge assembly can be releasably coupled to and detached from the device. Case tabs 192 of the case assembly may protrude from the edge of the device. In any of the embodiments disclosed herein, the cartridge tab and the piercing activator/vacuum activator (eg, button 115/167) can be located on different sides (eg, opposite ends) of the housing. Additional details regarding vacuum activators and piercing activators are described herein.

Sample collection devices for collecting blood samples may be modular (ie, "modular devices"), having two or more components for performing specific actions or functions on the device. FIG. 1B illustrates various components and subassemblies of modular sample acquisition device 100 . A modular device may include multiple modules (or subassemblies). Individual modules may be replaceable or exchangeable units. In some cases, after a single use of a modular device, a single module of the device can be replaced with a new module, while one or more other modules of the device can be reused. One or more modules of a modular device are reusable for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more uses of the device. Modular units may include one or more benefits, such as ease of partial replacement, partial maintenance or repair, partial upgrade, cleaning, manufacturing or packaging costs, compared to non-modular units (e.g., cannot be easily disassembled into multiple components) reduce. In some embodiments, as shown in FIG. 1B , the modular device can include (1) a housing cover 152 that includes a through hole 153 through which a button 167 of a piercing activator 166 can be inserted, (2) Lancing assembly, which includes button 167 of piercing activator 166, and (3) housing base 110, which includes vacuum activator 114 (eg, button 115). In some cases, housing base 110 may function as a vacuum chamber and/or a deposition chamber. In some cases, the lancing assembly can include a lancing mechanism to pierce the skin of a subject (eg, through an opening in housing base 110). The lancing assembly may be configured to activate a lancing mechanism disposed within housing base 110 to pierce the skin of a subject.

Figure IB further illustrates a sample chamber configured to be operatively coupled to the modular device. For example, a sample chamber may be a cartridge assembly 180, which may be releasably coupled to a modular device. The cartridge assembly can be part of a modular device and can be decoupled from the device. The cartridge assembly can be inserted through opening 128 into the deposition chamber (or cartridge chamber) of the housing base of the modular device. The cartridge assembly may include a cartridge 182 and a cartridge holder 190 . The cartridge holder may be configured to support a cartridge. The cartridge holder may include cartridge tabs 192 , seals/gaskets 194 and spring clips 196 . A user (eg, subject) can use the cartridge tabs to handle or hold the cartridge assembly. For example, the subject can insert the cartridge assembly into the deposition chamber (cartridge chamber) of the modular device by pushing in the cartridge tab. After sample collection is complete, the subject can remove the cartridge assembly from the deposition chamber (cartridge chamber) of the modular device by pulling on the cartridge tab. The subject can also hold the cartridge assembly by the cartridge tabs to avoid contamination of the cartridge and/or sample. Once the cartridge assembly is properly inserted into the modular device, the seal/gasket 194 can hermetically seal the deposition chamber (cartridge chamber). Spring clips 196 allow the cartridge to be held in place by the cartridge holder.

The cartridge 182 of the cartridge assembly may be configured to support one or more substrates 186 on which a fluid sample (eg, blood) is collected. In some embodiments, a cassette can support two or more matrices. Two or more substrates may be separated by one or more spacers. The cassette may include a cassette port 184 and access to the matrix (not shown). The cartridge may be configured to support one or more absorbent pads (not shown) to retain excess liquid. Absorbent pads help ensure that a predetermined volume of fluid can be acquired on each substrate. Additional details about the cartridge components are described, for example, in Section II, Part C of the specification.

The housing base 110 and the housing cover 152 may each be provided separately and coupled together to form the housing. The enclosure base may include a vacuum chamber and a deposition chamber. The vacuum chamber and deposition chamber may be separated by one or more walls. The walls can be substantially impermeable to liquids (eg, gases and liquids). The lid can hermetically seal the vacuum chamber and the deposition chamber. The cover can include a flow meter. Deposition chambers can also be used as cassettes and are referred to interchangeably herein. The cartridge assembly 180 can be inserted into a deposition chamber (or cartridge chamber). Once the cartridge assembly is fully inserted into the deposition chamber, the seal/gasket 194 can hermetically seal the deposition chamber. The housing cover may include wings 155 having a U- or V-shape to prevent obscuring the flow meter on the cover of the base of the housing. Accordingly, the housing cover can be shaped in a manner that allows a user (eg, a subject or a third party user) to view the flow meter and monitor the progress of liquid sample collection. The housing cover may have a vertical (Z-height) clearance to allow the piercing module to be placed therein (eg, it would be part of a lancing assembly as shown in FIG. 1B ). The piercing module may include one or more piercing elements configured to extend and retract through the opening of the groove.

In alternative embodiments, the sample chamber (eg, cartridge assembly) or components thereof containing the collected sample may be removed from the sample collection device and stored in the storage/transport device. Figure 2A shows a perspective view of a transport sleeve 200 that may be used to package filled sample chambers or samples from the sample chambers. The sleeve may include a hollow interior for storage of filled sample chambers or samples during shipping/transportation. The sleeve may include an opening for receiving a sample chamber (eg, a cartridge assembly). In some embodiments, the sleeve may include a cover 212 (eg, a peelable foil) for covering the opening prior to use of the sleeve. Cover 212 may be, for example, a foil which may be attached to the opening by adhesive and peeled off by the user prior to use of the sleeve. A desiccant (not shown) may be disposed within the cartridge for drying and/or keeping the sample dry. A foil cover can help protect the inside of the sleeve from moisture and contamination until use. Figure 2B shows a perspective view of shipping sleeve 200 after cassette assembly 180 has been inserted into the shipping sleeve. For example, additional details about the cartridge components are described in Section III of the specification.

One or more components of the device or one or more components operably coupled to the device (eg, any one module, any type of sample chamber, transport sleeve, etc.) can be formed to have any shape and/or size. Such components may be formed using any number of techniques known in the art, such as injection molding, blow molding, three-dimensional (3D) printing, and the like. Depending on the particular application, such components configured to contact a patient may include materials suitable for healthcare applications (eg, housing materials compatible with biomaterials for use). For example, components of the housing of the sample acquisition device may comprise or be made of materials such as copolyesters (e.g., polyethylene terephthalate (PET), polyethylene terephthalate (PET), PETG), polypropylene, polycarbonate, cellophane, vinyl, acetate, polyacrylic acid, butyl rubber, ethylene-vinyl acetate, natural rubber, nitrile rubber, silicone rubber, styrene block copolymer, vinyl Ether or tackifier. In any of the embodiments disclosed herein, such components may include antimicrobial and/or antiseptic materials such as sodium bicarbonate; hydrogen peroxide; benzalkonium chloride; chlorhexidine; hexachlorophene; iodine compounds; and combinations thereof.

In any of the embodiments disclosed herein, one or more components of the device or one or more components operatively coupled to the device (e.g., any one module, any type of sample chamber, transport sleeve, etc.) may include Materials such as polyvinyl chloride, polyvinylidene chloride, low density polyethylene, linear low density polyethylene, polyisobutylene, poly[ethylene-vinyl acetate] copolymer, lightweight aluminum foil and Combinations thereof, stainless steel alloys, commercially pure titanium, titanium alloys, silver alloys, copper alloys, grade 5 titanium, superelastic titanium alloys, cobalt-chromium alloys, stainless steel alloys, superelastic metal alloys (e.g., Nitinol, superelastic metal , such as GUM manufactured by Toyota Material Incorporated of Japan ), ceramics and their composites, such as calcium phosphate (eg, SKELITE ^TM manufactured by Biologix Inc.), thermoplastics, such as polyaryletherketone (PAEK), including polyetheretherketone (PEEK), polyetherketoneketone ( PEKK) and polyetherketone (PEK), carbon-PEEK composites, PEEK-BaSO4 polymer rubber, fabric, silicone, polyurethane, silicone-polyurethane copolymer, polymer rubber, polyolefin rubber, hydrogel, semi Rigid and rigid materials, elastomers, rubber, thermoplastic elastomers, thermoset elastomers, elastic composites, rigid polymers including polyphenylene, polyamide, polyimide, polyetherimide, polyethylene, epoxy , partially resorbable materials, such as composites of metal and calcium shell-based ceramics, composites of PEEK and calcium shell-based ceramics, composites of PEEK and absorbable polymers, fully resorbable materials, such as calcium shell-based ceramics, such as Calcium phosphate, tricalcium phosphate (TCP), hydroxyapatite (HA)-TCP, calcium sulfate, or other resorbable polymers such as polyglycolide, polyglycolide, polytyrosine carbonate, poly Carotene and combinations thereof.

One or more components of the device or one or more components operably coupled to the device (e.g., any one module, any type of sample chamber, transport sleeve, etc.) may have a composite of materials, including One or more to achieve various desired properties such as strength, stiffness, elasticity, compliance, biomechanical properties, durability and/or radiolucency preferences. Such components, individually or collectively, may also be made of heterogeneous materials, such as combinations of two or more of the aforementioned materials. The components of the device may be formed monolithically or integrally connected.

One or more components of the device or one or more components operably coupled to the device (e.g., any one module, any type of sample chamber, transport sleeve, etc.) may be ergonomically designed such that the user (e.g., Subject) is able to comfortably hold and/or manipulate the device and/or sample chamber with one or both hands. The device can have a compact form factor, making it highly portable (eg, easily carried around in a user's bag or purse). Exemplary dimensions (eg, length, width, and height) of sample chambers are described elsewhere herein.

A. Grooves for skin suction

In some embodiments, the housing base 102 of the device may include a recess 136 (shown in FIGS. 3D and 8C below). The groove may be disposed on a portion of the housing base (eg, the bottom surface). The groove may be formed as a sunken cavity or groove in the base of the housing. In some cases, the groove may be formed as a molded extrusion into the housing base. The grooves can be shaped like cups and configured to provide a skin "cupping" effect with the help of vacuum pressure. The groove may be sized and/or shaped to receive a portion of a surface, such as a subject's skin, and allow the surface, such as skin, to substantially conform to the groove upon application of vacuum pressure. The surface of the groove may be in substantial contact with the skin drawn into the groove. When the skin is drawn into the groove, the gap between the skin and the groove is negligible. The grooves can be used as suction chambers for drawing the skin into them and increasing the capillary pressure differential.

In some alternative embodiments, the device may be configured to draw other types of objects (eg, objects other than skin or the surface of the skin) into the recess under vacuum and further extract liquid samples from these objects. Examples of biological samples suitable for use with the devices of the present disclosure may include sweat, tears, urine, saliva, feces, vaginal secretions, semen, interstitial fluid, mucus, sebum, tears, aqueous humor, vitreous humor, bile, breast milk, Cerebrospinal fluid, cerumen, lymph, perilymph, gastric juice, peritoneal fluid, vomit, etc. In some embodiments, a liquid sample may be a solid sample that has been modified with a liquid medium. In some cases, a biological sample can be obtained from a subject in a hospital, laboratory, clinical or medical laboratory.

The recess of the device may be configured to remain in contact with the subject's skin surface area under vacuum pressure prior to and while collecting blood from the penetrating skin of the subject. In some embodiments, the volume enclosed within the groove can be substantially the same as the internal volume of the groove. In some embodiments, the groove can be configured to provide a security feature. In one example, the lancet may be configured to protrude a short distance into the cavity of the device such that the length of the protruding portion of the lancet is shorter than the height of the recess. Thus, the tip of the lancet may not be in contact with the subject's skin when protruding. The tip can be in contact with the skin as the skin is drawn towards the groove. Such a feature may prevent cutting the skin during undesired (eg, accidental) actuation of the lancet or without a vacuum to draw the skin toward the groove.

B. Vacuum Chamber and Deposition Chamber

The apparatus may include a vacuum chamber and/or a deposition chamber. The vacuum chamber and deposition chamber may be housed in the housing (eg, integrated into the base of the housing). The vacuum chamber and deposition chamber can be operably coupled to a separately provided housing or housing body (eg, as shown in FIG. 1B ). A vacuum chamber may be configured in fluid communication with the recess and the deposition chamber. The vacuum chamber and deposition chamber can be part of the housing base. The vacuum chamber and deposition chamber can be located in different parts (eg, compartments) of the housing base and come in various shapes or configurations. The vacuum chamber and deposition chamber may be separated by one or more walls. In some alternatives, the vacuum chamber and deposition chamber need not be separated (eg, by a wall). For example, the vacuum chamber and deposition chamber can be the same chamber in the device as the packaging. The combined vacuum chamber and deposition chamber can be a monolithic chamber.

The deposition chamber may be interchangeably referred to as a cartridge chamber and may be considered part of a sample acquisition device, as the deposition chamber may be configured to receive a sample chamber (eg, cartridge assembly 180 ) therein. For example, blood may be collected from a subject and transported from the well into a deposition chamber for collection and storage in a sample chamber, eg, a cartridge of cartridge assembly 180 .

In some embodiments, a mechanical device such as a vacuum pump can be used to evacuate a vacuum chamber or similar chamber (eg, before or after packaging). Mechanical devices may include components such as pistons, motors, blowers, pressure regulators, venturis, etc. In some cases, non-mechanical devices, such as chemicals or other reactants, can be introduced into the vacuum chamber and react to reduce the pressure within the vacuum chamber (eg, create a vacuum state). In other embodiments, the vacuum chamber may not require mechanical means to evacuate the vacuum chamber. For example, the sample chamber may be under vacuum, and mounting the sample chamber to a sample acquisition device (eg, device 100) may induce a negative pressure in the device (eg, the device body and/or the remaining internal chambers and channels of the device).

The volume and flow rate of blood collection by the system (eg, sample collection device) may depend on the start or initial vacuum pressure of the vacuum chamber. The starting or initial vacuum pressure may correspond to the pressure of the vacuum chamber after evacuation. In some embodiments, the initial vacuum pressure of the vacuum chamber can range from about -4 pounds per square inch (psig) to about -15 psig (eg, -14.7 psig at sea level), preferably about -8 psig to about -12 psig. In some preferred embodiments, the initial vacuum pressure of the vacuum chamber may be about -12 psig. In some other embodiments, the initial vacuum pressure of the vacuum chamber may be less than about -12 psig, eg, about -13 psig or -14 psig.

In some embodiments, device 100, or any other sample collection device disclosed herein, can be configured to collect a smaller amount of blood from a subject within a time window from the time the subject's skin portion is incised or penetrated ( For example, less than 150 microliters (μL), 140 μL, 130 μL, 120 μL, 110 μL, 100 μL, 90 μL, 80 μL, 70 μL, 60 μL, 50 μL, 40 μL, 30 μL, or 25 μL). In some embodiments, device 100 or any other sample collection device disclosed herein can be configured to collect larger volumes of blood, for example, at least 150 μL, 200 μL, 300 μL, 400 μL, 500 μL, 600 μL, 700 μL, 800 μL, 900 μL, 1,000 μL , 2,000 μL, 3,000 μL, 4,000 μL, 5,000 μL or more. In some embodiments, the time window can be less than about 30 minutes, 25 minutes, 20 minutes, 15 minutes, 10 minutes, 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes, or less. In one example, the time window may be less than 5 minutes, preferably less than 3 minutes. In another example, the time window may be less than 2 minutes. In a different example, the time window may be less than one minute.

C. Pierce module

The sample acquisition device may include a piercing module for piercing the subject's skin when the skin is drawn into the recess under vacuum pressure. In some alternatives, the device need not include a piercing module. In some embodiments, the piercing module can be positioned within the lancing assembly module, as shown in FIG. 1B . Piercing elements may include lancets, lancets, blades, needles, microneedles, scalpels, sharps, sticks, and the like. Any number of piercing elements are contemplated (eg, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more piercing elements). In some embodiments, the piercing element may preferably comprise two lancets.

The piercing module may also include one or more actuation elements (eg, spring elements) for actuating the lancet holder and moving the piercing element. Other non-limiting examples of actuating elements may include magnets, electromagnets, pneumatic actuators, hydraulic actuators, motors (e.g., brushless motors, direct current (DC) brushed motors, rotary motors, servo motors , direct drive rotary motors, DC torque motors, linear solenoid stepper motors, ultrasonic motors, gear motors, geared motors or piggyback motor combinations), gears, cams, linear drives, belts, pulleys, conveyor belts, etc. Non-limiting examples of spring elements may include a variety of suitable spring types such as nested compression springs, buckling posts, conical springs, variable pitch springs, snap rings, dual torsion springs, wire forms, limited travel extension springs, Braided wire springs, leaf springs, etc. Additionally, the actuation element (eg, spring element) may be made from any of a variety of metal, plastic, or composite materials.

D. Vacuum activators and piercing activators

The device may include a vacuum activator 114 configured to activate a (evacuated) vacuum chamber that generates a vacuum pressure that may draw the skin into the groove and subsequently facilitate removal from the penetrated skin. Collect blood. The device may also include a piercing activator 166 configured to activate a deployment spring for actuating the piercing element. The vacuum activator can be separated from the piercing activator. For example, the vacuum activator and the piercing activator may be two separate discrete components of the device. In some alternative embodiments (not shown), the vacuum activator and piercing activator can be integrated together as a single component, which can be used to activate the vacuum and piercing elements simultaneously or sequentially.

In some embodiments, the vacuum activator may be activated first, followed by the piercing activator. In other words, vacuum pressure may be activated prior to activation of the piercing element. In certain embodiments, the piercing activator may only be activated after the vacuum activator and vacuum have been activated. For example, the piercing activator may initially be in a locked state and cannot activate one or more piercing elements until the vacuum is activated. The piercing activator can only be unlocked after the vacuum activator is activated. The foregoing effects may be achieved by providing a locking mechanism coupling the piercing activator to the vacuum activator. The locking mechanism may be configured such that the piercing activator is initially in a locked state. The vacuum activator can be used as a key to unlock the piercing activator, when the vacuum activator is activated, the piercing activator can be unlocked at the same time.

In some embodiments, the piercing activator can be configured to activate the one or more piercing elements after the skin is drawn into the groove. The piercing activator may be configured to activate the one or more piercing elements after the skin has been vacuumed into the recess for a predetermined length of time. The predetermined length of time can be, for example, at least about 1 second, 5 seconds, 10 seconds, 20 seconds, 30 seconds, 40 seconds, 50 seconds, 60 seconds or longer. The predetermined length of time may be at most about 60 seconds, 50 seconds, 40 seconds, 30 seconds, 20 seconds, 10 seconds, 5 seconds, 1 second or less.

In any of the embodiments disclosed herein, vacuum activation can be semi-automatic or fully automatic. In some embodiments, the device does not require manual vacuum activation. For example, the device may be configured to automatically apply a vacuum upon sensing or detecting that the device has been placed on a surface (eg, on the subject's skin) or that a recess of the device is properly placed on the surface. In any of the embodiments disclosed herein, the activation of the piercing element can be semi-automatic or fully automatic. For example, upon sensing or detecting that a surface is drawn into a recess of the device and/or that the surface approaches an opening (e.g., 140) of the recess, the piercing element may be automatically activated to penetrate the surface (e.g., the subject's skin). ). Any kind or number of sensors may be used to enable the sensing or detection described above (for vacuum activation and/or piercing activation). Sensors may be included in (eg, on) the device or remote from the device. Non-limiting examples of sensors that may be used with any of the embodiments herein include proximity sensors, tactile sensors, acoustic sensors, motion sensors, pressure sensors, interference sensors, inertial sensors, thermal sensors, image sensors, and the like. In some cases, a button for the piercing activator and/or piercing activator may be included (or omitted) in the device if the vacuum activation and/or piercing activation are configured to be semi-automatic or fully automatic. In some embodiments, the device can be configured to automatically apply a vacuum (eg, by exhausting the vacuum from the cartridge assembly and towards the device) when the cartridge assembly is fully installed (eg, inserted) into the device.

E. Sample room

As previously described, a sample acquisition device (eg, a cartridge of the device) may be configured to receive a sample chamber. A sample chamber can be a body configured to be operably coupled to a sample acquisition device to receive, store, and/or process at least a portion of a sample from a subject. As disclosed herein, a sample chamber may be used with one or more types of sample acquisition devices. For example, the sample chamber may be used interchangeably with sample acquisition device 100 as shown in FIG. 1A and modular sample acquisition device 900b as in FIG. 8A. In some cases, the sample chamber can be a container (eg, a tube) to collect a fluid sample (eg, liquid blood) from the subject. In some cases, the sample chamber may include one or more cartridges to collect other types or forms of subject samples (eg, plasma or serum). In some examples, the sample chamber can be a cartridge assembly including a cartridge. A cartridge may include one or more matrices (eg, one or more solid matrices) for sample collection and/or storage. In some embodiments, a sample chamber can include a cartridge assembly configured to hold one or more substrates for storing and/or processing a liquid sample (e.g., blood) thereon, and a cartridge holder for the cartridge holder. in the support box. The cartridge holder may be releasably coupled to a cartridge or other component in the cartridge assembly using, for example, spring clips. The cartridge assembly may be configured to be releasably coupled to device 100 for collecting blood from a subject. The cartridge holder may include a cartridge tab configured to releasably couple to the distal end of the cartridge chamber. The case tab may be designed such that a user (e.g., a subject) can (1) support the case assembly by gripping the case tab, (2) couple the case assembly to the device by pushing in the case tab, and/or ( 3) Decouple the cartridge assembly from the device by pulling on the cartridge tab. In alternative embodiments, the cartridge holder may be part of the cartridge assembly, for example, the cartridge holder may be a permanent part of the cartridge assembly and thus may not or need not be releasably coupled to the cartridge assembly.

The sample chamber may be coupled to the cartridge before blood is collected from the subject and decoupled from the cartridge after blood from the subject has been collected into at least a portion of the sample chamber. In some embodiments, a sample chamber can include one or more matrices for collecting, storing, and/or stabilizing a collected blood sample. The matrix may be provided in strip form (as a strip). As used herein, a strip can refer to a solid matrix sized and/or shaped to maximize blood collection volume while still fitting into commonly used containers (eg, 3ml BD vacuum blood collection tubes, deep well plates, or 2ml Eppendorf tubes). Substrates as used herein are interchangeably referred to herein as substrate strips, strips, solid substrates, solid substrate strips, and the like.

In some embodiments, the matrices herein can also enable lateral transport/flow of blood. Non-limiting examples of matrices may include absorbent paper strips such as cellulose fibers or 100% cotton linters, or membrane polymers such as nitrocellulose, polyvinylidene fluoride, nylon, Fusion 5 ^™ , or polyether sulfone. In some embodiments, the substrate may comprise cellulose fiber-based paper (e.g., Whatman ^™ 903 or Ahlstrom 226 paper), treated with a chemical or reagent to stabilize the sample or one or more components of the sample (e.g., RNA stabilizing matrix or protein-stabilized matrix) paper. In some embodiments, the matrix includes cellulose filter paper. Any suitable commercially available filter paper can be used. Examples of commercially available filter papers include, but are not limited to, fiberglass filter materials, from Filter paper such as 903 sample collection card and rapid transport analysis /> Card. In some embodiments, the matrix can include nitrocellulose filter paper. In some embodiments, the matrix does not or need not contain any filter paper.

Collection of liquid samples can be aided by natural wicking or capillary action associated with the substrate, which can enhance and accelerate absorption or collection of liquid samples on the substrate. In some cases, the matrix may be composed of a material comprising a plurality of capillary beds such that when in contact with the liquid sample, the liquid sample is transported laterally through the matrix. The liquid sample may flow along a flow path from the proximal end to the distal end of the matrix, for example by wicking or capillary action.

The sample chamber may include a self-metering capability, which may be advantageous for collecting a predetermined volume of blood (e.g., into a sample container, into a cartridge into the sample chamber, etc.) for each individual regardless of variations in blood flow into the sample chamber for different individuals . Since capillary pressure and blood flow often vary from person to person (eg, due to age, sex, health, etc.), the volume of transfused blood into the sample chamber may vary. Alternatively or in addition, the amount of blood input into the sample chamber may vary depending on the operation of the operator (for example, the speed or quality of the coupling between the sample chamber and the sample collection device) or after (1) completion of sample collection into the sample chamber and (2) the time required between removing the sample chamber, or at least a portion thereof, from the sample acquisition device. In some examples, the sample chamber can be a cartridge assembly that includes a matrix strip, and the cartridge assembly can be designed to ensure that the matrix strip always contains a target blood volume (within a predefined range or up to a predefined scope). The cartridge assembly may also include one or more absorbent pads configured to absorb excess sample (eg, excess blood) and enable metering capability.

The sample chambers described herein can be used to collect a sample (eg, blood) from a subject. The sample chamber may also be configured for processing, stabilization and/or storage of the sample. In some cases, a sample chamber can store a sample (eg, in liquid form, solid form, semi-solid form, etc.) and subsequently process and/or stabilize the sample. This processing can be automatic or triggered by the user. In some cases, the sample chamber can be configured to process and/or stabilize the sample prior to storing the sample. In such cases, (1) when the subject's sample is collected into the sample chamber (e.g., from a sample collection device disclosed herein) and/or (2) when the subject's sample is collected into the sample chamber Thereafter, the sample chamber can be configured to process and/or stabilize the sample. In some examples, a cartridge assembly can include a containment unit and a processing/stabilization unit. The holding unit may be configured to hold the sample prior to processing and/or stabilization of the sample. A processing/stabilization unit (eg, one or more blood separation membranes, sample collection medium, etc.) may be configured to process and/or stabilize a sample directed or provided from a containment unit or sample collection device. The sample chamber may also include a storage unit (eg, container, vessel, compartment, etc.) to store the final product of processing and/or stabilizing the sample by the processing/stabilization unit. In other examples, the processing/stabilization unit may be configured to store the final product, and the cartridge assembly may not, and need not, include a separate storage unit. In a different example, the sample chamber itself may be a storage unit. The interior surface of the sample chamber may include active molecules for processing/stabilizing the sample. Alternatively, samples collected within the sample chamber may not and need not be processed and/or stabilized during storage.

The sample chambers disclosed herein may be modular. For example, the sample chamber can be a modular cartridge assembly. The cartridge assembly may include a plurality of modules (or subassemblies), such as a housing unit, a connection unit configured to couple to a sample acquisition device, a containment unit, a processing/stabilization unit, a storage unit, and/or a handle (e.g., for user handling box assembly). Individual units or modules of the cartridge assembly may be replaceable or exchangeable units. In some cases, after a single use of the cartridge assembly, a single unit of the cartridge assembly may be replaced with a new unit, while one or more other units of the cartridge assembly may be reusable. One or more units of the cartridge assembly are reusable for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more uses of the cartridge assembly. Modular cartridge assemblies may include one or more advantages over non-modular cartridge assemblies (e.g., assemblies that cannot be easily broken down into multiple components), such as ease of partial replacement, partial maintenance or repair, partial upgrade, cleaning, reduced Manufacturing or packaging costs, etc. Modular cartridge assemblies may be configured for single use only. In other embodiments, the cassette assembly may not and need not be modular. In one example, the cartridge assembly may be configured for a single use only and may not require any part replacement or cleaning.

The sample chamber can be configured to separate one or more components from the collected sample. There can be many methods for blood separation, some of which use size, deformability, shape or any combination thereof. Separation can be by one or more membranes, chambers, filters, polymers or other materials. The membranes, substrates, filters, and other components of the device can be chemically treated to selectively stabilize the components, facilitate sample flow, dry the sample, or any combination thereof. Alternative separation mechanisms may include liquid-liquid extraction, solid-liquid extraction and selective precipitation of target or non-target elements, charge separation, binding affinity, or any combination thereof. The separation phase can consist of one or more steps, each relying on a different mechanism to separate the samples. One such mechanism may utilize size, shape, or deformation to separate larger components from smaller ones. Cell separation can be performed by a sorter that can, for example, utilize one or more filters or other size exclusion methods to separate components of a sample. Separation can also be performed by selective binding, where specific components are separated by binding events, while unbound eluate enters or passes through alternate chambers.

In some devices, systems, methods or kits disclosed herein, a single membrane, substrate or filter can be used to separate and collect one or more sample components from a large number of samples. Single membrane, substrate or filter methods can include a device in which a sample can be applied to one end of the membrane, substrate or filter. When a sample flows through a membrane, substrate or filter, a first component of the sample (eg cells) can be separated from a second component of the sample (eg plasma) depending on the size of the membrane, substrate or filter pores. After the device is in operation, the membrane, substrate or filter containing the first component of the sample (in this example cells) can be severed from the portion containing the second component of the sample (in this example plasma) requiring the following Additional step: Severing the membrane, substrate or filter. In another approach, two separate membranes, substrates, or filters can be used to separate and collect sample components; for example, a first membrane, substrate, or filter to separate one component (e.g., blood cells), and A second membrane, substrate or filter for collection of other components such as blood plasma. The membranes, substrates or filters may be arranged such that the distal end of a first membrane, substrate or filter contacts the proximal end of a second membrane to facilitate separation of bulk components, such as cells, by the first membrane, substrate or filter, and by the second membrane, substrate or filter. A second membrane, substrate, or filter collects a second, smaller fraction, such as blood plasma.

1. Blood Separation

One aspect of the present disclosure provides a sample chamber for processing a sample (eg, blood) from a subject. As disclosed herein, such processing may include separating at least a portion of the collected blood from the remainder of the collected blood. In some embodiments, the sample chamber can be a cartridge assembly comprising cartridges (eg, at least 1, 2, 3, 4, 5 or more cartridges). In some embodiments, the cartridge assembly can be configured to separate (eg, sequester or filter) one or more components of blood. Blood components can include plasma, serum, cells (e.g., white blood cells (leukocytes) and/or erythrocytes (erythrocytes)), polypeptide molecules (e.g., proteins, such as growth factors), polynucleotide molecules (e.g., DNA, RNA, free DNA (cfDNA), free RNA (cfRNA), etc.), ions and/or small molecules (eg, nutrients). In some examples, the cartridge assembly can be configured to selectively isolate any number of sample components, including cells, plasma, serum, platelets, specific cell types, DNA (e.g., tumor cfDNA), RNA, proteins, inorganic materials, drug or any other component.

The cartridge assembly may include a cartridge port (ie, inlet port) configured to couple to a sample acquisition device. A sample collection device may be configured to retrieve blood from a subject, such as any sample collection device disclosed herein (eg, device 100 as shown in FIG. 1 ). The cartridge assembly can also include a slot (eg, bag) configured to support at least one blood separation membrane. At least one blood separation membrane may be configured to separate plasma or serum from blood. In some embodiments, the cartridge port can include a pathway configured to direct blood from the sample collection device to flow through the pathway and toward the at least one blood separation membrane.

In some embodiments, the direction of blood flow through the at least one blood separation membrane can be different than the direction of blood flow through the cartridge ports. In some examples, the direction of blood flow through the cartridge ports can be substantially parallel to the longitudinal axis of the cartridge assembly, and the direction of blood flow through the at least one blood separation membrane can be different than the longitudinal axis of the cartridge assembly. The direction of blood flow through the at least one blood separation membrane may not be in the same sample plane as the longitudinal axis of the cartridge assembly. The direction of blood flow through the at least one blood separation membrane may be offset by at least about 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees, 100 degrees, 110 degrees, 120 degrees, 130 degrees, 140 degrees, 150 degrees, 160 degrees, 170 degrees, 175 degrees or more. The direction of blood flow through the at least one blood separation membrane may be offset by up to about 170 degrees, 160 degrees, 150 degrees, 140 degrees, 130 degrees, 120 degrees, 110 degrees, 100 degrees, 90 degrees, 80 degrees, 70 degrees, 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees or less. In a preferred example, the direction of blood flow through the at least one blood separation membrane may be substantially orthogonal to the direction of blood flow through the cartridge ports.

In some cases, the pathway may be configured to direct blood from the sample acquisition device into the proximal end of the pathway in a first direction, through the pathway, and out of the distal end of the pathway in a second direction different from the first direction toward ( For example, to) at least one blood separation membrane. In some examples, the proximal end of the pathway can be configured to receive blood from a recessed opening in any of the sample acquisition devices disclosed herein.

The blood separation membrane may be liquid, semi-liquid, solid, semi-solid, gel, paste, slurry, powder, gas, or mixtures thereof. The structure of the blood separation membrane can be solid, porous, symmetrical, asymmetrical or a mixture thereof. A variety of membranes and fibrous elements are suitable for use as blood separation membranes, such as polymeric membranes and polymeric fibrous elements. Examples of suitable polymers may include, but are not limited to, polyolefins, polyesters, polyamides, polysulfones, acrylics, polyacrylonitriles, polyaramides, polyarylene oxides, and sulfides, as well as halogenated olefins and Polymers and copolymers of saturated nitriles. For example, polyvinylidene fluoride (PVDF), polyethylene, polypropylene, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), or any nylon such as nylon 6, 11, 46, 66 and 610, can be used as part of the blood separation membrane. Other suitable materials for blood separation membranes may include cellulose derivatives such as cellulose acetate, cellulose propionate, cellulose acetate propionate, cellulose acetate butyrate, and cellulose butyrate. Non-resin materials, such as fiberglass, including, for example, borosilicate glass fibers may also be used.

