NL2036036B1 - Cartridge interface features - Google Patents
Cartridge interface features Download PDFInfo
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- NL2036036B1 NL2036036B1 NL2036036A NL2036036A NL2036036B1 NL 2036036 B1 NL2036036 B1 NL 2036036B1 NL 2036036 A NL2036036 A NL 2036036A NL 2036036 A NL2036036 A NL 2036036A NL 2036036 B1 NL2036036 B1 NL 2036036B1
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- Netherlands
- Prior art keywords
- cartridge
- fluid
- head
- conduit
- pneumatic
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L9/00—Supporting devices; Holding devices
- B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
- B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
- G01N15/0205—Investigating particle size or size distribution by optical means
- G01N15/0227—Investigating particle size or size distribution by optical means using imaging; using holography
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1429—Signal processing
- G01N15/1433—Signal processing using image recognition
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1456—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
- G01N15/1459—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals the analysis being performed on a sample stream
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1468—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle
- G01N15/147—Optical investigation techniques, e.g. flow cytometry with spatial resolution of the texture or inner structure of the particle the analysis being performed on a sample stream
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/1484—Optical investigation techniques, e.g. flow cytometry microstructural devices
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N15/149—Optical investigation techniques, e.g. flow cytometry specially adapted for sorting particles, e.g. by their size or optical properties
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1011—Control of the position or alignment of the transfer device
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/0004—Microscopes specially adapted for specific applications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0633—Valves, specific forms thereof with moving parts
- B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
- G01N2015/0294—Particle shape
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N2015/1006—Investigating individual particles for cytology
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N2015/1493—Particle size
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N2015/1497—Particle shape
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00039—Transport arrangements specific to flat sample substrates, e.g. pusher blade
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
- G01N2035/1044—Using pneumatic means
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1065—Multiple transfer devices
- G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
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- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Optics & Photonics (AREA)
- Signal Processing (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
A cartridge has a first layer, a first fluid input port to receive fluid to flow through the cartridge, a first fluid output port to convey fluid from the cartridge, and a first pneumatic port to convey pneumatic pressure to the cartridge. The first fluid input port includes a first opening in the first layer. The first fluid output port includes a second opening in the first layer. The first pneumatic port includes a third opening in the first layer. A first fluid conduit, including a first flexible tube, may be removably inserted into the first fluid input port via the first opening. A second fluid conduit, including a second flexible tube, may be removably inserted into the first fluid output port via the second opening. A first pneumatic conduit, including a third flexible tube, may be removably inserted into the first pneumatic port via the third opening. 1 O l 5
Description
CARTRIDGE INTERFACE FEATURES
[0001] The properties of cells may be analyzed to diagnose diseases and other conditions. Such analysis may include evaluation of cell morphology to determine cell type (e.g., stem cell or differentiated cell) or cell state (e.g., healthy state or disease state). In some cases, cells may be directed through a channel of a cartridge, under fluidic guidance, through a microscope imaging field. The images captured through the microscope may be processed to evaluate cell morphology. While a variety of devices, systems, and methods have been made and used to process and analyze cells, it is believed that no one prior to the inventor(s) has made or used the devices and techniques described herein.
[8602] FIG. 1 depicts a schematic view of an example of a cell analysis system.
[0003] FIG. 2 depicts a perspective view of an example of a cartridge that may be used in examples of the cell analysis system of FIG. 1.
[0604] FIG. 3 depicts an exploded perspective view of the cartridge of FIG. 2.
[6005] FIG. 4 depicts a perspective view of an example underside of a first layer of the cartridge of
FIG. 2.
[0006] FIG. 5 depicts a perspective view of an example underside of a second layer of the cartridge of
FIG. 2.
[0007] FIG. 6 depicts a top plan view of the cartridge of FIG. 2.
[0008] FIG. 7 depicts a top schematic view of the cartridge of FIG. 2 with a plurality of fluid conduits coupled with the cartridge and a plurality of pneumatic conduits coupled with the cartridge.
[0009] FIG. 8 depicts a perspective view of an example instrument that may be incorporated into the system of FIG. 1.
[6010] FIG. 9 depicts a perspective view of example imaging components and an example cartridge support assembly of the instrument of FIG. 8.
[0011] FIG. 10 depicts a top plan view of the imaging components and cartridge support assembly of
FIG. 9.
[6012] FIG. 11 depicts a side elevation view of the imaging components and cartridge support assembly of FIG. 9.
[0013] FIG. 12 depicts a front elevation view of the imaging components and cartridge support assembly of FIG. 9.
[0014] FIG. 13 depicts a perspective view of an example stage assembly of the instrument of FIG. 8.
[0015] FIG. 14 depicts a perspective view of the stage assembly of FIG. 13 with an upper member removed.
[0016] FIG. 15 depicts a right side elevation view of the stage assembly of FIG. 13.
[0017] FIG. 16 depicts a left side elevation view of the stage assembly of FIG. 13.
[6018] FIG. 17A depicts a top plan view of the stage assembly of FIG. 13, with the cartridge support assembly of FIG. 9 in an example first position along an x-y plane;
[0019] FIG. 17B depicts a top plan view of the stage assembly of FIG. 13, with the cartridge support assembly of FIG. 9 in an example second position along an x-y plane;
[6020] FIG. 17C depicts a top plan view of the stage assembly of FIG. 13, with the cartridge support assembly of FIG. 9 in an example third position along an x-y plane;
[0621] FIG. 18 depicts a perspective view of the cartridge support assembly of FIG. 9, with the cartridge of FIG. 2 seated in the cartridge support assembly.
[0022] FIG. 19 depicts a perspective view of the cartridge support assembly of FIG. 9, with the cartridge of FIG. 2 removed from the cartridge support assembly.
[0023] FIG. 20A depicts an enlarged top plan view of the cartridge support assembly of FIG. 9, with the cartridge of FIG. 2 seated in the cartridge support assembly, and with an example cartridge retainer in an example first position.
[0024] FIG. 20B depicts an enlarged top plan view of the cartridge support assembly of FIG. 9, with the cartridge of FIG. 2 seated in the cartridge support assembly, and with the cartridge retainer in an example second position.
[0025] FIG. 21 depicts a perspective view of an example first fluid conduit guide assembly of the cartridge support assembly of FIG. 9.
[6026] FIG. 22 depicts a perspective view of an example head of the first fluid conduit guide assembly of FIG. 21.
[0027] FIG. 23 depicts a cross-sectional view of the head of FIG. 22, taken along line 23-23 of FIG. 22.
[0028] FIG. 24 depicts a perspective view of an example pneumatic conduit guide assembly of the cartridge support assembly of FIG. 9.
[8029] FIG. 25 depicts an exploded perspective view of the pneumatic conduit guide assembly of FIG. 24.
[0030] FIG. 26 depicts a top plan view of an example head of the pneumatic conduit guide assembly of FIG. 24.
[0031] FIG. 27 depicts a rear elevation view of the head of FIG. 26.
[0032] FIG. 28 depicts a perspective view of an example second fluid conduit guide assembly of the cartridge support assembly of FIG. 9.
[0033] FIG. 29 depicts an exploded perspective view of the second fluid conduit guide assembly of
FIG. 28.
[0034] FIG. 30 depicts a perspective view of an example head of the second fluid conduit guide assembly of FIG. 28.
[0035] FIG. 31 depicts a cross-sectional view of the head of FIG. 30, taken along line 30-30 of FIG. 30.
[0036] FIG. 32 depicts another cross-sectional view of the head of FIG. 30, taken along line 32-32 of
FIG. 30.
[6037] FIG. 33A depicts a top plan view of the cartridge support assembly of FIG. 9, with the first fluid conduit guide assembly of FIG. 21 at an example first angular position along an x-y plane, with the pneumatic conduit guide assembly of FIG. 24 at an example first angular position along the x-y plane, and with the second fluid conduit guide assembly of FIG. 28 at an example first angular position along the x-y plane.
[0038] FIG. 33B depicts a top plan view of the cartridge support assembly of FIG. 9, with the first fluid conduit guide assembly of FIG. 21 at an example second angular position along an x-y plane, with the pneumatic conduit guide assembly of FIG. 24 at an example second angular position along the x-y plane, and with the second fluid conduit guide assembly of FIG. 28 at an example second angular position along the x-y plane.
[0039] FIG. 33C depicts a top plan view of the cartridge support assembly of FIG. 9, with the first fluid conduit guide assembly of FIG. 21 at the first angular position of FIG. 33A, with the pneumatic conduit guide assembly of FIG. 24 at an example third angular position along the x- y plane, and with the second fluid conduit guide assembly of FIG. 28 at the first angular position of FIG. 33A.
[0040] FIG. 34 depicts an enlarged partial view of the cartridge the stage assembly of FIG. 13 with components removed to show routing of a fluid conduit through a fluid conduit guide assembly.
[0041] FIG. 35 depicts a schematic side view of an example fluid conduit that may be used with the cartridge of FIG. 2 and the instrument of FIG. 8.
[0042] FIG. 36 depicts a schematic cross-sectional side view of the fluid conduit of FIG. 35 inserted into a fluid port of the cartridge of FIG. 2.
[6043] FIG. 37 depicts a schematic side view of an example pneumatic conduit that may be used with the cartridge of FIG. 2 and the instrument of FIG. 8.
[0044] FIG. 38 depicts a schematic cross-sectional side view of the pneumatic conduit of FIG. 37 inserted into a pneumatic port of the cartridge of FIG. 2.
[6045] FIG. 39 depicts a schematic view of another example of a cartridge that may be used in examples of the cell analysis system of FIG. 1.
[0046] The following detailed description of certain examples will be better understood when read in conjunction with the appended drawings. To the extent that the figures illustrate diagrams of the functional blocks of various examples, the functional blocks are not necessarily indicative of the division between hardware components. Thus, for example, one or more of the functional blocks {e.g., processors or memories) may be implemented in a single piece of hardware (e.g.,
a general purpose signal processor or random access memory, hard disk, or the like). Similarly, the programs may be stand-alone programs, may be incorporated as subroutines in an operating system, may be functions in an installed software package, and the like. It should be understood that the various examples are not limited to the arrangements and instrumentality shown in the 5 drawings.
[0047] 1 Terminology
[0048] Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise,” and variations such as “comprises” and “comprising” means various components may be co-jointly employed in the methods and articles (e.g., compositions and apparatuses including device and methods). For example, the term “comprising” will be understood to imply the inclusion of any stated elements or steps but not the exclusion of any other elements or steps. In general, any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and/or steps may alternatively be exclusive and may be expressed as “consisting of” or alternatively “consisting essentially of” the various components, steps, sub-components, or sub-steps. Furthermore, references to “one example” are not intended to be interpreted as excluding the existence of additional examples that also incorporate the recited features. The use of “including,” “comprising,” “having,” or “in which,” and variations thereof, herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
[0049] As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”.
[0050] When used in the claims, the term “set” should be understood as one or more things which are grouped together. Similarly, when used in the claims “based on” should be understood as indicating that one thing is determined at least in part by what it is specified as being “based on.” Where one thing is required to be exclusively determined by another thing, then that thing will be referred to as being “exclusively based on” that which it is determined by.
[0051] Spatially relative terms, such as “under,” “below,” “lower,” “over,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the term “under” may encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly,” “downwardly,” “vertical,” “horizontal,” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise. In addition, terms such as “outer” and “inner” are used herein for purposes of description and are not intended to indicate or imply relative importance or significance.
[0052] When a feature or element is herein referred to as being “on” or “over” another feature or element, it may be directly on or over the other feature or element; or intervening features and/or elements may also be present. In other words, when a feature or element is herein referred to as being “on” or “over” another feature or element, it may be indirectly on or over the other feature or element. In contrast, when a feature or element is referred to as being “directly on” or “directly over” another feature or element, there are no intervening features or elements present.
[0053] When a feature or element is referred to as being “mounted,” “connected,” “supported,” “attached.” or “coupled” to another feature or element, it may be directly mounted, connected, supported, attached, or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly mounted,” “directly connected,” “directly supported,” “directly attached,” or “directly coupled” to another feature or element, there are no intervening features or elements present.
Although described or shown with respect to one embodiment, the features and elements so described or shown may apply to other embodiments. It will also be appreciated by those skilled in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
[0054] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, the terms “about” or “approximately” for any numerical values or ranges indicate a suitable dimensional tolerance, or other form of reasonable expected range, that allows the part or collection of components to function for its intended purpose as described herein. More specifically, “about” or “approximately” may refer to the range of values that are within £10% of the recited value (e.g., “about 100” may refer to the range of values from 90 to 110, including 90, 110, 100, and all other values within the range of 90 and 110). Any numerical values given herein should also be understood to include about or approximately that value unless the context indicates otherwise. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Any numerical range recited herein is intended to include all sub- ranges subsumed therein. The terms “approximately” and “about” are thus utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.
