WO2025207813A1 - Biofluid collection metering and related kits and methods - Google Patents

Abstract

Inserts for a specimen collection tube and kits for collecting and metering biofluids are described. In an example, the insert comprises a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and a plurality of legs extending outwardly from a side of the fluidic channel separator. In an example, the kit comprises a specimen collection tube and an insert sized and shaped to fit in the sample collection tube, such as to meter a biofluid provided to the specimen collection tube. In an example, the insert comprises a flange extending from a disc of the fluidic channel separator.

Description

BIOFLUID COLLECTION METERING AND RELATED KITS AND METHODS

CROSS-REFERENCE(S) TO RELATED APPLICATION S)

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63/571,012, filed March 28, 2024, the contents of which are incorporated by reference herein in their entirety.

BACKGROUND

[0002] Gene expression analyses using RNA are established methods of monitoring health and disease over time, allowing for immunological studies of diseases including Covid- 19 and cancers. Blood is commonly used for such studies, because it circulates through the entire body and contains immune cells including lymphocytes that are part of the lymphatic system. However, blood collection has also historically presented challenges for participation in transcriptomics studies because venous blood draws have to be performed by a trained phlebotomist in a clinic, leading to barriers caused by scheduling, aversion to needles, or proximity to a clinic. Shifting sample collection from a clinic to a participant’s home therefore addresses previous barriers to participation in transcriptomics studies.

[0003] Dried blood spots (DBS) are a previously existing method of remote blood sample collection for biomolecule analysis, but rapid degradation of RNA after collection can prevent accurate gene expression profiling.

SUMMARY

[0004] To address these and related challenges, the present disclosure, in various aspects, provides inserts for a specimen collection tube and kits for collecting and metering biofluids.

[0005] In certain embodiments, the present disclosure describes an insert for a specimen collection container, such as any standard specimen collection vessel. In certain embodiments, the standard specimen collection vessel is a standard specimen collection tube, a specimen collection tub, or a specimen collection cup. In certain embodiments, the standard specimen collection tube is a BD microtainer® tube for collecting blood stabilized with, for example, RNAlater®, which divides the tube into two compartments separated by a fluidic cone channel separator. In an embodiment, the fluidic channel separator is held in place in the biofluid collection tube with attached legs. In an embodiment, a length of the legs determines, at least in part, the ratio of volume available in each section (such as on opposing sides of the fluidic channel separator). In an embodiment, the legs are configured to control the volumes of respective biofluids and reagent solutions, which often have a specific optimal ratio.

[0006] In an embodiment, and without being bound by theory, the fluidic channel separator prevents or limits liquid from moving between a first compartment and a second compartment due to hydrostatic forces and due to the shape of the cone channel. In an embodiment, and without being bound by theory, the fluidic channel separator prevents or limits movement of a liquid, such as a biofluid or reagent, from moving between a first compartment to a second compartment due to capillary forces. When a biofluid (e.g. blood, urine, saliva) is collected it is stopped on the top of the aperture due to capillary pinning and hydrostatic forces, as well. In this regard, a total volume of biofluid collected is metered. In an embodiment, while the biofluid is stopped during collection, the fluidic channel allows for transfer and mixing of the two compartments after collection upon shaking or other agitation of the sample collection tube containing the insert, thus allowing for simple, user-initiated stabilization of the biofluid of interest.

[0007] Accordingly, in an aspect, the present disclosure provides an insert for a specimen collection tube. In an embodiment, the insert comprises a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and a plurality of legs extending outwardly from a side of the fluidic channel separator.

[0008] In an embodiment, the aperture defines a shape selected from a conical shape, a cylindrical shape, a pyramidal shape; a pyramidal frustum; and a conical frustum.

[0009] In an embodiment, the fluidic channel separator comprises a disc defining the aperture.

[0010] In an embodiment, the side of the fluidic channel separator is a first side, and wherein the insert further comprises a flange extending from the disc from a second side opposite to the first side.

[0011] In an embodiment, a diameter of legs of the plurality defines a draft of at least about 1 degree narrowing in a direction away from the fluidic channel separator. [0012] In an embodiment, the insert comprises a material selected from the group consisting of a polycarbonate, a polystyrene, a polypropylene, or any combination thereof. In an embodiment, the insert comprises a polypropylene.