In some cases, a cartridge assembly may include one or more different types of cartridge ports. Different types of cartridge ports can be configured or customized to be compatible with different types of sample acquisition devices. Different types of cartridge ports can be configured to control or vary the blood collection (eg, speed, volume, etc.) of the cartridge assembly.

Figure 3A illustrates a perspective view of an example cartridge assembly 300, according to some implementations. Cartridge assembly 300 may include a cartridge 310 enclosing a processing/stabilizing unit 320 including at least one blood separation membrane. In some cases, a cartridge may enclose (eg, completely seal) the entire processing/stabilization unit. In other examples, the cassette may partially cover the processing/stabilization unit. The cartridge may be in direct contact with the outer surface of the processing/stabilization unit. Alternatively, the cartridge may be separated from the outer surface of the processing/stabilization unit by a spacer or spacer (eg, by air, gas, liquid, or other solid or semi-solid material). The position of the processing/stabilizing unit relative to the cartridge may be fixed (eg immobilized). Alternatively, the position of the processing/stabilizing unit relative to the cartridge may be movable, for example, to control the flow of blood into the processing/stabilizing unit, or to move the processing/stabilizing unit into the cartridge assembly before, during and/or after the separation procedure. other locations.

FIG. 3B illustrates a side cross-sectional view of cartridge assembly 300 including cartridge 310 . Cartridge 310 may include a cartridge port 330, which may be configured to couple to a sample acquisition device. Various coupling mechanisms can be utilized to couple the cartridge port to the sample acquisition device. Examples of coupling mechanisms may include, but are not limited to, male-to-female fasteners (e.g., mating or interlocking fasteners, hooks and holes, hooks and loops such as Velcro ^™ , female nuts threaded onto male bolts, inserted into female notches male protrusions, male threaded pipe installed in female elbows in pipes, male threaded Universal Serial Bus (USB) plugs that fit into female threaded USB receptacles, etc.), tethers (e.g., ropes), adhesives ( For example, solids, semi-solids, gels, viscous liquids, etc.), magnets (eg, electromagnets or permanent magnets), and other grasping mechanisms (eg, one or more robotic arms). In one example, the coupling can be performed using an electric field between the inlet port and the sample acquisition device. In another example, the cartridge port may include a Luer-type fitting (eg, as shown in FIG. 3B ) to couple (or mate) with a sample acquisition device. The female portion of the connector can close off part of the blood inlet groove to help control blood flow until it is close to the stack. The coupling mechanism may be reversible such that the cartridge can be removed from the sample collection device once sample collection from the subject is complete. The coupling mechanism may be leak-free, eg, to prevent leakage of the sample during collection and/or separation.

In some embodiments, as shown in FIGS. 3B and 3C , the cartridge port 330 of the cartridge 310 can include a path 340 that can be configured to direct blood in a first direction from the sample acquisition device into the proximal end of the path (as indicated by the arrow 342), through the path, and along a second direction different from the first direction (as shown by arrow 344) from the far end of the path to a portion of the treatment/stabilization unit 320 (e.g., a corner, edge, side, or on the surface). The pathway may include one or more entry grooves (or channels). In some cases, the path may include a single groove that directs blood flow. In other examples, the path may include multiple grooves, eg, at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or more grooves. Multiple grooves may be in fluid communication with each other at one or more junctions. Alternatively, multiple grooves may not or need not be in fluid communication with each other. The distal ends of the plurality of grooves may point towards the same part of the treatment/stabilization unit. Alternatively, the distal ends of the plurality of grooves may be directed towards different parts of the treatment/stabilization unit, eg, to enhance exposure of the treatment/stabilization unit to blood. The distal ends of the multiple grooves can allow blood to flow out in the same direction. Multiple grooves at the distal end can allow blood to flow out in different directions.

In some cases, the angle between the first direction (eg, arrow 342 ) and the longitudinal axis of the cartridge (eg, as shown by arrow 346 in FIG. 3B ) can be greater than zero degrees and less than 180 degrees. The angle between the first direction and the longitudinal axis may be greater than at least 0 degrees, 1 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees degrees, 100 degrees, 110 degrees, 120 degrees, 130 degrees, 140 degrees, 150 degrees, 160 degrees, 170 degrees, 175 degrees or more. The angle between the first direction and the longitudinal axis may be less than at most 180 degrees, 170 degrees, 160 degrees, 150 degrees, 140 degrees, 130 degrees, 120 degrees, 110 degrees, 100 degrees, 90 degrees, 80 degrees, 70 degrees, 60 degrees degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees, 1 degree or less.

In some cases, the angle between the second direction (eg, arrow 344 ) and the longitudinal axis of the cartridge (eg, arrow 346 ) can be greater than zero degrees and less than 180 degrees. The angle between the second direction and the longitudinal axis may be greater than at least 0 degrees, 1 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees degrees, 100 degrees, 110 degrees, 120 degrees, 130 degrees, 140 degrees, 150 degrees, 160 degrees, 170 degrees, 175 degrees or more. The angle between the second direction and the longitudinal axis may be less than at most 180 degrees, 170 degrees, 160 degrees, 150 degrees, 140 degrees, 130 degrees, 120 degrees, 110 degrees, 100 degrees, 90 degrees, 80 degrees, 70 degrees, 60 degrees degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees, 1 degree or less.

In some cases, the angle of intersection between the first direction (eg, arrow 342 ) and the second direction (eg, arrow 344 ) is greater than zero degrees and less than 180 degrees. The angle of intersection between the first direction and the second direction may be greater than at least 0 degrees, 1 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees , 90 degrees, 100 degrees, 110 degrees, 120 degrees, 130 degrees, 140 degrees, 150 degrees, 160 degrees, 170 degrees, 175 degrees or more. The angle of intersection between the first direction and the second direction may be less than at most 180 degrees, 170 degrees, 160 degrees, 150 degrees, 140 degrees, 130 degrees, 120 degrees, 110 degrees, 100 degrees, 90 degrees, 80 degrees, 70 degrees , 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees, 1 degree or less.

The path may include at least one turn such that the proximal and distal ends are oriented or facing different directions. In some examples, the path may include one or more curved, bent, or angled sections between the proximal and distal ends. The change in angle within the path within the turn may be sudden or gradual. A path may include multiple turns such that the proximal and distal ends are oriented in the same direction.

As with any of the subject cassette assemblies disclosed herein, the surfaces of the pathways (eg, pathway 340 as shown in FIG. 3B ) can be coated with a protective agent. The protectant can help maintain the integrity or quality of the blood as it is delivered to the processing/stabilization unit. In some embodiments, the protective agent prevents blood clotting. Protective agents may include anticoagulants such as, but not limited to, unfractionated heparin (“UFH”), low molecular weight heparin (“LMWH”), fondaparinux, and other antithrombin-binding anticoagulants, direct factor Xa, and factor IIa Inhibitors, dabigatran, or argatroban or /> Rivaroxaban or /> Apixaban or /> Edoxaban or /> Fondaparinux or /> wait. In some cases, the protectant may include EDTA. In some embodiments, the surface of the pathway may be free of any coagulation activators. This may be useful, for example, when the processing/stabilization unit is used to separate plasma from non-clotted blood. In other examples, the processing/stabilization unit may be configured to separate serum from clotted blood, and in this case, coagulation of the blood may begin after blood has flowed from the distal end of the path to the processing/stabilization unit. In alternative embodiments, at least a portion of the pathway surface may be coated with a coagulation activator, such as, but not limited to, thrombin activator, fibrinogen activator, metal salt (eg, calcium chloride, calcium gluconate), and the like. In some examples, the distal end of the pathway may include a coagulation activator to activate coagulation of the collected blood as it reaches the processing/stabilization unit.

For any of the subject cartridge assemblies disclosed herein, the surface of the pathway may be coated with an anti-adhesive agent configured to prevent blood (or one or more components thereof) from adhering to the surface. In some cases, the anti-adhesive agent may be a polymer, such as a fluoropolymer. Examples of fluoropolymers may include, but are not limited to, polyvinylidene fluoride (PVDF), ethylene chlorotrifluoroethylene (ECTFE), ethylene tetrafluoroethylene (ETFE), polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA) and modified fluoroalkoxy (copolymer of tetrafluoroethylene and perfluoromethyl vinyl ether, also known as MFA).

For any of the subject cartridge assemblies disclosed herein, at least a portion of the surface of the sample chamber can be coated with a binding moiety configured to bind to a specific target molecule within the collected blood. For example, a binding moiety can be coupled (e.g., coated) to a processing/stabilization unit (e.g., one or more blood separation membranes, sample collection media, etc.) as disclosed herein such that the binding moiety can interact with at least a portion of the collected blood touch. Examples of binding moieties may include, but are not limited to, small molecules, lipids, polypeptides (e.g., peptides or proteins, such as antibodies, fragments thereof, or functional variants thereof), polynucleotides (e.g., ribonucleic acid, deoxyribonucleic acid, peptide nucleic acid, etc. ), cells or fragments thereof, variants and combinations thereof. For example, a binding moiety may be an antibody or functional variant thereof configured to bind to a specific target molecule (ie, an antigen) in collected blood. Non-limiting examples of such antigens can include small molecules or polypeptides (eg, proteins or fragments thereof). Small molecules can be drugs, for example, to determine the persistence or half-life of a drug in a subject. The polypeptide can be a target protein or a fragment thereof that is modulated by a drug administered to the subject, eg, to determine the efficacy of a drug therapy in modulating (eg, upregulating, maintaining, or downregulating) expression of the target protein in the subject. Binding moieties can be used to identify or determine the presence of a particular cell type, disease or condition (eg, pregnancy, tumor, cancer, etc.) in a subject. In some cases, binding moieties can be labeled (e.g., with colored and/or magnetic particles (e.g., nanoparticles or microparticles) or fluorophores) to allow qualitative and/or quantitative measurement of target molecules bound by the initial binding moiety . For example, changes in the magnetism, fluorescence, and/or movement (eg, vibration) of such labels can be measured as indicators of target molecule binding to the initial binding moiety. An additional binding moiety (coupled to a portion of the sample chamber) different from the initial binding moiety can be used to analyze the amount of target molecule bound by the initial binding moiety. In some examples, similar to a sandwich enzyme-linked immunosorbent assay (ELISA), the additional binding moiety can be an antibody that binds to a different region of the target molecule than the initial binding moiety. Additional binding moieties can be labeled (eg, with colored and/or magnetic particles (eg, nanoparticles or microparticles) or fluorophores) to qualitatively and/or quantitatively measure target molecules bound by the initial binding moiety.

As used herein, the term "antibody" refers to a protein binding molecule with immunoglobulin-like function. The term antibody includes antibodies (eg, monoclonal and polyclonal antibodies), as well as derivatives, variants and fragments thereof. Antibodies can include immunoglobulins (Ig) of different classes (ie, IgA, IgG, IgM, IgD, and dIgE) and subclasses (eg, IgGl, IgG2, etc.). Derivatives, variants or fragments thereof may refer to functional derivatives or fragments that retain the binding specificity (eg, complete and/or partial) of the corresponding antibody. Antigen-binding fragments include Fab, Fab', F(ab')2, variable fragment (Fv), single chain variable fragment (scFv), minibody, diabody, and single domain antibody ("sdAb" or "nanobody" or "Camel"). The term antibody includes optimized, engineered or chemically conjugated antibodies and antigen-binding fragments of antibodies. Examples of optimized antibodies include affinity matured antibodies. Examples of antibodies that have been engineered include Fc-optimized antibodies (eg, antibodies optimized in the fragment crystallizable region) and multispecific antibodies (eg, bispecific antibodies). In some cases, the antibody can be a humanized antibody.

Examples of cells that may be identified by binding moieties may include, but are not limited to, lymphoid cells such as B cells, T cells (cytotoxic T cells, natural killer T cells, regulatory T cells, helper T cells), natural killer cells, Cytokines Cytokine-induced killer (CIK) cells; myeloid cells such as granulocytes (basophils, eosinophils, neutrophils/hypersegmented neutrophils), monocytes/macrophages cells, erythrocytes (reticulocytes), mast cells, platelets/megakaryocytes, dendritic cells; cells from the endocrine system, including thyroid (thyroid epithelial cells, parafollicular cells), parathyroid glands (parathyroid principal cells , eosinophils), adrenal glands (chromaffin cells), pineal gland (pineal cells) cells; cells of the nervous system, including glial cells (astrocytes, microglia), magnocytic neurosecretory cells cells, stellate cells, Boettcher cells, and pituitary gland (gonadotropin, corticotropin, thyroid-stimulating hormone, growth-stimulating hormone, prolactin); respiratory system cells, including pneumocytes (type I pneumocytes, type II pneumocytes) , Clara cells, goblet cells, dust cells; cells of the circulatory system, including cardiomyocytes, pericytes; cells of the digestive system, including stomach (gastric chief cells, parietal cells), goblet cells, Paneth cells, G cells, D cells, ECL cells, I cells, K cells, S cells; enteroendocrine cells, including enterochromaffin cells, APUD cells, liver (hepatocytes, Kupffer cells), cartilage/bone/muscle; bone cells, including osteoblasts cells, bone cells, osteoclasts, teeth (osteoblasts, ameloblasts); chondrocytes, including chondrocytes, chondrocytes; skin cells, including hair cells, keratinocytes, melanocytes (nevocytes); muscle Cells, including muscle cells; urinary system cells, including podocytes, juxtaglomerular cells, intra-/extra-glomerular mesangial cells, proximal tubule brush border cells, macula densa cells; germline Systemic cells, including spermatozoa, Sertoli cells, Leydig cells, ova; and other cells, including adipocytes, fibroblasts, tenocytes, epidermal keratinocytes (differentiated epidermal cells), epidermal basal cells (stem cells), nail and Keratinocytes of toenails, nail bed basal cells (stem cells), medullary hair stem cells, cortical hair stem cells, epidermal hair stem cells, epidermal hair root sheath cells, Huxley layer hair root sheath cells, Henle layer hair root sheath cells, outer hair root sheath cells , hair stromal cells (stem cells), moist stratified barrier epithelium, cornea, tongue, oral cavity, esophagus, anal canal, distal urethra and superficial epithelium of vaginal stratified squamous epithelium, cornea, tongue, oral cavity, esophagus, anal basal cells (stem cells) of the distal urethral and vaginal epithelium, urothelial cells (lining of the bladder and urinary ducts), exocrine epithelium, salivary gland mucus cells (polysaccharide-rich secretions), salivary gland serous cells (sugar-rich protease secretion), Von Ebner gland cells in the tongue (washing taste buds), mammary gland cells (milk secretion), lacrimal gland cells (tear secretion), ear cerumen gland cells (wax secretion), eccrine sweat gland dark cells (glycoprotein secretion) , eccrine sweat glands clear cells (small molecule secretions), apocrine cells (odourous secretions, sensitive to sex hormones), eyelid Moll cell glands (specialized sweat glands), sebocytes (lipid-rich sebum secretions) , Bowman's glands in the nose (cleanse the olfactory epithelium), Brunner's glands in the duodenum (enzymes and alkaline mucus), seminal vesicles (secrete semen components, including fructose for swimming sperm), prostate cells (secrete semen Gland cells of the bulbourethra (mucus secretion), Bartholin gland cells (vaginal lubricant secretion), Littre cell glands (mucus secretion), endometrial cells (carbohydrate secretion), isolated goblet cells of the respiratory and digestive tracts (mucus secretion secretion), mucous cells of the gastric mucosa (secretion of mucus), gastric gland zymogen cells (pepsinogen secretion), gastric acinar cells (hydrochloric acid secretion), pancreatic acinar cells (bicarbonate and digestive enzyme secretion), small intestinal Paneth cells (bacteriolytic enzyme secretion), lung type II pneumocytes (surfactant secretion), lung Clara cells, hormone-secreting cells, anterior pituitary cells, growth hormone, prolactin, thyrotropin, gonadotropin, corticotropin, pituitary intermediate cells, large cell neurosecretory cells, intestinal and respiratory cells, thyroid cells, thyroid epithelial cells, parafollicular cells, parathyroid cells, parathyroid chief cells, eosinophils, adrenal cells, chromaffin cells, Leydig cells Cells, follicular endometrium cells, ruptured follicular corpus luteum cells, granular lutein cells, lutein membranous cells, juxtaglomerular cells (renin secretion), dense plaque cells of the kidney, metabolic and storage cells, barrier function cells ( lung, intestine, exocrine glands and genitourinary tract), kidney, type I pneumocytes (air spaces lining the lungs), pancreatic duct cells (central acinar cells), non-striated duct cells (sweat glands, salivary glands, mammary glands, etc.), Tube cells (seminal vesicles, prostate, etc.), epithelial cells in enclosed lumens, ciliated cells with propulsive function, extracellular matrix secreting cells, contractile cells; skeletal muscle cells, stem cells, cardiomyocytes, blood and immune system cells, red blood cells (red blood cells), megakaryocytes (platelet precursors), monocytes, connective tissue macrophages (various types), epidermal Langerhans cells, osteoclasts (in bone), dendritic cells (in lymphoid tissue), small Glial cells (in the central nervous system), neutrophils, eosinophils, basophils, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, Natural killer cells, reticulocytes, stem cells and committed progenitors of the blood and immune system (various types), pluripotent stem cells, totipotent stem cells, induced pluripotent stem cells, adult stem cells, sensory sensor cells, autonomic neuronal cells, sensory organs and peripheral neuronal supporting cells, CNS neurons and glial cells, lens cells, pigment cells, melanocytes, retinal pigment epithelium, germ cells, oogonia/oocytes, sperm cells, spermatocytes, Spermatogonia (stem cells of spermatocytes), spermatozoa, nurse cells, ovarian follicular cells, Sertoli cells (in the testes), thymic epithelial cells, mesenchymal cells, mesenchymal kidney cells, and fetal cells (eg, fetal blood cells, For example, fetal nucleated red blood cells, which are used to detect fetal abnormalities during pregnancy).

Other examples of cells that may be identified by binding moieties may include, but are not limited to, cancer or tumor cells, such as those from cancers, including acanthoma, acinar cell carcinoma, acoustic neuroma, acral melanoma, snail tumor, acute phagocytosis Acute myeloid leukemia, acute lymphoblastic leukemia, acute megakaryocytic leukemia, acute monocytic leukemia, mature acute myeloid leukemia, acute myeloid dendritic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, Auroma, adenocarcinoma, adenoid cystic carcinoma, adenoma, adenomatous odontogenic tumor, adrenocortical carcinoma, adult T-cell leukemia, aggressive NK-cell leukemia, AIDS-related cancer, AIDS-related lymphoma, alveolar soft part Sarcoma, ameloblastic fibroma, anal carcinoma, anaplastic large cell lymphoma, anaplastic thyroid carcinoma, angioimmunoblastic T-cell lymphoma, angiomyolipoma, angiosarcoma, appendix carcinoma, astrocytoma, atypical Teratoid rhabdoid tumor, basal cell carcinoma, basaloid carcinoma, B cell leukemia, B cell lymphoma, Bellini ductal carcinoma, biliary tract carcinoma, bladder cancer, blastoma, bone cancer, bone tumor, brainstem glioma, brain Neoplasms, breast cancer, Brenner tumor, bronchial neoplasm, bronchioloalveolar carcinoma, brown tumor, Burkitt lymphoma, carcinoma of unknown primary site, carcinoid tumor, carcinoma, carcinoma in situ, penile carcinoma, carcinoma of unknown primary site, carcinosarcoma , Castleman's disease, central nervous system embryonal tumor, cerebellar astrocytoma, cerebral astrocytoma, cervical cancer, cholangiocarcinoma, chondroma, chondrosarcoma, chordoma, choriocarcinoma, choroid plexus papilloma, chronic lymphocytic leukemia, chronic monocytic leukemia, chronic myeloid leukemia, chronic myeloproliferative disease, chronic neutrophil leukemia, clear cell tumor, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoid Dermoid tumor, Degos disease, dermatofibrosarcoma protuberans, dermoid cyst, desmoplastic small round cell tumor, diffuse large B-cell lymphoma, dysembryoplastic neuroepithelial tumor, embryonal carcinoma, endodermal sinus tumor, Endometrial cancer, endometrial uterine cancer, endometrioid tumor, enteropathy-associated T-cell lymphoma, ependymal blastoma, ependymoma, epithelioid sarcoma, erythroleukemia, esophageal cancer, sensory neuroblastoma Cell tumor, Ewing family tumor, Ewing family sarcoma, Ewing sarcoma, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic cholangiocarcinoma, extramammary Paget's disease, fallopian tube cancer, fetus in fetus, fibroma, fibrosarcoma, Follicular lymphoma, follicular thyroid carcinoma, gallbladder carcinoma, gallbladder carcinoma, ganglioglioma, ganglioneuroma, gastric cancer, gastric lymphoma, gastrointestinal cancer, gastrointestinal carcinoid, gastrointestinal interstitial Stromal tumor, gastrointestinal stromal tumor, germ cell tumor, germ cell tumor, gestational choriocarcinoma, gestational trophoblastic tumor, giant cell tumor of bone, glioblastoma multiforme, glioma, glioma glomeruloma, glucagonoma, gonadoblastoma, granulosa cell tumor, hairy cell leukemia, hairy cell leukemia, head and neck cancer, head and neck cancer, heart cancer, hemangioblastoma, hemangiopericytoma, vascular Sarcoma, hematologic malignancies, hepatocellular carcinoma, hepatosplenic T-cell lymphoma, hereditary breast-ovarian cancer syndrome, Hodgkin's lymphoma, Hodgkin's lymphoma, hypopharyngeal carcinoma, hypothalamic glioma, inflammatory breast cancer , Intraocular Melanoma, Islet Cell Carcinoma, Islet Cell Tumor, Juvenile Myelomonocytic Leukemia, Kaposi Sarcoma, Kaposi Sarcoma, Kidney Cancer, Klatskin Tumor, Krukenberg Tumor, Laryngeal Cancer, Throat Cancer, Malignant Melanoma, Leukemia, Leukemia , lip and mouth cancer, liposarcoma, lung cancer, luteinoma, lymphangioma, lymphangiosarcoma, lymphoepithelioma, lymphoid leukemia, lymphoma, macroglobulinemia, malignant fibrous histiocytoma, malignant fibrous histiocytoma , malignant fibrous histiocytoma of bone, malignant glioma, malignant mesothelioma, malignant peripheral nerve sheath tumor, malignant rhabdomyoma, malignant tritoma, MALT lymphoma, mantle cell lymphoma, mast cell leukemia, mediastinal germ cell tumor , mediastinal tumors, medullary thyroid carcinoma, medulloblastoma, medulloblastoma, medullary epithelioma, melanoma, melanoma, meningioma, Merkel cell carcinoma, mesothelioma, mesothelioma, metastatic squamous neck carcinoma With occult primary, metastatic urethral carcinoma, mixed Müllerian tumor, monocytic leukemia, oral carcinoma, mucinous neoplasia, multiple endocrine neoplasia syndrome, multiple myeloma, multiple myeloma, mycosis fungoides Mycosis, mycosis fungoides, myelodysplastic disease, myelodysplastic syndrome, myeloid leukemia, myelosarcoma, myeloproliferative disorder, myxoma, nasal cavity carcinoma, nasopharyngeal carcinoma, nasopharyngeal carcinoma, tumor, neuronal tumor, neuroblastoma, neuroblastoma, neurofibroma, neuroma, nodular melanoma, non-Hodgkin lymphoma, non-Hodgkin lymphoma, non-melanoma skin cancer, non-small cell lung cancer, eye tumors, less Astrocytoma, oligodendroglioma, oncocytoma, optic nerve sheath meningioma, oral cavity cancer, oral cavity cancer, oropharyngeal cancer, osteosarcoma, osteosarcoma, ovarian cancer, ovarian cancer, ovarian epithelial cancer, ovarian Germ cell tumors, ovarian low malignant potential tumors, breast Paget disease, pancreatic neoplasms, pancreatic cancer, pancreatic cancer, thyroid papillary carcinoma, papilloma, paraganglioma, sinus carcinoma, parathyroid carcinoma, penile carcinoma, perivascular Epithelioid cell tumor, pharyngeal carcinoma, pheochromocytoma, intermediate differentiated pineal mesenchymal tumor, pinealoblastoma, pituitary cell tumor, pituitary adenoma, pituitary tumor, plasma cell tumor, pleuropulmonary blastoma , polyembryoma, precursor T lymphocytic lymphoma, primary central nervous system lymphoma, primary effusion lymphoma, primary hepatocellular carcinoma, primary liver cancer, primary peritoneal carcinoma, primary Neuroectodermal tumor, prostate cancer, pseudomyxoma peritonei, rectal cancer, renal cell carcinoma, chromosome 15 NUT gene-related respiratory cancer, retinoblastoma, rhabdomyoma, rhabdomyosarcoma, Richter's transformation, sacrococcygeal teratosis Tumor, salivary gland carcinoma, sarcoma, schwannomatosis, sebaceous gland carcinoma, secondary neoplasm, seminoma, serous neoplasm, Sertoli-stromal tumor, sex cord stromal tumor, Sezary syndrome, signet ring cell carcinoma , skin cancer, small blue round cell tumor, small cell carcinoma, small cell lung cancer, small cell lymphoma, small bowel cancer, soft tissue sarcoma, somatostatinoma, sooty warts, spinal tumors, spinal cord tumors, splenic marginal zone lymphoma, Squamous cell carcinoma, gastric cancer, superficial spreading melanoma, supratentorial primitive neuroectodermal tumor, superficial epithelial stromal tumor, synovial sarcoma, T-cell acute lymphoblastic leukemia, T-cell large granular lymphocytic leukemia, T-cell leukemia, T-cell lymphoma, T-cell prolymphocytic leukemia, teratoma, advanced lymphoma, testicular cancer, theca cell tumor, laryngeal cancer, thymus cancer, thymoma, thyroid cancer, renal pelvis and ureter transitional cell carcinoma, transitional cell carcinoma , urachal cancer, urethral cancer, urogenital tumors, uterine sarcoma, uveal melanoma, vaginal cancer, Verner Morrison syndrome, verrucous carcinoma, visual pathway glioma, vulvar cancer, Waldenstrom's macroglobulinemia , Warthin tumor and Wilms tumor.

As with any of the subject cartridge assemblies disclosed herein, a slot (eg, slot 350 of cartridge 310, as shown in FIG. 3B ) can be configured to support a handling/stabilizing unit. The handling/stabilizing unit may be supported and held in the space within the slot by means of an adhesive. The adhesive can be hydrogel, acrylic, polyurethane gel, hydrocolloid or silicone gel. Alternatively, the handling/stabilizing unit may be supported and held in the space within the slot without the aid of an adhesive.

At least one blood separation membrane 322 may be part of a processing/stabilization unit 320, as shown in FIG. 3B. The cartridge assembly may include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more blood separation membranes. In some examples, a cartridge assembly can include a plurality of blood separation membranes. Multiple blood separation membranes may be in fluid communication with each other, eg, to allow a blood sample to undergo multiple separation processes. Multiple blood separation membranes may be arranged in series. Alternatively, the plurality of blood separation membranes may not and need not be in fluid communication with each other, eg, each blood separation membrane may be configured to separate a different portion of the collected blood. In some embodiments, multiple blood separation membranes may be positioned in parallel.

The slots may also be configured to support a collection medium (or collection agent) for collecting blood separation products (eg, separated plasma or serum) of the blood separation membrane. The acquisition medium can be paper, such as cellulose paper. The acquisition medium may be a fibrous material, such as a cellulose fibrous material. The acquisition medium may comprise, for example, one or more materials selected from the group consisting of polyester, polyethersulfone (PES), polyamide (nylon), polypropylene, polytetrafluoroethylene (PTFE), polycarbonate, nitrocellulose , cellulose acetate and aluminum oxide. A slot can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more acquisition media (eg, one or more sheets of cellulose paper). As shown in FIG. 3B , collection medium 324 may be positioned adjacent to blood separation membrane 322 . In some cases, the collection medium and the blood separation membrane may be positioned directly adjacent to each other without any gap (eg, an air gap) therebetween. Alternatively, the collection medium and the blood separation membrane may be positioned adjacent to each other with a space therebetween, eg, to allow time for the collection medium to absorb the products of the blood separation process from the blood separation membrane. The acquisition medium may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more sheets of paper disclosed herein.

The collection medium may have a volume sufficient to collect a desired amount of a blood separation membrane product such as serum or plasma. The acquisition medium can be configured to hold (or contain) at least about 1 μL, 5 μL, 10 μL, 20 μL, 30 μL, 40 μL, 50 μL, 60 μL, 70 μL, 80 μL, 90 μL, 100 μL, 110 μL, 120 μL, 130 μL, 140 μL, 150 μL, 200 μL, 300 μL , 400μL, 500μL, 600μL, 700μL, 800μL, 900μL, 1,000μL or more blood separation membrane products. The collection medium can be configured to hold (or contain) at most about 1,000 μL, 900 μL, 800 μL, 700 μL, 600 μL, 500 μL, 400 μL, 300 μL, 200 μL, 100 μL, 50 μL, 10 μL, 1 μL or less of blood separation membrane product.

The slot can be configured to support a pre-filter. A pre-filter may be configured to filter blood prior to separating plasma or serum from the blood. The pre-filter can help increase the amount and/or velocity of blood separation per unit area of the at least one blood separation membrane (e.g., at least 1-fold, 2-fold, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 15 times, 20 times, 30 times or more). The pre-filter may be filter paper, such as glass fiber paper or cellulose filter paper. Any suitable commercially available filter paper can be used. Examples of commercially available filter papers include, but are not limited to, those from filter papers such as fast-pass analysis /> Card. In some embodiments, the pre-filter may comprise nitrocellulose filter paper. A pre-filter may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more filter papers disclosed herein. As shown in FIGS. 3B and 3C , a pre-filter 326 may be positioned adjacent to the blood separation membrane 322 . Prefilter 326 and collection medium 324 may be disposed on different portions (eg, opposing sides or surfaces) of separation membrane 322 . In some cases, the blood separation membrane and prefilter may be positioned directly adjacent to each other without any gap (eg, air gap) therebetween. Alternatively, the blood separation membrane and pre-filter may be positioned adjacent to each other with a space therebetween, eg, to allow time for the blood separation membrane to absorb and/or filter blood. As shown in FIGS. 3B and 3C , the distal end of path 340 may be positioned or oriented such that blood is conveyed from the sample acquisition device and toward (eg, directly toward) pre-filter 326 . In some examples, the blood separation membrane of the cartridge assembly can be configured to separate plasma or serum from collected blood, so the pre-filter can filter (e.g., retain) any number of other unwanted sample components, including cells, Platelets, specific cell types, DNA (eg, tumor cfDNA), RNA, proteins, inorganic materials, drugs, or any other component.

In some embodiments, the cartridge assembly may not and need not have a pre-filter in the slot. For example, the distal end of the path of the cartridge may be positioned such that blood is conveyed from the sample acquisition device and towards (eg, directly towards) the blood separation membrane.

As shown in FIG. 3B , blood separation membrane 322 , collection medium 324 , and pre-filter 326 may be collectively provided as treatment/stabilization unit 320 within slot 350 . The processing/stabilizing unit is interchangeably referred to herein as a stack. A cartridge may comprise a single processing/stabilization unit. Alternatively, a cartridge may include multiple processing/stabilization units (eg, multiple processing/stabilization units arranged in parallel or in series). In some examples, multiple processing/stabilization units may be positioned on the same plane within the cartridge. In other examples, multiple processing/stabilization units may be positioned on different planes within the cartridge. A cassette may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more stacks. A cassette may comprise up to 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 stack.