[0055] The term “substantially” is also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. The term “substantially” shall therefore be understood to include a range of conditions or results that provide a functional equivalent to an explicitly stated condition or result. For instance, if a task is “substantially complete,” the result of the task having been substantially completed is functionally equivalent to the result that would have been achieved if the task had been perfectly completed. As another non-limiting example, a component that is “substantially straight” or “substantially flat,” an apparatus including a component that is “substantially straight” or “substantially flat” may provide a result or effect that is functionally equivalent to a result or effect that would be achieved by the same apparatus including the same component in a perfectly straight or perfectly flat configuration. The range implied by the term “substantially” should also be read to include the perfect result that is within that range. Thus, the term “substantially complete” shall be read as including “perfectly complete” while also including a range of completeness that is functionally equivalent to perfectly complete. As another example, terms such as “substantially straight” and “substantially flat” shall be read as including “perfectly straight” and ‘perfectly flat,” respectively; while also including a range of straightness or flatness that is functionally equivalent to perfectly straight or flat, respectively. As with the terms “approximately” and “about,” the term “substantially” may indicate a suitable dimensional tolerance, or other form of reasonable expected range, that allows a part or collection of components to function for its intended purpose as described herein.
[0056] The term “perpendicular” shall be understood to include arrangements where one element (e.g., surface, feature, component, axis, etc.) defines an angle of 90 degrees with another element (e.g., surface, feature, component, axis, etc.). The term “perpendicular” shall also be understood to include arrangements where one element {e.g., surface, feature, component, axis, etc.) defines an angle of approximately 90 degrees with another element (e.g., surface, feature, component, axis, etc.).
[0057] It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value,” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “X” is disclosed the “less than or equal to X as well as “greater than or equal to X” (e.g., where X is a numerical value) is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
[0058] Although the terms ‘first’ and “second” may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms are used to distinguish one feature/element from another feature/element, and unless specifically pointed out, do not denote a certain order. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention. The terms “first,” “second,” and “third,” etc. are thus used merely as labels, and are not intended to impose numerical requirements on their objects.
[0059] As used herein, the terms “system,” “apparatus,” and “device” may be read as being interchangeable with each other. A system, apparatus, and device may each include a plurality of components having various kinds of structural and/or functional relationships with each other.
[0060] The term “fluid” shall be understood to include liquids and gases, including pneumatic pressure. Similarly, “fluidic communication” shall be understood to include the communication of liquids and the communication of gases, including pneumatic pressure.
[0061] The term “morphology” or “morphological characteristic” of a cell as used herein generally refers to the form, structure, and/or configuration of the cell. The morphology of a cell may comprise one or more aspects of a cell’s appearance, such as, for example, shape, size, arrangement, form, structure, pattern(s) of one or more internal and/or external parts of the cell,
or shade (e.g., color, greyscale, etc.). Non-limiting examples of a shape of a cell may include, but are not limited to, circular, elliptic, dumbbell, star-like, flat, scale-like, columnar, invaginated, having one or more concavely formed walls, having one or more convexly formed walls, prolongated, having appendices, having cilia, having angle(s), having corner(s), etc. A morphological feature of a cell may be visible with treatment of a cell (e.g., small molecule or antibody staining). In other examples, the morphological feature of the cell may not and need not require any treatment to be visualized in an image or video.
[0662] The terms “unstructured” or “unsorted,” as used interchangeably herein, generally refers to a mixture of cells (e.g., an initial mixture of cells) that is not substantially sorted {or rearranged) into separate partitions. An unstructured population of cells may comprise at least two types of cells that can be distinguished by exhibiting different properties (e.g., one or more physical properties, such as one or more different morphological characteristics as disclosed herein).
The unstructured population of cells may be a random (or randomized) mixture of the at least two types of cells. The cells as disclosed herein may be viable cells. A viable cell, as disclosed herein, may be a cell that is not undergoing necrosis or a cell that is not in an early or late apoptotic state. In other examples, the cells may not and need not be viable (e.g., fixed cells).
[0063] The term “resilient” as used herein refers to a material property where the material has shape memory and stiffness such that it is structurally biased toward a neutral shape or structural arrangement. As an example, a resilient member may have a resilient bias toward a neutral shape or structural arrangement where the resilient member is straight along a central longitudinal axis. That same resilient member may be deformed relative to the neutral shape or structural arrangement, such as by being bent away from that central longitudinal axis, in response to a force (e.g., when a force is imparted on the resilient member, where the force has a directional component that is transverse to the central longitudinal axis). While the resilient member is being deformed relative to the neutral shape in response to the force, the resilient member may be under stress whereby the resilient property of the material of the resilient member generates a force in a direction that is opposite to the force that is causing the deformation of the resilient member. In other words, the resilient property of the material of the resilient member may impart a mechanical bias urging the resilient member back toward the neutral shape or structural arrangement. After the force causing the deformation of the resilient member is removed, the resilient bias of the material of the resilient member may cause the resilient member to return to (or at least toward) the neutral shape or structural arrangement. While the foregoing example provides a straight configuration as a neutral shape or structural arrangement, other examples of resilient members may have other kinds of neutral shapes or structural arrangements.
[6064] IL Example of Cell Analysis System
[0065] The systems and methods described herein may be utilized to analyze a cell and/or sort (or partition) the cell from a population of cells. A cell may be directed through a flow channel, and one or more imaging devices (e.g., sensor(s), camera(s)) may capture one or more images/videos of the cell passing through the flow channel. Subsequently, the image(s)/video(s) of the cell may be analyzed in real-time, such that a decision may be made in real-time {e.g., automatically by the machine learning algorithm) to determine (i) whether to sort the cell or not and/or (ii) which sub-channel of a plurality of sub-channels to sort the cell into.
[0066] FIG, 1 shows an example of a cell analysis system (100), which may be used to capture images of cells, and apply machine learning or artificial intelligence to analyze the captured images of the cells, and automatically sort the cells based on the analysis. System (100) of this example includes a pump (110) that is operable to drive a sample cell-containing fluid from a reservoir (112) into a cartridge (120). Cartridge (120) may be provided as a modular component, such that cartridge (120) may be readily replaced within system (100) (e.g., to analyze different batches of sample cells, etc.). The remaining components of system (100) that do not get replaced each time cartridge (120) is replaced may be collectively referred to as “the instrument.” The instrument of system (100) may include pump (110); or pump (110) may be considered as a separate component such that a different pump (110) may be used when a different batch of sample cells is being analyzed. Similarly, the instrument of system (100) may include reservoir (112); or reservoir (112) may be considered as a separate component such that a different reservoir (112) may be used when a different batch of sample cells is being analyzed.
[0067] In some examples, reservoir (112) comprises a syringe barrel; and pump (110) comprises a syringe pump. In other examples, pump (110) may take any other suitable form, including but not limited to a gravity feed, a peristaltic pump, etc. Reservoir (112) may also take any other suitable form, including but not limited to a vial, tube, etc. The sample in reservoir (112) may be prepared by fixation and staining; and may contain viable cells. The fluid in which the sample cells are contained may include an aqueous solution (e.g., water, buffer, saline, etc.), an oil, or any other suitable fluid.
[0068] Cartridge (120) includes a flow channel (122) fluidically coupled with pump (110), such that pump (110) is operable to drive the sample cell-containing fluid from reservoir (112) through flow channel (122). Cartridge (120) may comprise a microfluidic chip, a flow cell, or any other kind of structure through which fluid may flow; and through which cells in the fluid may be imaged. A light source (130) generates light for such imaging. In particular, an optical assembly (132) directs light from light source (130) toward an imaging region of flow channel (122). In some examples, light source (130) comprises a source of incoherent white light, such as an arc lamp, etc. In other examples, light source (130) may take any other suitable form.
Optical assembly (132) may comprise any suitable number and/or arrangement of lenses and/or other elements as will be apparent to those skilled in the art in view of the teachings herein.
[6069] The light from light source (130), as directed by optical assembly (132), illuminates cells as the cells pass through the imaging region of flow channel (122). An objective lens assembly (140) is positioned on the opposite side of the imaging region of flow channel (122), magnifies the images of cells passing through the imaging region of flow channel (122), and directs the magnified images to a camera (142). Objective lens assembly (140) and camera (142) thus cooperate to capture high resolution images of cells that pass through the imaging region of flow channel (122), as illuminated by light source (130) and optical assembly (132). By way of example only, objective lens assembly (140) may provide magnification ranging from approximately 10x to approximately 200x. In other examples, objective lens assembly (140) may provide any other suitable level of magnification. By way of further example only, camera (142) may provide an exposure time ranging from approximately 0.001 us to approximately 1 ms. In other examples, camera (142) may provide any other suitable exposure time. In some example, objective lens assembly (140) and camera (142) have an optical axis along the z- dimension.
[0070] An image processing module (144) receives images from camera (142) and processes those received images in real time. Image processing module (144) may include one or more processors, one or more memories, and various other suitable electrical components. Image processing module (144) may also include software, firmware and/or hardware. In some examples, image processing module (144) is in communication with a remote server and/or with other components. The one or more processors of image processing module (144) may comprise one or more of a programmable processor, a programmable controller, a microprocessor, a microcontroller, a graphics processing unit (GPU), a digital signal processor (DSP), a reduced-instruction set computer (RISC), an application specific integrated circuit
(ASIC), a field programmable gate array (FPGA), a field programmable logic device (FPLD), a logic circuit, and/or another logic-based device executing various functions including the ones described herein.
[0071] Image processing module (144) may utilize any of a number of techniques to classify or otherwise analyze images of cells captured by camera (142). For instance, cell image data may be analyzed to plot a plurality of cells into a cell clustering map. The image data may comprise tag-free images of single cells. In other examples, the image data may comprise images of single cells that are tagged (e.g., with a heterologous marker). The image data may be processed to generate a cell morphology map. The cell morphology map may comprise a plurality of morphologically distinct clusters corresponding to different types or states of the cells. In some cases, a classifier (e.g., a cell clustering machine learning algorithm or deep learning algorithm) may be trained by using the cell morphology map. The classifier may be configured to classify a cell image sample based on its proximity, correlation, or commonality with one or more of the morphologically distinct clusters. Thus, in some cases, the classifier may be used to classify the sample cell image sample accordingly. This classification may be fully automatic, such that the classification is accomplished solely by software executed through image processing module (144), without additional human operator review of the sample cell image. In some other examples, the classification is at least partially manual such that a human operator verifies or otherwise intervenes to inform or approve the classification of the sample cell image.
[0072] Regardless of the technique(s) used by image processing module (144) to classify or otherwise analyze images of cells captured by camera (142), system (100) may provide sorting of cells in cartridge (120) based on such image processing. In some examples, cartridge (120) may include two or more outlet channels from flow channel, and system (100) may automatically activate one or more valves to direct an imaged cell through a selected one of those outlet channels based on the image analysis of the cell by image processing module (144). For instance, a certain outlet channel may be selected if classification or other analysis by image processing module (144) determines that the cell appears to be a certain cell type of interest.
In other examples, system (100) may provide cell sorting in any other suitable fashion; and based on any suitable criterion or criteria. In some other examples, system (100) provides imaging and analysis of cells without subsequent sorting of cells. In such examples, the imaged cells may remain contained in cartridge (120) after imaging or may exit cartridge (120) via an outlet port after imaging.
[0073] As noted above, the remaining components of system (100) that do not get replaced each time cartridge (120) is replaced may be collectively referred to as “the instrument.” In some examples, the instrument includes light source (130), optical assembly (132), objective lens assembly (140), camera (142), and various other components that removably receive cartridge (120) and provide any fluidic couplings, etc, that are needed for system (100) to perform properly. The instrument may further include image processing module (144). In other examples, image processing module (144) may be provided as a separate component {e.g., computer, etc.) that is coupled with camera (142) of the instrument to process images captured by camera (142). As further noted above, the instrument may further include or omit either or both of pump (110) and/or reservoir (112).
[6974] IIL Example of Cartridge
[0075] FIGS. 2-6 show an example of a form that may be taken by cartridge (120). In particular, FIGS. 2-6 show an example of a cartridge (200) that may be used in system (100) to provide imaging, analysis, and sorting of cells flowed through cartridge (200). Cartridge (200) of this example includes a first layer (300), a second layer {400), and a third layer (500). In the present example each of layers (300, 400) comprises a polymer (e.g., a siloxane-containing polymer, such as polydimethylsiloxane (PDMS), thermoset plastic, hydrogel, thermoplastic elastomer (TPE), thermoplastic polyurethane (TPU). polycarbonate (PC), polystyrene (PS), poly(methyl methacrylate) (PMMA), cyclic olefin copolymer (COC), etc.). Layer (500) may comprise a glass (e.g., borosilicate or other silicate glass, etc.) or a polymer (e.g., polycarbonate (PC), polystyrene (PS), poly(methyl methacrylate) (PMMA), cyclic olefin copolymer (COC), etc.).
In other examples, each layer (300, 400, 500) may comprise any other suitable material or combination of materials. Layers (300, 400, 500) are arranged such that a top surface (302) of layer (300) is exposed, a bottom surface (304) of layer (300) is apposed with a top surface (402) of layer (400), and a bottom surface (404) of layer (400) is apposed with a top surface (502) of layer (500). Layer (500) acts as a substrate, providing structural support to layers (300, 400), with a bottom surface (502) of layer (500) being placed upon a mounting surface (not shown) in an instrument of system (100).
