Sample collecting device

Abstract

A device for collecting metered samples from sample materials, in particular soft materials or semi-solid materials such as faeces, food, soil, environmental and / or industrial materials, as well as methods and kits for collecting metered samples of materials for analysis using the techniques.

Description

[0001] This application claims priority to U.S. Provisional Application Serial No. 63 / 381,031, filed Oct. 26, 2022, and Serial No. for an industrial design application, now International Registration No. DM / 231747, filed Apr. 26, 2023, each of which is incorporated herein by reference in its entirety. Field of the Invention

[0002] Provided herein are techniques related to collecting and preparing samples. For example, the technology specifically (but not exclusively) relates to devices, systems, and kits that allow for the collection and preparation of samples of soft matter compositions (e.g., fecal material) for analysis, as well as methods of using such devices. Background of the Invention

[0004] In many environments, such as in the food industry, for environmental testing, and in fields such as medicine, generating a defined volume or mass of a sample for subsequent testing is an important initial step. For example, in a medical setting, laboratory examination of a soft matter composition (e.g., a fecal sample) is an important part of some diagnoses. In a food testing environment, sampling a soft matter composition may include sampling a pre-prepared food, such as a canned main course, a spread or scoopable food (such as nut butter, cheese, yogurt, paste, etc.), and in an environmental testing environment, the soft matter composition to be sampled may include wet soil, clay, sludge, etc.

[0005] Diagnostic tests often require the isolation and determination of biomolecules from samples (e.g., tissue, body fluid, feces) collected from a subject. Biomolecules for analysis include, for example, nucleic acids, proteins, fats, or other molecules present in the sample.

[0006] Fecal samples for testing are preferably collected by the subject at home at a time convenient to the subject. For reliability and compliance, devices used by untrained personnel (i.e., persons not trained in medical sample collection) at home for sample collection are preferably easy to use correctly and can be reliably sealed for transporting the sample to a medical facility. For samples that some subjects may dislike handling, such as fecal samples, the device is preferably configured to minimize the subject's exposure to the sample material. Sample integrity and reproducibility of the sample volume are also crucial for subsequent processing and testing steps.

[0007] Devices available for at-home fecal sample collection are generally larger or smaller than what is needed to collect a fecal volume suitable for nucleic acid analysis, particularly for the analysis of human nucleic acids in the sample (e.g., cell-free nucleic acids, nucleic acids in colorectal cells of a human subject from an excreted fecal sample). Large kits that are typically configured to collect the entire feces from a subject for nucleic acid testing are more costly to manufacture and transport. Additionally, both the collected sample and the device used are discarded after testing and both must be disposed of and scrapped as hazardous waste. Thus, collecting a larger sample creates a larger hazardous waste stream. Further, only a portion of the entire fecal sample (e.g., typically no more than 10 grams) is needed to yield a sufficient amount of human nucleic acids or other analytes for analysis, while an entire fecal sample collected using a large container may provide hundreds of grams of material.

[0008] Additionally, collecting the entire fecal sample creates a large variation in the ratio between the fecal sample and the stabilizing buffer that the subject adds at home before returning the collected sample. For example, the mass of an entire fecal sample collected at home can range from 1 gram to nearly 1000 grams. However, a fixed volume of stabilizing buffer is typically provided to the subject to stabilize the entire fecal sample after collection and during transport. If the sample is small, the buffer volume may over-dilute the sample, resulting in a low yield of nucleic acids or other analytes. If the sample is large, the amount of stabilizing buffer may not be sufficient to properly stabilize the nucleic acids or other analytes in the sample. Further still, processing the entire fecal sample in a large collection container (e.g., homogenizing the sample in buffer before nucleic acid extraction) requires larger specialized laboratory equipment.

[0009] Available smaller devices are generally configured for immunoassays of blood proteins (fecal immunochemical test or “FIT”), a procedure that requires a very small amount of feces, e.g., typically a few milligrams of feces that can be collected from the entire feces using, for example, a spoon, paddle, brush, swab, etc. Thus, devices configured to collect fecal samples for FIT testing generally cannot collect enough feces to analyze human nucleic acids in the sample.

[0010] There are some medium-sized devices that are generally configured for the analysis of non-human nucleic acids and other materials, such as for the analysis of bacterial or viral materials, for infectious disease or gut microbiome analysis. These types of devices typically use a spoon-shaped implement to collect a small portion of the feces, typically about 1 gram or less. A large amount of microbial nucleic acids are generally present in a fecal sample in an amount far exceeding the amount of human nucleic acids in the same fecal sample. Thus, a sample of 1 gram or less is generally suitable for microbial analysis but not sufficient to analyze the nucleic acids of the human from whom the fecal sample was excreted. SUMMARY OF THE INVENTION

[0011] The present disclosure provides techniques for collecting samples of soft matter compositions, where the samples have a defined size or a size within an acceptable size range for analyzing analytes in the sample. In particular, the techniques provide devices, kits, and methods related to collecting metered samples from soft matter compositions (e.g., fecal samples). Embodiments of the techniques include, but are not limited to:

[0012] 1. A device for collecting and containing a metered sample, the device comprising a sampling rod including a sampling head, where the sampling head includes:

[0013] i) A sampling head sidewall including a plurality of orifices therethrough;

[0014] ii) A sampling head closed end; and

[0015] iii) A sampling head opening defined by a distal edge;

[0016] wherein the sampling head sidewall, the sampling head closed end, and the sampling head opening define and enclose a sampling head internal void having an internal volume.

[0017] 2. The device according to embodiment 1, wherein the sampling head opening is in a plane defined by the distal edge.