[0013] In an embodiment, wherein the insert comprises a material that is at least partially hydrophilic. In an embodiment, the insert comprises a material that is at least partially hydrophobic.

[0014] In another aspect, the present disclosure provides a kit for collecting and metering biofluids. In an embodiment, the kit comprises a specimen collection tube; and an insert sized and shaped to fit within an interior portion of the specimen collection tube. In an embodiment, the insert comprises a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and a plurality of legs extending outwardly from a side of the fluidic channel separator.

[0015] In an embodiment, the fluidic channel separator comprises a disc defining the aperture.

[0016] In an embodiment, an outer circumference of the disc is shaped and sized to contact the interior portion of the sample collection tube when the insert is disposed in the sample collection tube.

[0017] In an embodiment, the side of the fluidic channel separator is a first side, and wherein the insert further comprises a flange extending from the fluidic channel separator on a second side opposite to the first side.

[0018] In an embodiment, the insert is configured to form a seal with an interior wall of the sample collection tube when the insert is disposed in the specimen collection tube.

[0019] In an embodiment, the kit defines a first compartment extending in a first direction from the disc and a second compartment extending in a second direction from the disc when the insert is disposed in the sample collection tube.

[0020] In an embodiment, a length of legs of the plurality of legs defines, at least in part, a ratio of volumes of the first compartment and the second compartment.

[0021] In an embodiment, the kit further comprises a reagent disposed in the second compartment. In an embodiment, the reagent comprises an RNA stabilization reagent. [0022] In an embodiment, the aperture is sized and shaped to allow a Pasteur pipette to pass through the aperture to the second compartment.

[0023] In an embodiment, when the insert is disposed in the specimen collection tube, the aperture is further configured to allow mixing of liquids in the first compartment and the second compartment upon agitation of the sample collection tube.

[0024] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.

DESCRIPTION OF THE DRAWINGS

[0025] Non-limiting and non-exhaustive embodiments of the claimed subject matter are described with reference to the following figures, wherein like reference numerals refer to like parts throughout the various views unless otherwise specified. Not all instances of an element are necessarily labeled so as not to clutter the drawings where appropriate. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles being described. To easily identify the discussion of any particular element or act, the most significant digit or digits in a reference number refer to the figure number in which that element is first introduced.

[0026] FIGURE 1 A is a perspective view of an insert according to embodiments of the present disclosure.

[0027] FIGURE IB is another perspective view of the insert of FIGURE 1 A, according to embodiments of the present disclosure.

[0028] FIGURE 1C is side view of the insert of FIGURE 1A, according to embodiments of the present disclosure.

[0029] FIGURE ID is cross sectional side view of the insert of FIGURE 1 A, according to embodiments of the present disclosure.

[0030] FIGURE IE is a top-down plan view of the insert of FIGURE 1A, according to embodiments of the present disclosure.

[0031] FIGURE IF is a bottom-up plan view of the insert of FIGURE 1A, according to embodiments of the present disclosure.

[0032] FIGURE 2A is a perspective view of an insert according to embodiments of the present disclosure. [0033] FIGURE 2B is another perspective view of the insert of FIGURE 2A, according to embodiments of the present disclosure.

[0034] FIGURE 2C is side view of the insert of FIGURE 2A, according to embodiments of the present disclosure.

[0035] FIGURE 2D is a cross-sectional view of the insert of FIGURE 2A, according to embodiments of the present disclosure.

[0036] FIGURE 2E is a top-down plan view of the insert of FIGURE 2A, according to embodiments of the present disclosure.

[0037] FIGURE 2F is a bottom-up plan view of the insert of FIGURE 2A, according to embodiments of the present disclosure.

[0038] FIGURE 3 is a side view of a kit according to an embodiment of the present disclosure.

[0039] FIGURE 4A schematically illustrates a method of using a kit according to an embodiment of the present disclosure.

[0040] FIGURE 4B is an image of a kit according to an embodiment of the present disclosure containing a biofluid and a reagent.

[0041] FIGURE 4C is an illustration of the kit of FIGURE 4B according to an embodiment of the present disclosure.

[0042] FIGURE 4D is an image of the kit of FIGURE 4B after mixing the biofluid and the reagent, according to embodiments of the present disclosure.

[0043] FIGURE 4E is an illustration of the kit of FIGURE 4D according to embodiments of the present disclosure.