[0076] As shown in FIGS. 2-4, layer (300) is substantially thicker than layer (400). As also shown in
FIGS. 2-4, layer (300) includes a plurality of fluid input ports (310), a plurality of fluid output ports (312), plurality of pneumatic ports (320), and a plurality of pneumatic channels (322), and a pair of tabs (306). Ports (310, 312, 320) are in the form of channels formed through the entire thickness of layer (300), such that each port (310, 312, 320) is open at top surface (302)
and at bottom surface (304). In some examples, fluid input conduits of system (100) are inserted into fluid input ports (310), fluid output conduits of system (100) are inserted into fluid output ports (312), and pneumatic input conduits of system (100) are inserted into pneumatic ports (320). An instrument of system (100) may thus communicate liquids to cartridge (200) via fluid input ports (310), receive liquids from cartridge (200) via fluid output ports (312), and provide pneumatic pressure to cartridge (200) via pneumatic ports (320). In some examples, the conduits of system (100) that are coupled with ports (310, 312, 320) comprise flexible tubes.
In other examples, such conduits may take any other suitable form.
[0077] As shown in FIG. 4, bottom surface (304) of layer (300) includes a plurality of pneumatic channels (322), with each pneumatic channel (322) being in fluidic communication with a corresponding pneumatic port (320). Pneumatic channels (322) thus receive pneumatic pressure communicated through pneumatic ports (320). Such pneumatic pressure may be used to provide deflection of regions of layer (400) underlying pneumatic channels (322), such that those regions of layer (400) may be operated as pinch valves to close fluidic communication between layers (400, 500) as described in greater detail below. Each pneumatic channel (322) is formed as a recess in bottom surface (304), such that pneumatic pressure is communicated along the space defined collectively by top surface (402) of layer (400) and each pneumatic channel (322). In other words, top surface (402) of layer (400) defines a bottom of each pneumatic channel (322).
[0078] As shown in FIGS. 2-3 and 5, layer (400) includes a plurality of fluid input ports (410), a plurality of fluid output ports (412), and a plurality of well openings (440). Ports (410, 412) and well openings (440) are in the form of openings formed through the entire thickness of layer (400). Fluid input ports (410) of layer (400) are positioned to align with fluid input ports (310) of layer (300), such that fluid may be communicated from an instrument of system (100) through layer (400) via fluid input ports (310, 410). Fluid output ports (412) of layer (400) are positioned to align with fluid output ports (312) of layer (300), such that fluid may be communicated through layer (400) to an instrument of system (100) via fluid output ports (312, 412). Well openings (440) of layer (400) are positioned to align with well channels (340) of layer (300), such that fluid may be communicated through layer (400) via well openings (440) into well channels (340).
[6079] Well openings (440), well channels (340), and top surface (502) of layer (500) thus cooperate to define a plurality of wells (750, 752, 754, 756, 758, 760), in which particles in fluid may be stored. In some examples, a removable layer (e.g., tape, film, foil, etc.) or other removable cover is provided over openings (440), such as to minimize, and in some instances even prevent, evaporation from the underlying wells, to minimize, and in some instances even prevent, contamination of the underlying wells, and/or for other reasons. In some such examples, an operator may remove such a layer or cover from a well to retrieve fluid from the well (e.g., via pipette, etc.). It should be understood that layer (400) does not include pneumatic openings or ports in this example, such that pneumatic pressure is not communicated through layer (400).
[0080] As shown in FIG. 5, bottom surface (404) of layer (400) includes a fluidic test input region (450), a pair of fluidic flush input regions (460), a pair of fluidic flush output regions (462), a sample fluid receiving region (600), a flow control fluid receiving region (620), a flow drive fluid receiving region (670), and a sample output region (680). A plurality of fluidic channels (442, 452, 464, 604, 662. 664, 672) are formed as recesses in bottom surface (304), such that fluid is communicated along the space defined collectively by top surface (502) of layer (500) and each fluidic channel (442, 452, 464, 604, 662. 664, 672).
[0081] Fluidic channel (452) terminates within layer (400), such that fluidic channel (452) lacks any kind of fluidic outlet. In some scenarios, a fluid input conduit may be coupled with the fluid input port (310) over fluidic test input region (450), and fluid may be communicated into fluidic channel (452) via the fluid input ports (310, 410) over fluidic test input region (450). This may be done to provide a quality control check, to ensure that layers (400, 500) are properly sealed together. In other words, if back pressure quickly accumulates in the fluid input conduit that is coupled with the fluid input port (310) over fluidic test input region (450), such back pressure may indicate that layers (300, 400) are properly sealed together. If such back pressure does not sufficiently accumulate, this may indicate that layers (400, 500) are not properly sealed together. It should be understood that similar quality control testing may be performed with pneumatic pressurization through a pneumatic port (320) into a pneumatic channel (322), to ensure that layers (300, 400) are properly sealed together.
[0082] A fluidic channel (464) extends between each flush input regions (460) and a corresponding flush output region (462). In some scenarios, a fluid input conduit may be coupled with the fluid input port (310) over flush input regions (460), and a fluid output conduit may be coupled the fluid output port (312) over flush output region (462). Fluid may be communicated into flush input region (460) via fluid input ports (310, 410) over flush input region (460), may flow along fluidic channel (464), then may exit flush output region (462) via fluid output ports (312, 412) over flush output region (462). This may be done to provide flushing of the fluid conduits that are coupled with these ports (310, 412), such as when a cartridge (200) has been replaced, to remove any contaminants that might otherwise be found in those fluid conduits. The combination of a flush input region (460), a fluidic channel {464) a flush output region (462), fluid input port (310), and fluid outlet port (312) may be collectively understood to form a flush assembly. In some examples, the fluid communicated through the flush assembly includes a bio-compatible fluid such as an aqueous based buffer fluid or liquid culture medium; or a bio- compatible oil based fluid. In other examples, other kinds of flush fluid may be used.
[0083] A fluidic channel (604) extends from sample fluid receiving region (600) to a junction (640).
A fluid input conduit may be coupled with the fluid input port (310) over sample fluid receiving region (600), and a fluid containing sample cells may be communicated to junction (640) via the fluid input ports (310, 410) over sample fluid receiving region (600) and via fluidic channel (604). A pair of fluidic channels (626) extend from flow control fluid receiving region (620) to junction (640), such that fluidic channels (604, 626) converge at junction (640). A fluid input conduit may be coupled with the fluid input port (310) over flow control fluid receiving region (620), and a flow control fluid may be communicated to junction (640) via the fluid input ports (310, 410) over flow control fluid receiving region (620) and via fluidic channels (626). The fluid from fluidic channels (604, 626) exits junction (640) along a sampling channel (650).
[0084] The fluid communicated along sampling channel (650) may contain sample cells as noted above. These cells may be imaged by the instrument of system (100) as also noted above.
Such imaging may be performed as the cells traverse sampling channel (650). For instance,
FIG. 6 shows an example of an imaging region (652) that may be positioned along sampling channel (650). In some examples, light source (130) and optical assembly (132) are positioned over cartridge (200) to illuminate imaging region (652); while objective lens assembly (140) and camera (142) are positioned under cartridge (200) to capture images of cells within imaging region (652). Other examples may provide imaging region (652) at any other suitable location or locations along sampling channel (650). Some examples may also provide a plurality of imaging regions (652) at different respective positions along sampling channel (650).
[0085] FIG. 7 shows an example of an arrangement where fluid conduits (802) are coupled with fluid input ports (310), a fluid conduit (802) is coupled with fluid output port (312), and pneumatic conduits (804) are coupled with pneumatic ports (320). As described in greater detail below, each fluid conduit (802) may comprise a flexible tube that is inserted into the corresponding port (310, 312), with the material of layer (300) providing a friction fit to retain and seal each fluid conduit (802) relative to cartridge (200). Similarly, each pneumatic conduit (804) may comprise a flexible tube that is inserted into the corresponding port (320), with the material of layer (300) providing a friction fit to retain and seal each pneumatic conduit (804) relative to cartridge (200).
[0086] In the example shown in FIG. 7, a fluid conduit (802) is inserted into fluid input port (310) over sample fluid receiving region (600) and is further coupled with a source (810) of a fluid containing one or more sample cells. For instance, source (810) may constitute pump (110) and reservoir (112) of system (100) as described above. Another fluid conduit (802) is inserted into fluid input port (310) over flow control fluid receiving region (620) and is further coupled with a source (812) of flow control fluid. In some examples, the flow control fluid includes a buffer fluid. In some examples the flow control fluid further includes beads; while in other examples the flow control fluid does not include beads. The flow control fluid may include a bio-compatible fluid. In some examples, the flow control fluid has a viscosity that differs from the viscosity of the fluid containing sample cells. In other examples, other kinds of fluid may be used for flow control fluid.
[0087] Another fluid conduit (802) is inserted into fluid input port (310) over flow control flow drive fluid receiving region (670) and is further coupled with a source {814) of flow drive fluid. In some examples, the same fluid that is communicated to flow control fluid receiving region (620) for flow control in cartridge (200) is also communicated to flow drive fluid receiving region (670) to boost fluid flow through and past secondary sorting region (204). In some such examples, source (812) and source (814) may be the same source. In some examples, the additional boosting fluid provided via flow drive fluid receiving region (670) may include any bio-compatible fluid, such as liquid culture medium, cell lysis solution, or an oil based fluid.
In other examples, other kinds of fluid may be used. In the present example, another fluid conduit (802) is inserted into fluid output port (312) over sample output region (680) and is further coupled with a receptacle (816) (e.g., vial, tube, etc.) that receives fluid communicated from cartridge (200) via sample output region (680).
[0088] As also shown in FIG. 7, each pneumatic conduit (804) is coupled with a respective pneumatic port (320); and all pneumatic conduits (804) are also coupled with a pneumatic pressure source (820). Pneumatic pressure source (820) is operable to provide pneumatic pressure in the form of pressurized air or some other gas. Pneumatic pressure source (820) may include various features such as a pump, a manifold, a set of valves (e.g., to selectively provide pneumatic pressure to different pneumatic conduits (802)), and/or other features. In some examples,
pneumatic pressure source (820) is integrated into the instrument of system (100). In some other examples, the instrument of system (100) is pneumatically coupled with an otherwise separate pneumatic pressure source (820).
[0089] IV. Example of Instrument
[0090] As noted above system (100) may include an instrument, which may removably receive cartridge (200) and may include various other features of system (100) as described herein.
FIG. 8 shows one example of an instrument (900) that may be part of system (100). Instrument (900) of this example includes a support frame (902) on a base (904), a microscope assembly (910), an illumination head (912), a stage assembly (1000), and a cartridge support assembly (1100). Cartridge support assembly (1100) is structurally configured to removably receive cartridge (200). Stage assembly (1000) is operable to move cartridge support assembly (1100) (with cartridge (200)) along the x-y plane. Microscope assembly (910) is operable to capture images of cells or other particles flowing along sampling channel (650) as described above, with illumination head (912) providing illumination of at least imaging region (652) of cartridge. Microscope assembly (910) may include the components and functionality of at least objective lens assembly (140) and camera (142) as described above. Illumination head (912) may include at least some of the components and functionality of optical assembly (132); and may be optically coupled with (or integrate) light source (130). It should be understood that instrument (900) may further include various other components not shown in FIG. 8, including but not limited to an outer housing, etc.
[0091] As best seen in FIGS. 9-12, when instrument (900) is arranged to allow microscope assembly (910) to capture images of cells or other particles flowing along sampling channel (650), illumination head (912) is positioned directly over cartridge (200) and in close proximity to cartridge (200). This may provide a reduced length of the optical path between illumination head (912) and imaging region (652), which may in turn provide optical efficiency in the illumination of imaging region (652). However, this position and proximity of illumination head (912) in relation to cartridge (200) may, in some examples, warrant movement of cartridge (200) away from illumination head (912) along the x-y plane to facilitate removal of cartridge (200) from instrument (900). In some examples where cartridge (200) is movable relative to illumination head (912) along the x-y plane, and where other components (e.g., fluid conduits (802) and/or pneumatic conduits (804) as described above in the context of FIG. 7) are inserted into cartridge (200), it may be desirable in some examples to avoid having any features of instrument (900) interfering with such components inserted into cartridge (200) as cartridge
(200) moves along the x-y plane. For instance, in some examples some interfering components of instrument (900) may tend to create tension in conduits (802, 804), which may create a risk of conduits (802, 804) being pulled out of ports (310, 320) of cartridge (200), of conduits (802, 804) kinking or rupturing, of conduits (802, 804) snagging, or other results that might not be desirable in some examples.
[0092] The following description provides examples of features of instrument (900) that may allow cartridge (200) to move along the x-y plane relative to illumination head (912), thereby facilitating replacement of cartridge (200) in cartridge support assembly (1100) while still providing a reduced distance between illumination head (912) and imaging region (652) while fluid containing cells or other particles flows along sampling channel (650). The following description also provides examples of features of instrument (900) that may reduce, and in some cases may prevent, a risk of interference between components of instrument (900) and conduits that are inserted into cartridge (200) as cartridge (200) moves along the x-y plane.