[0018] 3. The device according to embodiment 1, wherein the sampling head has a sampling head central axis, and wherein the sampling head opening has a center point on the sampling head central axis.

[0019] 4. The device according to any one of embodiments 1 to 3, wherein the sampling rod includes a cap.

[0020] 5. The device according to embodiment 4, wherein the cap is attached to the sampling head by a rod, preferably attached to the sampling head closed end.

[0021] 6. The device according to embodiment 4 or embodiment 5, wherein the cap has a center point on a cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening.

[0022] 7. The device according to any one of embodiments 1 to 6, wherein the distal edge of the sampling head includes one or more teeth.

[0023] 8. The device according to any one of embodiments 1 to 7, wherein the size of the sampling head internal void is designed to accommodate from about 0.1 grams to about 50 grams of sample material, preferably fecal sample material.

[0024] 9. The device according to embodiment 8, wherein the size of the internal void of the sampling head is designed to accommodate a sample material of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 grams, including any intermediate fraction thereof, preferably a fecal sample material.

[0025] 10. The device according to embodiment 9, wherein the size of the internal void of the sampling head is designed to accommodate a sample material of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 grams, including any intermediate fraction thereof, preferably a fecal sample material.

[0026] 11. The device according to any one of embodiments 4 to 10, further comprising a collection tube, the collection tube including a bottom wall connected to the tube wall, wherein the top edge of the collection tube defines a tube opening.

[0027] 12. The device according to embodiment 11, wherein the cap includes a cap engagement portion and the collection tube includes a mating engagement portion.

[0028] 13. The device according to embodiment 12, wherein the cap engagement portion includes a cap thread, and wherein the mating engagement portion includes a tube thread.

[0029] 14. The device according to embodiment 12 or embodiment 13, wherein the cap engagement portion and the mating engagement portion are engaged, and the sampling rod and the collection tube form a sealing device.

[0030] 15. The device according to embodiment 14, wherein the collection tube has an internal void defined by the tube wall, the bottom wall, and a plane defined by the top edge, and the maximum volume of the internal void of the tube internal void is at least 5 mL, preferably between about 5 mL and 250 mL, including any intermediate number of mL or fraction thereof, preferably between about 10 mL and 100 mL, including 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and 99.999 mL, including any intermediate fraction thereof.

[0031] 16. The device according to embodiment 14 or embodiment 15, wherein the bottom wall of the collection tube includes a displacement member that protrudes into the internal void of the collection tube.

[0032] 17. The device according to embodiment 16, wherein the collection tube has a tube central axis defined by the collection tube opening and the center point of the displacement member, and wherein the cap has a center point on the cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening.

[0033] 18. The device according to embodiment 17, wherein the cap has a center point on the cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening, and wherein when the sampling rod and the collection tube form a sealing device, the rod central axis and the tube central axis are collinear.

[0034] 19. The device according to any one of embodiments 16 to 18, wherein when the sampling rod and the collection tube form a sealing device, the displacement member of the collection tube is positioned within the sampling head and fills at least a portion of the internal void of the sampling head.

[0035] 20. The device according to embodiment 19, wherein when the sampling rod and the collection tube form a sealing device, the displacement member of the collection tube fills at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% of the internal volume of the internal void of the sampling head.

[0036] 21. The device according to embodiment 20, wherein the displacement member of the collection tube fills substantially all of the internal void of the sampling head.

[0037] 22. The device according to any one of embodiments 16 to 21, wherein the device has a primary remaining volume of the internal void of the collection tube, and the primary remaining volume is equal to the maximum volume of the internal void minus the volume of the internal void displaced by the sampling head and the sampling rod.

[0038] 23. The device according to embodiment 22, wherein the ratio (v:v) of the internal void of the sampling head to the primary remaining volume of the internal void of the collection tube is at least about 1:2, preferably between about 1:2 and 1:300, preferably between about 1:2 and 1:100, preferably between about 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:5.

[0039] 24. The device according to any one of embodiments 16 to 23, wherein the device further comprises a certain volume of solution contained in the collection tube.

[0040] 25. The device according to embodiment 24, wherein the ratio (v:v) of the volume of the internal void of the sampling head to the volume of the solution in the collection tube is at least about 1:2, preferably between 1:2 and 1:300, preferably between 1:2 and 1:100, preferably between 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:5.

[0041] 26. The device according to embodiment 24 or embodiment 25, wherein the solution comprises one or more agents selected from the group consisting of:

[0042] i) a buffer

[0043] ii) a salt;

[0044] iii) a preservative;

[0045] iv) a detergent;

[0046] v) a sugar or a polysaccharide;

[0047] vi) Protoporphyrin;

[0048] vii) Polyvalent cations;

[0049] viii) Penetrant;

[0050] ix) Horseradish peroxidase (HRP) stabilizing component;

[0051] x) Surfactant;

[0052] xi) Nuclease inhibitor;

[0053] xii) Protease inhibitor

[0054] xiii) Chelating agent;

[0055] xiv) Chaotropic salt; and

[0056] xv) Inhibitor binder.

[0057] 27. The device according to any one of embodiments 16 to 23, wherein the device further comprises at least one dried agent contained in the collection tube.

[0058] 28. The device according to embodiment 27, wherein the at least one dried agent comprises one or more reagents selected from the group consisting of:

[0059] i) Buffer

[0060] ii) Salt;

[0061] iii) Preservative;

[0062] iv) Detergent;

[0063] v) Sugar or polysaccharide;

[0064] vi) Protoporphyrin;

[0065] vii) Polyvalent cations;

[0066] viii) Penetrant;

[0067] ix) Horseradish peroxidase (HRP) stabilizing component;

[0068] x) Surfactant;

[0069] xi) Nuclease inhibitor;

[0070] xii) Protease inhibitor

[0071] xiii) Chelating agent;

[0072] xiv) chaotropic salts;

[0073] xv) inhibitor binders; and

[0074] xvi) desiccants.