In some embodiments, the stack (e.g., processing/stabilizing unit 320) can be positioned to allow blood to flow transversely through the thickness of the stack in a third direction (e.g., different from longitudinal axis 346), and/or in at least one and a third direction. Configurations in which the planar flow traverses the planar region of the stack in various other directions (eg, in the same planar direction as the longitudinal axis 346 ). In some cases, the third direction may be different than the first direction and/or the second direction. The angle between the third direction (for lateral flow of blood or one or more components thereof) and the longitudinal axis may be greater than at least 0 degrees, 1 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees , 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees or more. The angle between the third direction (for lateral flow of blood) and the longitudinal axis may be less than at most 90 degrees, 80 degrees, 70 degrees, 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees , 1 degree or less. At least one other direction (for planar flow of blood or one or more components thereof) may be the same as longitudinal axis 346 . Alternatively, the angle between at least one other direction and the longitudinal axis 346 (for planar flow of blood or one or more components thereof) may be greater than at least 0 degrees, 1 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees or more. The angle between at least one other direction and the longitudinal axis 346 (for planar flow of blood or one or more components thereof) may be at most 90 degrees, 80 degrees, 70 degrees, 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees, 1 degree or less. As shown in Figure 3C, blood 370 is transported from the sample collection device, through the pathway, and toward the stack. Blood can be directed to a flat surface of the stack (eg, a flat surface of a pre-filter). The third direction (ie, the direction through the thickness of the stack) may be substantially normal to the longitudinal axis 346 of the cartridge. Furthermore, the third direction (eg, a direction through the thickness of the stack) and at least one other direction (ie, a direction through a planar region of the stack) may be substantially orthogonal to each other.

Each layer of the stack (eg, prefilter, blood separation membrane, and/or collection media) can have various shapes and sizes. For example, a layer may be in the shape of a rectangle, sphere, cuboid, or disc, or any partial shape or combination of shapes thereof. The layer may have a circular, oval, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-section of any partial shape or combination of shapes thereof. In some embodiments, each layer of the stack can have the same shape, thickness, length, width, depth, volume, or surface area. In other embodiments, each layer of the stack may not and need not be of the same shape or size. In some cases, the stacked layers can have different shapes and sizes to achieve different separation throughputs, total yields, and volumes collected. In one example, the width of the acquisition medium (ie, the acquisition strip) can be longer than the other layers in order to create a "tail" end to aid separation from the other layers. This separation can help reduce the loss of collected products, such as serum or plasma, from the collection medium.

In some embodiments, the distal end of the path may deviate from a linear axis extending between (1) the proximal end of the path and (2) the edge thickness portion of the stack. As shown in Figure 3B, the edge thickness portion of the stack 320 (where the bracket symbol "{" is located in Figure 3B) may be located between the proximal and distal ends of the path. The distal end of the path may be adjacent to the flat surface of the pre-filter, but need not touch. In some cases, blood may flow into the septum or void 360 from the distal end of the pathway. Blood from compartment 360 may then be directed or pumped toward the stack (eg, the exposed surface of pre-filter 326 or the exposed surface of blood separation membrane 322 ). In some examples, spacer 360 may be in fluid communication with accumulation region 362 disposed near the distal end of the pathway and stack 320 . The pooling area may include a separate blood holding container or cup configured to hold a volume of blood. The blood holding cup may be configured to contain blood as it is absorbed into a portion of the blood separation membrane. In some cases, a blood holding cup may be configured to hold a predetermined volume of blood to be processed (eg, separated) by stack 320 . The shape of the cup (or bag) can be optimized to direct different volumes of blood to different parts of the stacking surface (e.g., to accommodate the bulk of the infused blood near the stacking surface near the far end of the channel, or to help the infused blood along the flat surface of the stack. surface spread). The shape of the cup can be optimized to adjust the concentration of blood passing through the pre-filter, or to adjust the volume of blood contained. For example, the cup may be in the shape of a sphere, cuboid, or disc, or any partial shape or combination of shapes thereof. The cup may have a circular, oval, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-section of any partial shape or combination of shapes thereof. The cup may be configured to hold a predetermined volume of collected blood.杯可以被配置为至少容纳约1μL、5μL、10μL、20μL、30μL、40μL、50μL、60μL、70μL、80μL、90μL、100μL、110μL、120μL、130μL、140μL、150μL、200μL、300μL、400μL、500μL、 600 μL, 700 μL, 800 μL, 900 μL, 1,000 μL or more of blood. The cup can be configured to hold up to about 1,000 μL, 900 μL, 800 μL, 700 μL, 600 μL, 500 μL, 400 μL, 300 μL, 200 μL, 100 μL, 50 μL, 10 μL, 1 μL, or less of blood. In some examples, the cup can be used as a metering device (eg, a metering window) to determine when (or if) enough blood has been collected into the cartridge assembly.

In some embodiments, the distal end of the path may be adjacent to or in direct contact with the planar surface of the pre-filter.

The path of the cartridge port (ie, inlet port) of the cartridge assembly may include an opening (or cutout) exposing a portion of the path along the length of the cartridge port. The pathway can be in fluid (eg, gas or liquid) communication with an interior portion (eg, recess) of a sample acquisition device disclosed herein through an opening. The opening can be sealed prior to use of the cartridge assembly. In some cases, the opening may be partially or fully exposed to an interior portion of the sample acquisition device when the cartridge assembly is fully installed (eg, inserted) into the device.

In some embodiments, the cartridge assembly can be subjected to vacuum pressure when a vacuum in the sample acquisition device is activated (eg, manually by a user or automatically through user manipulation of the sample acquisition device). Vacuum pressure may be configured to assist blood flow laterally and/or through stacks on the cassette. In alternative embodiments, the cartridge assembly may be under vacuum pressure prior to its installation into the sample acquisition device. In some examples, while vacuum pressure may be vented into the sample acquisition device when the cartridge assembly is fully installed in the sample acquisition device, sufficient negative pressure may be maintained within the cartridge assembly to assist blood flow laterally and/or through the cartridge within the stack.

Figure 3D illustrates a side cross-sectional view of sample acquisition device 100 operably coupled to cartridge assembly 300, according to some embodiments. As shown, blood can be delivered from the opening in the groove 136 of the device 100, through the channels of the cartridge, and toward the stack (including at least one blood separation membrane). Cartridge assembly 300 may include a cartridge holder/tab 380 configured to seal the cartridge inside the device, eg, within a deposition/separation chamber. The cartridge assembly may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more absorbent pads. Depending on the position of the absorbent pad relative to the blood separation membrane (or stack), the absorbent pad can be used to absorb excess blood and/or excess serum or plasma. In some cases, one or more absorbent pads may be positioned directly adjacent to the blood separation membrane (or stack). Alternatively or in addition to the embodiments described above, one or more absorbent pads may be in fluid communication with, but physically separated from, the blood separation membrane (or stack). Isolation of one or more absorbent pads can reduce the risk of (1) contamination of blood (or serum/plasma) from the blood separation membrane (or stack) or (2) excessive absorption or wicking.

One or more components of the cartridge assembly may be configured to be released and decoupled. In some embodiments, the collection medium can be configured to be released and separated from the cartridge ( and sample collection device) decoupled. In some examples, the remaining components of the cartridge assembly can be configured to remain coupled to the sample acquisition device after the acquisition medium has been released and decoupled from the cartridge. In other examples, release of the acquisition medium from the cartridge may be configured to trigger release of the cartridge from the sample acquisition device. In other examples, the cartridge assembly can be configured to be released from the sample acquisition device before the acquisition medium is released from the cartridge. The released acquisition medium can then be stored in a separate shipping housing (eg, shipping sleeve 200 in Figure 2A) for shipping. In alternative embodiments, the cartridge assembly may be configured to be released from the sample acquisition device, but the acquisition medium may not and need not be configured to be released from the cartridge. In some examples, the cartridge assembly (which includes the acquisition medium) as a whole can be used as a shipping medium, and/or the cartridge assembly can be stored in a separate shipping housing (eg, shipping sleeve 200 in FIG. 2A ) for shipping.

In some embodiments, at least a portion of the cartridge 310 of the cartridge assembly 300 can include a transparent or translucent window. The window can be configured to allow the user to observe (1) blood flow within the path 340 of the inlet port, (2) blood flow distal to the path 340 toward the cup 362 or the exposed surface of the stack 320 (e.g., the exposed surface of the pre-filter 326). ), and/or (3) the blood flow in the stack, for example, the blood separation process of the collection medium by the blood separation membrane 322 . In some cases, a window can be located adjacent to at least one blood separation membrane, collection medium, and/or prefilter. The window of the cartridge can be aligned with the viewing window or open structure of the device (eg, device 100). In some cases, depending on the orientation of the cartridge assembly relative to the device, it is possible to view (1) blood input to the blood separation membrane (or stack of prefilters) or (2) blood output from the blood separation membrane (or stack) plasma or serum. In one example, the user can see the plasma or serum output from the blood separation membrane when the pre-filter facing the side of the cartridge assembly faces the subject's skin. In another example, the user can see blood input into the blood separation membrane (or stack of pre-filters) when the collection medium facing the side of the cartridge assembly faces the subject's skin.

3E and 3F schematically illustrate side cross-sectional views of another example of a sample chamber. The sample chamber may be a cartridge assembly 300b. The cartridge assembly may include one or more components of cartridge assembly 300 as disclosed herein (eg, in FIGS. 3B and 3C ). Referring to FIG. 3E , cartridge assembly 300 b may include cartridge port 330 coupled to cartridge 310 . Cartridge port 330 may be configured to couple (eg, releasably couple) to a sample acquisition device using any of the coupling mechanisms described herein. The cartridge may include a slot 350 surrounding the processing/stabilization unit 320 . The processing/stabilization unit 320 may include at least one blood separation membrane 322 . In some cases, processing/stabilization unit 320 may also include acquisition media 324 and/or pre-filter 326 . Cartridge port 330 may include a path 340 configured to direct a sample (eg, blood) of a subject from a sample acquisition device to cartridge 310 . The cartridge may also include a compartment 360 in fluid communication with the pathway 340 . The compartment 360 may also be in fluid communication with an accumulation area 362 (eg, a container or cup) configured to hold a volume of collected sample. Accumulation region 362 may be positioned adjacent processing/stabilization unit 320 such that collected samples may be contained within cartridge 310 while at least a portion of the collected samples are processed/stabilized by flowing through processing/stabilization unit 320 . As shown in FIG. 3F, the direction of sample flow through path 340 may be substantially the same as the longitudinal axis of the cartridge assembly (as indicated by arrow 346). The direction of sample flow through path 340 may be different than the direction of blood flow through processing/stabilization unit 320 . In one example, the direction of sample flow through path 340 may be substantially orthogonal to the direction of blood flow through processing/stabilization unit 320 .

Figure 4 shows a side cross-sectional view of a different example of a sample chamber. The sample chamber may be a cartridge assembly 400 . Cartridge assembly 400 may include one or more components of cartridge assembly 300 disclosed herein (eg, in FIGS. 3B and 3C ). Cartridge assembly 400 may include a cartridge port 410 that provides a path 440 for blood to be conveyed from a sample collection device (eg, a sample collection device disclosed herein) and toward a processing/stabilization unit 420 (ie, stack). Cartridge port 410 may be configured to couple (eg, releasably couple) to a sample acquisition device using any of the coupling mechanisms described herein. For example, cartridge port 410 may have a luer-type fitting that mates with a sample acquisition device. Processing/stabilization unit 420 may include one or more processing/stabilization components. For example, processing/stabilization unit 420 may include a first processing/stabilization component 420a and a second processing/stabilization component 420b. Two handling/stabilizing assemblies can be positioned adjacent to each other. In one example, as shown in Figure 4, two handling/stabilizing components may be in direct contact with each other. Alternatively, the handling/stabilizing components may be separated by a space or gap (not shown). As shown in FIGS. 3B-3D , the cartridge assembly 300 can be configured to receive collected blood on a stacked flat surface to allow separation of the blood to occur at a location other than the longitudinal axis 346 of the cartridge 300 (as shown in FIGS. 3B-3F ). (eg, substantially orthogonal) directions. In the example of FIG. 4 , cartridge assembly 400 may be configured to receive collected blood at an edge of processing/stabilization unit 420 and/or on a portion of a flat surface near the edge to allow separation of blood in the following directions: (i ) substantially the same as and/or (ii) on the same plane as the longitudinal axis 405 of the cartridge assembly 400 (shown in FIG. 4 ). In this case, the upper part of the processing/stabilizing component will contain the filtered part of the sample (eg blood cells), while the lower part of the processing/stabilizing component will contain another part of the sample (eg plasma or serum). In some embodiments, each processing/stabilization component may comprise multiple components, eg, pre-filters, blood separation membranes, and/or collection media as disclosed herein. In some examples, the top portion 422 of the processing/stabilization unit 420 adjacent the path 440 can include a pre-filter 422 that can be configured to filter cells from collected blood, for example. Intermediate portion 424 of processing/stabilization unit 420 may include one or more blood separation membranes. The bottom portion 426 of the processing/stabilization unit 420 remote from the path 440 may include the acquisition medium. In some examples, a single processing/stabilization component (eg, only one of 420a or 420b) may be used. Alternatively, more than two processing/stabilizing components (e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or more processing/stabilizing components) may be used, all, some, or none direct contact with each other. In some examples, a pre-filter assembly may be positioned next to the upper portion of one or more processing/stabilization assemblies to initially receive blood and filter out the sample before allowing the remainder of the sample to flow to and onto the surface of the processing/stabilization assembly. At least a portion (eg, cells, debris, etc.). As shown in FIG. 4, the features of cartridge assembly 400 may be applied to any device, system, method or kit for sample collection, as disclosed herein.

Another aspect of the present disclosure provides a system for blood collection and blood separation. The system can include a sample acquisition device (eg, a sample acquisition device) and a sample chamber (eg, a cartridge assembly) as disclosed herein. In some embodiments, a sample acquisition device can include a built-in vacuum. This vacuum is sufficient to pull the subject's skin toward the sample collection device, allowing blood to be drawn from the subject after the skin has been pierced. In an alternative embodiment, the chamber of the sample acquisition device containing the cartridge assembly may be prepackaged with a built-in vacuum, and venting this vacuum into the sample acquisition device may be sufficient to pull the subject's skin towards the sample acquisition device, once the skin Was impaled to draw blood from subject.

Another aspect of the disclosure provides a method (eg, for blood collection and blood separation). The method can include using a sample collection device as disclosed herein to collect blood from the subject. The method can also include separating plasma or serum from blood using a sample chamber (eg, cartridge assembly) as disclosed herein. In some embodiments, the method can also include storing plasma or serum separated from the blood (eg, in collection medium 324 of cartridge assembly 300, as shown in Figure 3B).

2. Liquid Blood Collection

Another aspect of the present disclosure provides a sample chamber, such as a cartridge assembly, for storing a fluid or fluid-like sample collected from a subject by a sample collection device, such as any of the sample collection devices disclosed herein. (eg, liquid blood). In some embodiments, a cartridge assembly can include a coupling unit configured to couple to a portion of a sample acquisition device, such as a cartridge chamber. The coupling unit may include an inlet port. The cartridge assembly may also include a container configured to store a liquid or a liquid-like sample. The cartridge assembly may also include a cartridge holder configured to support the container. The proximal end of the container may be configured to be coupled to the coupling unit and the distal end of the container may be configured to be coupled to the cartridge holder. The liquid or fluid-like sample may be one or more members selected from the group consisting of liquid blood, sweat, tears, urine, saliva, feces, vaginal secretions, semen, interstitial fluid, mucus, sebum, lacrimal trough fluid, Aqueous humor, vitreous humor, bile, breast milk, cerebrospinal fluid, cerumen, lymph, perilymph, gastric juice, peritoneal fluid, vomit, etc. In one example, the liquid sample may be liquid blood.

In some embodiments, the proximal end of the container of the cartridge assembly can be configured to be releasably coupled to the coupling unit using any of the coupling mechanisms described herein. In some cases, the container may include a container port configured to releasably couple to the coupling unit. A container port can be part of a container. A container port can be releasably coupled to the proximal end of the container. In other embodiments, the proximal end of the container may not or need not be configured to releasably couple to the coupling unit. For example, the proximal end of the container may be permanently coupled to the coupling unit. In some embodiments, the distal end of the container can be configured to be releasably coupled to the cartridge holder using any of the coupling mechanisms described herein. In other embodiments, the distal end of the container may not or need not be configured to releasably couple to the cartridge holder. For example, the distal end of the container can be permanently coupled to the cartridge holder. Alternatively, the cartridge holder may be manufactured as part of the container, eg as part of the distal end of the container. The proximal end of the container may include one or more openings configured to receive a liquid sample (eg, liquid blood). The distal end of the container may not include any opening and may be closed to allow collection of a sample within at least a portion of the container.

FIG. 5A illustrates a side sectional view (left side of FIG. 5A ) and perspective view (right side of FIG. 5A ) of an example cartridge assembly 500 that may be configured to collect a fluid or fluid-like sample (eg, liquid blood). Cassette assembly 500 may include a coupling unit 510 (interchangeably referred to herein as an adapter or tube inlet adapter). The coupling unit may be configured to couple (eg, releasably or permanently couple) to a sample acquisition device (eg, a port in a cartridge of any sample acquisition device disclosed herein) using any coupling mechanism described herein. For example, coupling unit 510 may have a luer-type fitting 512 to mate with a cartridge port of a sample acquisition device. Coupling unit 510 may include an opening, inlet, or channel configured to serve as a path 514 for blood to flow from the sample collection device to the cartridge assembly (eg, into the cartridge assembly). The cartridge assembly 500 may include a container 520 coupled with a coupling unit 510 and a cartridge holder 540 . The container may have a circular, oval, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-sectional view of any partial shape or combination of shapes. The container may include a container port (eg, cap or cap) 530 . The container may include a collection tube 535 configured to contain collected blood. A container port can be coupled to the proximal end of the container. For example, the container port (eg, cap) and the proximal end of the collection tube can be releasably coupled using any of the coupling mechanisms described herein (eg, luer-type, thread-type, friction fit, etc.). In another example, container port 530 and collection tube 535 may be permanently coupled (eg, glued) to each other. The proximal end of the collection tube may be configured to be coupled to the coupling unit through the container port. For example, the coupling unit and container port may be releasably coupled using any of the coupling mechanisms described herein (eg, luer-type, thread-type, friction fit, etc.). In another example, the coupling unit and the container port may be permanently coupled (eg glued) to each other. In some cases, the coupling unit and a port in the cartridge of the sample acquisition device may be permanently coupled. In some cases, container port 530 and collection tube 535 may need to be aligned (eg, rotationally aligned) to insert cartridge assembly 500 into a sample collection device in a preferred orientation. When the components are aligned, the container port 530 and collection tube 535 can utilize any of the coupling mechanisms described herein to interlock the two components. In other embodiments, the container 520 may not and does not require the container port 530 to couple to the coupling unit 510 . In one example, collection tube 535 may be directly coupled (eg, releasably coupled or permanently coupled) to coupling unit 510 .

In some embodiments, at least a portion of the collection tube can include a transparent or translucent window. The window can be configured to allow the user to observe blood flowing into the collection tube. In other embodiments, the collection tube itself may be transparent or translucent, for example, the collection tube may comprise one or more transparent or translucent materials. In some embodiments, the bottom of the collection tube 535 can be configured to allow the container 520 to stand on, for example, a flat surface. For example, at least a portion of the bottom of collection tube 535 may be flat.

In some embodiments, the container port of the container may include one or more openings configured to open and allow liquid (e.g., gas such as air, liquid such as liquid blood, etc.) to enter when the container port is coupled to the coupling unit container. The opening of the container port may have a circular, oval, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-section of any partial shape or combination of shapes. In some cases, the opening may utilize a liquid regulator to control the passage of liquid into the container (eg, from the sample acquisition device into the container) or from within the container (eg, from the container into the sample acquisition device). Fluid regulators may include mechanical regulators (eg, spring regulators or self-closing flaps), hydraulic regulators, pneumatic regulators, manual regulators, solenoid regulators, or motorized regulators. Examples of liquid regulators may include, but are not limited to, seals, flaps, valves, gates, switches, levers, pumps, and the like. In one example, as shown in FIG. 5A , the container port 530 of the container 520 may include an integrated self-closing valve 532 (eg, a duckbill valve) configured to (i) open when the container port 530 is coupled to the coupling unit 510 to allow liquid to enter the container 520 and (ii) close to reduce (eg, inhibit or prohibit) liquid from entering the container 520 when the container port 530 is not coupled to the coupling unit 510 . In other examples, the opening may permanently allow passage of liquid (eg, one-way liquid passage in a direction from outside the cartridge assembly 500 and into the cartridge assembly 500 ) without the need for a liquid regulator.

In some embodiments, the coupling unit may include one or more fluid paths (shown as 516 in FIG. Paths allow air to escape from the container. In some cases, a coupling unit may connect a blood port of a sample acquisition device to a container of a cartridge (eg, via a container port). As a result, at least a portion of the cartridge can be located inside the sample acquisition device (eg, within the cartridge chamber of the sample acquisition device). When the cartridge is coupled to the sample acquisition device, the cartridge chamber may be under vacuum (eg, by activating the vacuum chamber below ambient pressure). Subsequently, upon coupling, air can be expelled from the container, through one or more fluid paths, and into the cartridge chamber. The one or more fluid paths may allow pressure (eg, vacuum pressure) within the cartridge chamber to equalize as blood is collected into the container. One or more liquid paths may allow the container to be evacuated, eg, to the same pressure level as the surrounding cartridge (eg, still below ambient pressure). The vacuum created in the container draws blood from the subject's pierced skin, through the entry port, and into the container of the cartridge. In some examples, air from within the container (eg, from within the collection tube) may continue to be expelled through the fluid pathways disclosed herein as blood is drawn into the container. In other examples, air from within the container may exit through one or more semi-permeable membranes integrated into the collection tube of the container. The semi-permeable membrane can be configured to allow the flow of air while preventing the flow of liquid (eg, out of the collection tube).

In some embodiments, blood may be drawn into the container until a desired volume of blood is collected. In some cases, the vacuum of the sample acquisition device may be configured to be sufficient to draw approximately a desired volume of blood into the container. In some cases, as shown in FIG. 5A , container 520 may include one or more indicators 522 (eg, markings, graphics, numerical indicators, etc.) that indicate to the user the approximate amount of blood drawn into container 520 . The container may include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more indicators. The user can then stop the blood drawing process (eg, by pressing a button located on the container or sample collection device). In alternative embodiments, the indicator may include a sensor configured to detect or measure the presence and/or amount (eg, weight, volume) of blood collected in the container. In one example, when the sensor measures and determines that a desired volume of blood has been collected, the device or cartridge may be configured to automatically stop the blood collection process. The indicator may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more sensors. Examples of sensors may include, but are not limited to, mechanical sensors (e.g., scales), optical sensors (e.g., cameras), ultrasonic sensors (e.g., non-contact ultrasonic liquid level sensors), radar sensors (e.g., radar level transmitters) , capacitive sensors (eg, capacitive measuring probes), chemical sensors, pressure sensors, liquid flow sensors, humidity sensors, vibration sensors, field sensors (eg, electromagnetic sensors), temperature sensors, etc. The sensor may be configured to contact the collected blood. Alternatively, the sensor may not and need not be in contact with the collected blood for its function. In some cases, the outer surface of tube 535 may be covered (eg, partially or fully covered) to allow the sensor to focus on a desired area of the tube for blood sensing.

In some cases, an indicator (eg, a sensor) may be operably coupled to an alarm system configured to alert the user when a desired amount of blood has been collected into tube 535 . In some examples, the alert system may be configured to generate audible, tactile, and/or visual alerts to the user (eg, via a speaker or light emitting diodes (LEDs)). The alarm system can be operatively coupled to the indicator through one or more wired (eg, digital circuits) or wireless communication channels. Examples of wireless communication channels can include WiFi, Near Field Communication (NFC), 3G, 4G and/or 5G networks. Signals for activating the alarm system may be transmitted remotely from the indicator (eg, a sensor of the indicator) to the alarm system via one or more communication channels. In some cases, a sensor (e.g., a computer processor operatively coupled to the sensor) may be configured (or programmed) to prevent blood droplets from being collected by, for example, (1) passing through the sensor and entering tube 535 or (2) The blood wets the inner surface of the tube 535 and falsely triggers the alarm system. In one example, the sensitivity and/or threshold of a sensor may be adjusted to prevent false triggering of an alarm system.

In some cases, one or more sensors can be used to determine one or more target analytes (e.g., cells, plasma, serum, platelets, specific cell types, DNA (e.g., , the presence and/or concentration of tumor cfDNA), RNA, protein, inorganic material, drug or any other component). For example, when liquid blood is collected into a container and brought into contact with a sensor, the sensor can determine the presence and/or absence of a target analyte in the liquid blood in the container based on detected changes in electron and ion mobility and charge accumulation.

容器可以被配置为容纳至少约1μL、5μL、10μL、20μL、30μL、40μL、50μL、60μL、70μL、80μL、90μL、100μL、110μL、120μL、130μL、140μL、150μL、200μL、300μL、400μL、500μL、 600μL, 700μL, 800μL, 900μL, 1,000μL or more blood. The container can be configured to hold up to about 1,000 μL, 900 μL, 800 μL, 700 μL, 600 μL, 500 μL, 400 μL, 300 μL, 200 μL, 100 μL, 50 μL, 10 μL, 1 μL, or less blood. The desired volume of blood collected in the container may be at least about 1 μL, 5 μL, 10 μL, 20 μL, 30 μL, 40 μL, 50 μL, 60 μL, 70 μL, 80 μL, 90 μL, 100 μL, 110 μL, 120 μL, 130 μL, 140 μL, 150 μL, 200 μL, 300 μL , 400 μL, 500 μL, 600 μL, 700 μL, 800 μL, 900 μL, 1,000 μL or more. The desired volume of blood collected in the container can be up to about 1,000 μL, 900 μL, 800 μL, 700 μL, 600 μL, 500 μL, 400 μL, 300 μL, 200 μL, 100 μL, 50 μL, 10 μL, 1 μL or less.

The coupling unit may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more liquid paths. The coupling unit may comprise at most 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 liquid paths. A separate liquid path can be placed near the surface of the coupling unit. In one example, the coupling unit may comprise a separate liquid path (eg, opening or channel) prior to coupling the coupling unit to the container of the cartridge assembly (or the container port of the container). In another example, the coupling unit may include at least one groove or open channel. When coupling the coupling unit to a container port, the groove may be positioned adjacent to a surface of the container (eg, a surface of the lid), thereby creating a separate liquid path. Individual liquid paths may be straight, curved, vertical, diagonal, zigzag (or angled), irregularly shaped, or mixed. The individual liquid paths may have a circular, elliptical, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-section of any partial shape or combination of shapes thereof. When multiple liquid paths are provided, each of the multiple liquid paths may have the same shape, thickness, length, width, depth, volume or surface area. In other cases, two fluid paths of the plurality of fluid paths may not and need not be of the same shape or size.

In some embodiments, the cartridge assembly or sample acquisition device may include a separate vent container configured to capture air expelled from the container through the fluid path.

As shown in FIG. 5A , the cartridge assembly may include a cartridge holder 540 configured to support a container 520 . In some cases, a portion of cartridge holder 540 may be configured to extend out of the cartridge chamber when the cartridge assembly is coupled to the cartridge chamber. Accordingly, a user can grasp the cartridge holder 540 (eg, by grasping the cartridge tab 542 ) to insert or remove the cartridge assembly from the sample acquisition device. In alternative embodiments, the cartridge holder may not or need not extend beyond the cartridge chamber when the cartridge assembly is coupled to the cartridge chamber. In this case, the cartridge holder can be concealed (eg, by a mechanical door, motorized door, or cover of the sample collection device), lay flat against the surface of the sample collection device, or be pressed into the sample collection device. In some examples, a cartridge assembly can be releasably coupled to a sample acquisition device using any of the coupling mechanisms described herein. By pressing a switch on the cartridge holder or sample acquisition device, the coupling mechanism can be partially or completely deactivated to allow the holder to protrude relative to the surface of the sample acquisition device, thereby allowing the user to grip the cartridge holder 540 to remove it from the sample acquisition device. Remove box components.

In some embodiments, the cartridge holder 540 can include a sealing layer 544 (e.g., a seal, gasket, liner, ring, etc.) configured to hermetically seal the sample acquisition device when the cartridge assembly 500 is coupled to the cartridge chamber box room. In some cases, a sealing layer may be disposed on a planar surface of the retainer. Alternatively, the sealing layer may be seated on a recess (eg groove) of the holder such that the outer surface of the sealing layer is exposed. In some cases, the sealing layer may be an elastomeric gasket. Examples of elastomeric materials may include, but are not limited to, any rubber or rubber-like material such as polyisoprene, butadiene, styrene butadiene, acrylonitrile butadiene, polychloroprene, isobutylene isoprene olefin, polysulfide, polymethane, chlorosulfonated polyethylene, ethylene propylene, fluoroelastomer, polysiloxane, polyester, polymethane, silicone, thermoplastic elastomer, etc.

Figure 5B illustrates a side cross-sectional view of sample acquisition device 100 operably coupled to cartridge assembly 500, according to some embodiments. The container 520 may be configured to receive blood flowing into the container 520 in a first direction 524 . One or more liquid pathways 516 may be configured to direct air to and out of container 520 in a second direction 526 different from the first direction. An angle between the first direction and the second direction may be greater than zero degrees and less than 180 degrees. The angle between the first direction and the second direction may be greater than at least 0 degrees, 1 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees, 100 degrees, 110 degrees, 120 degrees, 130 degrees, 140 degrees, 150 degrees, 160 degrees, 170 degrees, 175 degrees or more. The angle between the first direction and the second direction may be less than at most 180 degrees, 170 degrees, 160 degrees, 150 degrees, 140 degrees, 130 degrees, 120 degrees, 110 degrees, 100 degrees, 90 degrees, 80 degrees, 70 degrees, 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees, 1 degree or less. In one example, the first direction and the second direction may be substantially opposite to each other. In another example, the first direction and the second direction may be substantially orthogonal to each other.

As shown in FIG. 5B , sample acquisition device 100 may include port 175 . The coupling unit 510 of the cartridge assembly 500 is configured to couple to the port 175 and the container port 530 of the cartridge assembly 500 . Coupling unit 510 may include a protrusion (eg, a tube or squeeze feature) configured to couple to container port 530 of cartridge assembly 500 . The protrusion may be in fluid communication with the collection tube 535 of the container 520 through the container port 530 . Alternatively, a protrusion may pass through container port 530 for direct fluid communication with collection tube 535 . In some cases, the proximal end of the protrusion (eg, the end opposite the collection tube 535 ) can be coupled to the end of the coupling unit. The protrusions may have a circular, oval, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-section of any partial shape or combination of shapes. The cross-section of the protrusions can be symmetrical or asymmetrical. For example, the diameter of the protrusion's fluid path (eg, the inner diameter of the sleeve) may decrease towards the end of the protrusion. Examples of protrusions may include, but are not limited to, needles, tubes, sleeves, open dilators, nozzles, and the like. In one example, the protrusions may be sleeves (eg, overmolded sleeves) to increase the strength of the protrusions or to reduce the thickness of the protrusions. In another example, the protrusion may be a needle (eg, an overmolded non-coring needle), and the cartridge assembly 500 may not or need not include the valve 532 . In the absence of valve 532, the cartridge assembly can utilize liquid path 516 for venting. As an alternative or in addition to the embodiments described above, the coupling unit 510 or the container port 530 may comprise a separate opening (eg, at least 1, 2, 3, 4, 5 or more needles) for venting. Alternatively or in addition, container 520 may include a semi-permeable membrane configured to allow air or other gases to escape while preventing passage of liquid.

5C illustrates a perspective view of flow meter 170 of sample acquisition device 100 operably coupled to cartridge assembly 500, according to some embodiments. The flow meter may include a transparent or translucent window (eg, a visible metering window) that allows the user to observe the progress of the liquid blood collection. At least a portion of the collection tube 535 of the container 520 can be aligned with the flow meter 170 when the cartridge assembly is operatively coupled to the sample collection device. Additional details regarding flow meters are described, for example, in Section II, Part F of the specification. As noted above, at least a portion of collection tube 535 may be transparent or translucent to allow observation of the collection of liquid blood into cartridge assembly 500 . Once the blood collection process is complete (e.g., indicated by indicator 522 or one or more sensors operatively coupled thereto), cartridge assembly 500 may be removed from device 100, and at least a portion of cartridge assembly 500 may be coupled to The transport sleeve 200 is used (eg, inserted) for eg subsequent storage or transport. In some examples, the entire cartridge assembly 500 can be removed from the device 100 and then inserted into the shipping sleeve 200 . In other examples, coupling unit 510 may remain coupled to device 100 while the remainder of cartridge assembly 500 is decoupled from coupling unit 510 for insertion into shipping sleeve 200 . In other examples, the entire cartridge assembly 500 can be removed from the device 100 and the coupling unit 510 can then be decoupled from the cartridge assembly 500 of the container 520 for insertion into the shipping sleeve 200 . When the coupling unit 510 is decoupled from the container 520 for storage or transportation, the valve 532 and the liquid path 516 may be closed to prevent blood leakage. In alternative embodiments, a separate sealing layer or covering may be applied to the container port 530 to prevent blood leakage. The seal/cover may be configured to protect the collected blood from the external environment prior to insertion of the container into transport sleeve 200 . FIG. 6 shows an example of the cassette assembly 500 inserted into the shipping sleeve 200 . Additional details regarding the transport sleeve are described, for example, in Section III of the specification.