[0693] A. Example of Cartridge Stage Assembly
[6994] As shown in FIG. 8, stage assembly (1000) is secured to frame assembly (902), which is secured to base {904). Frame assembly (902) and base (904) thus support stage assembly (1000) in this example. FIGS. 13-17C show examples of features and operability of stage assembly (1000) in further detail. As shown in FIG. 13, stage assembly (1000) includes an upper member (1010), and a lower member (1020), with a plurality of struts (1030) extending between members (1010, 1020) to thereby support upper member (1010) above lower member (1020) along the z-dimension. Upper member (1010) includes a rigid plate in this example, though upper member (1010) may include any other suitable components. Similarly, lower member (1020) includes a rigid plate in this example, though lower member (1020) may include any other suitable components. Cartridge support assembly { 1100) is positioned in the space between members (1010, 1020) along the z-dimension; and is movable within this space along the x-y dimension as will be described in greater detail below.
[0095] As best seen in FIGS. 14-16, stage assembly (1000) further includes a pair of y-drive assemblies (1040). Y-drive assemblies (1040) are positioned at each side of upper member (1010) along the x-dimension. Each y-drive assembly (1040) includes an actuator (1042) and a rail assembly (1044) extending distally from actuator (1042). Each rail assembly (1044) extends along the y-dimension, from one end of upper member (1010) along the y-dimension to the other end of upper member (1010) along the y-dimension.
[0096] As shown in FIGS. 15-16, cartridge support assembly (1100) is coupled with each rail assembly (1044) via a respective bracket (1046). In some examples, one or more other components (e.g., one or more components of x-drive assembly (1050), as described below) is/are interposed between cartridge support assembly (1100) and brackets (1046). It should be understood that a strut (1030) is omitted in FIG. 15 and in FIG. 16 to provide an unobstructed view of each bracket (1046). In some examples, each actuator (1042) includes a motor, each rail assembly (1044) includes a screw gear, and an upper portion of each bracket (1046) includes a nut or is secured to a nut. In some such examples, the motor of actuator (1042) drives rotation of the screw gear of rail assembly (1044), and the rotation of the screw gear of rail assembly (1044) drives translation of the nut of bracket (1046) along the y-dimension. Actuators (1042) may be operated simultaneously to drive simultaneous movement of brackets (1046) along the y- dimension, thereby driving cartridge support assembly (1100) along the y-dimension. An example of such movement is shown in FIGS. 17A-17B, in which y-drive assemblies (1040) cooperate to drive cartridge support assembly (1100) from a first position along the y- dimension (FIG. 17A) to a second position along the y-dimension (FIG. 17B). While the example described above includes motors, screw gears, and nuts being included in y-drive assemblies (1040), other examples of y-drive assemblies (1040) may have any other suitable components and arrangements to drive movement of cartridge support assembly (1100) along the y-dimension.
[0097] Stage assembly (1000) of this example further includes an x-drive assembly (1050), portions of which are shown in FIG, 17C. X-drive assembly (1050) of this example includes a platform (1052) and a rail (1054). In some examples, cartridge support assembly (1100) is secured to brackets (1046) via rail (1054) and/or via other components of x-drive assembly (1050).
Platform (1052) is fixedly secured to cartridge support assembly { 1100); and slidably supported on rail (1054). X-drive assembly (1050) may further include an actuator (not shown), which may be structurally configured and operable similar to actuator (1042) described above. In other examples, the actuator of x-drive assembly (1050) may have any other suitable structural configuration or operability. In the present example, x-drive assembly (1050) is operable to drive movement of cartridge support assembly (1100) along the x-dimension. An example of such movement is shown in FIGS. 17B-17A, in which -drive assembly (1050) drives cartridge support assembly (1100) from a first position along the x-dimension (FIG. 17B) to a second position along the x-dimension (FIG. 17C).
[6098] As described above, stage assembly (1000) is operable to provide structural support to cartridge support assembly (1100), drive movement of cartridge support assembly (1100) along the y- dimension, and drive movement of cartridge support assembly (1100) along the x-dimension.
As also described above, FIGS. 17A-17C show cartridge support assembly (1100) at three different positions along the x-y plane, as driven by stage assembly (1000). However, it should be understood that the positions along the x-y plane are only depicted in FIGS. 17A-17C for purpose of illustration, to show the operability of stage assembly (1000) to move cartridge support assembly {1100) along the x-y plane. During use of instrument (900), cartridge support assembly (1100) may be positioned at various different positions along the x-y plane, including positions not depicted in FIGS. 17A-17C. Similarly, during some examples of use of instrument (900), cartridge support assembly (1100) might not reach one or more of the positions along the x-y plane depicted in FIGS. 17A-17C. Similarly, cartridge support assembly (1100) may encounter different ranges of movement along the x-dimension and/or along the y-dimension during use of instrument (900), including ranges of movement that are smaller or larger than those depicted in FIGS. 17A-17C.
[0099] In the state shown in FIG. 17A, cartridge support assembly (1100) is positioned in relation to stage assembly (1000) such that a portion of cartridge (200) is underneath a slot (1012) in upper member {1010) along the z-dimension. Slot (1012) extends along the x-dimension and the y- dimension; and is positioned to allow illumination head (912) to illuminate imaging region (652) without being obstructed when cartridge (200) is in the position shown in FIG. 17A. For instance, a portion of illumination head (912) may be fixedly positioned within slot (1012). In some examples, other components that provide illumination via illumination head (912) may be fixedly positioned within slot (1012). ln some examples, other components of instrument (900) may be positioned within slot (1012).
[60100] In some examples, it may be relatively difficult to remove cartridge (200) from cartridge support assembly (1100) when cartridge support assembly (1100) is in the position shown in
FIG. 17A. In some such examples, y-drive assemblies (1040) may be activated to drive cartridge support assembly (1100) to the position shown in FIG. 17B. In some examples, with cartridge support assembly (1100) in the position shown in FIG. 17B, it may be relatively easier for an operator to remove cartridge (200) from cartridge support assembly (1100) than such removal would be when cartridge support assembly (1100) is in the position shown in FIG. 17A.
[00101] In addition to including slot (1012), upper member (1010) also includes slot (1014). Slot (1014) extends along the x-dimension and the y-dimension. In some examples, slot (1014)
further facilitates removal of cartridge (200) from cartridge support assembly (1100) when cartridge support assembly (1100) is in the position shown in FIG, 17B. In some examples, slot (1014) may provide spatial clearance for other components of instrument (900); and/or may serve any other purposes).
[00102] As noted above, FIGS. 17B-17C show movement of cartridge support assembly (1100) along the x-dimension. As also noted above, the movements and positions of cartridge support assembly (1100) along the x-y plane shown in FIGS. 17A-17C are not necessarily the same movements and positions that would be executed during use of instrument (900). In some examples, cartridge support assembly (1100) only moves along the x-dimension when cartridge support assembly (1100) is positioned in the vertical space (i.e., along the z-dimension) between members (1010, 1012). In some examples, such movement of cartridge support assembly (1100) along the x-dimension during a path of movement when cartridge support assembly (1100) moves from the position shown in FIG. 17B to the position shown in FIG. 17A. In some such examples, a combination of movement of cartridge support assembly (1100) along the y-dimension and the along the z-dimension is provided to prevent, minimize, or reduce strain on one or more conduits (802, 804) as will be described in greater detail below,
[00103] B. Example of Cartridge Support Assembly
[00104] FIGS. 18-20B show cartridge support assembly (1100) in greater detail. As shown, cartridge support assembly (1100) of this example includes a base assembly (1110), a frame assembly (1120), a cartridge seat assembly (1140), a first fluid conduit guide assembly (1300), a pneumatic conduit guide assembly (1400), and a second fluid conduit guide assembly (1500).
Base assembly (1110) supports cartridge seat assembly (1140) and couples cartridge support assembly (1100) with stage assembly (1000) via platform (1052). Frame assembly (1120) supports a pneumatic assembly (1130) and other components; and is fixed to base assembly (1110) such that frame assembly (1120) and base assembly (1110) move together unitarily along the x-y plane.
[60105] Pneumatic assembly (1130) includes a plurality of pneumatic ports (1132). Each pneumatic port (1132) is structurally configured to couple with a respective pneumatic conduit, such as pneumatic conduits (804) described above. Each pneumatic port (1132) is further operable to communicate pressurized air (or other gas) lo pneumatic conduits via pneumatic ports (1132).
Pneumatic assembly (1130) may further include various other components, such as a pump, a manifold, a set of valves (e.g., a separate valve for each pneumatic port (1132), etc.). In some examples, pneumatic assembly (1130) may serve as pneumatic pressure source (820) described above with reference to FIG. 7. Pneumatic assembly (1130) may thus drive pneumatic valves in cartridge (200).
[00106] As best seen in FIGS. 19-20B, cartridge seat assembly (1140) includes a recessed platform (1142) on which cartridge (200) may be seated. Platform (1142) may include an optically transmissive material (e.g., glass, etc.), such that microscope assembly (910) may view imaging region (652) through platform (1142), from beneath platform (1142).
[00107] As best seen in FIGS. 20A-20B, cartridge seat assembly (1140) further includes a first lateral guide (1144) and a second lateral guide (1146), which are separated from each other along the x-dimension by a width approximating the width of cartridge (200) along the x-dimension.
Guides (1144, 1146) may provide appropriate positioning of cartridge (200) along the x- dimension when cartridge (200) is seated on platform (1142) with the side edges of cartridge engaging guides (1144, 1146). In some examples, cartridge seat assembly (1140) further includes resilient features that bias guides (1144, 1146) toward each other along the x- dimension; and/or some other kind(s) of feature(s) that allow(s) guides (1144, 1146) to be separated further from each other along the x-dimension during loading of cartridge (200) and then urged toward each other after cartridge (200) has been placed on platform (1142). In some such examples, guides (1144, 1146) may further promote appropriate positioning of cartridge {200) along the x-dimension.
[00108] Cartridge seat assembly (1140) of the present example further includes a first cartridge retainer assembly (1150) and a second cartridge retainer assembly (1160). First cartridge retainer assembly (1150) is positioned at the rear of cartridge seat assembly (1140); and includes a frame (1152) that is fixed to base assembly (1110). A pair of retainers (1156) are secured to frame (1152). In this example, each retainer (1156) includes a beam that is cantilevered over platform (1142). Each retainer (1156) defines a space with platform (1142) along the z- dimension that corresponds to a thickness of layer (500) along the z-dimension. Thus, as shown in FIGS. 20A-20B, a portion near the rear edge of layer (500) may be positioned under retainers (1156); and retainers (1156) may thereby retain the region of cartridge (200) engaged by retainers (1156). In other words, retainers (1156) may restrict movement of the rear portion of cartridge (200) along the z-dimension. Frame (1152) also includes a set of stops (1151) that restrict movement of cartridge along the y-dimension, as stops (1151) are positioned to engage the rear edge of layer (500) while the rear portion of layer (500) is disposed under retainers (1156).
[00109] Second cartridge retainer assembly (1160) is positioned at the front of cartridge seat assembly; and includes a frame (1162) that is secured to fixed to base assembly (1110). A movable retainer assembly (1164) is coupled with frame (1162). Movable retainer assembly (1164) includes a pair of retainers (1164), a handle (1168), and a pair of stops (1169). In this example, each retainer (1164) includes a beam that is cantilevered over platform (1142). Each retainer (1164) defines a space with platform (1142) along the z-dimension that corresponds to a thickness of layer (500) along the z-dimension. One or more resilient members (not shown) may be interposed between movable retainer assembly (1164) and frame (1162) to resiliently urge retainer assembly (1164) along the y-dimension to the position shown in FIG. 20B. Such one or more resilient members may include one or more leaf springs, one or more coil springs, etc.
[00110] With retainer assembly (1164) in the position shown in FIG. 20B, a portion near the front edge of layer (500) may be positioned under retainers (1164); and retainers (1164) may thereby retain the region of cartridge (200) engaged by retainers (1164). In other words, retainers (1164) may restrict movement of the front portion of cartridge (200) along the z-dimension.
Stops (1169) are positioned to restrict movement of cartridge along the y-dimension, as stops (1169) are positioned to engage the front edge of layer (500) while the rear portion of layer (500) is disposed under retainers (1164). An operator may manipulate handle (1168) to move retainer assembly (1164) along the y-dimension from the position shown in FIG. 20B to the position shown in FIG. 20A.
[90111] With retainer assembly (1164) in the position shown in FIG, 20A, retainers (1164) are no longer positioned over layer (500); and stops (1169) no longer engage the front edge of layer (500).
This may facilitate removal of cartridge (200) from cartridge seat assembly (1140). For instance, while retainer assembly (1164) is held in the position shown in FIG. 20A, cartridge (200) may be slid along the y-dimension to move the rear portion of layer (500) from the space under retainers (1156), and then cartridge (200) may be removed from platform (1142) along the z-dimension. To seat another cartridge (200) in cartridge seat assembly (1140), the other cartridge (200) may be placed on platform (1142) while retainer assembly (1164) is held in the position shown in FIG. 20A. Cartridge (200) may then be slid along the y-dimension to move the rear portion of layer (500) into the space under retainers (1156), with the rear edge of layer (500) engaging stops (1151). Handle (1168) may then be released, allowing the resilient member(s) to return retainer assembly (1164) to the position shown in FIG. 20B. At that stage. the front region of layer (500) may again be positioned in the space under retainers (1166); and stops (1167) may engage the front edge of layer (500).