DETAILED DESCRIPTION

[0044] Embodiments of inserts for a specimen collection tube and kits and methods for collecting and metering biofluids are described herein. In the following description numerous specific details are set forth to provide a thorough understanding of the embodiments. One skilled in the relevant art will recognize, however, that the techniques described herein can be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring certain aspects. [0045] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. INSERTS

[0046] In an aspect, the present disclosure provides an insert for a specimen collection tube. In an embodiment, the insert comprises a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and a plurality of legs extending outwardly from a side of the fluidic channel separator.

[0047] In this regard, attention is directed to FIGURES 1A-1F in which an insert 100 according to embodiments of the present disclosure is illustrated. FIGURE 1A is a perspective view of the insert 100 according to embodiments of the present disclosure. FIGURE IB is another perspective view of the insert 100. FIGURE 1C is side view of the insert 100. FIGURE ID is a cross-sectional view of the insert 100. FIGURE IE is a top- down plan view of the insert 100. FIGURE IF is a bottom-up plan view of the insert 100.

[0048] As discussed further herein, in embodiments, the insert 100 is for use with a specimen collection tube, such as to meter a volume of a biofluid for collection or other use in the specimen collection tube. In embodiments, the insert 100 is shaped and sized to fit within a specimen collection tube, such as is discussed further herein with respect to FIGURE 3. Further, as discussed further herein with respect to FIGURES 4A-4E, in embodiments, the insert 100 is configured to meter a volume of a biofluid and separate the biofluid from a reagent disposed in another chamber of the specimen collection tube, such as until agitation by a user.

[0049] Referring again to FIGURES 1A-1F, the insert 100 is shown to comprise a fluidic channel separator 106 defining an aperture 108; and a plurality of legs 110 extending outwardly from a side 118 of the fluidic channel separator 106.

[0050] In an embodiment, wherein the aperture 108 is configured to limit flow of a fluid therethrough by hydrostatic forces between the biofluid and the aperture 108. In an embodiment, the aperture 108 is sized, shaped, and otherwise configured to limit and, in embodiments, prevent flow of the biofluid through the aperture 108 in the absence of agitation of the insert 100, such as by shaking. In this regard, in an embodiment, when disposed in a specimen collection tube, the insert 100 is configured to meter a volume of biofluid collected in the specimen collection tube as no additional biofluid will fit in the specimen collection tube, such as without overflowing from the specimen collection tube.

[0051] The aperture 108 can define various shapes and configurations, such as cross-sectional configurations of the aperture 108. In embodiments, a shape of the aperture 108 contributes to generating hydrostatic forces between the insert 100 and a biofluid. In an embodiment, the aperture 108 defines a shape selected from a conical shape, a cylindrical shape, a pyramidal shape; a pyramidal frustum; and a conical frustum.

[0052] In an embodiment, hydrostatic forces are generated, at least in part, due to differences in hydrophobicity between an insert 100 material and the biofluid. In an embodiment, the insert 100 comprises a material that is at least partially hydrophilic. In an embodiment, the insert 100 comprises a material that is at least partially hydrophobic.

[0053] In an embodiment, the insert 100 comprises a material selected from the group consisting of a polycarbonate, a polystyrene, a polypropylene, or any combination thereof. In an embodiment, the insert 100 comprises a polypropylene.

[0054] In addition to contributing to hydrostatic forces between the insert 100 and a biofluid in contact with the insert 100, a material of the insert 100 can contribute other beneficial characteristics of the insert 100. In this regard, in an embodiment, the material of the insert 100 is flexible or otherwise deformable such that a portion of the insert 100 can conform to an inner surface of a specimen collection tube, such as to form a seal between the insert 100 and the specimen collection tube. In embodiments, a flexible material, such as a polypropylene, is beneficial for biofluid collection and metering when used in conjunction with a specimen collection tube into which the insert 100 is disposed and in contact therewith.