In some embodiments, the coupling unit 510 may be coupled to the container 520 during assembly of the cartridge assembly 500 . In an alternative embodiment, the coupling unit 510 may be coupled (temporarily or permanently) to a port within the housing of the device during assembly. In an alternative embodiment, the coupling unit 510 may be coupled to the container 520 by a user. In some embodiments, when coupling the cartridge assembly 500 to the device, the force connecting the coupling unit 510 to a port in the device (e.g., a cartridge port) can be greater than the frictional force between the coupling unit 510 and the container port 530 such that Coupling unit 510 may remain in place (eg, remain coupled to the sample acquisition device) even when container 520 is pulled and decoupled from the sample acquisition device. In an alternative embodiment, the force connecting the coupling unit 510 to the device may be less than the frictional force between the coupling unit 510 and the container port 530 such that the coupling unit 510 may be decoupled from the device when the container 520 is pulled and decoupled from the device .

In some embodiments, at least a portion of the cartridge assembly that comes into contact with the collected blood (e.g., the pathway 514 of the coupling unit 510, the valve 532, the container port 530, the inner surface of the collection tube 535, the indicator 522, or is operably coupled to any sensor thereof) can be coated with any of the protectants disclosed herein. For example, collection tube 535 may contain or be coated with a substance such as heparin or EDTA to help stabilize collected blood.

In some embodiments, the cartridge assembly can also be configured to selectively separate any number of components of collected liquid blood, such as cells, plasma, serum, platelets, specific cell types, DNA (e.g., tumor cfDNA), RNA, protein, inorganic material, drug or any other component. For example, cartridge assembly 500 may include one or more components of cartridge assemblies 300, 400 (e.g., blood separation membrane 322, collection medium 324, prefilter 326, etc.) Separate serum or plasma. The cartridge assembly 500 may be configured to selectively separate serum or plasma while blood is being collected into the cartridge assembly 500 or after blood is collected into the cartridge assembly 500 .

Another aspect of the present disclosure provides a system for collecting and storing blood (eg, liquid blood) from a subject. The system can include any sample acquisition device (eg, sample acquisition device) and cartridge assembly (eg, cartridge assembly 500 , as shown in FIGS. 5A-5C ) disclosed herein. For example, in some embodiments, the sample acquisition device of the system may include a built-in vacuum.

Another aspect of the present disclosure provides a method for collecting blood. The method can include using any sample collection device (eg, a sample collection device) disclosed herein to collect blood from the subject. The method can also include using any of the cartridge assemblies disclosed herein (eg, cartridge assembly 500 as shown in FIGS. 5A-5C ) to receive the subject's blood from a sample collection device. In some embodiments, a cartridge assembly can be used to store blood as liquid blood.

3. Modular sample chamber

Other aspects of the present disclosure provide a sample chamber for storing a sample (eg, blood) collected from a subject. The sample chamber can be modular. Such modular sample chambers may be referred to as "modular sample chamber assemblies" or "modular chamber assemblies" as used interchangeably herein. The modular chamber assembly can be operatively coupled to any sample acquisition device (also referred to as a sample acquisition device) disclosed herein, eg, device 100 as shown in FIG. 1 . In some embodiments, a modular chamber assembly can include an inlet port configured to couple to a body (or base) of a sample acquisition device. In some cases, the body of the sample acquisition device can include a cartridge. A modular chamber assembly may include a housing (eg, chamber) configured to couple to an inlet port. In some embodiments, a housing can be formed within a modular chamber assembly when the chamber is coupled to the inlet port. The housing can be configured to support at least one cartridge assembly of a variety of different cartridge assembly types therein. A variety of different cartridge assembly types can allow blood to be collected, processed or stored in a variety of different formats. Various forms may include plasma, serum, dried blood, liquid blood or clotted blood. In some embodiments, the chambers of the modular chamber assembly or components therein (e.g., a single cartridge assembly of multiple different cartridge assembly types) can utilize any of the sample chambers described herein (e.g., the processing/stabilization in FIG. 3 One or more components in unit 320). In some embodiments, the inlet port can be part of a cover that seals the modular chamber assembly. In some embodiments, the modular chamber assembly may not and need not include a cartridge assembly, and samples may be collected directly into the housing, eg, as described in sample chamber 500 of FIG. 5A .

In some embodiments, a portion of the chamber of the modular chamber assembly can be configured to release from the base of the sample acquisition device when the inlet port is coupled to a mating feature of the sample acquisition device (e.g., protrusion 975 as shown in FIG. 8B ). stick out. The portion of the chamber protruding from the sample acquisition device may serve as a handle for the user to hold the modular chamber assembly during insertion of the modular chamber assembly into the sample acquisition device and during removal of the modular chamber assembly from the sample acquisition device. In alternative embodiments, the entire chamber of the modular chamber assembly may be configured to be inserted into the base of the sample acquisition device. In such cases, the chambers of the modular chamber assembly may not be visible when the modular chamber assembly is operably coupled to the sample acquisition device.

In some embodiments, the inlet port of the modular chamber assembly can include a port configured as a sealed housing. In some cases, the port may be a pierceable port configured to hermetically seal the housing (eg, a pierceable self-sealing port). In some cases, the sealing layer may be an elastomeric gasket. Examples of elastomeric materials may include, but are not limited to, any rubber or rubber-like material such as polyisoprene, butadiene, styrene butadiene, acrylonitrile butadiene, polychloroprene, isobutylene isoprene olefin, polysulfide, polymethane, chlorosulfonated polyethylene, ethylene propylene, fluoroelastomer, polysiloxane, polyester, polymethane, silicone, thermoplastic elastomer, etc. In some examples, the inlet port including the pierceable self-sealing port can be a cover of the modular chamber assembly.

In some embodiments, an inlet port of a modular chamber assembly can be configured to couple to at least one cassette assembly. In one example, the inlet port can be a cover as disclosed herein, and the cover can be coupled to the cartridge assembly. This coupling can enclose the cartridge assembly within the modular chamber assembly. In some cases, the cartridge assembly can be configured to couple (eg, releasably couple) to an interior portion of the modular chamber assembly (eg, within a sample tube), and the cover can also be coupled to the cartridge assembly. The inlet port can be in fluid communication with the cartridge assembly such that a sample retrieved from the subject by the sample collection device can be collected through the inlet port into the cartridge assembly inside the modular chamber assembly. Alternatively, where the inlet port can be coupled to the cartridge assembly, the cartridge assembly can be configured in direct fluid communication with the base of the sample acquisition device to collect a sample from the subject. The inlet port and cartridge assembly can be coupled to each other using any of the coupling mechanisms described herein. In alternative embodiments, the inlet port and the cartridge assembly may be indirectly coupled to each other via one or more connecting channels or coupling units.

In some embodiments, the plurality of different cartridge assembly types may include two or more of: (1) a first cartridge assembly type configured to separate plasma or serum from collected blood, (2) ) a second cartridge assembly type configured to collect and store liquid blood, (3) a third cartridge assembly type configured to house one or more matrices for collecting and storing blood as dried blood, or ( 4) A fourth cartridge assembly type configured to store clotted blood. In some cases, the plurality of different cartridge assembly types may include three or more of: (1) a first cartridge assembly type configured to separate plasma or serum from collected blood, (2) A second cartridge assembly type configured to collect and store liquid blood, (3) a third cartridge assembly type configured to house one or more matrices for collecting and storing blood as dried blood, or (4 ) A fourth cartridge assembly type configured to store clotted blood. In some cases, a plurality of different cartridge assembly types may include: (1) a first cartridge assembly type configured to separate plasma or serum from collected blood, (2) a second cartridge assembly type configured For collection and storage of liquid blood, (3) a third cartridge assembly type configured to house one or more substrates for collection and storage of blood as dried blood, and (4) a fourth cartridge assembly type that is Configured to store clotted blood. Multiple different cartridge assembly types may have the same shape, thickness, length, width, depth, volume or surface area. Alternatively, the various cartridge assembly types may not or need not be of the same shape or size.

In some embodiments, the modular chamber assembly can be configured to be released and disengaged from the sample acquisition device when the inlet port is decoupled from a mating feature of the sample acquisition device. After decoupling from the base or body of the sample acquisition device, the inlet port can be sealed (e.g., the pierceable self-sealing port can be closed) to protect the sample collected in the cartridge assembly from the surrounding environment and/or Protect users or others who may handle modular chamber components. In use, the modular chamber assembly can be coupled to a sample acquisition device, and a protrusion (eg, needle) of the sample acquisition device can pass through the inlet port to establish fluid communication with at least the cartridge assembly of the modular chamber assembly. After sample collection, the modular chamber assembly can be separated from the sample collection device and the inlet port can be closed by self-sealing, eg, by using a self-healing or self-sealing polymer. Alternatively, a separate cover can be applied to the inlet port of the modular chamber assembly to seal and protect the sample collected in the cartridge assembly.

In some embodiments, the modular chamber assembly can be configured to be released and disengaged from the sample acquisition device after a sample (eg, a subject's blood) is collected, processed, or stored on a cartridge assembly of the modular chamber assembly. In some cases, the modular chamber assembly may be manually released and disengaged from the sample acquisition device by a user, eg, via one or more switches operably coupled to the sample acquisition device or the modular chamber assembly. Users can track blood collection or processing through the transparent or translucent windows of the modular chamber assembly. This window may be directly exposed to the user (as shown in FIG. 8A ), or partially or fully covered by the flow meter of the sample collection device (as shown in FIG. 1A ). Alternatively, the modular chamber assembly may include one or more sensors configured to detect (1) the presence of collected blood, (2) the volume (e.g., volume) of collected blood, or (3) the blood processing process ( For example, serum/plasma separation). The sensor can be operably coupled to a coupling/decoupling mechanism between the sample acquisition device and the modular chamber assembly, eg, any coupling/decoupling mechanism between the sample acquisition device and the inlet port of the modular chamber assembly. The sensor can be any of those described elsewhere herein.

As described above, the coupling of the inlet port and the chamber may form a housing within the modular chamber assembly. In some embodiments, the housing can be configured to protect the cartridge from the external environment after blood is collected, processed, or stored on the cartridge assembly, and after the modular chamber assembly is released and disengaged from the sample collection device. The housing of the modular chamber assembly may serve as or utilize one or more components of any transport sleeve as disclosed herein, for example, as described in Section III of the specification. Thus, in some examples, the inlet port/chamber housing itself may serve as storage/shipping packaging.

In some embodiments, a modular chamber assembly may comprise a single cartridge assembly. In alternative embodiments, a modular chamber assembly may include two or more cartridge assemblies, eg, two or more of a plurality of different cartridge types. In some cases, a modular chamber assembly can include at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or more cassette assemblies. A modular chamber assembly may comprise up to 10, 9, 8, 7, 6, 5, 4, 3 or 2 cassette assemblies. In some examples, a modular assembly can be coupled to two cartridges of different types (ie, first and second cartridge assemblies of different types). The modular chamber assembly can be configured to (1) direct a first portion of collected blood into a first cartridge assembly, and (2) direct a second portion of collected blood into a second cartridge assembly. The switching between the acquired first cartridge assembly and the second cartridge assembly can be manual (e.g., by a user via a switch operably coupled to the modular chamber assembly) or automatic (e.g., via one or more sensors as disclosed herein). )implement. In some examples, multiple cartridge assemblies can be coupled in series, eg, forming fluid communication from the sample acquisition device to a first cartridge assembly and a second cartridge assembly.

In some embodiments, the cartridge assembly can be releasably coupled to the chamber of the modular chamber assembly such that the cartridge assembly can be released from the chamber. In some cases, modular chamber assemblies can be reused with new cassette assemblies. For example, a modular chamber assembly can be used more than once, such as two, three, four, five, five, Six, seven, eight, nine, ten or more times. In some cases, the modular chamber assembly may be under vacuum prior to coupling to the sample acquisition device. In this case, when installing a new cartridge assembly, a vacuum may be established within the modular chamber assembly by using a separate vacuum device before using the reusable modular chamber assembly including the new cartridge assembly.

7A-7D illustrate different embodiments of modular chamber assemblies as disclosed herein. Figure 7A shows a perspective view (second from left) and a side cross-sectional view (far right) of a modular chamber assembly 600 for sample collection, processing and storage. Modular chamber assembly 600 may include inlet port 610 . In some cases, the inlet port can be a cover. The cap may be a pierceable self-sealing cap. The cover is removable from the rest of the modular chamber assembly. The modular chamber assembly 600 may also include a chamber 620 (eg, a tube or tube assembly). Chamber 620 may include a cartridge assembly 630 . The cartridge assembly may comprise one of a number of different cartridge assembly types that allow blood to be collected, processed, or stored in a number of different formats. Various forms may include plasma, serum, dried blood, liquid blood or clotted blood. For example, cartridge assembly 630 may include cartridge 640 . Cassette 640 may include one or more matrix strips 642 to absorb and collect blood or a portion thereof from a subject. Cassette 640 may also include one or more absorbent pads 644 for containing and metering excess blood. Matrix strip 642 and absorbent pad 644 may be in fluid communication with each other. The cartridge assembly may also include a connection port 646 . Connection port 646 may be configured to couple (eg, releasably couple) to inlet port 610 and cartridge assembly 630 . For example, a connection port may be in fluid communication with the inlet port and the matrix strip to allow collection of blood from the sample collection device, through the inlet port, and into/onto the matrix strip. Connection ports can be of various shapes and sizes. For example, the connection port may be in the shape of a sphere, a cuboid or a disc, or any partial shape or combination thereof. The connection ports may have a circular, oval, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-section of any partial shape or combination of their shapes. In some cases, the connection port can be pre-assembled or manufactured as part of the inlet port or cartridge assembly. In one example, connection port 646 may be a funnel that acts as a blood flow path between the inlet port and cartridge assembly 630 .

In some embodiments, as shown in FIG. 7A, the modular chamber assembly 600 can also include a desiccant 650 that can be used to dry and/or keep the sample dry. A desiccant may be disposed within chamber 620 . The desiccant can be a single solid material. The desiccant may include a plurality of desiccant particles. The desiccant particles can be stored within a container (eg, bag).

7B illustrates principles of operation and use of a modular chamber assembly and sample collection device for collecting and storing blood samples from a subject, according to some embodiments. The sample acquisition device 900a can include a protruding or piercing element 975 (e.g., a needle) configured to pass through the inlet port 610 (e.g., a pierceable self-sealing cap) to establish integration with the modular chamber assembly 600 (e.g., Fluid communication of at least a portion of cartridge assembly 630) including cartridge 640. In some cases, piercing element 975 may be configured to pass through connection port 646 . Alternatively, as shown in the right diagram of FIG. 7B, when the modular chamber assembly 600 is coupled to the sample acquisition device 900b, the distal end of the piercing element 975 can be placed within the connection port 646 but not completely through the connection port 646, so that the connection Port 646 can receive collected blood and direct the collected blood into cartridge assembly 630 . Figure 7C shows a different perspective view of the coupling of the modular chamber assembly 600 to the sample acquisition device 900a. Modular chamber assemblies can have various lengths and/or diameters (as shown at 600 and 601), and sample acquisition device 900a can be configured to be compatible with different types and sizes of modular chamber assemblies. Sample acquisition device 900a may include a recess 980 configured to receive the skin of a subject. Recess 980 may include opening 985 configured to allow the piercing element of lancet 910 to pierce the skin of the subject. The lancet may include a piercing activator 166 . The piercing activator may include a button 167 .

In some embodiments, a modular chamber assembly or components thereof (eg, a cassette assembly) can be pre-evacuated (eg, below ambient pressure) to provide a vacuum for drawing blood from a subject. The inlet port (eg, cap) can create a seal to maintain a vacuum prior to use. In alternative embodiments, a vacuum may be provided by the sample collection device for blood withdrawal. In some embodiments, after the sample is collected into the modular chamber assembly, the inlet port can create a seal to maintain the environment within the modular chamber assembly during storage/transportation.

In some embodiments, a modular chamber assembly can be used as a vacuum chamber and/or a deposition chamber (or cassette chamber, sample chamber, etc.). For example, full coupling between the modular chamber assembly and the sample acquisition device, e.g., by fully inserting the modular chamber assembly into the body of the sample acquisition device, can trigger a protrusion (e.g., a needle) of the sample acquisition device body to pierce the modular chamber assembly. Cover the chamber assembly and activate the vacuum. Thus, in this example, the sample acquisition device may not or need a separate vacuum actuator button. Coupling and uncoupling between the modular chamber assembly and the body of the sample acquisition device can be performed with one or two hands. In some cases, full coupling between the modular chamber assembly and the sample acquisition device may be indicated by a hard stop or marking on the modular device, an audible click, or other mechanism.

As noted above, a modular chamber assembly may include chambers configured to support (eg, couple to) a plurality of different cartridge assembly types to allow blood to be collected, processed, or stored in a variety of different formats. As shown in FIG. 7D, modular chamber assembly 600 may include a cartridge assembly 630, which in turn includes one or more matrix strips 642 configured to absorb and collect blood, or a portion thereof, from a subject. In another example, modular chamber assembly 700 may include a cassette assembly that in turn includes a container (eg, tube collector) 710 configured to collect liquid blood. Container 710 may utilize one or more components of cartridge assembly 500 to collect a fluid sample (as shown in FIGS. 5A-5C ). Referring to Figure 7D, a different modular chamber assembly 800 may include a cartridge assembly that in turn includes one or more blood separation membranes 810 for, eg, serum or plasma separation and storage. Blood separation membrane 810 may utilize one or more components of cartridge 300 or 400 for blood separation and collection (as shown in FIGS. 3A-3F and FIG. 4 ).

In some embodiments, the chambers (or housings) of the modular chamber assembly can have various shapes and sizes. For example, the chamber may be in the shape of a sphere, cuboid, or disk, or any partial shape or combination of shapes thereof. The chamber may have a circular, oval, oval, triangular, square, rectangular, pentagonal, hexagonal or cross-section of any partial shape or combination of shapes thereof. In some cases, the chambers may have the same cross-sectional dimension along the length of the chamber. Alternatively, the chambers may have different cross-sectional dimensions along the length of the chamber. In some examples, the chamber may be tubular for compatibility with one or more implements for storage (eg, a benchtop rack) or processing (eg, a centrifuge or standard tube rack for blood separation). Compatibility enables modular chamber components to be integrated with automated laboratory procedures.

The cross-sectional diameter of a chamber of a modular chamber assembly (eg, chamber 620 , as shown in FIG. 7A ) may be referred to as an outside diameter (OD) or an internal diameter (ID). The cross-sectional diameter may be at least about 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 25mm, 30mm, 35mm, 40mm, 45mm, 50mm or more. The cross-sectional diameter of the housing may be up to about 50mm, 45mm, 40mm, 35mm, 30mm, 25mm, 20mm, 19mm, 18mm, 17mm, 16mm, 15mm, 14mm, 13mm, 12mm, 11mm, 10mm, 9mm, 8mm, 7mm, 6mm , 5mm, 4mm, 3mm, 2mm, 1mm, 0.9mm, 0.8mm, 0.7mm, 0.6mm, 0.5mm or smaller. The longitudinal length of the chamber (e.g., chamber 620) can be at least about 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm, 5.5 mm, 6 mm, 6.5 mm, 7 mm, 7.5 mm, 8 mm , 8.5mm, 9mm, 9.5mm, 10mm, 15mm, 20mm, 25mm, 30mm, 35mm, 40mm, 45mm, 50mm, 55mm, 60mm, 65mm, 70mm, 75mm, 80mm, 85mm, 90mm, 95mm, 100mm, 110mm, 120mm , 130mm, 140mm, 150mm, 200mm, 250mm, 300mm, 350mm or larger. The longitudinal length of the housing may be at most about 350mm, 300mm, 250mm, 200mm, 150mm, 140mm, 130mm, 120mm, 110mm, 100mm, 95mm, 90mm, 85mm, 80mm, 75mm, 70mm, 65mm, 60mm, 55mm, 50mm, 45mm, 40mm, 35mm, 30mm, 25mm, 20mm, 15mm, 10mm, 9.5mm, 9mm, 8.5mm, 8mm, 7.5mm, 7mm, 6.5mm, 6mm, 5.5mm, 5mm, 4.5mm, 4mm, 3.5mm, 3mm, 2.5 mm, 2mm, 1.5mm, 1mm or smaller. In some examples, the chambers of the modular chamber assembly can be about 13 mm in diameter and about 100 mm in length, about 13 mm in diameter and about 75 mm in length, about 13 mm in diameter and about 66 mm in length, about 13 mm in diameter and about 50 mm in length, about 16 mm in diameter and about 50 mm in length About 100mm, about 16mm in diameter and about 75mm in length, about 16mm in diameter and about 50mm in length, or preferably about 16mm in diameter and about 46mm in length. In some preferred embodiments, the chamber length of the modular chamber assembly may be up to about 75 mm or less.

In some embodiments, the volume (eg, closed or sealed volume) of the closed chamber of a sample chamber (eg, modular chamber assembly 600 ) as disclosed herein can be selected to provide sufficient vacuum pressure for sample collection. In some cases, the volume of the closed chamber may be designed to provide a greater vacuum pressure than is required or required for sample collection, for example, to accommodate pressure loss during shelf storage (eg, due to leaks). In some cases, the volume of the enclosure may be selected based on the type of sample collected and/or the type of processing of the sample collected, as disclosed herein. For example, the interior volume of the modular chamber assembly can be at least about 1 cubic centimeter (cm ³ ), 1.5 cm ³ , 2 cm ³ , 2.5 cm ³ , 3 cm ³ , 3.5 cm ³ , 4 cm ³ , 4.5 cm ³ , 5 cm ³ , 6 cm 3 ³ , ^{7cm 3} , 8cm ³ , 9cm ³ , 10cm ³ , 11cm ³ , 12cm 3 , 13cm ³ , 14cm ³ , 15cm ³ , 20cm ³ , 25cm ³ or more. The interior volume of the modular chamber assembly may be up to about 100 cm ³ , 90 cm ³ , 80 cm 3 , 70 cm ³ , 60 cm ³ , 50 cm ³ , 45 cm ³ , 40 cm ³ , 35 ^{cm 3 ,} 30 cm ³ , 25 cm ³ , 20 cm ³ , 15 cm ³ , 14cm ³ , 13cm ³ , 12cm 3 , 11cm ³ , 10cm ³ , 9cm ³ , 8cm ³ , 7cm ³ , 6cm ³ , 5cm ³ , 4.5cm ³ , 4cm ^{3 ,} 3.5cm ³ , 3cm ³ , 2.5cm ³ , 2cm ³ , 1.5cm ³ , 1cm ³ or smaller. In some examples, the interior volume of the modular chamber assembly can range from about 5 cm ³ to about 8 cm ³ , from about 6.5 cm ³ to about 7.5 cm ³ , or preferably from about 5.5 cm ³ to about 6 cm ³ .

A cover (eg, inlet port 610, as shown in FIG. 7A ) of a modular chamber assembly can be characterized by having a height and a cross-sectional dimension (eg, diameter). The height of the cover may be at least about 0.1mm, 0.2mm, 0.3mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1mm, 1.1mm, 1.2mm, 1.3mm, 1.4mm, 1.5mm , 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 15mm, 20mm, 30mm or more. The height of the cover may be up to about 30mm, 20mm, 15mm, 10mm, 9mm, 8mm, 7mm, 6mm, 5mm, 4mm, 3mm, 2mm, 1.5mm, 1.4mm, 1.3mm, 1.2mm, 1.1mm, 1mm, 0.9mm , 0.8mm, 0.7mm, 0.6mm, 0.5mm, 0.4mm, 0.3mm, 0.2mm, 0.1mm or smaller. The cross-sectional diameter of the cap may be at least about 0.1mm, 0.2mm, 0.3mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1mm, 1.1mm, 1.2mm, 1.3mm, 1.4mm, 1.5mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, 25mm, 30mm or more. The cross-sectional diameter of the cover may be up to about 30mm, 25mm, 20mm, 19mm, 18mm, 17mm, 16mm, 15mm, 14mm, 13mm, 12mm, 11mm, 10mm, 9mm, 8mm, 7mm, 6mm, 5mm, 4mm, 3mm, 2mm , 1.5mm, 1.4mm, 1.3mm, 1.2mm, 1.1mm, 1mm, 0.9mm, 0.8mm, 0.7mm, 0.6mm, 0.5mm, 0.4mm, 0.3mm, 0.2mm, 0.1mm or smaller. The cross-sectional diameter of the cap may range from about 0.5 mm to about 1.1 mm, from about 0.8 mm to about 1.4 mm, or preferably from about 0.7 mm to about 1 mm.

In any of the devices, systems, methods or kits disclosed herein, the sample acquisition device (ie, sample acquisition device) can be modular. Such devices may be referred to as "modular sample collection devices". A modular sample acquisition device may include one or more components of any sample acquisition device disclosed herein, such as device 100 in Figures 1A, 3D, and 5B and device 900a in Figures 7B and 7C. In use, a modular sample acquisition device may be operably coupled to any of the sample chambers disclosed herein, such as both non-modular and modular sample chambers.

Figure 8A shows a perspective view of various components of a modular sample acquisition device 900b, according to some embodiments. In some cases, device 900b in FIG. 8A may be more compact than device 100 in FIG. 1B because the device in FIG. 8A includes fewer components for operation and function. For example, the device shown in FIG. 8A may not and does not require a housing (eg, cover 152 in FIG. 1B ). Alternatively, the device in Figure 8A may still include a housing. The device 900b shown in FIG. 8A may include modular components, such as a lancing component 910 and a base or body 920 . Apparatus 900b may be operably coupled to modular chamber assembly 600 comprising cassette assembly 630 . In one example, device 900b may require only body (or base) 920 and lancing assembly 910, and modular chamber assembly 600 for collecting a sample from a subject. Modular sample acquisition device 900b can include a recess 980 configured to receive the skin of a subject. Recess 980 may include opening 985 configured to allow the piercing element of lancing assembly 910 to pierce the skin of the subject. Lancet assembly 910 may be similar to the lancet described in FIG. 1A . For example, lancing assembly 910 may include piercing activator 166 . The piercing activator may include a button 167 . The body of the modular sample acquisition device 900b can include a sleeve 990 configured to support or receive a variety of different configurations of modular chamber assemblies, as disclosed elsewhere in this disclosure. Sleeve 990 may include cutouts 995 to allow the user to view the progress of sample collection into the modular chamber assembly. In one example, the modular chamber assembly 600 shown in FIG. 8A can be configured to serve as (1) a collection unit for collecting a sample (e.g., blood or components thereof) from a subject and (2) for storing/ A transport unit for transporting collected samples without the need for any separate storage/transportation unit. The modular chamber assembly shown in Figure 8C can provide a vacuum with pre-evacuation. When the modular chamber assembly is coupled to the body of the modular sample acquisition device, a vacuum in the modular chamber assembly can be activated, which draws the subject's skin into the groove 980 on the body 920 (as shown in FIG. 8B ) to Prepare to pierce the skin with the lancet from the lancing set. Figure 8C shows a perspective view of the modular sample acquisition device 900b without the modular chamber assembly. Modular sample acquisition device 900b includes a lancing assembly 910 coupled to a body 920 . The body 920 can include at least one protrusion 975 configured to penetrate at least a portion of the modular chamber assembly 600 for fluid communication between the modular sample acquisition device 900b and the modular chamber assembly 600 .

As further shown in FIG. 8D , the modular sample acquisition device 900b can include a lancing assembly 910 operably coupled to a base/body 920 . Briefly, base 920 can be brought into contact with a subject's skin, and lancing assembly 910 can make an incision in the skin for collecting a sample (eg, blood) from the subject. Base 920 may include ports configured to receive any of the modular chamber assemblies disclosed herein (eg, modular assemblies 600, 700, or 800). For example, a modular chamber assembly 600 including an inlet port 610 (eg, a pierceable self-sealing cap) and a cartridge assembly 630 may be used in conjunction with the sample acquisition device 900 . Modular chamber assembly 600 can be inserted into device 900 during which piercing element 975 of modular sample acquisition device 900 pierces inlet port 610 to create fluid communication with connection port 646 of modular chamber assembly 600 and cartridge assembly 630 . Blood can then be collected into cartridge assembly 630 and can be processed. After harvesting, the modular chamber assembly 600 can be retracted from the device 900 for storage or transport.

Figure 8E illustrates the principles of operation and use of an example modular sample acquisition device 900b and modular chamber assembly 600, according to some embodiments. It should be noted that any of the processes described in FIG. 8E can be performed with any of the sample acquisition devices and sample chambers of the present disclosure. Referring to Figure 8E, the modular chamber assembly 600 may be packaged (or provided separately) separately from the modular sample acquisition device 900b. In some alternative embodiments, the modular chamber assembly 600 may be packaged as part of a coupled unit to a modular sample acquisition device. Whether decoupled or partially coupled, the protrusion (e.g., needle 975) of the modular sample acquisition device 900b may not penetrate the modular chamber assembly 600 (e.g., the inlet port 610) to avoid activation prior to use/operation vacuum. To activate the vacuum in the modular sample acquisition device 900b, for example by vacuum pressure from the modular chamber assembly 600, the modular chamber assembly 600 can be fully coupled to the modular sample acquisition device 900b, for example as indicated by arrow 1005 in FIG. 8E direction. After collecting and/or processing blood from a subject using the system comprising modular sample acquisition device 900b and modular chamber assembly 600, modular chamber assembly 600 may be decoupled from modular sample acquisition device 900b, for example, as indicated by arrow 1010 in the direction indicated. Modular chamber assembly 600 may be configured to protect collected blood samples during storage or transport. In order to retrieve collected samples (e.g., samples stored on matrix strip 642) for further processing or analysis (e.g., blood separation, blood testing, genetic screening, etc.), at least the cover of chamber assembly 600 (e.g., , inlet port 610) can be decoupled from the modular chamber assembly 600, such as in the direction indicated by arrow 1015, to allow access to collected samples.

9 illustrates an example of a modular sample acquisition device 900b operably coupled to a modular chamber assembly 600a or 600b (cartridge assembly or desiccant not shown). Modular chamber assemblies 600a and 600b may have different dimensions, such as different longitudinal lengths. Sample acquisition device 900b may include lancing assembly 910 and base/body 920, as described herein. Base 920 can be configured, for example, to (1) couple to lancing assembly 910, (2) contact the subject's skin (eg, through a groove or suction lumen of base 920), and (3) couple to (eg, releasably coupled to) the modular chamber assembly. The base 920 may include a flange 930 . A user may use his or her fingers to press against flange 930 to operate the system including modular sample acquisition device 900b and modular chamber assemblies 600a/600b. In some cases, flange 930 can include a notch 935 (eg, a recessed portion) for a user's finger or thumb to press against for support during use of the modular sample acquisition device and modular chamber assembly. For example, in one-handed operation, the user can press his or her thumb against flange 930 and use one or more other fingers or other parts of the same hand (such as the palm) to couple the modular chamber assembly (e.g. push) to the modular sample acquisition device, or decouple (eg, pull) the modular chamber assembly from the modular sample acquisition device. Alternatively, the user can press his or her thumb against the remainder 940 of the body of the modular sample acquisition device 900b and use one or more other fingers or part of the same hand to couple the modular chamber assembly to the modular sample acquisition device 900b. acquisition device. In some cases, notch 935 may be positioned on a left, middle, or right portion of flange 930 . For example, the location of notch 935 within flange 930 may depend on right-handed or left-handed use (chirality) of the sample acquisition device. In some cases, handle 930 may include more than one notch, eg, at least 2, 3, 4, 5 or more notches. For example, flange 930 may include two notches (on either side of the flange) for left-handed and right-handed compatibility.

Another aspect of the present disclosure provides a system for collecting and storing blood from a subject. The system can include any sample acquisition device described herein (eg, a modular sample acquisition device and/or a non-modular sample acquisition device). The system can also include any of the modular chamber assemblies described herein or other types of sample chambers. In some embodiments, a sample acquisition device can include a built-in vacuum. This vacuum may be sufficient to pull the subject's skin toward the sample collection device so that blood is drawn from the subject when the skin is pierced. In alternative embodiments, the modular chamber assembly may be pre-packaged with a built-in vacuum, and venting this vacuum to other parts of the sample acquisition device may be sufficient to pull the subject's skin toward the sample Blood was drawn from the subject over time.