[00112] In some examples, each retainer (1156, 1166) has a resilient bias toward a relaxed position where the gap defined between at least part of each retainer (1156, 1166) and platform (1142) along the z-dimension is smaller than the thickness of layer (500) along the z-dimension. In some such examples, retainers (1156, 1166) deflect upwardly along the z-dimension when layer (500) is positioned between retainers (1156, 1166) and platform (1142), such that retainers (1156, 1166) resiliently bear downwardly on the front and rear regions of layer (500). In some such examples, retainers (1156, 1166) may provide a firm seating of cartridge (200) on platform (1142). Such firm seating of cartridge (200) on platform (1142) may further promote appropriate positioning of cartridge (200) on platform (1142) as cartridge support assembly (1100) is moved along the x-y plane by stage assembly (1000).
[00113] Referring back to FIG. 18, base assembly (1110) of the present example further includes integral jack screws (1112). A jack screws (1112) are positioned at each of three corners of base assembly (1110) to form a core geometry of a kinematic mount. In some examples, jack screws (1122) are also provided at each rear corner of base assembly (1110). Jack screws (1112) may be adjusted to change the height the corresponding corner of base assembly (1110) along the z-dimension. In some examples, such adjustments may be provided to fine tune the orientation of platform (1142), such as to make platform (1142) coplanar with a predefined x- y plane. In some examples, each jack screw (1112) includes a spherical feature that permits base assembly (1110) to move freely within limits without binding, providing the repeatability of a kinematic constraint. Each jack screw (111) may further include a fastener that runs concentrically through the center of jack screw (1112) that allows base assembly (1110) to be locked down after adjustment and preserving the kinematic mounting arrangement. This may in turn provide appropriate orientation of cartridge (200) relative to the predefined x-y plane.
Such orientation of cartridge (200) relative to the predefined x-y plane may facilitate appropriate imaging of imaging region (652) by microscope assembly (912) and/or may provide appropriate performance of other optical components (and/or non-optical components) of instrument (900).
[00114] C. Examples of Conduit Guide Assemblies
[00115] As described above with reference to FIG. 7, in some examples several fluid conduits (802) coupled with cartridge (200) (e.g., via fluid output port (312) and fluid input ports (310)) while also being coupled with components that are external to cartridge (e.g., fluid sources (810, 812,
814) and receptacle (816)). As also described above with reference to FIG. 7, in some examples several pneumatic conduits (804) are coupled with cartridge (200) {e.g., via pneumatic ports (320)) while also being coupled with a component that is external to cartridge (e.g., pneumatic pressure source (820) or pneumatic assembly (1130). As described above with reference to
FIGS. 17A-17C base assembly (1110) (including cartridge (200)) may move along the x-y plane relative to stage assembly (1000) and relative to various other components of instrument (900). In some examples, such movement may tend to create a risk of interference between the various conduits (802, 804) coupled with cartridge (200) and one or more other components of instrument (900). lt may therefore be desirable in some examples to guide conduits (802, 804), provide strain relief to conduits (802, 804), and/or otherwise mitigate any risks of damage or decoupling from cartridge {200) that conduits (802, 804) might otherwise face as base assembly (1110) (including cartridge (200)) moves along the x-y plane relative to stage assembly (1000) and relative to various other components of instrument (900).
[00116] FIGS. 8 and 13-17C show one fluid conduit guide assembly (920) that may provide some degree of guidance and/or protection to one or more fluid conduits (802). In some examples, fluid conduit guide assembly (920) engages a fluid conduit (802) that is coupled with fluid input port (310) of sample fluid receiving region (600) and source (810); and with a fluid conduit (802) that is coupled with fluid input port (310) of flow control fluid receiving region (620) and source (812). Fluid conduit guide assembly (920) of this example includes a bracket (922), a shaft (924), and a head (926). Bracket (922) is secured to bottom member (1020) of stage assembly (1010). Shaft (924) extends upwardly from bracket (922) along the z- dimension. Head (926) is mounted to the top of shaft (924). Head (926) includes a cylindraceous body defining a passageway (928). In some examples, head (926) freely rotates relative to shaft (924) about a z-axis. In some other examples, head (926) and shaft (924) rotate together relative to bracket (922) about a z-axis.
[00117] In some examples, one or more fluid conduits (802) is/are positioned within passageway (928) en route between one or more of sources (810, 812) and cartridge support assembly (1100).
Also in some examples, shaft (924) includes one or more central channels and/or one or more side channels extending along at least part of the length of shaft (924), with such channel(s) also being structurally configured to receive one or more fluid conduits (802). In the present example, fluid conduit guide assembly (920) provides guidance and/or protection to the one or more fluid conduits (802) that is/are engaged with fluid conduit guide assembly (920), including during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane.
[00118] FIG. 34 shows an example of a fluid conduit (802) engaged with fluid conduit guide assembly (920). Fluid conduit (802) of this example is coupled with source (810) of a fluid containing one or more sample cells; and with fluid input port (310) over sample fluid receiving region (600) of cartridge (200). Fluid conduit (802) of this example includes a flexible tube. In the example shown in FIG. 34, fluid conduit (802) extends generally upwardly from source (810) along the z-dimension and is positioned along shaft (924) of fluid conduit guide assembly (920). A set of retainers (925) secure fluid conduit (802) relative to shaft (924). Retainers (925) include hose clamps in this example, though retainers (925) may take any other suitable form. In some other examples, retainers (925) are omitted. While fluid conduit (802) is shown extending alongside an exterior surface of shaft (924) in FIG. 34, in some other examples fluid conduit (802) extends along a hollow interior region of shaft (924). In some other examples, fluid conduit (802) is at least partially seated within a side channel extending along at least part of the length of shaft (924).
[00119] Continuing with the example shown in FIG. 34, fluid conduit (802) continues through passageway (928) of head (926) and descends downwardly along the z-dimension to enter head (1320) of fluid conduit guide assembly (1300) as described in greater detail below. While FIG. 34 shows fluid conduit (802) positioned along a substantially straight path between head (926) and head (1320), in some examples this path may be substantially curved or have some other configuration. After passing through head (1320), fluid conduit (802) terminates in fluid input port (310) over sample fluid receiving region (600) of cartridge (200) as described herein.
[00120] As described above and shown in FIG. 34, fluid conduit (802) traverses a path that extends upwardly along the z-dimension and then downwardly along the z-dimension between source (810) and cartridge (200). In some examples, this path substantially lacks any horizontal regions. In other words, to the extent that any region of the length of fluid conduit (802) traverses a path having a substantially horizontal component (e.g., through head (926)), such a region of the length of fluid conduit (802) may be substantially short. By minimizing the length of fluid conduit (802) that traverses a substantially horizontal path, this arrangement may tend to minimize or otherwise reduce a tendency of cells or other particles in fluid conduit (802) to settle along an inner sidewall of fluid conduit (802). By minimizing or otherwise reducing a tendency of cells or other particles in fluid conduit (802) to settle along an inner sidewall of fluid conduit (802), this arrangement may tend (0 minimize or otherwise reduce an effective loss of cells or other particles in fluid conduit (802) during transit from source (810) to cartridge
[60121] FIGS. 13-16 show another fluid conduit guide assembly (930) that may provide some degree of guidance and/or protection to one or more fluid conduits (802). Fluid conduit guide assembly (930) of this example includes a shaft (932) and a head (934). Shaft (932) is secured to bottom member { 1920) of stage assembly (1010). Shaft (932) extends upwardly from bottom member (1020) along the z-dimension. Head (934) is mounted to the top of shaft (932). In some examples, head (934) includes one or more pivoting links or other pivoting features. Such pivoting features may pivot about a z-axis, an x-axis, a y-axis, and/or any other axis/axes. In some examples, one or more fluid conduits (802) is/are coupled with head (934) en route between source (814) and cartridge support assembly (1100) and/or en route between receptacle (816) and cartridge support assembly (1100). In the present example, fluid conduit guide assembly (930) provides guidance and/or protection to the one or more fluid conduits (802) that is/are engaged with fluid conduit guide assembly (930), including during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane.
[00122] FIGS. 21-23 show fluid conduit guide assembly (1300) in greater detail. Fluid conduit guide assembly (1300) of this example includes a shaft (1310) and a head (1320). The bottom of shaft (1310) is secured to base assembly (1110). Head (1320) is mounted to the top of shaft (1310). In some examples, head (1320) is rotatable relative to shaft (1310) about a z-axis, as shown in FIGS. 33A-33B. In some other examples, head (1320) and shaft (1310) are rotatable together unitarily relative to base assembly (1110) about the z-axis. In examples where head (1320) and/or shaft (1310) is/are rotatable about the z-axis, one or more resilient members {e.g., torsion springs, etc.) may resiliently bias head (1320) and/or shaft (1310) toward a neutral angular position about the z-axis. In other words, the one or more resilient members may allow head (1320) and/or shaft (1310) to be rotated away from the neutral angular position about the z-axis when a force is applied to (1320) and/or shaft (1310) when an external force is applied to head (1320) (e.g., when tension is applied to one or more fluid conduits (802) disposed in head (1320). However, when an externally applied force is removed from head (1320) (e.g., when tension in one or more fluid conduits (802) disposed in head (1320) is relieved), the resilient bias of the one or more resilient members may drive head (1320) and/or shaft (1310) back toward the neutral angular position.
[00123] Head (1320) includes a body (1322) having a first opening (1320) and a second opening (1334).
Second opening (1334) is recessed within body (1322) relative to first opening (1320), with an inner surface (1332) providing a tapered channel from opening (1330) to opening (1334). A recess (1342) is in a curved surface (1340) of body (1322). As best seen in FIG. 23, second opening (1334) is positioned at a top region of recess (1342). Each opening (1330, 1334) has a stadium shape in this example. Openings (1320, 1334) are sized to slidably receive one or more fluid conduits (802). Recess (1342) is also sized to accommodate one or more fluid conduits (802). In some examples, one or more fluid conduits (802) enters head (1320) in a generally vertical orientation {via recess (1342)) and exits head (1320) in a generally horizontal orientation (via openings (1334, 1330). In some other examples, one or more fluid conduits (802) enters head (1320) in a generally horizontal orientation {via openings (1330, 1334)) and exits head (1320) in a generally vertical orientation (via recess (1342)).
[00124] Fluid conduit guide assembly (1300) may provide some degree of guidance and/or protection to one or more fluid conduits (802). In some examples, fluid conduit guide assembly (1300) engages a fluid conduit (802) that is coupled with fluid input port (310) of sample fluid receiving region (600) and source (810); and with a fluid conduit (802) that is coupled with fluid input port (310) of flow control fluid receiving region (620) and source (812). Such fluid conduit(s) (802) may enter head (1320) (e.g., from fluid conduit guide assembly (920)) via recess (1342) pass through second opening (1334) and then through first opening (1330) before connecting with cartridge (200).
[00125] The rotatability of head (1320) about the z-axis, combined with the stadium shapes of openings (1330, 1334) and the tapered channel defined by surface (1332), may provide guidance some degree of guidance and/or protection to the one or more fluid conduits (802) that is/are engaged with fluid conduit guide assembly (1330), including during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane. For instance, in the event that one or more components of instrument {900) engage the one or more fluid conduits (802) passing through head (1320) during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane and create tension in the one or more engaged fluid conduits (802), head (1320) may rotate about the z-axis to at least partially relieve such tension and thereby reduce strain that might otherwise occur in the one or more engaged fluid conduits (802) (and/or at the couplings of the one or more engaged fluid conduits (802)). By way of further example, the guidance and/or protection provided by fluid conduit guide assembly (1300) may tend to reduce a risk of fluid conduits (802) being pulled out of ports (310) of cartridge (200), of fluid conduits (802) kinking or rupturing, of fluid conduits (802) snagging, or other results that might not be desirable in some examples.
[00126] FIGS. 24-27 show pneumatic conduit guide assembly (1400) in greater detail. Pneumatic conduit guide assembly (1400) of this example includes a base (1410), a shaft (1430), a first clamp-on flange (1440), a second clamp-on flange (1460), a head assembly (1470), and pins (1420, 1422, 1450). Base (1410) is secured to base assembly (1110) and includes a pair of circular pin openings (1412, 1414). Pins (1420, 1422) are disposed in pin openings (1412, 1414). The bottom of shaft (1430) is pivotably disposed within base (1410). A pair of torsion springs (1432, 1434) are disposed about shaft (1430). First clamp-on flange (1440) includes a central opening (1442) and an arcuate opening (1444). Shaft (1430) is disposed in central opening (1442); and clamp-on flange (1440) is securely clamped onto shaft (1430). Pin (1450) is disposed in arcuate opening (1444) and is operable to move along the arcuate path defined by arcuate opening (1444). Second clamp-on flange (1460) includes a central opening (1462) and a circular opening (1464). Shaft (1430) is disposed in central opening (1462): and clamp- on flange (1460) is securely clamped onto shaft (1430). Pin (1450) is secured within circular opening (1464).