[0055] As shown, the fluidic channel separator 106 comprises a disc 114 defining, such as in an interior portion, the aperture 108. In the illustrated embodiment, the plurality of legs 110 is shown extending from the side 118 of the disc 114 in a direction opposite the second side 112. As discussed further herein, such as with respect to FIGURE 3, a length 134 of the plurality of legs 110 defines, at least in part, a ratio of volumes of compartments defined by the insert 100 when disposed in an interior portion of a specimen collection tube. [0056] In the illustrated embodiment, such as in FIGURES IE and IF, the discshaped fluidic channel separator 106 defines a circular outer circumference 126 and a diameter 120. In embodiments, such a circular outer circumference 126 is shaped and sized to form a seal between an interior portion, such as an interior wall, of a specimen collection tube into which the insert 100 is disposed. In an embodiment, the diameter 120 of the insert 100 is sized and shaped to match a diameter of at least a portion of an interior wall or other portion of the specimen collection tube, thereby forming a seal between the insert 100 and the specimen collection tube and the insert 100. In this regard, for example, a reagent also disposed in the interior portion of the specimen collection tube (see, for example, FIGURE 3) does not leak from the specimen collection tube as flow is limited by the seal and the aperture 108.

[0057] In an embodiment, the diameter 120 and outer circumference 126 are sized and shaped to fit into an interior portion of a standard biofluid collection tube, such as a BD microtainer®. In an embodiment, the diameter 120 is about 8 mm.

[0058] In an embodiment, a diameter 121 of legs 110 of the plurality of legs 110 defines a draft, such as a draft of at least about 1 degree, about 2 degrees, or more, narrowing in a direction away from the fluidic channel separator 106. In an embodiment, the diameter of legs 110 of the plurality defines a draft, such as a draft in a range of about 1 degree to about 10 degrees. Such a draft can allow for injection molding of the insert 100 where the insert 100 can be removed from a mold used to injection mold the insert 100.

[0059] Another insert 200 according to embodiments of the present disclosure will now be described with respect to FIGURES 2A-2F. FIGURE 2A is a perspective view of the insert 200. FIGURE 2B is another perspective view of the insert 200. FIGURE 2C is a side view of the insert 200. FIGURE 2D is a cross-sectional view of the insert 200. FIGURE 2E is a top-down plan view of the insert 200. FIGURE 2F is a bottom-up plan view of the insert 200.

[0060] In embodiments, the insert 200 is for use with a specimen collection tube, as discussed further herein with respect to FIGURES 1A-1F. In embodiments, the insert 200 shares components, materials, shapes, dimensions, and other characteristics with the insert 100 discussed further herein with respect to FIGURES 1 A-1F.

[0061] As shown, the insert 200 includes a fluidic channel separator 206 defining an aperture 208; and a plurality of legs 210 extending outwardly from a side 218 of the fluidic channel separator 206. In an embodiment, the aperture 208 is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture 208.

[0062] In the illustrated embodiment, the fluidic channel separator 206 comprises a disc 214 defining the aperture 208. As shown, the side 218 of the fluidic channel separator 206 is a first side 218, and the insert 200 further comprises a flange 216 extending from the disc 214 from a second side 212 opposite to the first side 218. In an embodiment, a thickness of the flange 216 is less than a thickness of the disc 214 of the fluidic channel separator 206 such that the flange 216 is more flexible than the disc 214. In an embodiment, the relatively flexible flange 216 is configured to conform to an interior wall of a specimen collection tube in which the insert 200 is disposed and which the flange 216 contacts. In an embodiment, the conformation of the flange 216 to the interior wall forms, at least in part, a seal between the insert 200 and the interior wall of the specimen collection tube.

[0063] In the illustrated embodiment, such as in FIGURES 2E and 2F, the discshaped fluidic channel separator 206 defines a circular outer circumference 226 and a diameter 220. In embodiments, such a circular outer circumference 226 is shaped and sized to form a seal between an interior portion, such as an interior wall, of a specimen collection tube into which the insert 200 is disposed. In an embodiment, the diameter 220 of the insert 200 is sized and shaped to match a diameter of at least a portion of an interior wall or other portion of the specimen collection tube, thereby forming a seal between the insert 200 and the specimen collection tube and the insert 200.

[0064] In an embodiment, a diameter 221 of the plurality of legs 210 define, at least in part, a volume of a second compartment formed between the insert 200 and a specimen collection tube into which the insert is disposed. In an embodiment, a length 234 of the plurality of legs 210 defines, at least in part, a ratio of volumes of compartments defined by the insert 200 when disposed in an interior portion of a specimen collection tube.

KITS

[0065] In another aspect, the present disclosure provides kits for collecting and metering biofluids. In an embodiment, the kits comprise a specimen collection tube; and an insert sized and shaped to fit within an interior portion of the specimen collection tube. In an embodiment, the insert comprises a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and a plurality of legs extending outwardly from a side of the fluidic channel separator.