[0075] 29. The device according to any one of embodiments 22 to 28, wherein the device has a secondary remaining volume of the internal void of the collection tube, the secondary remaining volume being equal to the maximum volume of the internal void of the collection tube minus the volume displaced by the sampling head and the sampling rod, minus the volume of the internal void of the sampling head.

[0076] 30. The device according to embodiment 29, wherein the ratio (v:v) of the internal void of the sampling head to the secondary remaining volume of the internal void of the collection tube is at least about 1:2, preferably between about 1:2 and 1:300, preferably between about 1:2 and 1:100, preferably between about 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:5.

[0077] 31. A method for metering a sample of a collection material, comprising:

[0078] a) providing a device comprising a sampling rod including a sampling head, wherein the sampling head comprises:

[0079] i) a sampling head sidewall including a plurality of orifices therethrough;

[0080] ii) a sampling head closed end; and

[0081] iii) a sampling head opening defined by a distal edge;

[0082] wherein the sampling head sidewall, the sampling head closed end and the sampling head opening define and enclose an internal void of the sampling head having an internal volume; and

[0083] b) collecting an amount of the material within the internal void of the sampling head.

[0084] 32. The method according to embodiment 31, wherein the sampling head opening is in a plane defined by the distal edge.

[0085] 33. The method according to embodiment 31 or embodiment 32, wherein the sampling rod includes a cap.

[0086] 34. The method according to embodiment 33, wherein the cap is attached to the sampling head by a rod, preferably attached to the closed end of the sampling head.

[0087] 35. The method according to embodiment 33 or embodiment 34, wherein the cap has a center point on the cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening.

[0088] 36. The method according to any one of embodiments 31 to 35, wherein the distal edge of the sampling head includes one or more teeth.

[0089] 37. The method according to any one of embodiments 31 to 36, wherein the size of the internal void of the sampling head is designed to accommodate from about 0.1 grams to about 50 grams of sample material, preferably fecal sample material.

[0090] 38. The method according to embodiment 37, wherein the size of the internal void of the sampling head is designed to accommodate about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 grams, including any intermediate fractions thereof, of sample material, preferably fecal sample material.

[0091] 39. The method according to embodiment 37, wherein the size of the internal void of the sampling head is designed to accommodate about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 grams, including any intermediate fractions thereof, of sample material, preferably fecal sample material.

[0092] 40. The method according to any one of embodiments 33 to 39, wherein the device further includes a collection tube, the collection tube including a bottom wall connected to the tube wall, wherein the top edge of the collection tube defines a tube opening.

[0093] 41. The method according to embodiment 40, wherein the cap includes a cap engagement portion and the collection tube includes a mating engagement portion.

[0094] 42. The method according to embodiment 41, wherein the cap engagement portion includes a cap thread, and wherein the mating engagement portion includes a tube thread.

[0095] 43. The method according to embodiment 41 or embodiment 42, wherein the cap engaging portion and the mating engaging portion are engaged, and the sampling rod and the collection tube form a sealing device.

[0096] 44. The method according to any one of embodiments 33 to 43, further comprising:

[0097] c) Inserting the sampling head into the collection tube.

[0098] 45. The method according to embodiment 44, wherein the collection tube has an internal void defined by the tube wall, the bottom wall, and the plane defined by the top edge, and the maximum volume of the internal void of the tube is at least 5 mL, preferably between about 5 mL and 250 mL, including any intermediate number of mL or fractions thereof, preferably between about 10 mL and 100 mL, including 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, and 99.999 mL, including any intermediate fractions thereof.

[0099] 46. The method according to any one of embodiments 40 to 45, wherein the bottom wall of the collection tube includes a displacement member protruding into the internal void of the collection tube.

[0100] 47. The method according to embodiment 46, wherein the collection tube has a tube central axis defined by the collection tube opening and the center point of the displacement member.

[0101] 48. The method according to embodiment 47, wherein the cap has a center point on the cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening, and wherein when the sampling rod and the collection tube form a sealing device, the rod central axis and the tube central axis are collinear.

[0102] 49. The method according to any one of embodiments 46 to 48, wherein when the sampling rod and the collection tube form a sealing device, the displacement member of the collection tube is positioned within the sampling head and fills at least a portion of the internal void of the sampling head, whereby at least a portion of the amount of material collected in the internal void of the sampling head is discharged from the internal void of the sampling head through an orifice in the sampling head and into the collection tube, wherein the metered sample of the material is selected from:

[0103] - the amount of material contained in the internal void of the sampling head; and

[0104] - the amount of material discharged from the internal void of the sampling head.

[0105] 50. The method according to embodiment 49, wherein the device further comprises a certain volume of solution contained in the collection tube.

[0106] 51. The method according to embodiment 50, wherein the ratio (v:v) of the volume of the metered sample to the volume of the solution in the collection tube, or the ratio (w:v) of the mass of the metered sample to the volume of the solution in the collection tube, is at least about 1:2, preferably between 1:2 and 1:300, preferably between 1:2 and 1:100, preferably between 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:5.

[0107] 52. The method according to embodiment 50 or embodiment 51, wherein the solution comprises one or more reagents selected from the group consisting of:

[0108] i) a buffer

[0109] ii) a salt;

[0110] iii) a preservative;

[0111] iv) a detergent;

[0112] v) a sugar or a polysaccharide;

[0113] vi) protoporphyrin;

[0114] vii) a polyvalent cation;

[0115] viii) a penetrant;

[0116] ix) a horseradish peroxidase (HRP) stabilizing component;

[0117] x) a surfactant;

[0118] xi) a nuclease inhibitor;

[0119] xii) Protease inhibitor

[0120] xiii) Chelating agent;

[0121] xiv) Chaotropic salt; and

[0122] xv) Inhibitor binder.