[00127] Head assembly (1470) is secured to the top of shaft (1430). As best seen in FIGS. 26-27, head assembly (1470) includes a first body (1472) and a second body (1474) secured to first body (1472). An arm (1476) extends from first body (1472) and defines a plurality of openings (1478), with each opening (1478) being surrounded by a corresponding lead-in surface (1477).
Each lead-in surface (1477) tapers downwardly toward the corresponding opening (1478) along the z-dimension. As shown in FIG. 27, bodies (1472, 1474) cooperate to define a gap (1480), with a pair of pins (1490, 1492) spanning across gap (1480). A first space (1482) is defined between pin (1490) and body (1474) along the z-dimension; and a second space (1484) is defined between pin {1492} and pin (1490) along the z-dimension.
[00128] Each opening (1478) is sized to slidably receive a respective pneumatic conduit (804). One or both of spaces (1482, 1484) may also slidably receive one or more pneumatic conduits (804).
For instance, pneumatic conduits (804) may pass through one or both of spaces (1482, 1484) en route from pneumatic ports (1132) toward cartridge (200). In some examples, pneumatic conduits (804) pass through space (1484) en route from pneumatic ports (1132) toward cartridge (200). Pins (1490, 1492) may serve to guide and neatly arrange pneumatic conduits (804) to prevent kinking; while permitting each pneumatic conduit (804) to move and slide to adjust for the movement of head assembly (1470); while also providing for a service loop of each pneumatic conduit (804) that may reduce the risk of pneumatic conduits (804) of being undesirably pull out of from cartridge (200) due to interference with other components of instrument (900) during operation. Pneumatic conduits (804) may continue through respective openings (1478) before being inserted into pneumatic ports (320) of cartridge (200). Further, each opening (1478) may be sized in diameter, and each space (1484) may be sized in width, to control the movement of pneumatic conduits (804) by adding just enough friction to permit the user to move pneumatic conduits (804) in and out of position to reach cartridge (200) and stay in-place when user is finished.
[00129] Head assembly (1470) and shaft (1430) are rotatable about a z-axis relative to base (1410). An example of such rotation is shown in shown in FIGS. 33A-33C. Torsion springs (1432, 1434) are structurally configured to impart a bi-directional angular bias to head assembly (1470) and shaft (1430) about the z-axis. In other words, if head assembly (1470) and shaft (1430) rotate in a first angular direction about the z-axis relative to base (1410), away from a neutral angular position about the z-axis, one torsion spring (1432, 1434) will resiliently urge head assembly (1470) and shaft (1430) in a second angular direction about the z-axis relative to base (1410), toward the neutral angular position about the z-axis. If head assembly (1470) and shaft (1430) rotate in the second angular direction about the z-axis relative to base (1410), away from the neutral angular position about the z-axis, the other torsion spring (1432, 1434) will resiliently urge head assembly (1470) and shaft (1430) in the first angular direction about the z-axis relative to base (1410), toward the neutral angular position about the z-axis. In this example, pins (1420, 1422) provide a grounding structure for torsion springs (1432, 1434) while pin (1450) and a structural feature of clamp-on flange (1440) provide a bearing structure for torsion springs during rotation of head assembly (1470) and shaft (1430) about the z-axis.
[00130] The rotatability of head assembly (1470) about the z-axis, combined with the stadium positioning of pneumatic conduits {804) in openings (1478) and the tapered lead-in surfaces (1477) around openings (1478) may provide guidance some degree of guidance and/or protection to the pneumatic conduits (804) that are engaged with pneumatic conduit guide assembly (1400), including during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane. For instance, in the event that one or more components of instrument (900) engage one or more pneumatic conduits (804) during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane and create tension in the one or more engaged pneumatic conduits (804), head assembly (1470) may rotate about the z-axis to at least partially relieve such tension and thereby reduce strain that might otherwise occur in the one or more engaged pneumatic conduits (804) (and/or at the couplings of the one or more engaged pneumatic conduits (804)). By way of further example, the guidance and/or protection provided by pneumatic conduit guide assembly (1400) may tend to reduce a risk of pneumatic conduits (804) being pulled out of ports (320) of cartridge (200), of pneumatic conduits (804) kinking or rupturing, of pneumatic conduits (804) snagging, or other results that might not be desirable in some examples.
[00131] FIGS. 28-32 show fluid conduit guide assembly (1500) in greater detail. Fluid conduit guide assembly (1500) of this example includes a base (1510), a shaft (1530), a first clamp-on flange (1540), a second clamp-on flange (1560), a head (1570), and pins (1520, 1522, 1550). Base (1510) is secured to base assembly (1110). Pins (1520, 1520) are secured within base (1510).
The bottom of shaft (1530) is pivotably disposed within base (1510). A pair of torsion springs (1532, 1534) are disposed about shaft (1530). First clamp-on flange (1540) includes a central opening (1542) and an arcuate opening (1544). Shaft (1530) is disposed in central opening (1542); and clamp-on flange (1540) is securely clamped onto shaft (1530). Pin (1550) is disposed in arcuate opening (1544) and is operable to move along the arcuate path defined by arcuate opening (1544). Second clamp-on flange (1560) includes a central opening (1562) and a circular opening (1564). Shaft (1530) is disposed in central opening (1562); and clamp-on flange (1560) is securely clamped onto shaft (1530). Pin (1550) is secured within circular opening (1564).
[00132] Head (1570) is secured to the top of shaft (1530). As best seen in FIGS. 30-32, head (1570) includes a body (1572) with a first surface (1574) having a first opening (1580) and a channel (1582) extending into body (1572) from first opening (1580). A second opening (1590) is in a second surface (1576) of body (1572). Channel (1582) passes through body (1572), from first opening (1580) to second opening (1590). As shown in FIG. 31, channel (1582) has a tapered cross-sectional profile along the x-y plane, flaring outwardly toward opening (1580). As shown in FIG. 32, channel (1582) has a curved profile along the x-z plane, providing a bend angle of approximately 90 degrees in view of first surface (1574) being perpendicular to second surface (1576). Openings (1580, 1590) are sized to slidably receive one or more fluid conduits (802).
Channel (1582) is also sized to accommodate one or more fluid conduits (802). In some examples, one or more fluid conduits (802) enters head (1570) in a generally vertical orientation (via opening (1590)) and exits head (1570) in a generally horizontal orientation (via opening (1580). In some other examples, one or more fluid conduits (802) enters head (1570) in a generally horizontal orientation (via opening (1580)) and exits head (1570) in a generally vertical orientation (via opening (1590)).
[00133] Head (1570) and shaft (1530) are rotatable about a z-axis relative to base (1510). An example of such rotation is shown in shown in FIGS. 33A-33B. Torsion springs (1532, 1534) are structurally configured to impart a bi-directional angular bias to head (1570) and shaft (1530) about the z-axis. In other words, if head (1570) and shaft (1530) rotate in a first angular direction about the z-axis relative to base (1510), away from a neutral angular position about the z-axis, one torsion spring (1532, 1534) will resiliently urge head (1570) and shaft (1530) in a second angular direction about the z-axis relative to base (1510), toward the neutral angular position about the z-axis. If head (1570) and shaft (1530) rotate in the second angular direction about the z-axis relative to base (1510), away from the neutral angular position about the z- axis, the other torsion spring (1532, 1534) will resiliently urge head (1570) and shaft (1530) in the first angular direction about the z-axis relative to base (1510), toward the neutral angular position about the z-axis. In this example, pins (1520, 1522) provide a grounding structure for torsion springs (1532, 1534) while pin (1550) and a structural feature of clamp-on flange (1540) provide a bearing structure for torsion springs during rotation of head (1570) and shaft (1530) about the z-axis.
[00134] Fluid conduit guide assembly (1500) may provide some degree of guidance and/or protection to one or more fluid conduits (802). In some examples, fluid conduit guide assembly (1500) engages a fluid conduit (802) that is coupled with fluid input port (310) of flow drive fluid receiving region (670) and source (814); and with a fluid conduit (802) that is coupled with fluid output port (310) of f sample output region (680) and receptacle (816). Such fluid conduit{s) (802) may enter head (1570) (e.g., from fluid conduit guide assembly (930)) via opening (1580) pass through channel (1582) and then through opening (1590) before connecting with cartridge (200).
[00135] The rotatability of head (1570) about the z-axis, combined with the wide shape of opening (1580) and the tapered configuration of channel (1582), may provide guidance some degree of guidance and/or protection to the one or more fluid conduits (802) that is/are engaged with fluid conduit guide assembly (1500), including during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane. For instance, in the event that one or more components of instrument (900) engage the one or more fluid conduits (802) passing through head (1570) during movement of cartridge support assembly (1100) (and cartridge (200)) along the x-y plane and create tension in the one or more engaged fluid conduits (802), head (1570) may rotate about the z-axis to at least partially relieve such tension and thereby reduce strain that might otherwise occur in the one or more engaged fluid conduits (802) (and/or at the couplings of the one or more engaged fluid conduits (802)). By way of further example, the guidance and/or protection provided by fluid conduit guide assembly (1500) may tend to reduce a risk of fluid conduits (802) being pulled out of ports (310, 320) of cartridge (200), of fluid conduits (802) kinking or rupturing, of fluid conduits (802) snagging, or other results that might not be desirable in some examples.
[00136] As noted above, FIGS. 33A-33C show rotation of heads (1320, 1570) and head assembly (1470) about respective z-axes relative to base assembly (1100). However, it should be understood that the angular positions of heads (1320, 1570) and head assembly (1470) about respective z-axes are only depicted in FIGS. 33A-33C for purpose of illustration, to show the operability of conduit guide assemblies (1300, 1400, 1500) to provide rotation about respective z-axes to relieve tension in conduits. During use of instrument (900), heads (1320, 1570) and head assembly (1470) may be positioned at various different angular orientations about their respective z-axes, including angular orientations not depicted in FIGS. 33A-33C. Similarly, during some examples of use of instrument (900), heads (1320, 1570) and/or head assembly (1470) might not reach one or more of the angular orientations about their respective z-axes as depicted in FIGS. 33A-33C. Similarly, heads (1320, 1570) and/or head assembly (1470) may encounter different ranges of angular movement about the respective z-axes during use of instrument (900), including ranges of angular movement that are smaller or larger than those depicted in FIGS. 33A-33C.
[00137] In some examples, heads (1320, 1570) and head assembly (1470) are at the respective angular positions about respective z-axes shown in FIG. 33A when cartridge support assembly (1100) is at the position along the x-y plane shown in FIG. 17B. Also in some examples, heads (1320, 1570) and head assembly (1470) are at the respective angular positions about respective z-axes shown in FIG. 33C when cartridge support assembly (1100) is at the position along the x-y plane shown in FIG. 17A. In some such examples, the presence of illumination head (912) over cartridge (200) in the operational state shown in FIG. 17A causes head assembly (1470) to be in the angular position about its z-axis as shown in FIG. 33C; while the presence of illumination head (912) over cartridge (200) in the operational state shown in FIG. 17A does not cause a change in the respective angular positions of heads (1320, 1570) about their respective z-axes to change relative to those angular positions shown in FIG. 33A. However, in some examples, heads (1320, 1570) may nevertheless rotate through some respective range(s) of angular motion about their respective z-axes during a transition between the operational state shown in FIG. 17B and the operational state shown in FIG. 17A.
[00138] D. Examples of Conduits
[00139] As noted above, a fluid conduit (802) may be inserted directly into a port (310, 312) of cartridge (200) to provide a fluidic coupling between cartridge (200) and a fluid source (810, 812, 814) or a receptacle (816). FIG. 35 shows an example of a fluid conduit (1600) that may be used in such a fashion. Fluid conduit (1600) may thus be used in accordance with the above descriptions of fluid conduits (802). Fluid conduit (1600) of this example includes a flexible tube (1602) with an open free end (1604). A grip (1610) is secured to fluid conduit (1600) in a region proximal to free end (1604). Grip (1610) includes a body (1612) and a hilt (1614).
Hilt (1614) is positioned at a first distance (D1) from free end (1604).
[00140] As shown in FIG. 36, first distance (D1) corresponds with a position of a fluidic channel (650) within cartridge (200). Thus, when fluid conduit (1600) is inserted into fluid input port (310), fluid conduit (1600) may be advanced along the z-dimension until hilt (1614) engages top surface (302) of layer (300). Due to the length of first distance (D1), free end (1604) will be positioned at or in fluidic channel (650) when hilt (1614) is engaged with top surface (302) of layer (300). Hilt (1614) may thus provide a depth stop that positions fluid conduit (1600) deeply enough into cartridge (200) to achieve a suitable fluid seal with layer (300) while also allowing fluid to be communicated from free end (1604) to fluidic channel (650). While fluid conduit (1600) is shown as being inserted in a fluid input port (310) in FIG. 36, fluid conduit (1600) may also be inserted into a fluid output port (312).