[0066] In an embodiment, the insert is an insert according to any embodiment of the present disclosure. In an embodiment, the insert is an example of inserts 100 or 200 described further herein with respect to FIGURES 1 A-1F or FIGURES 2A-2F.

[0067] FIGURE 3 is a side view of a kit 304 according to an embodiment of the present disclosure. As shown, the kit 304 comprises a specimen collection tube 302; and an insert 300 sized and shaped to fit within an interior portion 324 of the specimen collection tube 302, the insert 300 comprising a fluidic channel separator 306 defining an aperture 308, wherein the aperture 308 is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture 308; and a plurality of legs 310 extending outwardly from a side of the fluidic channel separator 306.

[0068] In the illustrated embodiment, the fluidic channel separator 306 comprises a disc 314 defining the aperture 308. As also shown, the side 318 of the fluidic channel separator 306 is a first side 318, and the insert 300 further comprises a flange 316 extending from the disc 314 from a second side 312 opposite to the first side 318, such as discussed further herein with respect to FIGURES 2A-2F. In the illustrated embodiment, the diameter 320 of the flange 316 matches diameter of the specimen collection tube 302 such that the flange 316 forms a seal with interior wall 328 of the specimen collection tube 302.

[0069] In an embodiment, the insert 300 is shaped, sized, and otherwise configured to form a seal with an interior wall 328 of the sample collection tube when the insert 300 is disposed in the specimen collection tube 302. In this regard, a reagent 336 disposed in the specimen collection tube 302 generally does not travel between the outer circumference (see outer circumference 126) of the insert 300 and the interior wall, nor does it travel through the aperture 308 without agitation sufficient to break the hydrostatic forces between the insert 300. In other words, the reagent 336 does not leak out from the specimen collection tube 302 or contact a user collecting a biofluid.

[0070] As shown, the insert 300 is disposed within the specimen collection tube 302. With the insert 300 disposed in the specimen collection tube 302, the kit 304 defines a first compartment 330 extending in a first direction 322 from the disc 314 and a second compartment 332 extending in a second direction 342 from the disc 314.

[0071] In embodiments, a length 334 of legs 310 of the plurality of legs 310 defines, at least in part, a ratio of volumes of the first compartment 330 and the second compartment 332. As shown, the plurality of legs 310 contacts a closed end of the specimen collection tube 302, such as to determine a position in the specimen collection tube 302 where the fluidic channel separator 306 or a flange 316 extending therefrom contacts the interior wall of the specimen collection tube 302. As discussed further herein, a seal formed between the fluidic channel separator 306 and the specimen collection tube 302 can define a separation between the first compartment 330 and the second compartment 332.

[0072] Other factors defining the ratio of volumes can include, for example a volume of the plurality of legs 310, a shape of the interior wall of the specimen collection tube 302, and a volume of the specimen collection tube 302 defining the second compartment 332. The volume of the second compartment 332 and the ratio of the volumes of the first compartment 330 and second compartment 332 can be tailored for particular pairs of biofluids and reagents 336 for use with the biofluids. For example, a particular ratio of blood to a blood stabilizer can be beneficial to stabilizing the blood for later use and analysis. By adjusting, tailoring, and/or manipulating the shape of the insert 300 and a specimen collection tube 302 with which it is paired, a ratio of volumes of the first compartment 330 and second compartment 332 can correspondingly be tailored for a particular application and pair of biofluids and reagents 336.

[0073] As shown, the specimen collection tube 302, and, in particular, the second compartment 332, comprises a reagent 336. In an embodiment, the reagent 336 comprises an RNA stabilization reagent 336. In an embodiment, the reagent 336 comprises RNAtoer®. Other reagents 336 can include, for example, PAXgene®, TRIzol®, and DNA/RNA Shield ®.

[0074] While in the illustrated embodiment, the kit 304, and in, particular, the specimen collection tube 302, is shown comprising a reagent 336, in other embodiments the specimen collection tube 302 and reagent 336 are shipped separately. In other embodiments, the kit 304 does not comprise a reagent 336, but is configured to accept a reagent 336, such as is discussed further herein with respect to Pasteur and other pipettes.