[0123] 53. A kit for metering a sample of a material to be collected, comprising:

[0124] i) The device according to any one of embodiments 1 to 30; and

[0125] ii) An agent selected from:

[0126] - Solution, and

[0127] - Dried active agent.

[0128] 54. The kit according to embodiment 53, wherein the device is a sealed device containing the agent.

[0129] 55. The kit according to embodiment 53 or embodiment 54, wherein the agent is a solution containing one or more reagents selected from the group consisting of:

[0130] i) Buffer

[0131] ii) Salt;

[0132] iii) Preservative;

[0133] iv) Detergent;

[0134] v) Sugar or polysaccharide;

[0135] vi) Protoporphyrin;

[0136] vii) Polyvalent cation;

[0137] viii) Osmotic agent;

[0138] ix) Horseradish peroxidase (HRP) stabilizing component;

[0139] x) Surfactant;

[0140] xi) Nuclease inhibitor;

[0141] xii) Protease inhibitor

[0142] xiii) Chelating agent;

[0143] xiv) Chaotropic salt; and

[0144] xv) Inhibitor binder.

[0145] 56. The kit according to embodiment 53 or embodiment 54, wherein the agent is a dried active agent comprising one or more reagents selected from the group consisting of:

[0146] i) Buffer

[0147] ii) Salt;

[0148] iii) Preservative;

[0149] iv) Detergent;

[0150] v) Sugar or polysaccharide;

[0151] vi) Protoporphyrin;

[0152] vii) Polyvalent cation;

[0153] viii) Osmotic agent;

[0154] ix) Horseradish peroxidase (HRP) stabilizing component;

[0155] x) Surfactant;

[0156] xi) Nuclease inhibitor;

[0157] xii) Protease inhibitor

[0158] xiii) Chelating agent;

[0159] xiv) Chaotropic salt;

[0160] xv) Inhibitor binder; and

[0161] xvi) Desiccant.

[0162] 57. The kit according to any one of embodiments 53 to 56, further comprising one or more of the following:

[0163] a) A package for transporting, storing or mailing the device;

[0164] b) Printed instructions for using the device to collect a metered sample;

[0165] c) A collection system for holding sample material when collecting a metered sample;

[0166] d) A holder for holding the unsealed device during collection of a metered sample from the sample; and

[0167] e) A retainer for fastening the sealing device in a transport container.

[0168] Embodiments of the present technology also include:

[0169] 58. A method for processing a fecal sample, the method comprising,

[0170] a) Obtaining a fecal sample by the method according to any one of claims 31 to 52;

[0171] b) Testing the fecal sample for the amount and / or presence of an analyte, wherein the analyte comprises one or more of the following:

[0172] i) Nucleic acid

[0173] ii) Protein

[0174] iii) Lipid

[0175] iv) Carbohydrate, and

[0176] v) Metabolite.

[0177] Definitions

[0178] To facilitate understanding of the present technology, the following defines a number of terms and phrases. Additional definitions are set forth throughout the detailed description.

[0179] As used herein, "a" or "an" or "the" may mean one or more than one. For example, "a" widget may mean one widget or more than one widget.

[0180] As used herein, the term "metered" means having a reproducible quantity with measurements within an acceptable range of variation.

[0181] As used herein, the term "analyte" should be broadly construed to mean any compound, molecule, element, ion, or other substance of interest to be detected, identified, or characterized.

[0182] As used herein, the terms "subject" and "patient" refer to an animal from which a fecal sample is collected, preferably a human. In some cases, the subject is also a "user" (and thus, the user is also a subject or patient).

[0183] As used herein, the transitional phrase "consisting essentially of" when referring to a composition, step, or other feature should be construed to mean "consisting of the specified materials, steps, or features", plus only those additional elements that are unavoidable, which do not materially affect the basic and novel characteristics of the materials, methods, steps, etc., such as unavoidable contaminants, unavoidable steps.

[0184] As used herein, the terms "comprising", "including", "containing", "having", and "characterized by" are used interchangeably and are inclusive or open-ended, without excluding additional unrecited elements, features, or method steps. The term "comprising" means that the named elements are essential, but other elements may be added and still form a structure within the scope of the claim.

[0185] The transitional phrase "consisting essentially of" limits the scope of the claim to the specified materials or steps and those materials or steps that do not materially affect the basic and novel characteristics of the claimed invention.

[0186] The transitional phrase "consisting of" excludes any element, step, or ingredient not specified in the claim.

[0187] As used herein, the terms "sample" and "specimen" are used interchangeably and are used in the broadest sense. In one sense, a sample means including a specimen or culture obtained from any source, as well as biological and environmental samples. Biological samples can be obtained from animals (including humans) and encompass fluids, solids, tissues, and gases. Biological samples include blood products such as plasma, serum, feces, urine, etc. Environmental samples include environmental materials such as surface substances, soil, mud, sludge, biofilms, water, crystals, and industrial samples. However, such examples should not be construed as limiting the types of samples applicable to the present invention.

[0188] As used herein, the term "soft matter composition" is used without limitation to refer to any soft composition material or specimen, which is preferably non-liquid and encompasses, for example, soft solids and semi-solids such as feces, pastes, gels, greases, butters, foams, sludges, clays, tissues, etc.