Another aspect of the disclosure provides a method (eg, for blood collection, processing, or storage). The method can include using any sample collection device described herein (eg, a modular sample collection device and/or a non-modular sample collection device) to collect blood from the subject. The method may also include using any of the modular chamber assemblies described herein or other types of sample chambers to collect, process or store blood in one or more of a number of different cartridge assembly types.

Another aspect of the present disclosure provides a kit comprising any of the sample collection devices described herein (e.g., a modular sample collection device and/or a non-modular sample collection device), any of the modular chambers described herein components, and any of the many different cartridge component types described herein. A kit may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more cassette components. A kit may comprise up to 20, 15, 10, 9, 8, 7, 6, 5, 4, 3 or 2 cassette components.

F. Flow meter

In some embodiments, the device may include a flow meter 170 on the housing, as shown in FIG. 1A . A flow meter is interchangeably referred to herein as a metering window (or windows). As a fluid sample is collected into the sample chamber, the flow meter can enable a subject or user to monitor the progress of fluid sample collection (eg, blood sample collection) in real time. For example, a user (eg, subject) may rely on a flow meter to determine whether fluid sample collection is complete or nearly complete. In some embodiments, a flow meter may be positioned on the housing base 110 . For example, the flow meter may be part of, or integrated into, the cover of the housing base. A flow meter can be located close to the deposition chamber (or cassette). The flow meter can be located directly above the deposition chamber (or cassette). The flow meter can be substantially aligned with at least a portion of the sample chamber (eg, cartridge 182 of the cartridge assembly) when the sample chamber is inserted into the cartridge chamber.

In some embodiments, the flow meter 170 can include a plurality of windows positioned parallel to the longitudinal axis of the sample chamber. Multiple windows may include three, four, five or more windows. The window can be made of an optically transparent material that allows the user (eg, the subject) to see the underlying substrate in the cartridge. A sample collected on the substrate (eg, a liquid sample) can be seen through the window. The liquid sample and the matrix of the cartridge may be of different colours, preferably highly contrasting colours, to allow easy observation of the flow of the liquid sample along the matrix. As the liquid sample is collected on the substrate in the cartridge, the color of the liquid sample (eg, the red color of blood) may sequentially fill each window. Each window may indicate a known volume of fluid sample collected. In some alternative embodiments (not shown), the flow meter may include one or more visible indicia. Visible markers can replace the window of the flow meter, or can be used in conjunction with the metering window. Visible markings are visible to the naked eye. Visible indicia may include images, shapes, symbols, letters, numbers, barcodes (eg, 1D, 2D, or 3D barcodes), quick response (QR) codes, or any other type of visually distinguishable feature. Visible indicia may include an arrangement or sequence of lights, including LED lights, that can be distinguished from each other.

In some cases, visible indicia may emit thermal or other IR spectral radiation, UV radiation, radiation along the electromagnetic spectrum. In another example, the sample acquisition device or flow meter may emit vibrations or sounds of different frequencies, pitches, harmonics, ranges, or sound patterns detectable by the user. For example, sounds may include words or tones. The human ear can discern vibrations/sounds. Vibration/sound can be used to indicate the progress of the liquid sample collection process. For example, a first vibration/sound may be generated when the liquid sample begins to flow onto the substrate, and a second vibration/sound different from the first vibration/sound may be generated when the liquid sample completely fills the substrate.

In some embodiments, flow meters can be used to detect (e.g., enable viewing by a user such as a subject) features, colorimetric changes, display of symbols, masking of symbols, or other means of indicating the progress of fluid sample collection, and indicate Fluid sample collection is complete.

In some embodiments, one or more graphical user interfaces (GUIs) may be provided on the sample acquisition device and/or the sample chamber. A GUI can complement the use of flow meters. In some embodiments, the functionality of the flow meter can be incorporated into the GUI. The GUI can be presented on a display screen of the device. A GUI is a type of interface that allows a user to interact with an electronic device through graphical icons and visual indicators (such as secondary symbols), as opposed to a text shell based interface, typed command labels, or text navigation. Actions in the GUI can be performed by directly manipulating graphical elements. Besides computers, GUIs can also be found in handheld devices such as MP3 players, portable media players, gaming devices and small home, office and industrial equipment. The GUI may be provided in the form of software, a software application, or the like. The GUI can be provided through a mobile application. The GUI may be presented through an application (eg, through an application programming interface (API) executing on the device). The GUI may allow the user to visually monitor the progress of sample collection. In some embodiments, the GUI can allow a user to monitor the level of an analyte of interest in a collected sample.

In some embodiments, the sample acquisition device and/or sample chamber may be capable of transmitting data to a remote server or mobile device. Data may include, for example, user details/information, date/time/location of sample collection from subject, sample size/volume collected, time taken to complete sample collection, maximum/minimum/average flow rates during sample collection, The position of the subject's arm during collection, whether any errors or accidents occurred during sample collection, etc. In some cases, data may be transmitted to a mobile device (eg, cell phone, tablet), computer, cloud application, or any combination thereof. Data may be transferred by any means used to transfer data, including, but not limited to, from the system (e.g., USB, RS-232 serial, or other industry standard communication protocols) and wirelessly (e.g., ANT+, NFC or other similar industry standard) to download data. This information can be displayed as a report. The report can be displayed on the screen of the device or a computer. This report can be transmitted to a healthcare provider or nursing staff. In some cases, data can be downloaded to electronic health records. Data may include or be part of an electronic health record. For example, data may be uploaded to an electronic health record of a user of the devices and methods described herein. In some cases, the data may be transmitted to the mobile device and displayed for the user on the mobile application.

III. Packaging and Shipping for Post-Box Sample Collection

Using a flow meter on the sample collection device may allow the user to monitor the progress of sample collection and know when sample collection is complete. The sample chamber can be removed from the sample acquisition device (eg, a deposition chamber of the device) by pulling on a portion of the sample chamber (eg, a cartridge tab). At least a portion of the sample chamber (eg, the filled cartridge) can then be packaged and shipped (eg, by storing the cartridge or components thereof in a shipping sleeve, as disclosed herein) to an external facility for further processing. For example, samples can be processed, stabilized and stored. In any of the embodiments described herein, the device can be configured to collect, process and store a sample. Samples drawn by the device can be stored in liquid or solid form. Samples may undergo optional processing prior to storage. Storage can be on the device, off the device, or in a removable container, vessel, compartment or box within the device.

In some embodiments, the transport sleeve can be configured to protect or stabilize a collected sample (eg, a liquid sample, such as liquid blood). The shipping sleeve can create a sealed environment to protect collected samples prior to testing them. The sealed environment within the transport sleeve can provide (eg, create) optimal/stable conditions around the collected sample.

In some cases, the transport sleeve may include one or more walls (e.g., double or triple walls that provide an insulating environment) to prevent environmental conditions from affecting one or more internal conditions (e.g., temperature, pressure, etc.) of the transport sleeve. , humidity, etc.).

In some cases, the sealed environment containing the collected sample can be cooled (or heated) to a temperature that increases the stability of the collected sample during storage and/or shipment at ambient temperature or shipping temperature. In one example, the transport sleeve can include at least one temperature regulator, eg, a thermoelectric cooling/heating device utilizing the Peltier effect. In another example, the transport sleeve may include at least one chemical ice pack. The ice pack and box may be contained in the same part of the shipping sleeve, or in separate parts of the shipping sleeve, eg, two parts separated by one or more walls. Examples of ice packs may include, but are not limited to, combinations of liquids (eg, aqueous liquids) and salts (eg, ammonium nitrate, ammonium thiocyanate, ammonium chloride, ammonium sulfate, potassium chloride, potassium iodide, potassium nitrate, sodium carbonate, etc.). Depending on the salt, the physical mixture of liquid and salt can produce an endothermic or exothermic reaction to regulate the temperature within the transport sleeve. Activation of the ice pack (e.g., by physically mixing the liquid and salt by breaking the barrier between them) can be done by inserting the cartridge into the transport sleeve (e.g., automatically by the transport sleeve’s mechanism) or by the user (e.g., by placing it in the transport sleeve). switch on the sleeve) to trigger. The physical mixing of liquid and salt can be immediate (eg, within seconds or less than a second). Alternatively, the rate of physical mixing can be controlled (eg, by timed release of salt from capsules, slowly dissolving salt tablets, etc.) to prevent overcooling or overheating and/or to prolong the duration of thermoregulation.

In some cases, the transport sleeve may comprise a material with a high thermal mass or specific heat. The temperature of the transport sleeve can be pre-conditioned (eg, cooled or heated) in a temperature-controlled environment such as a cooler or oven. Thanks to the material with high thermal mass, the transport sleeve can maintain the pre-adjusted temperature for a long time. Temperatures can be maintained for longer periods of time in the presence of additional insulation or components. Examples of high specific heat materials may include, but are not limited to, cyanimide, ethanol, diethyl ether, glycerin, isoamyl alcohol, isobutanol, lithium hydride, methanol, sodium acetate, water, ethylene glycol, and paraffin.

In some cases, the interior volume of the transport sleeve may be partially or fully evacuated (eg, to a pressure below ambient pressure) to isolate the liquid blood sample. The internal pressure of the transport sleeve can be manually adjusted with a pressure regulator (eg, a pump such as a diaphragm pump).

In some cases, one or more graphical user interfaces (GUIs) disclosed herein may be disposed on the transport sleeve. A GUI can supplement the use of a transport sleeve. In some embodiments, the functionality of the transport sleeve can be incorporated into the GUI. The GUI may be presented on a display screen of the transport sleeve. The GUI may be capable of monitoring one or more conditions of the transport sleeve (eg, temperature, pressure, humidity, duration of sample storage via time stamp, etc.). The transport sleeve may include one or more cameras, and the GUI may be capable of visualizing samples contained within the transport sleeve.

IV. Additional Embodiments

In some cases, any subject sample chamber (e.g., cartridge assembly 180, 300, 400, 500, modular chamber assembly 600, 700, 800, etc.) can be associated with any subject sample collection device (e.g., sample collection device 100) are used interchangeably.

In some cases, the sample chamber may be configured to perform additional processing steps on the sample (eg, the subject's blood). After or while blood is collected into the cartridge assembly (eg, by using a sample collection device), the sample can be processed, stabilized, and/or stored. In some embodiments, a collection device, such as the devices disclosed in this application, can be configured to collect, process, and store a sample. Samples drawn by the device can be stored in liquid or solid form. Samples may undergo optional processing prior to storage. Storage can be on the device, off the device, or in a removable container, vessel, compartment or box within the device.

The sample collection device can be configured to collect, process, stabilize and store collected samples. Additional processing (e.g., processing, stabilization, and storage) may include steps or methods configured to concentrate the sample, regulate or meter flow of the sample, expose the sample to one or more reagents, and deposit the sample on a solid substrate or matrix and Device components. Methods of using a sample collection device may include the steps of performing one or more of the following: collection, processing, stabilization, and storage of a sample. Acquisition, processing, stabilization and storage can be performed in a single device. Processing may include filtering the sample to separate components or analytes of interest. In some embodiments, collected samples can be collected, processed, and stabilized prior to transfer to a removable cartridge for storage. In other embodiments, one or more steps including acquisition, processing and stabilization may occur on a removable cartridge.

The devices, systems, and methods disclosed herein can stabilize samples on matrices (e.g., blood storage matrices, sample collection matrices, matrices, sample stabilizing matrices, stabilizing matrices (e.g., RNA stabilizing matrices, protein stabilizing matrices), solid matrices, solid matrices, solid support matrix or solid support). The matrix can be integrated into the device or external to the device. In some embodiments, the matrix can be incorporated into the cartridge for removal (eg, after sample collection). In some embodiments, the matrix can include a planar dimension of at least 176 mm ² . The matrices can be prepared according to the methods of US Patent No. 9,040,675, US Patent No. 9,040,679, US Patent No. 9,044,738, or US Patent No. 9,480,966, all of which are incorporated herein by reference in their entireties.

The matrix can be configured to selectively stabilize sample preparation reagents comprising proteins and/or nucleic acids. The matrix can be configured to stabilize proteins and the nucleic acids can comprise oligosaccharides (eg, trisaccharides) in a substantially dry state. The oligosaccharide or trisaccharide may be selected from the group consisting of melezitose, raffinose, maltotriulose, isomaltotriose, black triose, maltotriose, ketose, cyclodextrin, trehalose or combinations thereof. In some embodiments, the matrix may comprise melezitose. In a further embodiment, melezitose may be in a substantially dry state. In some embodiments, melezitose in a substantially dry state can have a water content of less than 2%. In the matrix, the concentration of melezitose may range from about 10% to about 30% by weight by weight (eg calculated as the mass of the solute divided by the mass of the solution, where the solution contains both the solute and the solvent). The concentration of melezitose may be 15% by weight. Melezitose can be impregnated in the matrix. In some embodiments, the impregnated melezitose concentration in the matrix results from immersing the matrix in a solution comprising from about 10% to about 30% melezitose. In some other embodiments, 15% melezitose is impregnated into the matrix in a dry state. Substrates can be passively coated or covalently modified with melezitose. In other embodiments, melezitose may be applied to the surface of the substrate (eg, by dipping, spraying, brushing, etc.). In some other embodiments, the matrix may be coated with a 15% melezitose solution. In some embodiments, the matrix can comprise a planar dimension with a surface area of at least 176 mm ² . The matrix may contain additional components to stabilize proteins and/or nucleic acids, including various stabilizing molecules. A non-limiting example of a stabilizing molecule is validamycin. In some embodiments, the matrix may comprise 31-ETF (eg, a cellulose-based matrix) and melezitose.

The matrix may contain buffer reagents. Buffer reagents can be impregnated into the matrix. Buffers stabilize sample preparation reagents and/or various sample components. The matrix may contain agents or compounds that minimize nuclease activity, such as nuclease inhibitors. The matrix may contain agents or compounds that minimize or inhibit protease activity, such as protease inhibitors. Protease inhibitors can be synthetic or naturally occurring (eg, naturally occurring peptides or proteins). The matrix may contain one or more free radical scavengers. The matrix may contain UV protectants or radical scavengers. The matrix may also contain oxygen scavengers such as ferrous carbonate and metal halides. Other oxygen scavengers may include ascorbate, sodium bicarbonate, and citrus. The matrix may contain cell lysis reagents. Cell lysis reagents may include guanidine thiocyanate, guanidine hydrochloride, sodium thiocyanate, potassium thiocyanate, arginine, sodium dodecyl sulfate (SDS), urea, or combinations thereof. A solid support matrix may contain a reducing agent.

In some embodiments, sample collection and stabilization may require user action to proceed between one or more stages of the sample collection, separation, and optional stabilization process. The system (eg, sample collection device, sample chamber, etc.) may require user action to activate sample collection and move the sample between isolation, stabilization, and storage. Alternatively, user action may be required to initiate sample collection and one or more additional steps of the sample collection, separation, or stabilization process. User actions may include any number of actions, including pressing buttons, tapping, shaking, breaking internal components, turning or rotating components of the device, forcing a sample through one or more components (eg, chambers), and any number of other mechanisms. Movement through these stages can occur concurrently with sample collection, or can occur after sample collection. At any time during or prior to the processing phase, the entire sample or components of the sample may be exposed to any number of techniques or processing strategies for the cells used to pretreat the biological components of the sample; potential treatments include, but are not limited to, treatment with reagents, Treatment with detergents, evaporation techniques, mechanical stress or any combination thereof.

In some embodiments, a sample acquisition device can be operably coupled to at least one valve (eg, a check valve) that couples the sample acquisition device to the sample chamber, and vice versa. At least 1, 2, 3, 4, 5 or more valves may be configured to couple the sample acquisition device to the cartridge assembly. For example, sample acquisition device 900b and modular chamber assembly 600, as shown in FIG. 8A, can be coupled to each other by at least one valve. In some cases, the valve may be part of (e.g., manufactured as part of) sample acquisition device 900b, and may be configured to releasably couple to a modular chamber assembly (e.g., to an inlet port of modular chamber assembly 600b). port 610, as shown in Figure 7A). Alternatively, the valve may be coupled to the sample acquisition device before the cartridge assembly is coupled to the sample acquisition device through the valve. During sample collection, even when the modular chamber assembly is decoupled from the sample collection device, the valve can be configured to maintain suction at the subject's skin through the sample collection device, thereby allowing replacement with a second modular chamber assembly Modular chamber components. Once the second modular chamber assembly is coupled to the sample acquisition device via the valve, the valve can be opened (eg, manually or automatically) to continue drawing blood through the sample acquisition device and into the second modular chamber assembly.

In some embodiments, the sample acquisition device and sample chamber (eg, modular device 900b and modular chamber assembly 600, as shown in FIG. 8A ) can be configured to be operable by a user. For example, a user may apply a sample acquisition device to the user's skin and then couple a sample chamber (eg, modular chamber assembly 600 ) to the sample acquisition device. In another example, the user may partially couple the sample chamber to the sample acquisition device (e.g., partially insert or rotate it), apply the sample acquisition device (which is partially coupled to the sample chamber) to the skin, and then fully attach the sample chamber. Coupled to a sample collection device, eg, for activating a blood collection procedure. Final coupling may require insertion of the sample chamber into the sample acquisition device, eg, longitudinal movement relative to the sample acquisition device. The longitudinal movement may be at least about 0.1 millimeter (mm), 0.2mm, 0.3mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm or more. The longitudinal movement may be at most about 10mm, 9mm, 8mm, 7mm, 6mm, 5mm, 4mm, 3mm, 2mm, 1mm, 0.9mm, 0.8mm, 0.7mm, 0.6mm, 0.5mm, 0.4mm, 0.3mm, 0.2mm, 0.1mm or less. Alternatively or in addition, final coupling may require rotation of the sample chamber relative to the sample acquisition device. The rotational movement may be at least about 1 degree, 2 degrees, 3 degrees, 4 degrees, 5 degrees, 6 degrees, 7 degrees, 8 degrees, 9 degrees, 10 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees , 90 degrees, 120 degrees, 150 degrees, 180 degrees, 270 degrees, 360 degrees or more angles. Rotational movement can be at up to about 360 degrees, 270 degrees, 180 degrees, 150 degrees, 120 degrees, 90 degrees, 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 9 degrees, 8 degrees, 7 degrees , 6 degrees, 5 degrees, 4 degrees, 3 degrees, 2 degrees, 1 degree or less. In some cases, the final coupling can be configured to activate a protrusion (e.g., a needle) of the sample acquisition device to penetrate the sample chamber (e.g., through the inlet port 610 of the modular chamber assembly 600) to activate the vacuum in the system ( For example, vacuum transfer from sample acquisition device to cartridge assembly, from cartridge assembly to sample acquisition device, etc.). In some cases, the lancet of the sample acquisition device can be configured to be activated upon fully coupling the sample chamber to the sample acquisition device. Alternatively, the lancet may be pre-activated prior to fully coupling the sample chamber to the sample acquisition device.

In some embodiments, the vacuum pressure that the sample collection device applies to the subject's skin prior to or during sample collection (e.g., blood draw) can be selected based on one or more conditions, e.g., the body of the subject to be collected portion of the sample, the expected volume of sample to be collected, etc. Examples of subject conditions may include, but are not limited to, skin characteristics (eg, elasticity, firmness, shape, thickness, wrinkling), gender, age, disease, number of previous uses of the device used for sample collection, and the like. In some examples, a particular type of sample acquisition device and/or sample chamber may be selected based on these conditions to create the vacuum pressure required by the subject. In an alternative embodiment, a set of sample collection devices and one or more sample chambers may be configured to provide sufficient vacuum pressure for sample collection from multiple individuals without damage to the skin (e.g., bruising) of each individual Minimal or none.

In some embodiments, when coupling a sample chamber to a sample acquisition device as disclosed herein (e.g., coupling modular chamber assembly 600 to sample acquisition device 900b), the vacuum pressure applied by the sample acquisition device to the subject's skin Can be less than about -0.5psig, -0.6psig, -0.7psig, -0.8psig, -0.9psig, -1psig, -2psig, -3psig, -4psig, -5psig, -6psig, -7psig, -8psig, -9psig, -10psig, -11psig, -12psig, -13psig, -14psig or lower. In some cases, the vacuum pressure applied by the sample acquisition device to the subject's skin may range from about -1 psig to about -14.7 psig, -1 psig to about -10 psig, preferably from about -2 psig to about -6 psig, or preferably from about –2.5psig to about -5.8psig.

In some embodiments, as described in this disclosure, a sample chamber (eg, modular chamber assembly 600 ) can be used as a vacuum chamber to provide sufficient vacuum to a sample acquisition device for sample acquisition. In some cases, the initial vacuum pressure of the modular chamber assembly (e.g., prior to coupling to the sample acquisition device) may be determined or selected by one or more of the following variables: (1) the volume of the vacuum chamber, (2) the vacuum applied to the The vacuum level of the chamber, (3) the dead volume in the sample acquisition device and cartridge assembly (e.g., cavities, channels, lancet area) that may be at ambient pressure prior to vacuum activation, (4) the sample acquisition device or module The age or number of previous uses of the chamber components, or (5) the expected shelf life of the sample collection device or modular chamber components. In one example, vacuum pressure applied to a vacuum chamber (eg, a modular chamber assembly) may be selected to accommodate vacuum decay due to material gas permeability due to vacuum decay over time. In some embodiments, the initial vacuum pressure of the vacuum chamber can be less than about -5 psig, -6 psig, -7 psig, -8 psig, -9 psig, -10 psig, -11 psig, -12 psig, -13 psig, -14 psig or less. In some cases, the initial vacuum pressure of the vacuum chamber may range from about -5 psig to about -14.7 psig, preferably from about -10 psig to about -14.7 psig, or preferably from about -12.5 psig to about -14.7 psig.

Figure 10 illustrates various dimensions and pressure parameters of a sample acquisition device and/or a sample chamber used for sample acquisition as disclosed herein. For example, the parameters shown in Figure 10 can be used for a modular chamber assembly as described in Figures 7-8. However, these parameters can be adapted (with or without modification) to other sample acquisition devices and sample chamber types. Referring to FIG. 10, parameters for sample collection may be based at least on vacuum chamber characteristics and dead volume characteristics. The vacuum chamber (e.g., modular chamber assembly 600) characteristics may depend on one or more parameters, including: (1) the internal chamber volume (V) of the modular chamber assembly, which includes chamber 620 volume, cartridge assembly 630 volume, and /or desiccant 650 volume, (2) initial internal pressure of the chamber (P_int), (3) external pressure (P_ext), (4) amount of gas in the chamber before evacuation (Mol_pre), or (5) evacuation The amount of gas in the back chamber (Mol_post). The dead volume (e.g., cavity, channel, lancet area) characteristics may depend on one or more parameters, including: (1) the interior of the sample collection device including the deposition chamber, lancet housing, and/or invasion chamber Chamber volume (V), (2) starting internal pressure (P_int), (3) external pressure (P_ext), or (4) amount of gas in the chamber of the sample collection device (Mol_pre). In one example, based on the parameters and values provided in FIG. 10, the final starting vacuum applied to the user's skin to initiate the sample collection process may be -5.83 psig.

4. Blood separation components

FIG. 11 illustrates an exemplary sample acquisition device 1100 as described herein that may be used with a cartridge assembly 1110 as described herein and an additional cartridge assembly 1105 as will be discussed. In any of the embodiments disclosed herein, the device may be reusable. For example, the device may be used more than once, such as two, three, four, five, five, six, seven, eight, nine, ten or more times. In any of the embodiments disclosed herein, the device may be single use and may be disposable. In any of the embodiments disclosed herein, sample acquisition device 1100 can be used with any of the cartridge assemblies described herein. In particular embodiments, sample acquisition device 1100 may be used with cartridge assembly 1100 for one purpose and may be used with cartridge assembly 1105 for another purpose.

FIG. 12 illustrates a cartridge assembly 1205 that may be used with sample acquisition device 1100 . Cartridge assembly 1205 may include several components. For example, a cartridge assembly may include a cartridge 1210 , a processing/stabilizing unit 1220 and a cartridge tab 1230 . In some embodiments, the processing/stabilizing unit 1220 is supported (eg, sandwiched) between the cartridge tab 1230 and the cartridge 1210 . Box tab 1230 may include a base. In some embodiments, a box tab can be coupled to the base. The base may be configured to support the processing/stabilization unit 1220 . For example, the perimeter of the substrate may be configured to be substantially the same shape and size as the perimeter of the processing/stabilization unit 1220 . The perimeter of the base may also be larger than the perimeter of the handling/stabilizing unit 1220 to ensure that the handling/stabilizing unit does not come into contact with the cartridge tab 1230 . Cassette 1210 may be positioned adjacent processing/stabilization unit 1220 . In some embodiments, the processing/stabilization unit 1220 is supported (eg, sandwiched) between the base and the cartridge 1210 .

The cartridge assembly can be releasably coupled to sample acquisition device 1100 and releasably detachable from the device. In any of the embodiments disclosed herein, the box tab 1230 can protrude from the edge of the device. In any of the embodiments disclosed herein, the cartridge tab and the piercing activator/vacuum activator (eg, button 115/167) can be located on different sides (eg, opposite ends) of the housing. Cartridge assembly 1205 can be releasably coupled to and detached from sample acquisition device 1100 like the other cartridge assemblies described herein.

Processing/stabilization unit 1220 may consist of several components in a hierarchical structure. In some embodiments, components of the processing/stabilization unit 1220 can include pre-filters, separation membranes, and acquisition matrices, eg, as described elsewhere herein. The pre-filter may be configured to be positioned adjacent to the cartridge 1210 and is the first component of the processing/stabilization unit with which the sample from the subject comes into contact. A separation membrane may be positioned adjacent to and sandwiched between the pre-filter and the acquisition matrix. The acquisition matrix can be positioned adjacent to and sandwiched between the separation membrane and cartridge tab 1230 . Cartridge 1210 of cartridge assemblies may be configured to support components of a processing/stabilization unit 1220 on which a fluid sample 1250 (eg, blood) is collected. The cartridge may be configured to support one or more absorbent pads (not shown) to retain excess liquid. The absorbent pad may be configured to rest on the bottom of the acquisition matrix of the processing/stabilization unit 1220 . Absorbent pads can absorb excess fluid samples and can help ensure that a predetermined volume of fluid can be collected on each component of the processing/stabilization unit.

Cassette assembly 1205 can be configured to receive blood from a subject at blood input region 1211 . The size and shape of the blood input region 1211 can be designed to affect and/or control the volume of sample entering the cartridge assembly. The cartridge assembly may also be configured to receive other types of biological samples other than blood. Examples of biological samples suitable for use with the devices of the present disclosure may include sweat, tears, urine, saliva, feces, vaginal secretions, semen, interstitial fluid, mucus, sebum, tears, aqueous humor, vitreous humor, bile, breast milk, Cerebrospinal fluid, cerumen, lymph, perilymph, gastric juice, peritoneal fluid, vomit, etc. In some embodiments, a liquid sample may be a solid sample that has been modified with a liquid medium. In some cases, a biological sample can be obtained from a subject in a hospital, laboratory, clinical or medical laboratory.

The processing/stabilization unit may be configured to collect and store blood as dried blood. The cassette assembly can be configured to receive blood in the blood input region 1211 . Cassette 1210 may be configured in a manner to direct blood flow towards cassette tabs 1230, thereby encouraging blood flow through each component of the processing/stabilization unit. In some embodiments, the direction of blood flow through the treatment/stabilization unit may be different than the direction of blood flow through the blood input region. In some examples, the direction of blood flow through the blood input region may be substantially parallel to the longitudinal axis 1260 of the blood separation assembly, and the direction of blood flow through the processing/stabilization unit may be different than the longitudinal axis of the blood separation assembly. The direction of blood flow through the processing/stabilization unit may not be in the same plane as the longitudinal axis of the blood separation assembly. The direction of blood flow through the treatment/stabilization unit may be offset by at least about 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees, 100 degrees, 110 degrees, 120 degrees, 130 degrees, 140 degrees, 150 degrees, 160 degrees, 170 degrees, 175 degrees or more. The direction of blood flow through the treatment/stabilization unit may be offset by up to about 170 degrees, 160 degrees, 150 degrees, 140 degrees, 130 degrees, 120 degrees, 110 degrees, 100 degrees, 90 degrees, 80 degrees, 70 degrees, 60 degrees, 50 degrees, 40 degrees, 30 degrees, 20 degrees, 10 degrees, 5 degrees or less. In a preferred example, the direction of blood flow through the treatment/stabilization unit may be substantially orthogonal to the direction of blood flow through the blood input region.

The cartridge assembly can be configured to separate multiple analytes from a blood sample. For example, the processing/stabilization unit can be configured to isolate cells, plasma, serum, lipids, platelets, specific cell types, DNA (eg, tumor cfDNA), RNA, proteins, inorganic materials, drugs, or any other components. In particular embodiments, the processing/stabilization unit may be configured to separate total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, creatinine, alanine aminotransferase, and glucose from a blood sample.

The cassette assembly may be configured to operate at an angle substantially normal to the ground. For example, the cartridge assembly may be configured to receive blood from a sample collection device attached to and substantially parallel to the patient's arm. The box assembly can also be configured to operate at any angle to the ground. The box assembly can be operated at an angle substantially parallel to the ground, or at approximately 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees , 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, 90 degrees, 95 degrees, 100 degrees, 105 degrees, 110 degrees, 115 degrees, 120 degrees, 125 degrees, 130 degrees, 135 degrees, 140 degrees degree, 145 degree, 150 degree, 155 degree, 160 degree, 165 degree, 170 degree, 175 degree or angle operation of about 180 degree.

13-18 illustrate embodiments of a blood separation assembly. Components of these implementations can be configured for use in any other implementation described herein. This may include modifying and/or reducing the overall dimensions of several components for other embodiments. For example, the components of FIGS. 13-18 may be configured for use in the embodiment of FIG. 12 .

Component 1300 of FIG. 13A may consist of several components. For example, first assembly structure 1310 , second assembly structure 1330 , and treatment/stabilization unit 1320 , which may include pre-filter 1322 , separation membrane 1324 , and acquisition matrix 1326 . The first assembly structure 1310 and the second assembly structure 1330 may be configured in a manner to maintain the components of the processing/stabilizing unit 1320 in a substantially vertical orientation. This allows the liquid sample 1350 to flow in a direction substantially parallel to the longitudinal axis 1360 of the blood separation assembly, and facilitates the flow of the liquid sample 1350 through and along the processing/stabilization unit with the aid of gravitational wicking forces. The first assembly structure 1310 and the second assembly structure 1330 may be configured such that the first assembly structure 1310 may slide and lock into the second assembly structure 1330 . Once in the locked position, as shown in the leftmost image of Figure 13A, the first assembly structure 1310 can be constrained in one or more degrees of freedom. For example, first assembly structure 1310 may only move in a direction away from second assembly structure 1330 . The first assembly structure 1310 can be brought into and out of the locked position to allow access to the components of the processing/stabilization unit 1320 sandwiched between the first assembly structure 1310 and the second assembly structure 1330 .

Acquisition matrix 1326 may be configured to be larger than both separation membrane 1324 and pre-filter 1322 . For example, the acquisition matrix can be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90% longer than the length of the separation membrane and prefilter , about 100%, about 110%, about 120%, about 130%, about 140%, or about 150% or more. In the assembled configuration, as shown in the leftmost image of Figure 13A, the bottom of the acquisition matrix can be exposed. For example, the exposed portion of the acquisition matrix can be about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, About 50%, about 55%, about 60%, about 65%, about 70%, or about 75% or more. The exposed portion of the collection matrix allows for easier access to the sample collected on the collection matrix after the fluid sample has passed through the blood separation assembly. For example, the exposed portion can be cut away from the remainder of the acquisition matrix without the need to separate the acquisition matrix from the other components of the processing/stabilization unit. Perforated lines can also be used to separate the exposed portion from the rest of the acquisition matrix. This may allow the exposed portion to be pulled away from the rest of the acquisition matrix without negatively impacting the viability and/or performance of the acquisition matrix itself.

FIG. 15 illustrates a perspective view of several components of blood separation assembly 1500 . Processing/stabilization unit 1520 may include several components. For example, a processing/stabilization unit may include a pre-filter 1522 , a separation membrane 1524 and a multi-component acquisition matrix including a top assembly 1527 and a bottom assembly 1528 . The bottom of the bottom component 1528 of the multi-component acquisition matrix can be configured to abut the absorbent pad 1529 . A pre-filter 1522 of the processing/stabilization unit may be positioned adjacent to the first assembly structure 1510 of the blood separation assembly 1500 . A separation membrane may be placed near the pre-filter 1522 . A multi-component acquisition matrix can be positioned adjacent to the separation membrane 1524 and the second component structure 1530 . The bottom component of the multicomponent collection matrix may be exposed when the blood separation component is in the assembled configuration. The bottom component of the multi-component acquisition matrix can be separated from the top component by cutting the bottom component from the top component. The top and bottom components of the multi-component acquisition matrix may also be separated by perforated lines, as explained above in Figure 13, allowing the bottom component to be pulled apart from the top component. The top and bottom components of the multi-component acquisition matrix can be configured such that there is an overlap between the top and bottom components. For example, the top and bottom components of a multi-component acquisition matrix may overlap by about 1 mm, 2 mm, 3 mm, 4 mm, or 5 mm or more.