[0075] Examples of biofluids for pairing with the reagent 336 can include, for example, whole blood, fractionated blood, serum, plasma, sweat, tears, ear flow, sputum, lymph, bone marrow suspension, lymph, urine, saliva, semen, vaginal flow, feces, transcervical lavage, cerebrospinal fluid, brain fluid, ascites, breast milk, vitreous humor, aqueous humor, sebum, endolymph, peritoneal fluid, pleural fluid, cerumen, epicardial fluid, and secretions of the respiratory, intestinal and genitourinary tracts.

[0076] As above, the kit 304 includes a fluidic channel separator 306 defining an aperture 308, wherein the aperture 308 is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture 308. In an embodiment, the aperture 308 defines a shape selected from a conical shape, a cylindrical shape, a pyramidal shape; a pyramidal frustum; and a conical frustum.

[0077] In an embodiment, the aperture 308 is sized and shaped to allow a Pasteur pipette to pass through the aperture 308 to the second compartment 332, such as to allow a user to dispose a reagent 336 into the second compartment 332 with the Pasteur or other pipette when the insert 300 is disposed in the specimen collective tube.

[0078] As above, the aperture 308 is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture 308. However, in an embodiment, wherein, when the insert 300 is disposed in the specimen collection tube 302, the aperture 308 is further configured to allow mixing of liquids in the first compartment 330 and the second compartment 332 upon agitation of the sample collection tube, such as by shaking the assembled kit 304 by hand or other agitation.

[0079] As above, in embodiments, the kit 304 comprises a specimen collection tube 302. In an embodiment, the kit 304 comprises a BD Microtainer®. However, in other embodiments, the kit 304 comprises other specimen collection containers, such as, but not limited to, a collection tube, a specimen collection tub, or a specimen collection cup.

[0080] A method of using the kit 404 according to embodiments of the present disclosure will now be described with respect to FIGURE 4A.

[0081] The method illustrated in FIGURE 4A can be a method of using the inserts according to embodiments of the present disclosure, such as inserts 100 and/or 200, described further herein with respect to FIGURES 1A-1F and 2A-2F, as well as kits according to embodiments of the present disclosure, such as kit 304 described herein with respect to FIGURE 3.

[0082] In embodiment, the method begins with inserting or placing an insert 400 into a specimen collection tube 402 or other specimen collection container. In an embodiment, the specimen collection tube 402 or container already contains the insert 400.

[0083] In an embodiment, inserting the insert 400 in the specimen collection tube/container 402 is followed by or the method begins with providing a reagent 436 in the specimen collection tube/container 402, such as in a second compartment 432 of the assembled kit 404. In an embodiment, the specimen collection tube/container 402 contains a reagent 436 and does not require further or additional reagent 436 to be provided. In an embodiment, the reagent 436 is an example of the reagents 336 described further herein with respect to FIGURE 3.

[0084] In an embodiment, providing a reagent 436 to the specimen collection tube/container 402 is followed by or the method begins with providing a biofluid 438 into the specimen collection tube/container 402, such as in a first compartment 430 of the specimen collection tube/container 402. In an embodiment, the biofluid 438 is an example of the biofluids described further herein with respect to FIGURE 3. As shown in FIGURE 4A, the biofluid 438 is at least initially separated from the reagent 436 by the aperture 408. As described further herein, due, for example, to the size and shape of the aperture 408 and the material of the fluidic channel separator, the aperture 408 is configured to limit flow of a fluid therethrough by hydrostatic forces between the biofluid 438 and the aperture 408. In this regard, a volume of the biofluid 438 in the specimen collection tube/container 402 is metered to below a predetermined volume. Additionally, the biofluid 438 and the reagent 436 are at least initially separated between the first compartment 430 and the second compartment 432, respectively.

[0085] In an embodiment, disposing the biofluid 438 in the specimen collection tube/container 402 is followed by agitating the kit 404, such as by manually shaking the kit 404. In an embodiment, agitation of the kit 404 combines the biofluid 438 and the reagent 436 due to movement of the biofluid 438 and the reagent 436 through the aperture 408, such as to provide a combined and/or mixed reagent and biofluid 440. EXAMPLES

[0086] Example 1 : Design and Production of Insert

[0087] Design iterations were generated using Solidworks® for Research. Prototypes were 3D printed using a Form 3B 3D printer (Formlabs®) and a CADworks® ProFluidics® 285D 3D printer (CADworks®) using clear printing resin. These designs were filled with 590 pL, then inverted three times for three seconds each to test for leakage. Preliminary designs also underwent a drop test procedure to simulate the shipping process in accordance with 49 CFR §178.603 (1990). For this process, five devices were filled with RNAtoer®, then placed in a shipping box and dropped from 1.2 m under the following conditions (one sample per condition): 1) flat on the bottom, 2) flat on the top, 3) flat on a long side, 4) flat on a short side, and 5) on a comer.