[0189] As used herein, the term "non-liquid", when used in reference to the consistency of a soft matter composition or material to be sampled, refers to a soft material that does not exhibit liquid characteristics, such as the property of being easily flowable and conforming its shape to the shape of a container, and the inability to maintain a fixed shape in the absence of a container.

[0190] As used herein, the term "metered sample" refers to a sample having a reproducible measured quantity, the measured quantity having an acceptable range of variation, for example, within an acceptable range of variation for the purpose of producing a metered sample.

[0191] As used herein, the term "integral" as used in reference to a portion or feature of a component means a feature or portion formed of the same material as part of the process of forming the component (e.g., by molding, carving, or machining). Features formed as an integral part of a component are distinguishable, for example, from features added to the component after the component is formed (e.g., by using fasteners or adhesives).

[0192] As used herein, the term "orifice" means an opening or hole through an element or feature of a device, preferably a hole through the sidewall (10) of a sampling head, whereby material (e.g., air, fluid, sample material) within the sampling head (8) is exposed to the environment external to the sampling head (8), and whereby such material within the sampling head (8) can be transferred between the internal void (9) of the sampling head and the environment external to the sampling head (8), and vice versa.

[0193] As used herein, the term "engagement feature" means a feature of a first element of a device (1) that is configured to interact with a feature of a second element of the device, e.g., to attach the first element to the second element reversibly or irreversibly. For example, in some embodiments, the engagement features of a cap and a collection tube are configured to interact with each other to seal the device (1). In some embodiments, the engagement features of a sampling head (8) are configured to interact with the engagement features of a collection tube (3), e.g., on the bottom wall (20) and / or displacement member (21) of the collection tube (3), such that the sampling head (8) can be reversibly or irreversibly attached to the collection tube (3), e.g., when sealing the device. In some embodiments, one component part (e.g., a cap (5)) has an engagement feature, while another component part (e.g., a collection tube (3)) has a mating engagement feature that is selected to engage effectively with the engagement feature of the cap. For example, in some embodiments, the cap (5) and the collection tube (3) have threaded features such that the cap (5) engages with the collection tube (3) by rotation, i.e., by "screwing" the cap onto the collection tube. Other engagement features include, but are not limited to, bayonet socket elements, snap closure portions, or portions that form a friction seal.

[0194] As used herein, a "sealed device" means a device (1) having a cap (5) and a collection tube (3), wherein the engagement features on the cap and the collection tube are engaged to such an extent that a sealed joint (27) prevents fluid, e.g., from passing from inside the sealed device (1) to the outside of the device (1).

[0195] As used herein, the term "substantially" as used in reference to the mass or quantity of a component or feature means a mass or quantity that permits a degree of variation, where the variation does not materially affect the basic and novel characteristics of the component or feature or the claimed embodiment.

[0196] As used herein, the term "analyte" refers to any component in a sample that is subjected to analysis. Non-limiting examples of analytes include biomolecules such as nucleic acids, proteins, carbohydrates, lipids, metabolites, organic and inorganic compounds; eukaryotic cells such as human cells or cell components (e.g., tumor-associated cells, tissue cells, blood cells, etc.); bacterial cells or cell components; plant cells or cell components; fungal cells or cell components; for each of the foregoing cells and cell types, including: whole cells, nucleic acids, organelles, membranes, proteins, small molecules, metabolites, and any molecule, substance or material produced in or associated with the cell or cell component due to, for example, recombinant engineering, conjugation, transfection, transformation and / or infection; viral components (e.g., whole viruses, viral nucleic acids, viral proteins, including capsid proteins and viral proteins produced by infected cells, including any molecule, substance or material produced in or associated with the virus or viral component due to, for example, recombinant engineering, conjugation, transfection, transformation and / or infection); organic compounds, inorganic compounds, etc.

[0197] As used herein, the term "kit" refers to any delivery system for delivering materials. In the context of a sample collection system, such delivery systems include systems that allow storage devices or samples collected with such devices (e.g., buffers, stabilizers, preservatives, etc. in a suitable container) and / or support materials (e.g., written instructions regarding performing the procedure, etc.) to be transported or delivered from one location to another. For example, a kit includes one or more housings (e.g., boxes) containing the relevant devices and / or support materials. As used herein, the term "fragmented kit" refers to a delivery system that includes two or more separate containers, each containing a sub-part of all the kit components. The containers can be delivered jointly or separately to a predetermined recipient. For example, the first container may contain materials and buffers for sample collection, while the second container contains sampling devices, separate transport materials, etc. The term "fragmented kit" is intended to cover kits that contain analyte-specific reagents (ASRs) regulated by Section 520(e) of the Federal Food, Drug, and Cosmetic Act, but is not limited thereto. In fact, any delivery system that includes two or more separate containers each containing a sub-part of all the kit components is included in the term "fragmented kit". In contrast, a "combined kit" refers to a delivery system that contains all the components in a single container (e.g., a single box that houses each desired component). The term "kit" includes both fragmented kits and combined kits.

[0198] As used herein, the term "system" refers to a collection of articles for a particular purpose. In some embodiments, the articles include instructions for use, provided as information on, for example, an article, paper, or recordable medium (such as a CD, flash drive, etc.). In some embodiments, the instructions direct the user to an online location, such as a website, a remote server of a service provider, etc.