Numerous benefits can be observed in liquid sample analysis by extracting only the exposed bottom components of the multi-component collection matrix. For example, if the multicomponent collection matrix absorbs a blood sample from a subject, extracting only the exposed bottom components of the multicomponent collection matrix can result in lower levels of hemolysis per surface area and higher analyte yields. The lower hemolysis of the exposed bottom component of the multicomponent acquisition matrix may be because this part of the multicomponent acquisition matrix is less constrained and thus cells in this area are less prone to rupture. The exposed bottom component of the multicomponent acquisition matrix may allow up to about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the unexposed top component of the multicomponent acquisition matrix. % or greater reduction in hemolysis. The exposed bottom component of the multicomponent acquisition matrix may allow up to about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the unexposed top component of the multicomponent acquisition matrix. % or greater increase in analyte yield per surface area.

16A illustrates a perspective view of a first assembly structure that may be configured to provide structural support to the processing/stabilization unit and blood separation assembly. Additionally, the first component may be configured to provide a containment mechanism for incoming sample and direct the sample onto a desired surface, such as a pre-filter, and prevent it from directly entering other surfaces, such as a matrix. The first assembly structure and the second assembly structure may be configured to hold the treatment/stabilization unit therein with a planar surface of the assembly in the treatment/stabilization unit substantially normal to the direction of the ground. In some embodiments, the planar surfaces of components in the processing/stabilization unit may also be substantially parallel to the ground. The first assembly structure can be configured to include a blood input region 1611 that can receive a blood sample from a subject. The size and shape of the blood input region 1611 can be designed to affect and/or control the volume of sample entering the blood separation assembly. By configuring the blood input region as an inlet channel rather than an open funnel design, the blood separation assembly can also be configured with a full perimeter seal. A blood sample from a subject may enter the blood input area and accumulate in the groove 1612 of the first assembly structure 1610 . The first component structure can also be configured to include several structural components. For example, it may include a first compression region 1614, a second compression region 1615, a third compression region 1616, and a compression stop 1613 that may rest on one or both sides of the first assembly structure.

The first compression region 1614 may be configured to provide a source of pressure to the central region of the processing/stabilization unit. The second compression region 1615 may be configured to provide a source of pressure to the lower region of the processing/stabilization unit. The third compression region 1616 can be configured to provide a source of pressure to the bottom component of the multi-component acquisition matrix. The compression stops 1613 may be configured in a manner to ensure that the first, second and third compression regions do not overcompress the processing/stabilization unit.

The compressive force exerted by the first, second and third compression regions may be configured to ensure good contact between components of the treatment/stabilization unit to allow optimized blood flow through the treatment/stabilization unit. The contact created between the components of the processing/stabilization unit by the compressive force may be sufficient to achieve the wicking force required for the blood sample to flow through the processing/stabilization unit. This compressive force may be sufficient to promote optimal flow of blood through the treatment/stabilization unit without damaging, deforming or otherwise damaging the materials of several components of the treatment/stabilization unit. The compressive force applied to the handling/stabilizing unit may be approximately 20 lbs, 19 lbs, 18 lbs, 17 lbs, 16 lbs, 15 lbs, 14 lbs, 13 lbs, 12 lbs, 11 lbs, 10 lbs, 9 lbs, 8 lbs , 7 lbs, 6 lbs, 5 lbs, 4 lbs, 3 lbs, 2 lbs, or 1 lb or less. The compressed thickness of the treatment/stabilization unit may be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, or about the uncompressed thickness of the treatment/stabilization unit. About 90% or more. The compressed thickness of the treatment/stabilization unit may be about 2.0mm, 1.75mm, 1.5mm, 1.25mm, 1.0mm, 0.75mm, 0.50mm or 0.25mm or less.

The first assembly structure and the second assembly structure may be held/clamped together using any suitable coupling mechanism. Examples of coupling mechanisms may include, but are not limited to, male-to-female fasteners (e.g., mating or interlocking fasteners, hooks and holes, hooks and loops such as Velcro ^™ , female nuts threaded onto male bolts, inserted into female notches male protrusions, male threaded pipe installed in female elbows in pipes, male threaded Universal Serial Bus (USB) plugs that fit into female threaded USB receptacles, etc.), tethers (e.g., ropes), adhesives ( For example, solids, semi-solids, gels, viscous liquids, etc.), magnets (eg, electromagnets or permanent magnets), and other grasping mechanisms (eg, one or more robotic arms). In one example, the coupling can be performed using an electric field between the inlet port and the sample acquisition device. The coupling mechanism may also include clamps, springs, screws, elastic bands, or other stretchable components that can reach around and hold the first and second component structures together. In other embodiments, the first assembly structure and the second assembly structure may be held together by grooves configured in the bodies of the two structures. The coupling mechanism holding the two structures together may be configured to achieve a desired compression force or a desired compression distance between components of the processing/stabilization unit. The coupling mechanism may be configured to apply a uniform force across the entire surface area of the treatment/stabilization unit. The coupling mechanism may also be configured to apply different forces to different regions of the treatment/stabilization unit.

The compression stop 1613 may be configured to ensure that a desired compression force or compression distance is encountered and not exceeded by the coupling mechanism holding the two structures together. The compression stop may also include a sensor that measures the compressive force applied to the treatment/stabilization unit and alerts the user when the force applied to the treatment/stabilization unit exceeds the maximum applied force. The compression stop may be configured to have the same thickness as the first assembly structure. For example, the thickness of the compression stop can be about 0.090, 0.080, 0.070, 0.060, 0.050, 0.040, 0.030, 0.020, or about 0.010 inches or less. The thickness of the compression stop may also be configured to be less than or greater than the thickness of the first assembly structure. For example, the thickness of the compression stop may be about 50%, about 60%, about 70%, about 80%, about 90%, about 100%, about 110%, about 120%, about 130%, about 140%, or about 150% or more.

Compression stops can be made of materials such as polypropylene, polyvinyl chloride, polyvinylidene chloride, low density polyethylene, linear low density polyethylene, polyisobutylene, poly[ethylene-vinyl acetate] copolymer, lightweight aluminum foil, and combinations thereof , stainless steel alloys, commercially pure titanium, titanium alloys, silver alloys, copper alloys, grade 5 titanium, superelastic titanium alloys, cobalt-chromium alloys, stainless steel alloys, superelastic metal alloys (e.g. Nitinol, superelastic plastic metals such as those made of GUM manufactured by Toyota Material Incorporated, Japan ), ceramics and their composites, such as calcium phosphate (eg, SKELITE ^TM manufactured by Biologix Inc.), thermoplastics, such as polyaryletherketone (PAEK), including polyetheretherketone (PEEK), polyetherketoneketone ( PEKK) and polyetherketone (PEK), carbon-PEEK composites, PEEK-BaSO ₄ polymerized rubber, fabric, silicone, polyurethane, silicone-polyurethane polymer, polymer rubber, polyolefin rubber, hydrogel, semi-rigid and Rigid materials, elastomers, rubber, thermoplastic elastomers, thermoset elastomers, elastic composites, rigid polymers including polyphenylene, polyamide, polyimide, polyetherimide, polyethylene, epoxy, parts Absorbable materials such as composites of metal and calcium shell-based ceramics, composites of PEEK and calcium shell-based ceramics, composites of PEEK and absorbable polymers, fully resorbable materials such as calcium shell-based ceramics such as calcium phosphate , tricalcium phosphate (TCP), hydroxyapatite (HA)-TCP, calcium sulfate or other resorbable polymers such as polyglycolide, polyglycolide, polytyrosine carbonate, polycarotene and its composite materials.

In other embodiments, the first assembly structure and the second assembly structure of the blood separation assembly may be configured as a single assembly. This can be achieved through the use of living hinges or other similar techniques, allowing flexibility in a single component. In other embodiments, the blood separation assembly may comprise more than two assemblies. Adding more components to the blood separation assembly can be configured to improve the functionality, formability, and/or manufacturability of the blood separation assembly.

The blood separation assembly can also be configured to include the addition of additional grooves that can be configured to regulate air exposure to the collection matrix. This helps control plasma concentration and drying rate. Plasma concentrations may be about 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1 μL/mm ² . Drying of the blood sample can occur in less than about 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 hour. The additional grooves can be of any size and shape as long as they do not affect the structural properties of other components of the blood separation assembly. The number of additional grooves can be selected to achieve the desired effect on temperature and humidity which may affect the drying rate. Additional grooves may allow air within the blood separation assembly to be displaced and pressure within the blood separation assembly to equalize with pressure conditions existing outside the blood separation assembly. The number of additional grooves can be limited if it is desired that the pressure conditions inside the blood separation assembly differ from the pressure conditions outside the blood separation assembly. For example, a desired pressure differential between internal components and the external environment can promote better blood flow through the processing/stabilization unit without causing excessive hemolysis of the blood sample.

Blood separation components can be 3D printed, injection molded or machined. The blood separation assembly may comprise or be made of materials such as polypropylene, polycarbonate, or other similar materials that do not interfere with or alter the properties of the sample passing through the processing/stabilization unit.

FIG. 17A illustrates an exemplary multi-component acquisition matrix including a top component 1727 and a bottom component 1728 disposed adjacent to a second component structure 1730 . A multi-component acquisition matrix can be configured to include two or more components. For example, a multi-component acquisition matrix can be configured to include two, three, four, five or more components.

The multi-component collection matrix can have a volume sufficient to collect a desired amount of product (eg, serum or plasma) on the separation membrane. The multi-component acquisition matrix can be configured to hold (or contain) at least about 1 μL, 5 μL, 10 μL, 20 μL, 30 μL, 40 μL, 50 μL, 60 μL, 70 μL, 80 μL, 90 μL, 100 μL, 110 μL, 120 μL, 130 μL, 140 μL, 150 μL, 200 μL , 300μL, 400μL, 500μL, 600μL, 700μL, 800μL, 900μL, 1,000μL or more separation membrane products. The multi-component acquisition matrix can be configured to hold (or contain) up to about 1,000 μL, 900 μL, 800 μL, 700 μL, 600 μL, 500 μL, 400 μL, 300 μL, 200 μL, 100 μL, 50 μL, 10 μL, 1 μL, or less of the separation membrane product.

The top assembly 1727 of the multi-component collection matrix can be configured such that the entire planar surface area of the top assembly is covered by the separation membrane in the assembled blood separation assembly. The bottom component of the multi-component collection matrix can be configured to be exposed and not touched by the separation membrane or pre-filter in the blood separation component. The bottom component of the multi-component acquisition matrix can be configured to be exposed to improve sample analysis. The exposed bottom component of the multicomponent acquisition matrix can have about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, Surface area of 240 or 250 or more ^mm2 . The exposed bottom component can be configured to simply pull away from the top component of the acquisition matrix, thereby avoiding the need to cut, tear or otherwise bifurcate the handling/stabilizing unit. For example, by using perforated lines that separate the top and bottom components. As shown in Figure 17A, the bottom component of the multi-component acquisition matrix can be further divided into multiple segments. The bottom assembly can be divided along a longitudinal axis, as shown in Figure 17A, or along a horizontal axis. The bottom assembly may also be divided along longitudinal and transverse axes.

The top and bottom components of the multi-component acquisition matrix can be configured such that each component can have different geometries, materials, thicknesses, coatings, and chemical compositions. The top assembly can be configured such that the top assembly concentrates the blood sample from the wider portion of the multi-component collection matrix to the narrower portion of the multi-component collection matrix. The bottom assembly can be configured to have a geometry optimized for the sample collection elution method, as will be discussed herein. Samples can also be analyzed from the top component of the multicomponent collection matrix. The top and bottom components of the multi-component acquisition matrix can be configured such that the top and bottom components have different thicknesses. The top component may be thicker than the bottom component, the bottom component may be thicker than the top component, or the top and bottom components may be the same thickness. The thickness of the multicomponent acquisition matrix can be configured to allow the multicomponent acquisition matrix to hold (or contain) a specified volume of liquid. The blood separation assembly can also be configured with multiple collection matrices. Multiple acquisition matrices can be configured as multi-component acquisition matrices, single-component acquisition matrices, or a combination of both.

Figure 17B illustrates a side cross-sectional view of a multi-component acquisition matrix positioned adjacent to a second assembled component 1730, wherein absorbent pad 1729 is configured to rest on the bottom of bottom component 1728 of the multi-component acquisition matrix. As shown in Figure 17B, the bottom and top components of the multi-component acquisition matrix can be configured such that the two components overlap each other. The two components can also be configured such that there is no overlap between the two components. For example, the top assembly and bottom assembly may be separated by a perforated strip, allowing the bottom assembly to be easily separated from the top assembly.

Absorbent pad 1729 is capable of metering blood samples collected in the blood separation assembly. The absorbent pad can be configured to collect any excess separated blood sample or fluid that exceeds the saturated volume of the multicomponent collection matrix. There can be one absorbent pad or multiple absorbent pads. If multiple absorbent pads are used, they may be configured such that they are placed on top of each other or aligned end-to-end. The absorbent pads can be thicker than the multicomponent acquisition matrix, or they can be thinner.

The absorbent pad can be configured to be directly integrated with the multicomponent acquisition matrix, or the absorbent pad can be separate from the multicomponent acquisition matrix. If the absorbent pad is configured to be directly integrated with the multi-component acquisition matrix, the absorbent pad may be a severed portion of the bottom component of the multi-component acquisition matrix, or may be a portion separated from the bottom component of the multi-component acquisition matrix by a perforated strip. If the absorbent pad is configured to be separate from the multi-component acquisition matrix, they can be configured such that substantial contact is achieved between the absorbent pad and the bottom component of the multi-component acquisition matrix. This can be achieved by adding an additional component beneath the absorbent pad that allows the absorbent pad to remain in contact with the bottom component of the multi-component acquisition matrix. The absorbent pad can be configured to contact the planar surface of the bottom component of the multi-component acquisition matrix on one or both sides of the bottom component.

The absorbent pad can be configured to vary in size and geometry in order to adjust the volume of blood sample or fluid that the absorbent pad is intended to hold (or contain). The absorbent pad may also be configured to rest in other areas of the blood separation assembly where blood samples or other fluids may leak and need to be collected.

An absorbent pad is incorporated into the cartridge assembly to contain any excess fluid that the collection matrix cannot hold, thereby allowing a volume of fluid to be collected from the patient that is larger than the collection matrix can hold. For example, if the saturation point of the acquisition matrix is 50 µL and the absorbent pad has an absorbent capacity of 300 µL, then allow for a variety of scenarios. For example, introducing 50 μL of sample into the processing/stabilization unit will result in approximately 50 μL of sample being collected in the collection matrix and approximately 0 μL of sample contained in the absorbent pad. Introduction of 75 μL of sample into the processing/stabilization unit will result in approximately 50 μL of sample being collected into the collection matrix and approximately 25 μL of sample contained in the absorbent pad. Thus, in addition to the capacity of the absorbent pad, the maximum input volume of sample fluid to the cartridge assembly will be the capacity of the acquisition matrix. The volume of the acquisition matrix and the volume of the absorbent pad can be adjusted to alter the desired and/or maximum volume of sample fluid obtained from the patient. The cartridge assembly including the absorbent pad can be configured to perform in this manner, because different blood samples from different patients may have different levels of hematocrit, which means that one volume of blood collected from one patient will be higher than that collected from a second The same volume of blood collected from each patient provides a greater or lesser volume of plasma. Absorbent pads can be helpful when measuring the exact amount of blood entering the cartridge assembly may not be feasible and the user may not have to worry about the cartridge assembly being overfilled. For example, obtaining a high hematocrit blood sample without an absorbent pad may result in the collection matrix not receiving enough plasma. On the other hand, without an absorbent pad, obtaining a blood sample with a low hematocrit may result in oversaturation of the collection matrix.

In an alternative embodiment, absorbent pad 1729 may be absorbent paper 1750, as shown in FIGS. 17B and 17C. Non-limiting examples of absorbent paper may include fibrous papers with high absorbent capacity, such as 31-ETF, CF-12, CF-9, and the like. As shown in Figure 17B, absorbent paper 1750 can be configured to be placed vertically on the bottom of the acquisition matrix. The absorbent paper can be folded or otherwise manipulated to create different geometries and create a spring-like action to keep the paper in contact with the substrate. Alternatively, as shown in Figure 17C, the absorbent paper 1750 can be parallel to the acquisition matrix. If the absorbent paper 1750 is parallel to the acquisition matrix, the absorbent paper may be flush with or overlap the bottom of the acquisition matrix. For example, the absorbent paper may have an overlap of 0 mm, 1 mm, 2 mm, 3 mm, 4 mm or 5 mm with the acquisition matrix. Absorbent paper 1750 may be configured to be pulled away from the bottom component of the acquisition matrix by using a perforated strip that separates the two components.

In addition to the absorbent paper 1750 of Figures 17B and 17C, an additional hydrophilic layer 1751 can be configured to rest on top of the acquisition matrix. The hydrophilic layer 1751 can be configured parallel to the acquisition matrix. If the hydrophilic layer 1751 is parallel to the acquisition matrix, the hydrophilic layer 1751 can be flush with the top of the acquisition matrix, or overlap the top of the acquisition matrix. For example, the hydrophilic layer may have an overlap of 0 mm, 1 mm, 2 mm, 3 mm, 4 mm or 5 mm with the acquisition matrix. The hydrophilic layer 1751 can be configured to be pulled away from the bottom component of the acquisition matrix by using a perforated strip that separates the two components. The use of absorbent paper and/or a hydrophilic layer can serve the same purpose as the use of absorbent pads described above, to absorb excess sample.

Figure 18 illustrates a perspective view of a processing/stabilization unit 1820 that may be used in embodiments described herein. Pre-filter 1822 may be configured as the first component that a blood sample or other fluid contacts in a blood separation component. The pre-filter 1822 may be configured to include a smaller surface area than the separation membrane 1824 disposed immediately after and adjacent to the pre-filter, as shown in FIG. 18 . The pre-filter may also be configured to include the same or larger surface area than the separation membrane. The pre-filter may be configured to separate or otherwise filter out certain components of the liquid or blood sample before the liquid or blood sample reaches other components of the processing/stabilization unit. The pre-filter can be coarser than the other components of the processing/stabilization unit and can increase the overall throughput. For example, a processing/stabilization unit can separate a 300 μL sample with a pre-filter, while a processing/stabilization unit can only separate a 100 μL sample without a pre-filter.

Separation membrane 1824 may be configured to separate and contain cellular components of a blood sample while allowing plasma/serum of the blood to be collected by a collection matrix positioned immediately after and adjacent to the separation membrane. For example, the separation membrane may be a Leukosorb material. The surface area of the separation membrane can be configured to be greater than the surface area of other components in the processing/stabilization unit to ensure that no blood sample bypasses the separation membrane before reaching the collection matrix.

Figures 19 and 20 illustrate the cartridge and cartridge assembly. Components of these implementations can be configured for use in any other implementation described herein. This may include modifying and/or reducing the overall dimensions of several components for other embodiments. For example, the components of FIGS. 19-20 may be configured for use in the embodiment of FIG. 12 .

19 illustrates a perspective view of an example cartridge 1910 that may be configured to implement a cartridge assembly of a processing/stabilization unit and configured to collect a fluid or fluid-like sample (eg, liquid blood) as described herein. Cartridge 1910 can include coupling unit 1912, which can be configured to couple (e.g., releasably or permanently) to a sample acquisition device (e.g., any of the same disclosed herein) using any of the coupling mechanisms described herein. port in the cartridge chamber of the collection device). For example, coupling unit 1912 may have a Luer type fitting to mate with a cartridge port of a sample acquisition device. Coupling unit 1912 may include an opening, inlet 1911 or channel configured to serve as a path for blood to flow from the sample collection device to the cartridge assembly (eg, into the cartridge assembly). For example, inlet 1911 may receive blood from a sample collection device and direct the blood through funnel 1914 and into groove 1915, thereby allowing the blood to accumulate in the space adjacent to the pre-filter surface of the processing/stabilization unit. Cassette 1910 may also be configured to include a first compression region 1916 . The cartridge may also include a second compression region 1917 which may serve to seal the entire perimeter of the processing/stabilization unit. Configuring cassette 1910 in this manner prevents blood flow from being able to bypass the pre-filter and separation membrane of the processing/stabilization unit. For example, where blood is introduced into the groove 1915 through the inlet 1911 faster than the processing/stabilizing unit can process the blood. Cassette 1910 may also be configured to include vents 1913 that may allow pressure equalization between recess 1915 and the environment outside of cassette 1910 . This may allow air to be displaced and/or vacuum or other pressure conditions existing outside the cartridge to equalize within groove 1915 , through inlet 1911 into the upstream portion of the blood collection device. Vents 1913 can directly reduce or completely eliminate the pressure differential across the processing/stabilization unit. In some examples, vent holes may be eliminated to allow a pressure differential across the treatment/stabilization unit to facilitate blood flow through components of the treatment/stabilization unit. The cartridge may be completely opaque, or completely or partially transparent to allow the user to observe blood accumulation in the groove 1915 during a blood draw. Visualization of blood accumulation in the groove 1915 can be used as an indication that the processing/stabilization unit has processed as much blood as possible and the draw can be stopped.

Implementing the blood separation assembly into the cartridge assembly as described herein allows the method of blood drawing to be performed using the entire system of the assembly including the processing/stabilization unit, the assembly having a planar surface substantially normal to the ground. Methods such as these are desirable in procedures where, for example, a sample collection device is configured to collect blood while attached to a patient's arm. This further allows for a low profile design of the sample acquisition device.

20 illustrates side sectional and perspective views of a cassette assembly 2010 that may be configured to include a visual gauge element to indicate to a user when a sufficient amount of blood from a patient has been received in the cassette assembly 2010 . The cartridge assembly can be configured to use a pre-metering chamber. The pre-measurement chamber may be configured to provide a visual indication to the user when the correct amount of blood has been collected by visual confirmation that the chamber has been filled. The user will be able to visually see that the pre-measurement chamber has been filled when the correct amount of blood has been filled. The pre-metering chamber may be configured to include a semi-permeable membrane that allows air to escape, but not blood or other liquid, so that air can be displaced when the entire chamber is filled with blood. Once filled with blood, the blood can be manually advanced to the processing/stabilization unit through a piston arrangement or a diaphragm, where a check valve can be implemented to prevent backflow. In another example, blood may advance automatically when the end-of-draw seal between the patient's skin and the sample collection device is broken. When this occurs, a large pressure differential is created across the inlet that can be used to advance the blood sample or trigger the advancement of the blood sample.

In another embodiment, a system may be used where the properties of the collection matrix cause it to close when the maximum volume of blood has been processed. Once the collection matrix has absorbed the maximum amount of blood from the patient, the blood will stop processing and begin to accumulate in the upstream groove. The accumulation may be configured to paint a visual indication to the user that enough blood has been collected. For example, in the rightmost image of FIG. 20, window 2045 may be configured to change from white to red when blood reaches it after pooling has occurred in the groove. Alternatively, the indicator may comprise an absorbent material that absorbs blood and changes color. Alternatively, the user may see a visual indication of blood accumulation in the groove from the side of the cartridge assembly, as shown in the two left images of FIG. 20 . The leftmost image in Figure 20 illustrates an empty groove 2040, while the middle image in Figure 20 illustrates a groove 2040 that has been filled with blood after the maximum volume of blood has been contained in the collection matrix.

21A-21C illustrate additional embodiments of cartridge assemblies for access to a processing/stabilization unit after the blood separation process is complete. As shown in Figure 21A, the cartridge may include a release mechanism 2110 configured to hold the processing/stabilization unit 2120 in place. Release mechanism 2110 may release treatment/stabilization unit 2120 upon application of force at pressure point 2130 . Features such as this enable the handling/stabilizing unit to be handled manually or automatically without having to directly contact the handling/stabilizing unit with additional components (eg forceps, clamps, disposable tips, etc.). This eliminates the possibility of contamination and prevents the need for cleaning or disinfection of the treatment/stabilization unit 2120 after release. For example, applying force to pressure point 2130 may be accomplished by squeezing pressure point 2130 with a finger. Alternatively, the pressure points 2130 may be highly positioned and may only be engaged by using clamps designed to apply pressure concentrated in specific areas (as shown by the dashed lines in FIG. 21A ).

FIG. 21B illustrates release mechanism 2110 with seal 2140 and clip 2150 added. As disclosed in other embodiments herein, seal 2140 may be configured to hermetically seal the cartridge chamber. As the pressure point 2130 of the release mechanism 2110 is squeezed, the clamp 2150 may release the handling/stabilizing unit 2120 . The clamp 2150 may be configured to include an absorbent pad configured to contact and hold the handling/stabilizing unit 2120 in place. After the handling/stabilizing unit 2120 is released, the absorbent pad may remain on the clamp 2150 . The absorbent pad may also be configured to be released from the gripper 2150 together with the handling/stabilization unit 2120 or separately.

FIG. 21C illustrates the release mechanism 2110 with the addition of a guard 2160 that prevents accidental release of the processing/stabilization unit 2120 . As discussed in the embodiments herein, the cartridge may be configured to be releasably coupled to a sample acquisition device or may be inserted into a transport sleeve. Shield 2160 may be configured as part of a sample acquisition device or transport sleeve, and processing/stabilization unit 2120 may only be released when the cartridge is detached from the sample acquisition device or transport sleeve. The shipping sleeve may be configured to receive the processing/stabilization unit 2120 when it is released and to hold the processing/stabilization unit 2120 until the processing/stabilization unit 2120 is ready for testing.

5. Elution method

Other aspects of the present disclosure provide methods for dissociating biomolecules, such as nucleic acid molecules, proteins, hormones, carbohydrates, lipids, from collection matrices for further processing. Such biomolecules are typically derived from a subject, such as a human, and can be used as biomarkers for in vitro diagnostics or monitoring of patient health.

I. Mechanical dissociation

Mechanical dissociation methods can be used to process harvested matrices. Such methods can be used to dissociate biomolecules from acquisition matrices. Non-limiting examples of mechanical dissociation methods include sonication, vortexing, shaking, shaking, nutation, inversion mixing, spinning, soaking, immersion, homogenization, and freeze/thaw cycles.

The collection matrix can be soaked to dissociate biomolecules. Soaking can be performed in the presence of various buffers or solvents. Alternatively, soaking with water can be performed. Buffers or solvents may include elution buffers, lysis buffers, wash buffers, and the like. In some cases, soaking can be performed in the presence of a chelating agent, reducing agent, oxidizing agent, surfactant, protein denaturant, one or more salts, one or more enzymes, or any organic solvent. Soaking can be performed before any other elution method. Alternatively, soaking can be performed after other elution methods.

In some cases, the period of soaking the harvest matrix can be less than 1 minute, less than 5 minutes, less than 10 minutes, less than 20 minutes, less than 30 minutes, less than 50 minutes, less than 60 minutes, less than 2 hours, less than 5 hours, less than 10 hours , less than 20 hours, less than 30 hours, less than 1 day, less than 2 days or less than 3 days. In some cases, the soaking time can be greater than 1 minute, greater than 5 minutes, greater than 10 minutes, greater than 20 minutes, greater than 30 minutes, greater than 50 minutes, greater than 60 minutes, greater than 2 hours, greater than 5 hours, greater than 10 hours, greater than 20 minutes hours, greater than 30 hours, greater than 1 day, greater than 2 days, or greater than 3 days.

The acquisition matrix may be at about 0°C, about 4°C, about 10°C, about 20°C, about 25°C, about 27°C, about 30°C, about 32°C, about 35°C, about 40°C, about 45°C, about 50°C °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, about 80 °C, about 85 °C, about 90 °C, about 92 °C, about 95 °C or about 98 °C. In some cases, the collection matrix can be collected at temperatures below 0°C, below 4°C, below 10°C, below 20°C, below 25°C, below 27°C, below 30°C, below 32°C, below At 35°C, below 40°C, below 45°C, below 50°C, below 55°C, below 60°C, below 65°C, below 70°C, below 75°C, below 80°C, low Soak at a temperature of 85°C, below 90°C, below 92°C, below 95°C or below 98°C. In some cases, the collection matrix may be above 0°C, above 4°C, above 10°C, above 20°C, above 25°C, above 27°C, above 30°C, above 32°C, above At 35°C, above 40°C, above 45°C, above 50°C, above 55°C, above 60°C, above 65°C, above 70°C, above 75°C, above 80°C, high Soaking at a temperature of 85°C, above 90°C, above 92°C, above 95°C or above 97°C.

The matrix can be harvested using sonication. Sonication can be performed prior to immersion or rehydration. Commercially available instruments can be used for sonication. Sonication can be performed in the presence of buffer, examples of which are provided elsewhere herein. It can be done at different speeds for different biomolecules. Sonication can be used to lyse cells or shear genomic DNA or proteins. Sonication can be performed with collection matrix or with collection matrix soaked on ice.

Sonication can be performed in pulses. For example, sonication can be performed for 10 seconds, and then the sample can be left for 40 seconds. The ultrasound amplitude can be adjusted according to the target biomolecules in the biological sample. The amplitude for sonication can be from about 1% to about 80%. The amplitude for sonication can be at least about 1%. The amplitude for sonication can be less than 5%, less than 10%, less than 15%, less than 20%, less than 25%, less than 30%, less than 50%, less than 60%, less than 70%, or less than 80%. In some cases, the amplitude for sonication may be greater than 1%, greater than 5%, greater than 10%, greater than 15%, greater than 20%, greater than 25%, greater than 30%, greater than 50%, greater than 60%, greater than 70% % or greater than 80%.

Any acquisition matrix herein can be processed using agitation. Stirring can include vortexing, shaking, mixing, shaking, and the like. The speed can be less than 5 revolutions per minute (rpm), less than 10 rpm, less than 15 rpm, less than 20 rpm, less than 30 rpm, less than 40 rpm, less than 50 rpm, less than 60 rpm, less than 70 rpm, less than 80 rpm, less than 90rpm, below 100rpm, below 150rpm, below 200rpm, below 250rpm, below 300rpm, below 350rpm, below 400rpm, below 500rpm, below 600rpm, below 700rpm, below 800rpm, below 900rpm, Less than 1,000rpm, less than 1,500rpm, less than 2,000rpm, less than 2,500rpm, less than 3,000rpm, less than 3,500rpm, less than 4,000rpm, less than 4,500rpm, less than 5,000rpm, less than 5,500rpm, Below 6,000 rpm, below 6,500 rpm, below 7,000 rpm, below 7,500 rpm, below 8,000 rpm, below 8,500 rpm, below 9,000 rpm, below 9,500 rpm or below 10,000 rpm. The speed may be about 50 rpm, 100 rpm, 200 rpm, 300 rpm, 400 rpm, 500 rpm, 600 rpm, 700 rpm, 800 rpm, 900 rpm, 1000 rpm, 1500 rpm or 5000 rpm. The speed may be at least 50 rpm, 100 rpm, 200 rpm, 300 rpm, 400 rpm, 500 rpm, 600 rpm, 700 rpm, 800 rpm, 900 rpm, 1000 rpm, 1500 rpm or 5000 rpm.

Agitation can be performed for at least about 1 second. Agitation can be performed for less than 1 second, less than 5 seconds, less than 10 seconds, less than 15 seconds, less than 20 seconds, less than 30 seconds, less than 50 seconds, less than 60 seconds, less than 80 seconds, less than 100 seconds, less than 120 seconds, less than 5 minutes, less than 10 minutes, less than 20 minutes, less than 30 minutes, less than 50 minutes, less than 60 minutes, less than 50 minutes, less than 60 minutes, less than 2 hours, less than 5 hours, less than 8 hours, less than 10 hours, less than 20 hours, less than 30 hours, or less than 50 hours. Stirring can be carried out for more than 1 second, more than 5 seconds, more than 10 seconds, more than 15 seconds, more than 20 seconds, more than 30 seconds, more than 50 seconds, more than 60 seconds, more than 80 seconds, more than 100 seconds, more than or 120 seconds, more than 5 seconds minutes, greater than 10 minutes, greater than 20 minutes, greater than 30 minutes, greater than 50 minutes, greater than 60 minutes, greater than 50 minutes, greater than 60 minutes, greater than 2 hours, greater than 5 hours, greater than 8 hours, greater than 10 hours, greater than 20 hours, Greater than 30 hours, greater than 48 hours, or greater than 50 hours.