[0088] Design considerations briefly include: 1) the height of the insert is designed to partition the BD Microtainer® into two compartments: the top holds 200 pL of blood and the bottom holds 590 pL of liquid stabilizer, 2) the diameter of the top of the insert is designed for a snug fit in the BD Microtainer®, and 3) the cone feature separating the two compartments is wide enough to allow a plastic Pasteur pipette to reach the bottom of the BD Microtainer® while also being as narrow as possible to prevent leaking between the compartments.

[0089] Design considerations for injection molding

[0090] The inserts were injection molded out of polypropylene (PP: RTP Permastat 100 Anti-static) by Protolabs®, Inc. Polypropylene was chosen for its increased flexibility compared to polycarbonate to address inconsistent material shrinkage in injection molding, ensuring any batch-to-batch variation will still allow a tight fit in the BD Microtainer®. Other considerations for injection molding include: 1) adding plastic to the struts to allow for ejector pin zones, 2) including at least 1° of draft on all vertical surfaces to prevent the part sticking to the mold, 3) including a thin ring of plastic above the cone feature with higher draft to increase flexibility as a consideration for the higher variability of the shrink rate of polypropylene, and 4) designing the insert to avoid any overhangs, to allow for a two piece mold.

[0091] Example 2:

[0092] In FIGURES 4B and 4C, human whole blood is collected at the top of the kit. Here, the insert (400) is placed into a BD microtainer® (402) tube as described in FIGURE 4A. The blood is separated from the stabilizing agent, RNAlater (436) and sits in the first compartment (430). Upon capping the BD microtainer®, the kit is shaken and the blood and RNAlater begin to mix in both compartments until homogenous, as seen in FIGURES 4D and 4E.

[0093] Embodiments

[0094] 1. An insert for a specimen collection tube, the insert comprising:

[0095] a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and [0096] a plurality of legs extending outwardly from a side of the fluidic channel separator.

[0097] 2. The insert of Embodiment 1, wherein the aperture defines a shape selected from a conical shape, a cylindrical shape, a pyramidal shape; a pyramidal frustum; and a conical frustum.

[0098] 3. The insert of any of Embodiment 1 or 2, wherein the fluidic channel separator comprises a disc defining the aperture.

[0099] 4. The insert of Embodiment 3, wherein the side of the fluidic channel separator is a first side, and wherein the insert further comprises a flange extending from the disc from a second side opposite to the first side.

[0100] 5. The insert of any of Embodiments 1-4, wherein a diameter of legs of the plurality defines a draft of at least about 1 degree narrowing in a direction away from the fluidic channel separator.

[0101] 6. The insert of any of Embodiments 1-5, wherein the insert comprises a material selected from the group consisting of a polycarbonate, a polystyrene, a polypropylene, or any combination thereof.

[0102] 7. The insert of any of Embodiments 1-6, wherein the insert comprises a polypropylene.

[0103] 8. The insert of any of Embodiments 1-7, wherein the insert comprises a material that is at least partially hydrophilic.

[0104] 9. The insert of any of Embodiments 1-8, wherein the insert comprises a material that is at least partially hydrophobic.

[0105] 10. A kit for collecting and metering biofluids, the kit comprising:

[0106] a specimen collection tube; and

[0107] an insert sized and shaped to fit within an interior portion of the specimen collection tube, the insert comprising:

[0108] a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and

[0109] a plurality of legs extending outwardly from a side of the fluidic channel separator.

[0110] 11. The kit of Embodiment 10, wherein the fluidic channel separator comprises a disc defining the aperture. [OHl] 12. The kit of any of Embodiments 10 or 11, wherein an outer circumference of the disc is shaped and sized to contact the interior portion of the sample collection tube when the insert is disposed in the sample collection tube.