[0199] As used herein, the term "central axis", as used in reference to a device or a component of a device, refers to the axis about which at least one element of the device has rotational symmetry. For example, in Figure 1 and Figure 2 the depicted device (1), the central axis (23) is indicated by a dashed line and is defined by the line between the point at the bottom center of the collection tube (3) and the point at the top center of the cap (5) when the cap is engaged with the collection tube. In the depicted embodiment, when the device is unassembled, the central axis of the sampling rod (2) is defined by the line between the point at the center of the sampling head opening (14) and the top center of the cap (5), while the central axis of the collection tube (3) is defined by the line between the point at the center of the tube opening (19) and the point at the center of the bottom wall (20) of the collection tube (3) and / or the point at the center of the displacement member (21). Embodiments may include asymmetric features, e.g., the sampling rod member (4) or the sampling head (8) includes one or more ridges, bumps, pits, grooves, or other protruding or recessed elements that vary from each other, for example, in size, shape, and / or distribution, such that they are not symmetric. In such embodiments, the basic or underlying shape of a device component, such as the sampling rod member (4) or the sampling head (8) (or other components of the sampling rod or collection tube) may be considered separately from such features. For example, the basic conical or tubular shape of the member (4) or the bell-shaped shape of the sampling head (8) (such as those shapes depicted in Figure 1 and Figure 7A in the corresponding depicted embodiments) may define the central axis, even if such member and / or sampling head also includes asymmetric elements (e.g., relative to the central axis). BRIEF DESCRIPTION OF THE DRAWINGS

[0200] Figure 1 is a view of an embodiment of the device provided herein, showing the sampling rod (2) and the collection tube (3), where the sampling rod is disengaged from the collection tube.

[0201] Figure 2 is a side view of an embodiment of the device provided herein, showing the device 1 in a sealed state, where the cap (5) of the sampling rod (2) is fastened to the collection tube (3). The member (4) and the sampling head (8) can be seen inside the collection tube (3).

[0202] Figure 3A and Figure 3BShows a side view of the sampling rod (2) and the collection tube (3) of an embodiment of the device provided herein, where the dimensions are shown in inches ( Figure 3A ) or millimeters ( Figure 3B ).

[0203] Figure 4A Shows a side view and a cross-sectional view of an embodiment of the device provided herein, where the cap (5) engages with the collection tube (3) to provide a sealing device. The embodiment shown includes a gasket (25) that provides a seal between the cap (5) and the top edge (18) of the collection tube (3).

[0204] Figure 4B Shows an exploded view of an embodiment of the sampling rod (2), which includes a cap (6), a grip ring (5a), a rod (4) with an attached sampling head (8), and a gasket (25).

[0205] Figure 5A Shows a top view of an embodiment of the device (1).

[0206] Figure 5B Shows a side view of an embodiment of the device (1), which shows exemplary dimensions (in inches).

[0207] Figure 5C Shows a bottom view of an embodiment of the device (1), which shows a notch (26) in the bottom wall (20) of the collection tube (3).

[0208] Figure 5D Shows Figure 5A A cross-sectional view of the device at position A-A.

[0209] Figure 5E Shows a side view of an embodiment of the device (1), which shows exemplary dimensions (in millimeters).

[0210] Figures 6A to 6C Shows an example of the internal volume of an embodiment of the device: A) the maximum volume of the internal void (22) of the collection tube (3) when the tube is empty; B) the remaining volume of the internal void (22) of the collection tube (3) after being displaced by the rod (4) and the sampling head (8); C) the volume of the internal void (9) of the sampling head (8).

[0211] Figure 7A Shows an embodiment of the device with raised or recessed features (16) (e.g., bumps, ridges, grooves, pits, etc.) having different arrangements, patterns, and distances on the outside of an exemplary cap. The top view shows 4 sealing devices including the sampling rod and the collection tube, and the bottom view shows only 4 exemplary sampling rods. Different embodiments of the cap and different embodiments of the sampling head are shown.

[0212] Figure 7B Illustrates different embodiments of the rod (4), which is shown in dashed lines to indicate the exemplary profile of 3D rods of different shapes and sizes. Embodiments of the present technology are not limited to any particular rod shape or size. The rod may have a circular cross-section, or the cross-section may have different shapes, such as oval or elliptical shapes, regular or irregular polygons (e.g., square, rectangular, triangular, hexagonal, preferably convex polygons), etc. Different parts of a single rod may have different cross-sectional shapes. The rod may include one or more ridges, bumps, pits, grooves or other protruding or recessed elements, and may include holes or orifices therethrough, as Figure 7B illustrated schematically by the two smaller ovals in Embodiment VI in

[0213] Figure 8A Shows different embodiments of the sampling head.

[0214] Figure 8B Shows an embodiment of the sampling head (8) including a notch (32) between the teeth (13).

[0215] Figure 9A And Figure 9B ( Figure 9A detailed view) illustrates the positioning of the sampling tip (e.g., of a pipetting device) relative to the displacement member (21) in the collection tube (3), e.g., such that the displacement member does not impede the sampling tip from entering the bottom of the collection tube.

[0216] Figure 10 Illustrates embodiments of the sealing device in the vertical direction (where the cap is at the top) and containing different volumes of fluid (40, 45 or 50 mL). The arrow indicates the liquid level covering the sampling head (8).

[0217] Figure 11 Illustrates embodiments of the sealing device in the horizontal direction and containing different volumes of fluid (40, 45 or 50 mL). The arrow indicates the liquid level partially or completely covering the sampling head (8).

[0218] Figure 12A Shows a detailed illustration of the joint between the flange portion (4a) of the rod (4) of the sampling rod (2) (see Figure 4B ) and the top edge (18) of the collection tube (3) when the cap thread (7) engages with the tube thread (24) as sealed by the washer (25).

[0219] Figure 12B Shows the flange portion (4a) of the rod (4) of the sampling rod (2) without sealing with a washer (see Figure 4BA detailed illustration of the sealing joint (27) between the top edge (18) of the collection tube (3).