[00141] A magnetic coupling member (1616) is provided in body (1612). In some examples, magnetic coupling member (1616) comprises a permanent magnet. In some other examples, magnetic coupling member (1616) comprises a ferrous member (e.g., a piece of steel, etc.). Referring back to FIGS. 18-20B, base assembly (1110) of the present example includes a first sidewall (1170) with a first magnetic coupling member (1172) at a first side of cartridge seat assembly (1140); and a second sidewall (1180) with a second magnetic coupling member (1182) at a second side of cartridge seat assembly (1140). In some examples where coupling member (1616) of fluid conduit (1600) comprises a permanent magnet, each magnetic coupling member (1172, 1182) comprises a ferrous member (e.g., a piece of steel, etc.). In some examples where coupling member (1616) of fluid conduit (1600) comprises a ferrous member {(e.g., a piece of steel, etc.), each magnetic coupling member (1172, 1182) comprises a permanent magnet. In either scenario, grip (1610) may be removably coupled to first magnetic coupling member (1172) via magnetic attraction between magnetic coupling members (1616, 1172); or to second magnetic coupling member (1182) via magnetic coupling between magnetic coupling members (1616, 1182).
[90142] During some examples of use of instrument (900), there may be scenarios where one or more fluid conduits (1600) is/are not coupled with cartridge (200). For instance, such a scenario may occur when a cartridge (200) is being replaced. During such scenarios, the one or more fluid conduits (1600) that is/are not coupled with cartridge (200) may be temporarily coupled with first magnetic coupling member (1172) or second magnetic coupling member (1182), by moving grip (1610) within sufficient proximity to magnetic coupling member (1172, 1182) to allow magnetic coupling members (1616) to magnetically couple with magnetic coupling member (1172, 1182). By having grip (1610) temporarily secured to a magnetic coupling member (1172, 1182) via magnetic coupling member (1616), the associated fluid conduit (1600) may be retained away from the space directly above cartridge seat assembly (1140), providing clearance for removal of a cartridge (200) from cartridge seat assembly (1140) and/or insertion of a cartridge into cartridge seat assembly {1140) without interference from any decoupled fluid conduits (1600). In some examples, fluid conduits (1600) that are routed through head (1300) may be selectively coupled with magnetic coupling member (1182); while fluid conduits (1600) that are routed through head (1500) may be selectively coupled with magnetic coupling member (1172).
[00143] In some other examples of fluid conduit (1600), magnetic coupling member (1616) is omitted.
Similarly, in some other examples of base assembly (1110), magnetic coupling members (1172, 1182) are omitted.
[00144] FIG. 37 shows an example of a pneumatic conduit (1650) that may be used in accordance with the above descriptions of pneumatic conduits (804). Pneumatic conduit (1650) of this example includes a flexible tube (1652) with an open free end (1654). A grip (1660) is secured to fluid conduit (1650) in a region proximal to free end (1654). Grip (1660) includes a body (1662) and a hilt (1664). Hilt (1664) is positioned at a second distance (D2) from free end (1654).
[00145] As shown in FIG. 38, second distance (D2) corresponds with a position of a pneumatic channel (322) within cartridge (200). Thus, when pneumatic conduit (1650) is inserted into pneumatic input port (320), pneumatic conduit (1650) may be advanced along the z-dimension until hilt (1664) engages top surface (302) of layer (300). Due to the length of second distance (D2), free end (1654) will be positioned at or in pneumatic channel (322) when hilt (1664) is engaged with top surface (302) of layer (300). Hilt (1664) may thus provide a depth stop that positions pneumatic conduit (1650) deeply enough into cartridge (200) to achieve a suitable fluid seal with layer (300) while also allowing pneumatic pressure to be communicated from free end (1654) to pneumatic channel (322).
[00146] A magnetic coupling member (1666) is provided in body (1662). In some examples, magnetic coupling member (1666) comprises a permanent magnet. In some other examples, magnetic coupling member (1666) comprises a ferrous member {e.g., a piece of steel, etc.). In either scenario, grip (1660) may be removably coupled to first magnetic coupling member (1172) via magnetic attraction between magnetic coupling members (1666, 1172); or to second magnetic coupling member (1182) via magnetic coupling between magnetic coupling members (1666, 1182).
[00147] During some examples of use of instrument (900), there may be scenarios where one or more pneumatic conduits (1650) is/are not coupled with cartridge (200). For instance, such a scenario may occur when a cartridge (200) is being replaced. During such scenarios, the one or more pneumatic conduits (1650) that is/are not coupled with cartridge (200) may be temporarily coupled with first magnetic coupling member (1172) or second magnetic coupling member (1182), by moving grip (1660) within sufficient proximity to magnetic coupling member (1172, 1182) to allow magnetic coupling members (1666) to magnetically couple with magnetic coupling member (1172, 1182). By having grip (1660) temporarily secured to a magnetic coupling member (1172, 1182) via magnetic coupling member (1666), the associated pneumatic conduit (1650) may be retained away from the space directly above cartridge seat assembly (1140), providing clearance for removal of a cartridge (200) from cartridge seat assembly (1140) and/or insertion of a cartridge into cartridge seat assembly (1140) without interference from any decoupled pneumatic conduits (1650).
[00148] In some other examples of pneumatic conduit (1650), magnetic coupling member (1666) is omitted.
[60149] V. Example of Another Cartridge
[00150] FIG. 39 shows an example of another cartridge (3000) that may be used with system (100) in place of cartridge (200). Except as otherwise noted below, cartridge (3000) of this example may be structurally configured and operable like cartridge (200). Cartridge (3000) of this example includes a sample fluid receiving region (3002) and a flow control fluid receiving region (3004). A flow channel (3006) leads from sample fluid receiving region (3002) to a junction (3006). A pair of flow channels (3008) lead from flow control fluid receiving region (3004) to junction (3006). A sampling channel (3012) extends from junction (3006) to a bend (3014), which leads to a sample output region (3018) via an outlet channel (3016).
[00151] A cell containing fluid may be communicated through sample fluid receiving region (3002),
and a flow control fluid may be communicated through flow control fluid receiving region (3004). These two fluids meet at junction (3010), which may provide a flow focusing feature, with the merged fluids being conveyed along sampling channel (3012). Light source (130) and optical assembly (132) illuminate imaging region (3020); while objective lens assembly (140) and camera (142) capture images of cells within imaging region (3020). The fluid continues around bend (3014), through outlet channel (3016), and exits cartridge (3000) at sample output region (3018). The fluid that exits cartridge (3000) at sample output region (3018) may be further conveyed to a reservoir that is either integrated into the instrument of system (100) or is external to the instrument.
[00152] Cartridge (3000) is thus similar to cartridge (200) except that cartridge (3000) lacks the sorting capabilities of cartridge (200). Nevertheless, the other teachings provided above in the context of cartridge (200) may be readily applied to cartridge (3000).
[00153] VI. Examples of Combinations
[00154] The following examples relate to various non-exhaustive ways in which the teachings herein may be combined or applied. The following examples are not intended to restrict the coverage of any claims that may be presented at any time in this application or in subsequent filings of this application. No disclaimer is intended. The following examples are being provided for nothing more than merely illustrative purposes. It is contemplated that the various teachings herein may be arranged and applied in numerous other ways. It is also contemplated that some variations may omit certain features referred to in the below examples. Therefore, none of the aspects or features referred to below should be deemed critical unless otherwise explicitly indicated as such at a later date by the inventors or by a successor in interest to the inventors.
If any claims are presented in this application or in subsequent filings related to this application that include additional features beyond those referred to below, those additional features shall not be presumed to have been added for any reason relating to patentability.
[00155] Example 1
[00156] An apparatus comprising: a cartridge including: a first layer, a first fluid input port to receive fluid to flow through the cartridge, the first fluid input port including a first opening in the first layer, a first fluid output port to convey fluid from the cartridge, the first fluid output port including a second opening in the first layer, and a first pneumatic port to convey pneumatic pressure to the cartridge, the first pneumatic port including a third opening in the first layer; a first fluid conduit to removably insert into the first fluid input port via the first opening, the first fluid conduit including a first flexible tube: a second fluid conduit to removably insert into the first fluid output port via the second opening, the second fluid conduit including a second flexible tube; and a first pneumatic conduit to removably insert into the first pneumatic port via the third opening, the first pneumatic conduit including a third flexile tube.
[00157] Example 2
[60158] The apparatus of Example 1, the first fluid input port to provide a friction fit with the first fluid conduit; the first fluid output port to provide a friction fit with the second fluid conduit; and the first pneumatic port to provide a friction fit with the first pneumatic conduit.
[00159] Example 3
[00160] The apparatus of any of Examples 1 through 2, further comprising a cartridge support assembly to removably receive the cartridge.
[00161] Example 4
[00162] The apparatus of Example 3, further comprising a stage assembly supporting the cartridge support assembly, and the stage assembly to move the cartridge support assembly along one or more dimensions and thereby move the cartridge along the one or more dimensions.
[00163] Example 5
[00164] The apparatus of Example 4, the cartridge support assembly including a fluid conduit guide to receive and guide one or both of the first fluid conduit or the second fluid conduit.
[00165] Example 6
[00166] The apparatus of Example 5, the fluid conduit guide including a head, and the one or both of the first fluid conduit or the second fluid conduit passing through the head.
[00167] Example 7
[00168] The apparatus of Example 6, the head including a channel having a tapered passageway, and the one or both of the first fluid conduit or the second fluid conduit passing through the tapered passageway.
[00169] Example 8
[00170] The apparatus of any of Examples 6 through 7, the fluid conduit to allow the one or both of the first fluid conduit or the second fluid conduit to enter the head along one dimension and exit the head along another dimension.
[00171] Example 9
[00172] The apparatus of any of Examples 6 through 8, the head to rotate about an axis with the one or both of the first fluid conduit or the second fluid conduit disposed in the head.
[00173] Example 10
[00174] The apparatus of Example 9, further comprising a first resilient member to resiliently bias the head toward a neutral angular position.
[00175] Example 11
[00176] The apparatus of Example 10, the first resilient member including a torsion spring.
[00177] Example 12
[00178] The apparatus of any of Examples 10 through 11, the first resilient member to resiliently bias the head in a first angular direction toward the neutral angular position, and the apparatus further comprising a second resilient member to resiliently bias the head in a second angular direction toward the neutral angular position.
[00179] Example 13
[00180] The apparatus of any of Examples 4 through 12, the cartridge support assembly including a pneumatic conduit guide to receive and guide the first pneumatic conduit.
[00181] Example 14
[00182] The apparatus of Example 13, the pneumatic conduit guide including a head, and the first pneumatic conduit passing through the head.
[00183] Example 15
[00184] The apparatus of Example 14, the head to rotate about an axis with the first pneumatic conduit disposed in the head.
[00185] Example 16
[00186] The apparatus of Example 15, further comprising a first resilient member to resiliently bias the head toward a neutral angular position.
[00187] Example 17
[00188] The apparatus of Example 16, the first resilient member including a torsion spring.
[00189] Example 18
[00190] The apparatus of any of Examples 16 through 17, the first resilient member to resiliently bias the head in a first angular direction toward the neutral angular position, and the apparatus further comprising a second resilient member to resiliently bias the head in a second angular direction toward the neutral angular position.
[00191] Example 19
[00192] The apparatus of any of Examples 3 through 18, the cartridge support assembly including: a platform, the cartridge to fit on the platform, and a plurality of retainers, the plurality of retainers to retain the cartridge on the platform.
[00193] Example 20
[00194] The apparatus of Example 19, the platform including an optically transmissive material to allow a camera to image a region of the cartridge through the platform.
[00195] Example 22
[00196] The apparatus of any of Examples 19 through 20, at least one retainer of the plurality of retainers being movable relative to the platform to selectively engage the cartridge.
[00197] Example 23
[00198] The apparatus of Example 22, the cartridge support assembly further including a resilient member to resiliently urge the at least one retainer of the plurality of retainers into engagement with the cartridge.
[00199] Example 24
[00200] The apparatus of any of Examples 1 through 23, the first fluid conduit having an open free end and a grip spaced away from the open free end, the open free end to fit in the first fluid input port.
[00201] Example 25
[00202] The apparatus of Example 24, the grip to restrict a dept of insertion of the first fluid conduit into the first fluid input port.
[00203] Example 26
[00204] The apparatus of any of Examples 24 through 25, the grip including a magnetic coupling element to magnetically couple with a complementary magnetic coupling element.
[00205] Example 27
[00206] The apparatus of Example 26, further comprising a cartridge support assembly to removably receive the cartridge, and the cartridge support assembly including the complementary magnetic coupling element.
[00207] Example 28
[00208] The apparatus of any of Examples 1 through 27, the cartridge further including a fluidic channel defining at least part of a fluid path between the first fluid input port and the first fluid output port.
[00209] Example 29
[00210] The apparatus of Example 28, the fluidic channel to receive a fluid containing particles, the apparatus further including a camera to capture one or more images of one or more of the particles in the fluid as the fluid flows through the fluidic channel.
[00211] Example 30
[00212] The apparatus of any of Examples 28 through 29, the cartridge further including a second layer having a recess defining the fluidic channel.