The matrix can be collected using homogenization. A commercially available homogenizer can be used to process the acquisition matrix. Non-limiting examples include MACS Octo dissociators, rotor-stator homogenizers, bead mills, high pressure homogenizers, and the like.

Homogenization can be performed at a speed of at least about 500 rpm. Homogenization can be performed at speeds below 500 rpm, below 1,000 rpm, below 2,000 rpm, below 4,000 rpm, below 5,000 rpm, below 6,000 rpm, below 8,000 rpm, below 10,000 rpm or below 12,000 rpm conduct. Homogenization may be performed at speeds greater than 100 rpm, greater than 500 rpm, greater than 1000 rpm, greater than 2000 rpm, greater than 4000 rpm, greater than 5000 rpm, greater than 6000 rpm, greater than 8000 rpm, greater than 10,000 rpm, or greater than 12,000 rpm .

Homogenization can be performed at a temperature of at least about 4°C. Homogenization can be performed at temperatures below 5°C, below 10°C, below 15°C, below 20°C, below 25°C, below 27°C, below 30°C, below 32°C, below 37°C, Below 40°C, below 42°C, below 45°C, below 50°C, below 55°C, below 60°C, below 65°C, below 70°C, below 75°C, below 80°C, Conducted at a temperature below 85°C, below 90°C, below 92°C, below 95°C or below 98°C. Homogenization can be performed at temperatures above 4°C, above 10°C, above 15°C, above 20°C, above 25°C, above 27°C, above 30°C, above 32°C, above 37°C, Above 40°C, above 42°C, above 45°C, above 50°C, above 55°C, above 60°C, above 65°C, above 70°C, above 75°C, above 80°C, Conducted at a temperature above 85°C, above 90°C, above 92°C, above 95°C or above 97°C.

II. Enzymatic Digestion

The matrix can be harvested using enzymatic treatment. Enzymatic hydrolysis can be performed with proteases, carbohydrate digesting molecules, nucleases, lipases, and the like. One or more enzymatic digestion methods can be used for the same collection matrix. For example, the acquisition matrix can be treated with proteases and nucleases simultaneously. Enzymes used may be naturally occurring or synthetic. They can be isolated from recombinant cells.

Protease can be used for enzymatic digestion. Non-limiting examples of proteases include trypsin, proteinase K, pepsin, chymotrypsin, papain, bromelain, subtilisin, or elastase. The protease may be a serine, cysteine, threonine, aspartic, glutamic, or metalloprotease, or an asparagine peptide lyase. Proteases can be used to dissociate target proteins. Alternatively, proteases can be used to dissociate proteins to separate other biomolecules such as nucleic acids. For example, proteases can be used to unwind nucleic acids from chromatin.

Protease digestion can be performed in the presence of buffers or solvents. The buffer used may be a commercially available buffer. Buffers can include EDTA, EGTA, citrate, sodium chloride, LiCl, potassium phosphate, ammonium sulfate, ammonium chloride, magnesium chloride, magnesium sulfate, Tris-HCl, MOPS, HEPES, MES, dithiothreitol (DTT ), β-mercaptoethanol, TECP, (SDS), guanidine hydrochloride, guanidine thiocyanate (GITC), urea, glutathione (GSH), glutathione disulfide (GSSG), NADPH, ascorbic acid, vitamin Formic acid and tocopherol or other salts and organic solvents.

Protease digestion can be performed for about 10 minutes. Protease digestion can be performed for less than 10 minutes, less than 15 minutes, less than 30 minutes, less than 50 minutes, or less than 60 minutes. Protease digestion can be performed in less than 1 hour, in less than 2 hours, in less than 3 hours, in less than 4 hours, in less than 5 hours, in less than 8 hours, in less than 10 hours, in less than 12 hours, in less than 14 hours, in less than Within 16 hours, less than 18 hours or less than 24 hours. Protease digestion can be performed for greater than 10 minutes, greater than 15 minutes, greater than 30 minutes, greater than 50 minutes, or greater than 60 minutes. Protease digestion can be performed for greater than 1 hour to greater than 18 hours. Protease digestion can be performed for greater than 1 hour, greater than 2 hours, greater than 3 hours, greater than 4 hours, greater than 5 hours, greater than 8 hours, greater than 10 hours, greater than 12 hours, greater than 14 hours, greater than 16 hours, greater than 18 hours, or greater than 24 hours Hour.

Enzymes are available for carbohydrate digestion. Enzymatic digestion of carbohydrates can be performed to degrade the polysaccharide coating on the collection matrix. Alternatively, it can be used to digest target biomolecules or biological samples, such as cells. Examples of such enzymes include, but are not limited to: Macerozyme R-10, pectinase, hemicellulase, amylase, xylanase, cellulase, sucrose, maltase, and the like.

Buffers for carbohydrate digestion are commercially available. Buffers may include sodium phosphate, sodium chloride, sodium hydroxide, ethylene glycol, sodium acetate buffer, EDTA, EGTA, citrate, sodium chloride, LiCl, potassium phosphate, ammonium sulfate, ammonium chloride, magnesium chloride, Magnesium Sulfate, Tris-HCl, MOPS, HEPES, MES Dithiothreitol (DTT), β-Mercaptoethanol, TECP, Glutathione (GSH), Glutathione Disulfide (GSSG), NADPH, Ascorbic Acid , retinoic acid and tocopherol or other salts or organic solvents.

Carbohydrate digestion can take about 10 minutes. Carbohydrate digestion can take place in less than 10 minutes, in less than 15 minutes, in less than 30 minutes, in less than 50 minutes, or in less than 60 minutes. Carbohydrate digestion can take place in less than 1 hour, in less than 2 hours, in less than 3 hours, in less than 4 hours, in less than 5 hours, in less than 8 hours, in less than 10 hours, in less than 12 hours, in less than 14 hours, Less than 16 hours or less than 18 hours. Carbohydrate digestion can be performed for greater than 10 minutes, greater than 15 minutes, greater than 30 minutes, greater than 50 minutes, or greater than 60 minutes. Carbohydrate digestion can be performed for greater than 1 hour to greater than 18 hours. Carbohydrate digestion can be performed for greater than 1 hour, greater than 2 hours, greater than 3 hours, greater than 4 hours, greater than 5 hours, greater than 8 hours, greater than 10 hours, greater than 12 hours, greater than 14 hours, greater than 16 hours, or greater than 18 hours.

The collection matrix can be treated with nucleases. Nucleases can be used to digest genomic DNA or RNA. Non-limiting examples include exonucleases, endonucleases (eg, restriction enzymes), DNase RNAse, and the like. Nuclease digestion can be performed in the presence of one or more buffers. For example, buffers can include made by /> Buffer RLT manufactured by /> Buffer RLN manufactured by Promega, RNA Lysis Buffer (RLA) manufactured by Promega, PureYieldTM Cell Lysis Solution (CLA) manufactured by Promega, PureYieldTM Endotoxin Removal Cleaning Solution manufactured by Promega, PureZOL ^TM RNA Isolation Reagent (Bio-Rad ^TM ) , RNA Lysis Buffer or DNA/RNA Binding Buffer manufactured by Zymo Research Corp, or RNA Capture Buffer manufactured by Pierce ^TM , Tris-HCL, MOPS, MES, HEPES, Magnesium Chloride, Calcium Chloride, PBS.

Nuclease digestion can be performed for about 10 minutes. Nuclease digestion can be performed for less than 10 minutes, less than 15 minutes, less than 30 minutes, less than 50 minutes, or less than 60 minutes. Nuclease digestion can be performed for less than 1 hour, less than 2 hours, less than 3 hours, less than 4 hours, less than 5 hours, less than 8 hours, less than 10 hours, less than 12 hours, less than 14 hours, Less than 16 hours or less than 18 hours. Nuclease digestion can be performed for greater than 10 minutes, greater than 15 minutes, greater than 30 minutes, greater than 50 minutes, or greater than 60 minutes. Nuclease digestion can be performed for greater than 1 hour to greater than 18 hours. Nuclease digestion can be performed for greater than 1 hour, greater than 2 hours, greater than 3 hours, greater than 4 hours, greater than 5 hours, greater than 8 hours, greater than 10 hours, greater than 12 hours, greater than 14 hours, greater than 16 hours, or greater than 18 hours.

Enzymes can be used for lipid digestion. Enzymatic digestion of lipids can be performed to degrade lipids in cells. Alternatively, digestion of target biomolecules can be performed. Examples of such enzymes include lipase, elastase, phospholipase, and the like. Lipid digestion can be performed in the presence of a buffer. Buffers are commercially available. Examples of buffers that may be used are presented elsewhere herein.

In some embodiments, more than one enzymatic digestion can be performed on one acquisition matrix or a combination of acquisition matrices. One or more enzymatic digestions can be performed simultaneously or one after the other. For example, collection matrices can be treated with proteases and amylases. In some cases, carbohydrate digestion of the harvested substrate can be performed after or concurrently with nuclease digestion. In some cases, nuclease digestion can be performed after or concurrently with lipase digestion. In some cases, more than 2 enzymatic digestions can be performed simultaneously. For example, protease digestion, carbohydrate digestion, nuclease digestion, and lipid digestion can be performed simultaneously on the collection matrix.

Enzymatic digestion can be performed simultaneously with mechanical dissociation. Alternatively, enzymatic digestion can be performed before or after mechanical dissociation. For example, protease digestion can be performed after soaking. Nuclease digestion can be performed simultaneously with shaking or reverse mixing. In some cases, protease and lipid digestion can be followed by sonication. Any of the other dissociation methods presented elsewhere herein may be used in addition to or in conjunction with enzymatic digestion methods.

III. Thermal dissociation

Processing of the collection matrix containing the biological sample may include heat-facilitated dissociation. Large molecules (eg, proteins, nucleic acids) that are prone to decomposition with temperature can be eluted from the acquisition matrix by temperature cycling or freeze/thaw cycles or elevated temperatures.

The thermal dissociation treatment of the harvested matrix may include cryogenic treatment. In some cases, cryogenic treatment includes freeze/thaw cycles. Low temperature processing of harvested substrates may include processing temperatures of about -80°C, about -40°C, about -20°C, about -4°C, about 0°C, or about 4°C. In some cases, the processing temperature may be less than -80°C, less than -40°C, less than -20°C, less than -4°C, less than 0°C, or less than 4°C. In some cases, the processing temperature may be greater than -80°C, greater than -40°C, greater than -20°C, greater than -4°C, greater than 0°C, or greater than 4°C.

Heat-facilitated dissociation may include incubating the harvest matrix solution at ambient temperature. Alternatively, heat-facilitated dissociation may involve incubating the harvested matrix solution at an elevated temperature. High temperature processing of the harvested substrate may include processing temperatures of less than 30°C, less than 37°C, less than 45°C, less than 50°C, less than 55°C, less than 60°C, less than 80°C, less than 95°C, less than 97°C, or less than 100°C. In some cases, high temperature processing of the harvested matrix may include greater than 30°C, greater than 37°C, greater than 45°C, greater than 50°C, greater than 55°C, greater than 60°C, greater than 80°C, greater than 95°C, greater than 97°C, or greater than 100°C °C processing temperature.

Thermally facilitated dissociation may include cycling the treatment temperature. This can include cycling between cryogenic and ambient temperatures. Alternatively, it may involve cycling the acquisition of the substrate between low and high temperatures or between ambient and high temperatures. Harvesting substrates can be processed by cycling through low temperature followed by high temperature followed by ambient temperature incubation or other combinations thereof.

In addition to mechanical dissociation procedures, heat-facilitated dissociation treatment procedures can also be performed. The thermal dissociation process can be performed simultaneously with mechanical dissociation. For example, soaking can be performed concurrently with temperature cycling. Additionally, vortexing can be performed after temperature cycling. Any of the other mechanical dissociation methods presented elsewhere herein can be combined with thermally facilitated dissociation methods.

In addition to the enzymatic digestion procedure, a heat-promoted dissociation treatment procedure can also be performed. The thermal dissociation process can be performed simultaneously with enzymatic digestion. For example, nuclease digestion can be performed concurrently with high temperature treatment. Additionally, protease digestion can be performed after temperature cycling. Any of the other enzymatic digestion methods presented elsewhere herein can be combined with the heat-promoted dissociation method.

In addition to enzymatic digestion and mechanical dissociation procedures, thermally facilitated dissociation procedures can also be performed. The thermal dissociation process can be performed simultaneously with enzymatic digestion and mechanical dissociation. For example, nuclease digestion can be performed concurrently with high temperature treatment and shaking of the soaked collection matrix.

IV. Time-Dependent Rehydration

Dried acquisition matrix can be rehydrated. Rehydration of the acquisition matrix can be performed for different times and temperatures depending on the target biomolecules. For example, highly soluble biomolecules may require less rehydration than insoluble biomolecules. In some cases, rehydration can be performed at several different temperatures. Some biomolecules can dissolve at room temperature, while others may require higher temperatures. In this case, the rehydration process may include temperature cycling.

The acquisition matrix can be rehydrated in less than 3 seconds, in less than 5 seconds, in less than 8 seconds, in less than 10 seconds, in less than 20 seconds, in less than 30 seconds, in less than 40 seconds, in less than 50 seconds, in less than 60 seconds, Less than 2 minutes, less than 5 minutes, less than 10 minutes, less than 20 minutes, less than 30 minutes, less than 50 minutes, less than 60 minutes, less than 50 minutes, less than 60 minutes, less than 2 hours, Less than 5 hours, less than 8 hours, less than 10 hours, less than 20 hours, less than 30 hours, less than 50 hours, less than 70 hours, less than 80 hours, or less than 100 hours. The acquisition matrix can be rehydrated for greater than 3 seconds, greater than 5 seconds, greater than 8 seconds, greater than 10 seconds, greater than 20 seconds, greater than 30 seconds, greater than 40 seconds, greater than 50 seconds, greater than 60 seconds, greater than 2 minutes, greater than 5 minutes, greater than 10 minutes, more than 20 minutes, more than 30 minutes, more than 50 minutes, more than 60 minutes, more than 50 minutes, more than 60 minutes, more than 2 hours, more than 5 hours, more than 8 hours, more than 10 hours, more than 20 hours, more than 30 hours , greater than 50 hours, greater than 70 hours, greater than 80 hours, or greater than 100 hours.

V. Chemical dissociation and stabilization

Processing of collection matrices containing biological samples may include chemically facilitated dissociation and stabilization. Chemical dissociation treatment may include introducing the acquisition matrix into an elution buffer. Buffers may contain various salts, organic solvents, surfactants, protein additives, ion exchangers, metal chelators, stabilizing elements, reducing agents, oxidizing agents or free radical scavengers.

Elution buffers may contain one or more surfactants. The one or more surfactants may be, for example, anionic, cationic, nonionic or amphoteric. The surfactants used are able to interact with the hydrophilic and hydrophobic parts of biomolecules and facilitate the dissolution and elution of these molecules. The one or more surfactants may be polyethoxylated alcohols; polyoxyethylene sorbitan; octylphenol, such as TritonX 100 ^™ (polyethylene glycol p-(1,1,3,3-tetramethyl butyl)-phenyl ether); polysorbates, such as Tween ^TM 20 ((for example, polysorbate 20) or Tween ^TM 80 (polysorbate 80); sodium lauryl sulfate; lauryl Sodium sulfate; nonylphenol ethoxylates such as Tergitol ^™ ; cyclodextrins; zwitterionic surfactants such as cocamidopropyl betaine. Other betaines include lauramidopropyl betaine, oleamidopropyl betaine Alkali, ricinoleamidopropyl betaine, cetyl betaine and dimerized dilinoleamidopropyl betaine, sultaine, hydroxysultaine, methylene chloride and sultaine or any of them Combination. Relative to the total volume of the elution buffer, one or more surfactants may be present in an amount of less than 0.001%, less than 0.005%, less than 0.01%, less than 0.015%, less than 0.02%, less than 0.025%, less than 0.03%, Less than 0.035%, less than 0.04%, less than 0.045%, less than 0.05%, less than 0.055%, less than 0.06%, less than 0.065%, less than 0.07%, less than 0.075%, less than 0.08%, less than 0.085%, less than 0.09%, less than 0.095 %, less than 0.1%, less than 0.15%, less than 0.2%, less than 0.25%, less than 0.3%, less than 0.35%, less than 0.4%, less than 0.45%, less than 0.5%, less than 0.55%, less than 0.6%, less than 0.65%, The concentration of less than 0.7%, less than 0.75%, less than 0.8%, less than 0.85%, less than 0.9%, less than 0.95%, or less than 0.1% (by volume) is present. The concentration of one or more surfactants may be about 0.01 %, 0.05%, 0.1%, 0.5%, 1%, 5% or 10%. The concentration of one or more surfactants can be less than 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5% or 10%. The concentration of one or more surfactants may be greater than 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5% or 10%.

The elution buffer may contain one or more organic solvent mixtures. Organic extraction using aqueous and organic solvent mixtures can be used to dissolve and elute biomolecules. The organic solvent may include butanol, ethanol, methanol, isopropanol, phenol, propanol, DMSO, DMF, dioxane, tetrahydrofuran, butanol, t-butanol, pentanol, acetone, chloroform, or combinations thereof. Relative to the total volume of the solution, the elution buffer may comprise less than 0.01%, less than 0.05%, less than 0.1%, less than 0.15%, less than 0.2%, less than 0.25%, less than 0.3%, less than 0.35%, less than 0.4%, less than 0.45%, less than 0.5%, less than 0.55%, less than 0.6%, less than 0.65%, less than 0.7%, less than 0.75%, less than 0.8%, less than 0.85%, less than 0.9%, less than 0.95%, less than 1%, less than 1.5% , less than 2%, less than 2.5%, less than 3%, less than 3.5%, less than 4%, less than 4.5%, less than 5%, less than 5.5%, less than 6%, less than 6.5%, less than 7%, less than 7.5%, less than 8%, less than 8.5%, less than 9%, less than 9.5%, less than 10%, less than 11%, less than 12%, less than 13%, less than 14%, less than 15%, less than 16%, less than 17%, less than 18% , less than 19%, less than 20%, less than 25%, less than 30%, less than 35%, less than 40%, less than 45%, less than 50%, less than 55%, less than 60%, less than 65%, less than 70%, less than 75%, less than 80%, less than 85%, less than 90%, less than 95%, less than 99%, or less than 100% (by volume) organic solvent. The concentration of one or more organic solvents in the elution buffer may be at least 1%, 5%, 10%, 50%, 75% or 100%. The concentration of one or more organic solvents in the elution buffer can be about 1%, 5%, 10%, 50%, 75%, or 100%.

The buffer may include a chaotropic agent such as guanidine chloride, guanidine hydrochloride, guanidine isothiocyanate, lithium perchlorate, lithium acetate, magnesium chloride, sodium iodide, sodium thiocyanate, thiourea, urea, or any combination thereof . The concentration of the chaotropic agent in the buffer may be about 0.1 mM, 1 mM, 10 mM, 100 mM, 1M, 6M or 8M. The concentration of the chaotropic agent in the buffer may be at least 0.1 mM, 1 mM, 10 mM, 100 mM, 1M, 6M or 8M. The concentration of the chaotropic agent in the buffer may be less than 0.1 mM, 1 mM, 10 mM, 100 mM, 1M, 6M or 8M.

Chemically facilitated dissociation and stabilization may include the addition of protein and/or nucleic acid additives to the elution buffer. Addition of proteins and/or nucleic acids to the elution solution can be used to drive biomolecules of interest from the polysaccharide-coated acquisition matrix through competitive binding of the acquisition matrix. In addition, additives can stabilize biomolecules and prevent non-specific binding of biomolecules to labware. Examples of additives include, but are not limited to: BSA, albumin, casein, milk powder, skim milk, egg whites, non-human serum, blood substitutes, nucleic acids, yeast RNA, herring sperm DNA, salmon sperm DNA, calf thymus DNA, COT -1 DNA, synthetic oligonucleotides. The elution buffer may comprise less than 0.0001%, less than 0.005%, less than 0.01%, less than 0.05%, less than 0.1%, less than 0.15%, less than 0.2%, less than 0.25%, less than 0.3%, less than 0.35%, less than 0.4%, less than 0.45%, less than 0.5%, less than 0.55%, less than 0.6%, less than 0.65%, less than 0.7%, less than 0.75%, less than 0.8%, less than 0.85%, less than 0.9%, less than 0.95% , less than 1%, less than 1.5%, less than 2%, less than 2.5%, less than 3%, less than 3.5%, less than 4%, less than 4.5%, less than 5%, less than 5.5%, less than 6%, less than 6.5%, less than 7%, less than 7.5%, less than 8%, less than 8.5%, less than 9%, less than 9.5%, less than 10%, less than 11%, less than 12%, less than 13%, less than 14%, less than 15%, less than 16% , less than 17%, less than 18%, less than 19%, less than 20%, less than 25%, less than 30%, less than 35%, less than 40%, less than 45%, less than 50%, less than 55%, less than 60%, less than 65%, less than 70% (by volume) of protein, nucleic acid or protein/nucleic acid mixture. The concentration of one or more proteins, nucleic acids or protein/nucleic acid mixtures in the elution buffer may be at least 0.0001%, 0.005%, 0.001%, 0.05%, 1%, 5%, 10% or 50%. The concentration of one or more proteins, nucleic acids or protein/nucleic acid mixtures in the elution buffer can be about 0.0001%, 0.005%, 0.001%, 0.05%, 1%, 5%, 10% or 50%.

Chemically facilitated dissociation and stabilization may include elution buffers comprising ion exchangers. Ion exchangers can include any reagent that can affect the ionic strength of a protein. Ionic strength can be affected due to changes in the solubility, activity, binding or stabilization properties of biomolecules. The salt or salts may be sodium chloride, sodium acetate, sodium bicarbonate, sodium bisulfate, sodium bromide, magnesium chloride, magnesium acetate, calcium chloride, potassium chloride, potassium acetate, potassium bicarbonate, potassium bisulfate , potassium bromate, potassium bromide or potassium carbonate. The concentration of one or more salts may be about 0.1 mM, 5 mM, 10 mM, 25 mM, 50 mM, 100 mM, 250 mM, 500 mM or 750 mM. The concentration of one or more salts may be less than 0.1 mM, 5 mM, 10 mM, 25 mM, 50 mM, 100 mM, 250 mM, 500 mM or 750 mM. The concentration of one or more salts may be at least 0.1 mM, 5 mM, 10 mM, 25 mM, 50 mM, 100 mM, 250 mM, 500 mM, 750 mM, or 1000 mM.

Ion exchangers may contain one or more buffers. The buffer(s) can be, for example, saline, citrate, phosphate, phosphate buffered saline, acetate, glycine, tris(hydroxymethyl)aminomethane(tri)hydrochloride, tris-buffered saline (TBS ), 3[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]propane-1-sulfonic acid (TAPS), diglycine N, trimethylglycine, 3[[[ 1,3-Dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]-2-hydroxypropane-1-sulfonic acid (TAPSO), 4-(2-hydroxyethyl)-1-piperazine Ethylsulfonic acid (HEPES), piperazine-N,N'-bis(2-ethanesulfonic acid) (PIPES), 3-(N-morpholino)propanesulfonic acid (MOPS), 2-(N-morpholine Generation) ethanesulfonic acid (MES), 2-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]ethanesulfonic acid (TES), cacodylate, glycine, Carbonates or any combination thereof. The buffering agent can be less than 500mM, less than 400mM, less than 300mM, less than 200mM, less than 100mM, less than 50mM, less than 25mM, less than 20mM, less than 15mM, less than 10mM, less than 5mM, less than 4mM, less than 3mM, less than 2mM, less than 1mM, less than A concentration of 0.9 mM, less than 0.8 mM, less than 0.7 mM, less than 0.6 mM, less than 0.5 mM, less than 0.4 mM, less than 0.3 mM, less than 0.2 mM or less than 0.1 mM is present. The buffering agent may be greater than 500 mM, greater than 400 mM, greater than 300 mM, greater than 200 mM, greater than 100 mM, greater than 50 mM, greater than 25 mM, greater than 20 mM, greater than 15 mM, greater than 10 mM, greater than 5 mM, greater than 4 mM, greater than 3 mM, greater than 2 mM, greater than 1 mM, greater than A concentration of 0.9 mM, greater than 0.8 mM, greater than 0.7 mM, greater than 0.6 mM, greater than 0.5 mM, greater than 0.4 mM, greater than 0.3 mM, greater than 0.2 mM, or greater than 0.1 mM is present.

Chemically facilitated dissociation and stabilization may include pH-promoting treatments. pH-facilitated chemical dissociation may include pH cycling. For example, the elution buffer can initially be a more basic solution with a pH in the range 9 to 12. Salts or acids can be added to the elution buffer to cycle the buffer from basic to acidic.

The pH of the elution buffer can be from about 1 to about 14. The pH of the elution buffer can be at least about 1. The pH of the elution buffer can be up to about 14. The pH of the elution buffer can be less than 2, less than 3, less than 4, less than 5, less than 6, less than 7, less than 8, less than 9, less than 10, less than 11, less than 12 or less than 14. The pH of the elution buffer can be greater than 1, greater than 3, greater than 4, greater than 5, greater than 6, greater than 7, greater than 8, greater than 9, greater than 10, greater than 11, greater than 12, or greater than 13.

Chemically facilitated dissociation and stabilization of the acquisition matrix may include treatment with chelating agents. The one or more chelating agents can be, for example, carbohydrates; lipids; steroids; amino acids or related compounds; phosphates; nucleotides; tetrapyrroles; feroxamines; ionophores; phenolic resins; ,2'-bipyridine, dimercaptopropanol, ethylenediaminotetraacetic acid (EDTA), ethylenedioxy-diethylene-dinitrile-tetraacetic acid, ethylene glycol-bis-(2-aminoethyl )-N,N,N',N'-tetraacetic acid (EGTA), metallic nitrilotriacetic acid (NTA), salicylic acid, citrate or triethanolamine (TEA). The concentration of one or more chelating agents in the buffer may be about 0.01 mM, 0.1 mM, 1 mM, 5 mM, 10 mM, 20 mM or 25 mM. The concentration of one or more chelating agents in the buffer may be less than 0.1 mM, 1 mM, 5 mM, 10 mM, 20 mM or 25 mM. The concentration of one or more chelating agents in the buffer may be greater than 0.1 mM, 1 mM, 5 mM, 10 mM, 20 mM or 25 mM.

Chemically facilitated dissociation and stabilization of the harvest matrix may include treatment with agents that prevent aggregation. The aggregation preventing agent may include polyhydric alcohol. The one or more polyols may be glycols, such as ethylene glycol or propylene glycol, or glycol polymers, such as polyethylene glycol (PEG) of various weights, such as PEG300, PEG400, PEG600, PEG1000, PEG3000, PEG6000 , PEG8000 or PEG10000. In some cases, one or more polyols can be sugars. In some cases, the sugar can be sucrose, glucose, fructose, trehalose, maltose, melezitose, galactose, lactose, or any combination thereof. In some cases, one or more polyols may be sugar alcohols. In some cases, the sugar alcohol may be glycerin, erythritol, threitol, xylitol, sorbitol, and the like. The concentration of the aggregation preventing agent in the elution buffer may be about 0.5%, about 1%, about 2%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 40% %, about 50% or about 60%. The concentration of the aggregation preventing agent in the elution buffer may be less than 0.5%, less than 1%, less than 2%, less than 5%, less than 10%, less than 15%, less than 20%, less than 25%, less than 30%, less than 40% , less than 50% or less than 60%. The concentration of the aggregation preventing agent in the elution buffer may be greater than 0.5%, greater than 1%, greater than 2%, greater than 5%, greater than 10%, greater than 15%, greater than 20%, greater than 25%, greater than 30%, greater than 40% , greater than 50% or greater than 60%.

The elution buffer may contain one or more reducing or oxidizing agents. Reducing agents can reduce or oxidize biomolecules by altering their solubility, activity, binding, and stability properties. The one or more reducing or oxidizing agents may be, for example, β-mercaptoethanol (BME), 2-aminoethanethiol (2MEA-HCl (cysteamine-HCl)), dithiothreitol (DTT), glutathione Glycine (GSH), glutathione disulfide (GSSG), tris(2-carboxyethyl)phosphine (TCEP), NADPH, ascorbic acid, retinoic acid, and tocopherol, or any combination thereof. The concentration of one or more reducing agents may be about 0.1 mM, 0.5 mM, 1 mM, 10 mM, 50 mM, 100 mM, 250 mM, or 500 mM. The concentration of one or more reducing or oxidizing agents may be less than 0.1 mM, 0.5 mM, 1 mM, 10 mM, 50 mM, 100 mM, 250 mM or 500 mM. For example, the concentration of DTT can be less than 0.05 mM to less than 100 mM, less than 0.5 mM to less than 50 mM, or less than 5 mM to less than 10 mM. The concentration of TCEP can be less than 0.05 mM, less than 5 mM, less than 10 mM, or less than 50 mM. The concentration of BME may be less than 0.05%, less than 5%, or less than 10%. The concentration of GSH may be less than 0.05 mM, less than 5 mM, or less than 10 mM. The concentration of one or more reducing or oxidizing agents may be about 1 mM, 10 mM, 50 mM, 100 mM, 250 mM or 500 mM.

The elution buffer may contain one or more free radical scavengers. Free radical scavengers can include hydroquinone derivatives including tetrahydroxy-1,4-benzoquinone (THQ) or monomethyl ether of hydroquinone; (MEHQ), glutathione (GSH), ascorbic acid, retinoic acid, and tocopheryl phenol. The concentration of one or more free radical scavengers in the buffer may be about 0.1 mM, 1 mM, 5 mM, 10 mM, 20 mM, 25 mM, 27 mM, 28 mM, 29 mM, 30 mM, 32 mM, 35 mM, 38 mM, 40 mM, 45 mM, 50 mM or 100mM. The concentration of one or more free radical scavengers in the buffer may be less than 0.1 mM, 1 mM, 5 mM, 10 mM, 20 mM, 25 mM, 27 mM, 28 mM, 29 mM, 30 mM, 32 mM, 35 mM, 38 mM, 40 mM, 45 mM, 50 mM or 100 mM . The concentration of one or more free radical scavengers in the buffer may be greater than 0.1 mM, 1 mM, 5 mM, 10 mM, 20 mM, 25 mM, 27 mM, 28 mM, 29 mM, 30 mM, 32 mM, 35 mM, 38 mM, 40 mM, 45 mM, 50 mM, or 100 mM .

Chemically facilitated dissociation and stabilization procedures can be performed in addition to or simultaneously with other dissociation methods. Chemical dissociation can be performed simultaneously with shaking the matrix or vortexing the matrix solution. Chemical dissociation methods can be performed before or after enzymatic digestion. For example, carbohydrate-digesting enzymes can first degrade the polysaccharide coating on the acquisition matrix, followed by treatment with elution buffer to elute nucleic acids. In addition to cycling different temperatures to facilitate thermal dissociation, chemical dissociation methods can also be performed at different temperatures. Chemical dissociation methods can be performed in addition to, or with, any of the mechanical dissociation presented elsewhere herein , enzymatic dissociation, heat-promoted dissociation, or time-dependent rehydration and dissociation methods simultaneously.

Acquisition matrix or part of acquisition matrix can be mixed with less than 5 μL, less than 10 μL, less than 15 μL, less than 20 μL, less than 25 μL, less than 30 μL, less than 35 μL, less than 40 μL, less than 45 μL, less than 50 μL, less than 55 μL, less than 60 μL, less than 65 μL, less than 70 μL , less than 75 μL, less than 80 μL, less than 85 μL, less than 90 μL, less than 95 μL, less than 100 μL, less than 110 μL, less than 120 μL, less than 130 μL, less than 140 μL, less than 150 μL, less than 160 μL, less than 170 μL, less than 180 μL, less than 190 μL, less than 200 μL, less than 250 μL, less than 300 μL, less than 350 μL, less than 400 μL, less than 450 μL, less than 500 μL, less than 550 μL, less than 600 μL, less than 650 μL, less than 700 μL, less than 750 μL, less than 800 μL, less than 850 μL, less than 900 μL, less than 950 μL, less than 1,000 μL, less than 1.5 mL, less than 2mL, less than 2.5mL, less than 3mL, less than 3.5mL, less than 4mL, less than 4.5mL, less than 5mL, less than 5.5mL, less than 6mL, less than 6.5mL, less than 7mL, less than 7.5mL, less than 8mL, less than 8.5mL , less than 9mL, less than 9.5mL or less than 10mL of a certain volume of elution buffer contact. The stable acquisition matrix or a portion of the stable acquisition matrix can be contacted with about 0.1 mL, 0.2 mL, 0.5 mL, 0.7 mL, 1 mL, 2 mL, 5 mL, 7 mL, or 10 mL of buffer.