[0220] Figure 12C A detailed illustration of the sealing joint (27) between the sealing lip (28) on the cap (5) without using a gasket for sealing and the sealing surface (29) on the inner side wall (30) of the collection tube (3) is shown. In some embodiments, the sealing lip (28) is formed as an integral part of the cap (5). Detailed Description

[0221] Embodiments of the present invention are described in this detailed description and the above - mentioned summary of the invention, which are incorporated herein by reference. Although the present invention has been described in connection with specific embodiments, it should be understood that the claimed invention should not be unduly limited to such specific embodiments. Those skilled in the art who review this disclosure will readily appreciate that many modifications are possible (e.g., changes in the size, dimensions, structure, shape, proportion of individual elements, changes in parameter values, installation arrangements, use of materials, orientation, etc.) without materially departing from the novel teachings and advantages of the subject matter of this technology. Accordingly, all such modifications are intended to be included within the scope of the present invention as defined in the appended claims. In particular, although the features of this technology are specifically described herein with reference to fecal samples, this technology is not limited to fecal samples, but can be applied to any soft - matter composition from which a metered sample can be obtained.

[0222] Sampling devices are provided herein that can be used to collect samples (e.g., fecal samples) of appropriately reproducible size, the sample volume of which is suitable for analytes (e.g., human nucleic acids, proteins, etc.) in the sample. The device can be particularly used to collect metered samples for disease screening, such as nucleic - acid - or protein - based screening for digestive system inflammation and / or cancer (e.g., colorectal cancer) in a subject's body.

[0223] In addition to facilitating the collection of samples of reproducible volume or mass by the subject, the devices provided herein can also actively discharge the collected sample material into a stabilizing buffer within the device, thereby enhancing the stabilization of analytes (e.g., cells, proteins, nucleic acids) within the sample material and / or reducing the loss of sample material, e.g., by sticking the collected sample to the device.

[0224] Embodiments of a collection device (1) are provided herein that are adapted to include one or more of the following features:

[0225] 1. Collecting a metered sample from a soft sample, such as fecal samples of different consistencies;

[0226] 2. Collect a metered sample that includes sample material from the external and internal regions of a fecal sample, and optionally from multiple locations within the sample, e.g., to maximize the opportunity to collect analytes associated with disorders such as inflammation, cancer, etc., e.g., analytes such as cells, nucleic acids, proteins, lipids, etc. (if present);

[0227] 3. Collect sufficient sample material to yield an amount of nucleic acid sufficient for nucleic acid analysis (e.g., methylation assays, gene expression assays);

[0228] 4. Actively disperse the metered sample into a stabilizing buffer within the device;

[0229] 5. Include the buffer prior to collecting the metered sample such that the user does not need to transfer the buffer from a separate container into the device; and

[0230] 6. Include sufficient buffer to cover the collected metered sample regardless of whether the device is placed upright or on its side.

[0231] Compared to a tube collection device configured for a FIT test, the device of the present technology can capture a sufficient amount of sample material, particularly fecal sample material, to analyze target analytes such as nucleic acids, e.g., human nucleic acids (e.g., >1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 grams, or any intermediate fraction thereof). In a preferred embodiment, the device of the present technology provides sufficient sample for at least two independent measurements of an analyte or group of analytes (e.g., target nucleic acid or group of target nucleic acids). Compared to a full fecal collection bucket-style home collection device, the sample collection device provided by the present technology is made with significantly less material, is much less cumbersome to package, transport, and process, and generates significantly less downstream waste (including hazardous medical waste) to be disposed of.

[0232] Device

[0233] As Figures 1 to 1 shown in FIG. 2, the device (1) includes a sampling rod (2) and a collection tube (3) as main components. The device is described below, particularly embodiments regarding the interaction of these and other components.

[0234] Sampling rod

[0235] The device includes a sampling rod (2) as a first component. In Figure 1 the illustrated embodiment, the sampling rod (2) includes a proximal portion adapted to contact and be manipulated by the user, and a distal portion adapted to capture a metered sample.

[0236] In Figure 1In the illustrated embodiments, the sampling rod (2) includes a rod member (4) located between the proximal portion and the distal portion of the rod. In the illustrated embodiments, the rod member (4) connects the cap (5) on the proximal portion to the sampling head (8) on the distal portion. In some embodiments, the sampling rod (2) includes a cap, while in some embodiments, the sampling rod (2) does not include a cap.

[0237] Cap

[0238] In Figure 1 the illustrated embodiments, a cap (5) is provided. The cap (5) provides a component for gripping or manipulating the sampling rod (2) by, for example, a user or a robotic device. The cap (5) also preferably includes a cap engagement feature, such as a cap thread (7), which is configured to engage with a mating engagement feature, such as a tube thread (24) on a collection tube, wherein when the cap engagement feature engages with the mating engagement feature, the cap and the tube form a sealing device. In some embodiments, the cap (5) includes a raised or textured feature, such as, as Figure 7A illustrated, bumps and / or ridges, for example, which can be used by a user to grip and manipulate the sampling rod (2).

[0239] Sampling head

[0240] The distal portion of the sampling rod (2) includes a sampling head (8) adapted to capture a metered sample. For example, in Figure 1 the illustrated embodiments, the sampling head (8) includes a sidewall (10) that defines a sampling head opening (14) at the distal end of the sampling rod (2). In certain preferred embodiments, the sidewall (10) includes a distal edge (12) at the distal end of the sampling rod (2). In some embodiments, the distal edge (12) includes a plurality of teeth (13). The teeth (13) on the distal edge (12) are not limited to any particular shape or edge profile. For example, the teeth (13) can be sharp or pointed (as illustrated in FIG. 8), or the edge profile of the teeth can be square, blunt, and / or rounded (e.g., as Figure 1as illustrated in FIGS. 3, or combinations thereof. The distal edge may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more teeth. In some embodiments, the teeth (13) are of the same length, while in some embodiments, some teeth are longer or shorter than adjacent teeth. In some embodiments, the teeth (13) on the sampling head (8) are all of substantially the same width, while in some embodiments, one or more teeth are wider or narrower than other teeth on the same sampling head (8). Additionally, in some embodiments, the plurality of teeth (13) are evenly distributed such that they are equidistant from adjacent teeth, while in some embodiments, at least some of the teeth are unevenly arranged such that not all teeth are equidistant from adjacent teeth.