[00213] Example 31
[00214] An apparatus including: a cartridge having a plurality of fluidic ports; a plurality of flexible conduits coupled with the plurality of fluidic ports; a stage assembly to move the cartridge along a plane defined by a first axis and a second axis; and at least one flexible conduit guide having a head, at least one flexible conduit of the plurality of flexible conduits passing through the head, the head to rotate about a third axis while the stage assembly moves the cartridge along the plane.
[00215] Example 32
[00216] An apparatus including: a cartridge having a plurality of fluidic ports; a plurality of flexible conduits to couple with the plurality of fluidic ports, each flexible conduit including a magnetic coupling element; and a cartridge support assembly to removably receive the cartridge, the cartridge support assembly including one or more magnetic coupling elements, the magnetic coupling elements of the plurality of flexile conduits to magnetically couple with the one or more magnetic coupling elements of the cartridge support assembly.
[90217] Example 33
[60218] The apparatus of Example 32, the magnetic coupling elements of a first flexible conduit of the plurality of flexile conduits to magnetically couple with the one or more magnetic coupling elements of the cartridge support assembly when the first flexible conduit is decoupled from the cartridge.
[00219] Example 34
[00220] The apparatus of any of Examples 32 through 33, each flexible conduit including a depth stop feature to restrict a depth of insertion of the flexible conduit into the cartridge.
[00221] Example 35
[00222] A method comprising: moving a cartridge along a plane defined by a first axis and a second axis, the cartridge including a first fluidic conduit extending from the cartridge while the cartridge moves along the plane, the first fluidic conduit passing through a head of a fluidic conduit guide, the head rotating about a third axis while the cartridge moves along the plane and while the first fluidic conduit is disposed in the head.
[00223] Example 36
[00224] The method of Example 36, the cartridge further including a second fluidic conduit extending from the cartridge while the cartridge moves along the plane, the second fluidic conduit passing through the head of a fluidic conduit guide, and the head rotating about the third axis while the cartridge moves along the plane and while the second fluidic conduit is disposed in the head.
[00225] Example 37
[00226] The method of any of Examples 35 through 36, moving the cartridge along the plane including moving the cartridge from a first position to a second position, the cartridge being located under an illumination head in the second position.
[00227] Example 38
[60228] The method of Example 37, the cartridge being positioned for removal from a cartridge support assembly in the first position.
[00229] Example 39
[00239] The method of any of Examples 37 through 38, further comprising capturing an image of a cell in fluid in the cartridge while the cartridge is in the second position.
[00231] Example 40
[60232] The method of any of Examples 35 through 39, the fluidic conduit engaging another component of an instrument, thereby inducing tension in the fluidic conduit, as the cartridge moves along the plane, the induced tension in the fluidic conduit causing the head to rotate about the third axis.
[00233] VIL Miscellaneous
[00234] While the examples provided above include cells or beads as particles, the teachings herein may be readily applied to other contexts where other kinds of particles are used in addition to or in leu of cells or beads.
[00235] The foregoing description is provided to enable a person skilled in the art to practice the various configurations described herein. While the subject technology has been particularly described with reference to the various figures and configurations, it should be understood that these are for illustration purposes only and should not be taken as limiting the scope of the subject technology. The subject matter described herein is not limited in its application to the details of construction and the arrangement of components set forth in the description herein or illustrated in the drawings hereof. The subject matter described herein is capable of other implementations and of being practiced or of being carried out in various ways.
[00236] It is to be understood that the above description is intended to be illustrative, and not restrictive.
For example, the above-described examples {and/or aspects thereof) may be used in combination with each other. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the presently described subject matter without departing from its scope. While the dimensions, types of materials and coatings described herein are intended to define the parameters of the disclosed subject matter, they are by no means limiting and instead illustrations. Many further examples will be apparent to those of skill in the art upon reviewing the above description. The scope of the disclosed subject matter should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. Further, the limitations of the following claims are not written in means—plus-function format and are not intended to be interpreted based on 35 U.S.C. §112(f), unless and until such claim limitations expressly use the phrase “means for” followed by a statement of function void of further structure.
[00237] The following claims recite aspects of certain examples of the disclosed subject matter and are considered to be part of the above disclosure. These aspects may be combined with one another.
The disclosure further comprises the following clauses, which correspond to the appended
Dutch-language claims:
CLAUSES
1. An apparatus comprising: a cartridge including: a first layer, a first fluid input port to receive fluid to flow through the cartridge, the first fluid input port including a first opening in the first layer, a first fluid output port to convey fluid from the cartridge, the first fluid output port including a second opening in the first layer, and a first pneumatic port to convey pneumatic pressure to the cartridge, the first pneumatic port including a third opening in the first layer: a first fluid conduit to removably insert into the first fluid input port via the first opening, the first fluid conduit including a first flexible tube; a second fluid conduit to removably insert into the first fluid output port via the second opening, the second fluid conduit including a second flexible tube; and a first pneumatic conduit to removably insert into the first pneumatic port via the third opening, the first pneumatic conduit including a third flexile tube. 2. The apparatus of clause 1, the first fluid input port to provide a friction fit with the first fluid conduit; the first fluid output port to provide a friction fit with the second fluid conduit; and the first pneumatic port to provide a friction fit with the first pneumatic conduit.
3. The apparatus of any of clauses 1 through 2, further comprising a cartridge support assembly to removably receive the cartridge.
4. The apparatus of clause 3, further comprising a stage assembly supporting the cartridge support assembly, and the stage assembly to move the cartridge support assembly along one or more dimensions and thereby move the cartridge along the one or more dimensions.
5. The apparatus of clause 4, the cartridge support assembly including a fluid conduit guide to receive and guide one or both of the first fluid conduit or the second fluid conduit.
6. The apparatus of clause 5, the fluid conduit guide including a head, and the one or both of the first fluid conduit or the second fluid conduit passing through the head.
7. The apparatus of clause 6, the head including a channel having a tapered passageway, and the one or both of the first fluid conduit or the second fluid conduit passing through the tapered passageway.
8. The apparatus of any of clauses 6 through 7, the fluid conduit to allow the one or both of the first fluid conduit or the second fluid conduit to enter the head along one dimension and exit the head along another dimension.
9, The apparatus of any of clauses 6 through 8, the head to rotate about an axis with the one or both of the first fluid conduit or the second fluid conduit disposed in the head.
10. The apparatus of clause 9, further comprising a first resilient member to resiliently bias the head toward a neutral angular position.
il.
The apparatus of clause 10, the first resilient member including a torsion spring.
12. The apparatus of any of clauses 10 through 11, the first resilient member to resiliently bias the head in a first angular direction toward the neutral angular position, and the apparatus further comprising a second resilient member to resiliently bias the head in a second angular direction toward the neutral angular position.
13. The apparatus of any of clauses 4 through 12, the cartridge support assembly including a pneumatic conduit guide to receive and guide the first pneumatic conduit. 14. The apparatus of clause 13, the pneumatic conduit guide including a head, and the first pneumatic conduit passing through the head. 15. The apparatus of clause 14, the head to rotate about an axis with the first pneumatic conduit disposed in the head.
16. The apparatus of clause 15, further comprising a first resilient member to resiliently bias the head toward a neutral angular position. 17. The apparatus of clause 16, the first resilient member including a torsion spring.
18. The apparatus of any of clauses 16 through 17, the first resilient member to resiliently bias the head in a first angular direction toward the neutral angular position, and the apparatus further comprising a second resilient member to resiliently bias the head in a second angular direction toward the neutral angular position.
19. The apparatus of any of clauses 3 through 18, the cartridge support assembly including: a platform, the cartridge to fit on the platform, and a plurality of retainers, the plurality of retainers to retain the cartridge on the platform.
20. The apparatus of clause 19, the platform including an optically transmissive material to allow a camera to image a region of the cartridge through the platform. 22. The apparatus of any of clauses 19 through 20, at least one retainer of the plurality of retainers being movable relative to the platform to selectively engage the cartridge. 23. The apparatus of clause 22, the cartridge support assembly further including a resilient member to resiliently urge the at least one retainer of the plurality of retainers into engagement with the cartridge.
24. The apparatus of any of clauses 1 through 23, the first fluid conduit having an open free end and a grip spaced away from the open free end, the open free end to fit in the first fluid input port. 25. The apparatus of clause 24, the grip to restrict a dept of insertion of the first fluid conduit into the first fluid input port. 26. The apparatus of any of clauses 24 through 25, the grip including a magnetic coupling element to magnetically couple with a complementary magnetic coupling element.
27. The apparatus of clause 26, further comprising a cartridge support assembly to removably receive the cartridge, and the cartridge support assembly including the complementary magnetic coupling element.
28. The apparatus of any of clauses | through 27, the cartridge further including a fluidic channel defining at least part of a fluid path between the first fluid input port and the first fluid output port.
29. The apparatus of clause 28, the fluidic channel to receive a fluid containing particles, the apparatus further including a camera to capture one or more images of one or more of the particles in the fluid as the fluid flows through the fluidic channel.
30. The apparatus of any of clauses 28 through 29, the cartridge further including a second layer having a recess defining the fluidic channel.
31. An apparatus including: a cartridge having a plurality of fluidic ports; a plurality of flexible conduits coupled with the plurality of fluidic ports; a stage assembly to move the cartridge along a plane defined by a first axis and a second axis; and at least one flexible conduit guide having a head, at least one flexible conduit of the plurality of flexible conduits passing through the head, the head to rotate about a third axis while the stage assembly moves the cartridge along the plane.
32. An apparatus including: a cartridge having a plurality of fluidic ports: a plurality of flexible conduits to couple with the plurality of fluidic ports, each flexible conduit including a magnetic coupling element; and a cartridge support assembly to removably receive the cartridge, the cartridge support assembly including one or more magnetic coupling elements, the magnetic coupling elements of the plurality of flexile conduits to magnetically couple with the one or more magnetic coupling elements of the cartridge support assembly. 33. The apparatus of clause 32, the magnetic coupling elements of a first flexible conduit of the plurality of flexile conduits to magnetically couple with the one or more magnetic coupling elements of the cartridge support assembly when the first flexible conduit is decoupled from the cartridge. 34. The apparatus of any of clauses 32 through 33, each flexible conduit including a depth stop feature to restrict a depth of insertion of the flexible conduit into the cartridge. 35. A method comprising: moving a cartridge along a plane defined by a first axis and a second axis, the cartridge including a first fluidic conduit extending from the cartridge while the cartridge moves along the plane, the first fluidic conduit passing through a head of a fluidic conduit guide, the head rotating about a third axis while the cartridge moves along the plane and while the first fluidic conduit is disposed in the head. 36. The method of clause 36, the cartridge further including a second fluidic conduit extending from the cartridge while the cartridge moves along the plane, the second fluidic conduit passing through the head of a fluidic conduit guide, and the head rotating about the third axis while the cartridge moves along the plane and while the second fluidic conduit is disposed in the head. 37. The method of any of clauses 35 through 36, moving the cartridge along the plane including moving the cartridge from a first position to a second position, the cartridge being located under an illumination head in the second position, 38. The method of clause 37, the cartridge being positioned for removal from a cartridge support assembly in the first position.
39. The method of any of clauses 37 through 38, further comprising capturing an image of a cell in fluid in the cartridge while the cartridge is in the second position. 40. The method of any of clauses 35 through 39, the fluidic conduit engaging another component of an instrument, thereby inducing tension in the fluidic conduit, as the cartridge moves along the plane, the induced tension in the fluidic conduit causing the head to rotate about the third axis.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2024/047699 WO2025064820A1 (en) | 2023-09-21 | 2024-09-20 | Methods and systems for cell analysis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202363539614P | 2023-09-21 | 2023-09-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL2036036B1 true NL2036036B1 (en) | 2025-03-26 |
Family
ID=95211548
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL2036036A NL2036036B1 (en) | 2023-09-21 | 2023-10-13 | Cartridge interface features |
Country Status (1)
| Country | Link |
|---|---|
| NL (1) | NL2036036B1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090075390A1 (en) * | 2007-09-19 | 2009-03-19 | Claros Diagnostics, Inc. | Liquid containment for integrated assays |
| US20140170645A1 (en) * | 2009-06-05 | 2014-06-19 | Integenx Inc. | Universal sample preparation system and use in an integrated analysis system |
| US20220065890A1 (en) * | 2019-05-31 | 2022-03-03 | Life Technologies Corporation | Device, System and Method for Fluid Delivery for Sequencing |
| WO2022112450A1 (en) * | 2020-11-25 | 2022-06-02 | Oxford NanoImaging Limited | Reagent cartridge and measurement devices incorporating such cartridges |
-
2023
- 2023-10-13 NL NL2036036A patent/NL2036036B1/en active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090075390A1 (en) * | 2007-09-19 | 2009-03-19 | Claros Diagnostics, Inc. | Liquid containment for integrated assays |
| US20140170645A1 (en) * | 2009-06-05 | 2014-06-19 | Integenx Inc. | Universal sample preparation system and use in an integrated analysis system |
| US20220065890A1 (en) * | 2019-05-31 | 2022-03-03 | Life Technologies Corporation | Device, System and Method for Fluid Delivery for Sequencing |
| WO2022112450A1 (en) * | 2020-11-25 | 2022-06-02 | Oxford NanoImaging Limited | Reagent cartridge and measurement devices incorporating such cartridges |
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