The volume of elution buffer in contact with the acquisition matrix can depend on the surface area of the acquisition matrix. The amount of elution buffer can be less than 1 μL/mm2, less than 2 μL/mm2, less than 3 μL/mm2, less than 4 μL/mm2, less than 5 μL/mm2, less than 6 μL/mm2, less than 7 μL/mm2, less than 8 μL/mm2, less than 9 μL/mm2 mm2, less than 10 μL/mm2, less than 12 μL/mm2, less than 14 μL/mm2, less than 16 μL/mm2, less than 18 μL/mm2, less than 20 μL/mm2, less than 25 μL/mm2, less than 30 μL/mm2, less than 35 μL/mm2, less than 40 μL/mm2 mm2, less than 45μL/mm2, less than 50μL/mm2, less than 55μL/mm2, less than 60μL/mm2, less than 65μL/mm2, less than 70μL/mm2, less than 75μL/mm2, less than 80μL/mm2, less than 85μL/mm2, less than 90μL/mm2 mm2, less than 95 μL/mm2, less than 100 μL/mm2, less than 150 μL/mm2, less than 200 μL/mm2, less than 250 μL/mm2, less than 300 μL/mm2, less than 350 μL/mm2, less than 400 μL/mm2, less than 450 μL/mm2, less than 500 μL/mm2 mm2, less than 550 μL/mm2, less than 600 μL/mm2, less than 650 μL/mm2, less than 700 μL/mm2, less than 750 μL/mm2, less than 800 μL/mm2, less than 850 μL/mm2, less than 900 μL/mm2, less than 950 μL/mm2, or less than 1,000 μL /mm2.

Non-limiting embodiments of the sample stabilization unit may also employ a sample separation module to separate other non-plasma or non-serum components. The sample separation component can be connected to the sample acquisition component, for example, by channels, including microchannels, wicking of absorbent material, or other means of allowing sample flow through the device. Systems and methods for separating samples are exemplary and non-limiting.

Typically, a sample may contain or be suspected of containing one or more analytes. As used herein, the term "analyte" may refer to any substance that can be analyzed using an assay or immunoassay device. For example, an immunoassay device can be configured to detect the presence of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more analytes in a sample. Non-limiting examples of analytes can include proteins, haptens, immunoglobulins, hormones, polynucleotides, steroids, drugs, infectious disease agents (e.g., of bacterial or viral origin), drugs of abuse, environmental agents, biomarkers wait.

As used in the specification and claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "cell" includes a plurality of cells, including mixtures thereof.

As used herein, the term "about" a number means that number plus or minus 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%.

As used herein, unless otherwise stated, the term "substantially" and similar terms are largely, but not necessarily completely, defined as understood by those of ordinary skill in the art. In any of the disclosed embodiments, the terms "substantially", "approximately", "generally" and "approximately" may be replaced with the specified "within [percentage]", where percentages include .1, 1, 5 and 10 %.

Example

Example 1: Cartridge assembly for blood separation.

3C, 3F and 4 illustrate various examples of cartridge assemblies for separating plasma or serum from blood collected from a subject. The cartridge assembly can be coupled to and in fluid communication with a sample acquisition device (eg, sample acquisition device 100 , as shown in FIG. 3D ) to receive blood from a subject. The cartridge assembly may include ports to provide a path for fluid communication between the cartridge assembly and the sample acquisition device. The cartridge assembly may include one or more blood processing/stabilization units to separate plasma or serum from blood. The blood treatment/stabilization unit may be a stack of multiple components (or layers). For example, a blood treatment/stabilization unit may comprise multiple layers, such as (1) a pre-filter layer for filtering cells and/or debris from the blood, (2) a pre-filter layer for A blood separation membrane for separating serum or plasma, and (3) a collection medium for collecting and/or storing the separated serum or plasma.

As shown in Figures 3C and 3F, at least a portion of the path of blood flow through the cartridge assembly ports may be directed in a different direction than the direction of blood flow through the blood processing/stabilization unit. Referring to FIG. 3C , the path 340 of the port 330 of the cartridge assembly 300 may include (i) a proximal end in fluid communication with the sample acquisition device and (ii) a distal end in fluid communication with the blood processing/stabilization unit 320 . Pathway 340 may direct blood from the sample collection device into the proximal end in a first direction, through path 340, and out the distal end to blood processing/stabilization unit 320 in a second direction different from the first direction. An intersection angle between the first direction and the second direction may be greater than 0 degrees and less than 180 degrees. The direction of blood flow through the blood processing/stabilization unit 320 may be substantially normal to the longitudinal axis 346 of the cartridge assembly 300 . 4F, the path 340 of the port 330 of the cartridge assembly 300b can be substantially parallel to the longitudinal axis 346 of the cartridge assembly 300b, and the direction of blood flow through the blood processing/stabilization unit 320 can be substantially orthogonal to the longitudinal axis of the cartridge assembly 300b 346. Additionally, cartridge assembly 300b may include a collection container 362 configured to hold blood collected from a sample collection device prior to or during separation of plasma or serum by blood processing/stabilization unit 320 .

Referring to FIG. 4 , the path 440 of the port 410 of the cartridge assembly 400 can direct blood from the sample collection device into the proximal end of the blood processing/stabilization unit 420a, 420b in a direction that is consistent with the flow of blood through the blood processing/stabilization unit 420a, 420b. directions are basically the same.

Example 2: Cartridge assembly for storing liquid blood.

FIG. 5A shows an example cartridge assembly 500 for storing a liquid sample, such as liquid blood. Cartridge assembly 500 may include a coupling unit 510 configured to couple to a cartridge chamber of a sample acquisition device (eg, sample acquisition device 100 as shown in FIG. Liquid blood is collected. Cassette assembly 500 may include a container 520 configured to store liquid blood. Cartridge assembly 500 may include a cartridge holder 540 configured to support container 520 . The proximal end of the container 520 may be configured to be coupled to the coupling unit 510 and the distal end of the container 520 may be configured to be coupled to the cartridge holder 540 . Coupling unit 510 may include one or more liquid paths 516 . As shown in FIG. 5B , container 520 may be configured to receive liquid blood flowing into container 520 in first direction 524 . One or more liquid paths 516 may be configured to direct air to and out of container 520 in a second direction 526 different from first direction 524 .

Example 3: Modular chamber assembly for storing blood in multiple different formats.

7A shows an exemplary modular chamber assembly 600 for storing blood collected from a subject in a variety of different forms selected from the group consisting of plasma, serum, dried blood, liquid blood, and clotted blood. Blood. Modular chamber assembly 600 may include an inlet port 610 (eg, a pierceable self-sealing cap) that is removable from the remainder of modular chamber assembly 600 . Modular chamber assembly 600 may include a chamber 620 including a cartridge assembly 630 . Cartridge assembly 630 may comprise one of a number of different cartridge assembly types that allow blood to be collected, processed, or stored in a number of different formats. For example, cartridge assembly 630 may include a cartridge 640 that includes one or more matrix strips 642 to absorb and collect blood, or a portion thereof, from a subject. Cassette 640 may also include one or more absorbent pads 644 for containing and metering excess blood.

As shown in FIG. 8A, modular chamber assembly 600 may be operably coupled to modular sample collection device 900b for collecting blood from a subject.

Example 4: Recovery of Analytes in Blood Samples.

Figure 14 illustrates a linear regression analysis of data from a study measuring the recovery of several analytes following separation of blood samples collected from a blood separation assembly as described herein. Analytes tested include: total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, ALT, and glucose.

The test first involves introducing a 225 μL blood sample into the apheresis assembly. By allowing the sample to dry overnight, the analyte is eluted from the collection matrix of the apheresis module. Eluted samples were tested with Beckman Coulter reagents on a Beckman Coulter AU480 analyzer. 66 independent samples were tested under these constant regimens.

The ^R2 values for each analyte recovery are shown in Figure 14. The y-axis in each graph represents the amount of analyte in the plasma sample received from the donor. The x-axis in each graph represents the amount of analyte recovered in the eluted samples adjusted for the hematocrit level of the plasma donor. The results are summarized in Table 1.

Table 1: Linear regression analysis of analyte recovery

Analyte ^R2 value Recovery rate total cholesterol .896 50% HDL-cholesterol .898 51% LDL-cholesterol .918 30% Triglycerides .965 45% ALT .999 57% glucose .927 52%

Example 5: Collection matrix elution scheme

As described herein, elution methods may be required to successfully recover isolated blood samples from the collection matrix. Materials required for an exemplary elution method include: tweezers, cutting mat, razor blade or scalpel with replaceable blades, 1-2 mL tubes, PBS buffer solution, Tween-80 solution, and rails for 1-2 mL tubes shaker. The first step of the elution method allows the sample to dry overnight in the collection matrix within the cartridge assembly. After drying, the multicomponent acquisition matrix can be removed from the rest of the processing/stabilization unit using forceps. The bottom component of the multi-component acquisition matrix can then be separated from the top component of the acquisition matrix by pulling the bottom component away from the top component of the acquisition matrix or cutting the bottom component from the top component of the acquisition matrix. Using a scalpel/razor blade, two vertical cuts can be made on the bottom component of the acquisition matrix to create four equal components. All four components can be approximately 7.5x6 mm in size each, allowing four smaller components to fit into the microtube. Once the four components are placed in the microtube, 225 mL of 10 mM PBS buffer with .02% Tween-80 can be added. Microtubes can be spun quickly to ensure that no droplets are left on the walls. In optimal elution, the liquid should cover at least 40% of the four smaller components of the bottom component of the acquisition matrix. The microtubes can then be placed on an orbital shaker and can be shaken at 850 rpm for 1 hour at room temperature. After shaking is complete, the four components will have a uniform color and at least 100-120 mL of elution volume can be recovered for analysis of the properties of the recovered sample in the acquisition matrix.

While preferred embodiments of the present invention have been shown and described herein, it will be readily understood by those skilled in the art that these embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims (131)

1. A cassette assembly for separating blood collected from a subject, the cassette assembly comprising:

a cartridge port configured to be coupled to a sample collection device operable to collect the blood from the subject;

at least one blood separation membrane configured to separate plasma or serum from the sample; and

a slot configured to support the at least one blood separation membrane,

wherein the cartridge port comprises a path configured to direct the blood from the sample acquisition device to flow in a first direction into a proximal end of the path, through the path, and out a distal end of the path to the at least one blood separation membrane in a second direction different from the first direction.

2. The cartridge assembly of claim 1, wherein the path comprises a groove or channel.

3. The cartridge assembly of claim 1, wherein an angle between the first direction and a longitudinal axis of the cartridge assembly is greater than 0 degrees and less than 180 degrees.

4. The cartridge assembly of claim 1, wherein an angle between the second direction and a longitudinal axis of the cartridge assembly is greater than 0 degrees and less than 180 degrees.

5. The cartridge assembly of claim 1, wherein an angle of intersection between the first direction and the second direction is greater than 0 degrees and less than 180 degrees.

6. The cartridge assembly of claim 1, wherein the slot is further configured to support a collection medium for collecting the separated plasma or serum.

7. The cartridge assembly of claim 6, wherein the slot is further configured to support a prefilter for filtering the blood prior to separating the plasma or serum from the blood.

8. The cartridge assembly of claim 7, wherein the at least one blood separation membrane, the collection media, and the prefilter are disposed in a stack within the slot.

9. The cartridge assembly of claim 8, wherein the stack is disposed in a configuration that allows the blood to flow laterally through a thickness of the stack in a third direction and across a planar area of the stack in at least one other direction different from the third direction.

10. The cartridge assembly of claim 9, wherein the third direction is different from the first direction or the second direction.

11. The cartridge assembly of claim 10, wherein the third direction is substantially orthogonal to a longitudinal axis of the cartridge.

12. The cartridge assembly of claim 9, wherein the third direction and the at least one other direction are substantially orthogonal to each other.

13. The cartridge assembly of claim 7, wherein the distal end of the path is configured to direct the blood to a planar surface of the prefilter prior to the blood flowing onto the at least one blood separation membrane.

14. The cartridge assembly of claim 1, wherein the proximal end of the path is configured to receive the blood from a recessed opening in the housing of the sample acquisition device.

15. The cartridge assembly of claim 1, wherein the proximal end and the distal end of the path are not disposed along a longitudinal axis of the cartridge assembly.

16. The cartridge assembly of claim 1, wherein the proximal end and the distal end of the path are not disposed along a straight line extending between the proximal end and the distal end.

17. The cartridge assembly of claim 1, wherein the distal end of the path is offset from (1) the proximal end of the path and (2) a linear axis extending between edge thickness portions of the stack between the proximal end and the distal end of the path.

18. The cartridge assembly of claim 13, wherein the distal end of the path is adjacent to but not in contact with the planar surface of the prefilter.

19. The cartridge assembly of claim 1, wherein the path comprises a curved, bent, or angled portion.

20. The cartridge assembly of claim 1, wherein the path comprises a cutout exposing a portion along a length of the inlet port.

21. The cartridge assembly of claim 9, wherein the cartridge is subjected to vacuum pressure when vacuum in the sample acquisition device is activated.

22. The cartridge assembly of claim 21, wherein the vacuum is configured to assist the blood to flow laterally across and/or across the stack.

23. The cartridge assembly of any one of the preceding claims, wherein the slot further comprises an accumulation region, wherein the accumulation region is configured to hold a volume of the blood to contain the blood when the blood is absorbed into at least a portion of the at least one blood separation membrane.

24. The cartridge assembly of claim 23, wherein the accumulation region is disposed adjacent to the prefilter.

25. The cartridge assembly of claim 23, wherein the accumulation region is configured to hold a predetermined volume of the blood.

26. The cartridge assembly of claim 6, wherein the cartridge is configured to be released and decoupled from the sample collection device after the plasma or serum has been separated and collected onto the collection medium.

27. The cartridge assembly of claim 6, wherein the collection media is configured to be released and decoupled from the cartridge assembly after the plasma or serum has been separated and collected onto the collection media.

28. The cartridge assembly of claim 27, wherein the cartridge assembly is configured to remain coupled to the sample acquisition device after the acquisition medium has been released and decoupled from the cartridge assembly.

29. The cartridge assembly of claim 6, wherein the at least one blood separation membrane comprises a plurality of blood separation membranes, and wherein the collection medium is disposed between the plurality of blood separation membranes.

30. The cartridge assembly of claim 8, further comprising a window allowing a user to view the blood separation process, wherein the window is positioned adjacent to the at least one blood separation membrane, the collection media, or the prefilter.

31. The cartridge assembly of claim 1, wherein the at least one blood separation membrane comprises an anticoagulant.

32. The cartridge assembly of claim 1, further comprising an anticoagulant coupled to the path surface.

33. A cassette assembly for separating blood collected from a subject, the cassette assembly comprising:

a cartridge port configured to be coupled to a sample collection device operable to collect the blood from the subject;

at least one blood separation membrane configured to separate plasma or serum from the blood; and

a slot configured to support the at least one blood separation membrane,

wherein the cartridge port comprises a path configured to direct the blood from the sample acquisition device, through the path, and to an interior portion of the cartridge assembly comprising the slot, and

wherein (i) the direction of blood flow through the at least one blood separation membrane is different from (ii) the direction of blood flow through the path and toward the inner portion of the cartridge assembly.

34. The cartridge assembly of claim 33, wherein (i) the direction of blood flow through the at least one blood separation membrane is substantially orthogonal to (ii) the direction of blood flow through the path.

35. The cartridge assembly of claim 33, wherein the slot is further configured to support one or both of: (1) A collection medium for collecting the separated plasma or serum and (2) a prefilter for filtering the blood prior to separating the plasma or serum from the blood.

36. The cartridge assembly of claim 35, wherein the at least one blood separation membrane is disposed between the collection medium and the prefilter.

37. A cassette assembly for separating blood collected from a subject, the cassette assembly comprising:

a cartridge port configured to be coupled to a sample collection device operable to collect the blood from the subject;

at least one blood separation membrane configured to separate plasma or serum from the blood;

a slot configured to support the at least one blood separation membrane; and

a collection container configured to contain the blood collected from the sample collection device prior to or during the separation of the plasma or serum by the at least one blood separation membrane,

wherein the cartridge port comprises a path configured to direct the blood from the sample acquisition device, through the path, and to the acquisition container.

38. The cartridge assembly of claim 37, wherein (i) a direction of the blood flow through the at least one blood separation membrane is different from (ii) a direction of the blood flow through the path and toward the collection container.

39. The cartridge assembly of claim 38, wherein (i) a direction of the blood flow through the at least one blood separation membrane is substantially orthogonal to (ii) a direction of the blood flow through the path and toward the collection container.

40. The cartridge assembly of claim 37, wherein the collection container is disposed adjacent to a planar surface of the at least one blood separation membrane.

41. The cartridge assembly of claim 37, wherein the slot is further configured to support one or both of: (1) A collection medium for collecting the separated plasma or serum and (2) a prefilter for filtering the blood prior to separating the plasma or serum from the blood.

42. The cartridge assembly of claim 41, wherein the at least one blood separation membrane is disposed between the collection medium and the prefilter.

43. The cartridge assembly of claim 42 wherein the collection container is disposed adjacent to a planar surface of the prefilter.

44. A system for blood collection and blood separation comprising:

the sample acquisition device and cartridge assembly of any one of claims 1-43.

45. The system of claim 44, wherein the sample acquisition device comprises a built-in vacuum.

46. A method, comprising:

collecting the blood from the subject using the sample collection device of any one of claims 1-43; and

separating the plasma or serum from the blood using a cartridge assembly according to any one of claims 1-43.

47. A cartridge assembly for storing liquid blood collected from a subject, the cartridge assembly comprising:

a coupling unit configured to couple to a cartridge chamber of a sample collection device, wherein the sample collection device is configured to collect the blood from the subject;

a container configured to store the liquid blood; and

a cartridge holder configured to support the container, wherein a proximal end of the container is configured to be coupled to the coupling unit and a distal end of the container is configured to be coupled to the cartridge holder.

48. The cartridge assembly of claim 47, wherein the container comprises a cap coupled to the proximal end of the container, and wherein the proximal end of the container is configured to be coupled to the coupling unit using the cap.

49. The cartridge assembly of claim 48, wherein the lid comprises one or more openings configured to open and allow liquid to enter the container when the lid is coupled to the coupling unit.

50. The cartridge assembly of claim 48, wherein the one or more openings are further configured to close and prevent liquid from entering the container when the lid is decoupled from the coupling unit.

51. The cartridge assembly of claim 48 wherein the coupling unit includes one or more liquid paths that allow air to exit the container and enter the cartridge chamber when the blood is collected in the container.

52. The cartridge assembly of claim 51 wherein the one or more liquid paths comprise one or more vent slots or channels.

53. The cartridge assembly of claim 51, wherein the one or more liquid paths are configured to allow for balancing of vacuum pressure within the cartridge chamber when the blood is collected into the container.

54. The cartridge assembly of claim 51, wherein the container is configured to receive the blood flowing into the container in a first direction, wherein the one or more liquid paths are configured to direct and expel the air out of the container in a second direction different from the first direction.

55. The cartridge assembly of claim 54 wherein the first direction and the second direction are substantially opposite each other.

56. The cartridge assembly of claim 54 wherein the first direction and the second direction are substantially orthogonal to each other.

57. The cartridge assembly of claim 47, wherein a portion of the cartridge holder is configured to extend outside of the cartridge chamber when the cartridge assembly is coupled to the cartridge chamber.

58. The cartridge assembly of claim 57 wherein a portion of the cartridge holder comprises a cartridge tab.

59. The cartridge assembly of claim 47, wherein the cartridge holder comprises a gasket configured to hermetically seal the cartridge chamber when the cartridge assembly is coupled to the cartridge chamber.

60. The cartridge assembly of claim 47, wherein the container and the cartridge holder comprise a set of interlocking mating features that allow the container to be secured to the cartridge holder.

61. The cartridge assembly of claim 47, wherein the cartridge chamber is under vacuum pressure due to activation of a vacuum in the sample acquisition device.

62. The cartridge assembly of claim 61, wherein the vacuum is configured to assist in the flow of blood from a recessed opening in the housing of the sample acquisition device into the container.

63. The cartridge assembly of claim 47, wherein at least a portion of the cartridge assembly is configured to be released and uncoupled from the cartridge chamber of the sample acquisition device after the blood has been acquired into the container.

64. The cartridge assembly of claim 47, wherein the container is configured to be released from and uncoupled from the coupling unit after the blood has been collected in the container.

65. The cartridge assembly of claim 47 wherein the container includes a window that allows a user to view the progress of the liquid blood collection.

66. The cartridge assembly of claim 47, further comprising: one or more sensors configured to detect an amount of blood collected in the container.

67. The cartridge assembly of claim 66, wherein the one or more sensors comprise an optical sensor.

68. The cartridge assembly of claim 66, wherein the one or more sensors are in communication with an electronic fill indicator, and wherein the electronic fill indicator is configured to provide information to a user regarding the amount of blood collected in the container.

69. The cartridge assembly of claim 68, wherein the electronic fill indicator is configured to generate one or more visual, audible, or tactile signals.

70. The cartridge assembly of claim 68, wherein the electronic fill indicator is located on or at the cartridge.

71. The cartridge assembly of claim 68, wherein the electronic fill indicator is located on or at the sample acquisition device.

72. The cartridge assembly of claim 47, wherein the coupling unit comprises a luer fitting.

73. The cartridge assembly of claim 47 wherein the container includes one or more indicator lines for monitoring the progress of the liquid blood collection.

74. The cartridge assembly of claim 47, wherein the one or more indicator lines are used to estimate the amount of blood collected in the container.

75. The cartridge assembly of claim 47 wherein the container comprises a tube.

76. A system for collecting and storing blood from a subject, comprising:

the sample acquisition device and cartridge assembly of any one of claims 47-75.

77. The system of claim 76, wherein the sample acquisition device comprises a built-in vacuum.

78. A method, comprising:

collecting the blood from the subject using the sample collection device of any one of claims 47-75; and

Storing the blood as liquid blood using the cartridge assembly of any one of claims 47-75.

79. A modular chamber assembly for storing blood collected from a subject, the modular chamber assembly comprising:

an inlet port configured to be coupled to a sample collection device, wherein the sample collection device is configured to collect the blood from the subject; and

a chamber configured to be coupled to the inlet port, wherein a housing is formed when the chamber is coupled to the inlet port, wherein the housing is configured to support a plurality of different cartridge assembly types of cartridge assemblies therein, and wherein the plurality of different cartridge assembly types allow for collection, processing, or storage of the blood in a plurality of different forms including plasma, serum, dry blood, liquid blood, or coagulated blood.

80. The modular chamber assembly of claim 79, wherein a portion of the sample acquisition device is configured to extend out of the sample acquisition device when the inlet port is coupled to a mating port of the sample acquisition device.

81. The modular chamber assembly of claim 80, wherein a portion of the sample acquisition device comprises a protrusion.

82. The modular chamber assembly of claim 79, wherein the inlet port comprises a pierceable self-sealing port configured to hermetically seal the housing.

83. The modular chamber assembly of claim 79, wherein the cartridge assembly is configured to be coupled to (1) at least a portion of the inlet port and/or (2) at least a portion of the chamber.

84. The modular chamber assembly of claim 79, wherein the plurality of different cartridge assembly types comprises two or more of: (1) a first cartridge assembly type configured to separate the plasma from the collected blood, (2) a second cartridge assembly type configured to collect and store the liquid blood, (3) a third cartridge assembly type configured to house one or more matrices for collecting and storing the blood as the dry blood, or (4) a fourth cartridge assembly type configured to store coagulated blood.

85. The modular chamber assembly of claim 79, wherein the modular chamber assembly is configured to release and disengage from the sample acquisition device when the inlet port is decoupled from the sample acquisition device.

86. The modular chamber assembly of claim 79, wherein the modular chamber assembly is configured to be released and disengaged from the sample collection device after the blood is collected, processed, or stored on the cartridge assembly.

87. The modular chamber assembly of claim 79, wherein the chamber is configured to protect the cartridge assembly from the external environment after the blood is collected, processed, or stored on the cartridge assembly and after the modular chamber assembly is released and disengaged from the sample collection device.

88. The modular chamber assembly of claim 79, wherein the chamber is tubular.

89. The modular chamber assembly of claim 79, wherein the modular chamber assembly is configured to function as a shipping container for shipping or transporting the blood after it is collected, processed or stored on the cartridge assembly.

90. The modular chamber assembly of claim 79, wherein the chamber comprises a desiccant.

91. The modular chamber assembly of claim 79, wherein the chamber comprises a transparent or translucent window to allow visualization of an interior portion of the chamber.

92. A system for collecting and storing blood from a subject, comprising:

the sample collection device of any one of claims 79-91 and the modular chamber assembly of any one of claims 79-91.

93. The system of claim 92, wherein the sample acquisition device comprises a built-in vacuum.

94. The system of claim 92, wherein the modular chamber assembly comprises a built-in vacuum.

95. The system of claim 92, wherein complete coupling of the sample collection device and the modular chamber assembly is configured to activate a sufficient vacuum to collect and store the blood from the subject.

96. A method, comprising:

collecting the blood from the subject using the sample collection device of any one of claims 79-91; and

use of the modular chamber assembly of any one of claims 79-91 to store the blood in one of the plurality of different forms.

97. A kit, comprising:

the sample acquisition device, modular chamber assembly, and plurality of different cartridge assembly types of any one of claims 79-91.

98. A sample acquisition device for acquiring blood from a subject, the sample acquisition device comprising:

A body including a recess having an opening;

one or more piercing elements extendable through the opening to pierce the skin of the subject, thereby enabling the blood to be collected into the sample collection device while the skin is drawn into the recess; and

a sample chamber comprising a connection port, wherein the connection port is sized and shaped to interchangeably and releasably couple to a cartridge assembly of a plurality of different cartridge assembly types, wherein the plurality of different cartridge assembly types allow collection, processing or storage of the blood in a plurality of different forms including dried plasma, dried serum, dried blood, liquid blood or coagulated blood.

99. The sample acquisition device of claim 98, wherein the body is operably coupled to a vacuum chamber, wherein the vacuum chamber is configured such that activation of the vacuum results in establishing fluid communication between the vacuum chamber and the groove to draw the skin of the subject into the groove, the groove serving as a suction lumen that sucks the skin.

100. The sample acquisition device of claim 98, wherein the modular chamber assembly comprises a built-in vacuum, wherein the modular chamber assembly is configured such that coupling of the modular chamber assembly to the body results in establishing fluid communication between the modular chamber assembly and the recess to draw the skin of the subject into the recess, the recess serving as a suction lumen for suctioning the skin.

101. The sample acquisition device of claim 98, wherein the cartridge assembly is configured to be releasably coupled to the body.

102. The sample acquisition device of claim 98, wherein the sample chamber is hermetically sealed when the cartridge assembly is coupled to the connection port of the sample chamber.

103. The sample acquisition device of claim 98, wherein the plurality of different cartridge assembly types comprises two or more of: (1) a first cartridge assembly type configured to separate the plasma or serum from the collected blood, (2) a second cartridge assembly type configured to collect and store the liquid blood, (3) a third cartridge assembly type configured to house one or more matrices for collecting and storing the blood as the dry blood, or (4) a fourth cartridge assembly type configured to store coagulated blood.

104. A kit, comprising:

a sample collection device configured to collect blood from a subject, wherein the sample collection device comprises a port sized and shaped to interchangeably and releasably couple to a plurality of cartridge assemblies of different cartridge assembly types; and

The plurality of different cartridge assembly types, wherein the plurality of different cartridge assembly types comprises two or more of: (1) a first cartridge component type configured to separate plasma or serum from collected blood, (2) a second cartridge component type configured to store the blood in liquid form, (3) a third cartridge component type configured to house one or more matrices for storing the blood in a substantially dry state, or (4) a fourth cartridge component type configured to store coagulated blood.

105. The kit of claim 104, further comprising a sample chamber, wherein the cartridge assemblies of the plurality of different cartridge assembly types are contained within the sample chamber, and wherein the sample chamber is sized and shaped to interchangeably and releasably couple to the cartridge assemblies.

106. The kit of claim 105, wherein the sample chamber comprises a built-in vacuum.

107. The kit of claim 104, wherein the sample acquisition device comprises a built-in vacuum.

108. A cassette assembly for separating blood collected from a subject, the cassette assembly comprising:

a cartridge comprising a cartridge port, wherein the cartridge is configured to be coupled through the cartridge port to a sample collection device operable to collect a blood sample from the subject;

A cartridge tab, the cartridge tab comprising a base; and

a treatment/stabilization unit supported between the cassette and the base of the cassette tab, wherein the treatment/stabilization unit comprises a multi-component collection matrix configured to separate plasma or serum from a blood sample, wherein the multi-component collection matrix comprises at least one sub-matrix having a different size or shape than one or more other sub-matrices of the multi-component collection matrix.

109. The cartridge assembly of claim 108, wherein the multicomponent acquisition substrate comprises at least three submatrices.

110. The cartridge assembly of claim 108, wherein the multi-component collection matrix is further configured to store the plasma or serum separated from the blood sample.

111. The cartridge assembly of claim 108, wherein the multi-component collection matrix is further configured to stabilize the plasma or serum separated from the blood sample.

112. The cartridge assembly of claim 108, wherein a portion of at least one sub-matrix of the multi-component collection matrix is exposed to an ambient environment.

113. The cartridge assembly of claim 112, wherein a portion of at least one sub-matrix of the multi-component collection matrix is located at a portion of the processing/stabilizing unit remote from the cartridge port.

114. The cartridge assembly of claim 112, wherein a portion of at least one submatrix of the multicomponent acquisition matrix is in contact with the substrate.

115. The cartridge assembly of claim 114, wherein a portion of at least one submatrix of the multicomponent acquisition matrix is not in contact with the cartridge.

116. The cartridge assembly of claim 112, wherein a surface area of a portion of at least one submatrix of the multicomponent acquisition matrix is about 100mm ² To about 150mm ² 。

117. The cartridge assembly of claim 112, wherein a portion of the at least one sub-matrix is disengageable from the multi-component collection matrix.

118. The cartridge assembly of claim 108, wherein the bases of the cartridge and the cartridge tabs are configured to support the process/stabilizing unit in a configuration that enables use or operation of the cartridge assembly in a substantially vertical orientation.

119. The cartridge assembly of claim 108, wherein the cartridge assembly is configured to be used or operated at an angle from about 40 degrees to about 140 degrees relative to a horizontal plane.

120. The cartridge assembly of claim 108, wherein the cartridge assembly is configured to be used or operated at an angle from about 60 degrees to about 120 degrees relative to a horizontal plane.

121. The cartridge assembly of claim 108, wherein the cartridge further comprises a compression region configured to apply a compressive force to a portion of the multicomponent acquisition substrate.

122. The cartridge assembly of claim 121, wherein the compressive force is about 1 pound to about 10 pounds.

123. The cartridge assembly of claim 121, wherein the compressive force is operable to improve or control the passage of the blood sample through or past the multicomponent collection matrix.

124. The cartridge assembly of claim 121, wherein the compressive force is configured to hold or maintain a portion of the multicomponent acquisition substrate at a compressive thickness that is about 30% to about 90% of an uncompressed thickness of the portion of the multicomponent acquisition substrate.

125. The cartridge assembly of claim 121, wherein the compressive force is configured to hold or maintain a portion of the multicomponent acquisition substrate at a thickness of about 0.75mm to about 1.0 mm.

126. The cartridge assembly of claim 121, wherein the cartridge further comprises a compression stop configured to limit (a) a compression force to less than or equal to a predetermined value and/or (b) a compression thickness of a portion of the multicomponent acquisition substrate to less than or equal to a predetermined thickness.

127. The cartridge assembly of claim 108, wherein the cartridge further comprises one or more vents configured to allow fluid communication between the multi-component collection matrix and an external ambient environment.

128. The cartridge assembly of claim 127, wherein the one or more vents are configured to control plasma concentration during separation of the blood sample by the multi-component collection matrix.

129. The cartridge assembly of claim 127, wherein the one or more vents are configured to control a rate of drying during separation of the blood sample by the multi-component collection matrix.

130. The cartridge assembly of claim 112, wherein a portion of at least one submatrix of the multicomponent acquisition matrix is not subjected to compressive forces.

131. The cartridge assembly of claim 130, wherein at least one other portion of the multicomponent acquisition substrate is subjected to the compressive force.