[0112] 13. The kit of any of Embodiments 10-12, wherein the side of the fluidic channel separator is a first side, and wherein the insert further comprises a flange extending from the fluidic channel separator on a second side opposite to the first side.

[0113] 14. The kit of any of Embodiments 10-13, wherein the insert is configured to form a seal with an interior wall of the sample collection tube when the insert is disposed in the specimen collection tube.

[0114] 15. The kit of any of Embodiments 10-14, wherein the kit defines a first compartment extending in a first direction from the disc and a second compartment extending in a second direction from the disc when the insert is disposed in the sample collection tube.

[0115] 16. The kit of Embodiment 15, wherein a length of legs of the plurality of legs defines, at least in part, a ratio of volumes of the first compartment and the second compartment.

[0116] 17. The kit of any of Embodiments 15 or 16, further comprising a reagent disposed in the second compartment.

[0117] 18. The kit of Embodiment 17, wherein the reagent comprises an RNA stabilization reagent.

[0118] 19. The kit of any of Embodiments 15-18, wherein the aperture is sized and shaped to allow a Pasteur pipette to pass through the aperture to the second compartment.

[0119] 20. The kit of any of Embodiments 15-19, wherein, when the insert is disposed in the specimen collection tube, the aperture is further configured to allow mixing of liquids in the first compartment and the second compartment upon agitation of the sample collection tube.

[0120] While illustrative embodiments have been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the disclosure.

Claims

CLAIMS The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. An insert for a specimen collection tube, the insert comprising: a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and a plurality of legs extending outwardly from a side of the fluidic channel separator.

2. The insert of Claim 1, wherein the aperture defines a shape selected from a conical shape, a cylindrical shape, a pyramidal shape; a pyramidal frustum; and a conical frustum.

3. The insert of Claim 1, wherein the fluidic channel separator comprises a disc defining the aperture.

4. The insert of Claim 3, wherein the side of the fluidic channel separator is a first side, and wherein the insert further comprises a flange extending from the disc from a second side opposite to the first side.

5. The insert of Claim 1, wherein a diameter of legs of the plurality defines a draft of at least about 1 degree narrowing in a direction away from the fluidic channel separator.

6. The insert of Claim 1, wherein the insert comprises a material selected from the group consisting of a polycarbonate, a polystyrene, a polypropylene, or any combination thereof.

7. The insert of Claim 1, wherein the insert comprises a polypropylene.

8. The insert of Claim 1, wherein the insert comprises a material that is at least partially hydrophilic.

9. The insert of Claim 1, wherein the insert comprises a material that is at least partially hydrophobic.

10. A kit for collecting and metering biofluids, the kit comprising: a specimen collection tube; and an insert sized and shaped to fit within an interior portion of the specimen collection tube, the insert comprising: a fluidic channel separator defining an aperture, wherein the aperture is configured to limit flow of a fluid therethrough by hydrostatic forces between the fluid and the aperture; and a plurality of legs extending outwardly from a side of the fluidic channel separator.

11. The kit of Claim 10, wherein the fluidic channel separator comprises a disc defining the aperture.

12. The kit of Claim 11, wherein an outer circumference of the disc is shaped and sized to contact the interior portion of the sample collection tube when the insert is disposed in the sample collection tube.

13. The kit of Claim 10, wherein the side of the fluidic channel separator is a first side, and wherein the insert further comprises a flange extending from the fluidic channel separator on a second side opposite to the first side.

14. The kit of Claim 10, wherein the insert is configured to form a seal with an interior wall of the sample collection tube when the insert is disposed in the specimen collection tube.

15. The kit of Claim 10, wherein the kit defines a first compartment extending in a first direction from the disc and a second compartment extending in a second direction from the disc when the insert is disposed in the sample collection tube.

16. The kit of Claim 15, wherein a length of legs of the plurality of legs defines, at least in part, a ratio of volumes of the first compartment and the second compartment.

17. The kit of Claim 15, further comprising a reagent disposed in the second compartment.

18. The kit of Claim 17, wherein the reagent comprises an RNA stabilization reagent.

19. The kit of Claim 15, wherein the aperture is sized and shaped to allow a Pasteur pipette to pass through the aperture to the second compartment.

20. The kit of Claim 15, wherein, when the insert is disposed in the specimen collection tube, the aperture is further configured to allow mixing of liquids in the first compartment and the second compartment upon agitation of the sample collection tube.