[0241] In a preferred embodiment, the sampling head opening (14) is circumferentially defined by the sampling head sidewall (10) such that the sampling head opening (14) is circular. In Figure 1 the illustrated embodiment, the sampling head (8) includes a closed end (15) at the end of the sampling head attached to the rod (4). The sampling head (8) includes an internal void (9) defined by a plane bounded by the sidewall (10), the closed end (15), and the distal edge (12) of the sampling head (8). In embodiments where the distal edge (12) includes a plurality of teeth (13), the plane defined by the distal edge (12) is defined by points on the ends of 3 or more of the teeth (preferably the longest teeth if not all the teeth are of the same length). In a preferred embodiment, the plane of the distal edge (12) is perpendicular to the central axis (23). In some embodiments, the sampling head sidewall (10) defines the sampling head opening (14), which is not circular but of a different shape, such as, for example, an oval or elliptical shape, or a regular or irregular polygon (such as, for example, a square, rectangle, triangle, hexagon, preferably a convex polygon), etc.

[0242] The sampling head sidewall (10) of the sampling head (8) includes at least one aperture (11), preferably a plurality of apertures (11), which provide a connection between the internal void (9) and the exterior of the sampling head (8). In a preferred embodiment, the sampling head sidewall (10) includes a plurality of apertures, which are preferably distributed to different positions on the sampling head (8), such as, for example, in some embodiments, the plurality of apertures are radially distributed around the central axis (23) of the sampling head (8). Additional examples of suitable arrangements of apertures (11) on the sampling head are provided in FIG. 8. In other embodiments, the sampling head (8) includes a plurality of apertures (11) arranged irregularly or asymmetrically on the sampling head (8). The apertures (11) are not limited to any particular shape and may, for example, include circular, oval, rectangular or irregular shapes or other suitable shapes, in any combination or arrangement. AsFigure 8B As illustrated, in some embodiments, the teeth (13) of the sampling head (8) are not connected to each other around the circumference of the sampling head sidewall (10). For example, in some embodiments, the sampling head sidewall (10) includes a notch (32) between at least a pair of teeth (13), such as connecting the orifice (11) to the distal edge (12), or between multiple pairs of teeth (13), or between all teeth (13). In some embodiments, adjacent teeth contact at the notch (32), while in some embodiments, the notch (32) provides a gap between adjacent teeth.

[0243] rod

[0244] In a preferred embodiment, the sampling head (8) is attached to the cap (5) by a rod (4). In some embodiments, the diameter of the rod (4) varies along its length. In some embodiments, the rod (4) is tapered along its length. For example, in Figure 1 the illustrated embodiment, the rod (4) has a large diameter at its proximal end and tapers between the proximal and distal portions of the sampling rod (2), thereby presenting a frustum of a cone.

[0245] In some embodiments, the shape of the rod (4) is selected to provide a specific ratio between the internal volume of the collection tube (3) and the internal void (9) of the sampling head, or to provide a specific ratio between the solution and the metered sample when the device (1) is in use. In some embodiments, for example, the shape of the rod (4) is selected to maximize the amount of the internal volume of the collection tube that it displaces in the sealed device (1), such that, for example, less solution is required to fill the remaining internal volume of the collection tube (3) and / or cover the sampling head (8). For example, Figure 1 and Figure 2 the illustrated tapered rod (4) displaces more internal volume of the collection tube (3) than a thin cylindrical rod (e.g., as shown in the Figure 7A illustrated embodiment). The rod (4) can be larger than these exemplary embodiments. For example, the rod (4) can be further thickened between the cap (5) and the sampling head (8), and can, for example, have a convex curvature or a protruding side.

[0246] The rod (4) of the device is not limited to any particular shape. As illustrated by the exemplary profiles of the embodiments showing the rod (4), Figure 7B any number of shapes can be used in the embodiments of the device, as long as the rod positions the sampling head (8) at the desired location within the collection tube (3).

[0247] As discussed in more detail below, in certain embodiments, the use of the device (1) includes discharging a metered sample from the internal void (9) of the sampling head (8) through the orifice (11) during closure of the device (e.g., when the cap (5) is screwed on or otherwise sealed to the collection tube (3)). Thus, in some embodiments, the shape and / or distribution of the orifices (11) on the sampling head (8) are generally selected to be suitable for a range of expected textural or plastic properties (e.g., firmness, hardness, tackiness, etc.) of the material to be sampled using the device. For example, if a certain type of metered sample is very firm, larger orifices may be preferably used because pressing such a sample through very small orifices may require an unacceptable amount of pressure. Alternatively, if the material is very soft, smaller orifices may be preferably used, for example, to improve the containment of the metered sample and / or to reduce or prevent leakage or loss of the metered sample through the orifice before the sampling rod (2) can be inserted into the collection tube (3).

[0248] In some embodiments, for example, in order to prepare a metered sample from a fecal sample, the size of the internal void (9) of the sampling head (8) is designed to collect an appropriate amount of sample based on the requirements of the test to be performed (preferably at least twice the amount required for the test). As a non-limiting example, for human DNA testing, it has been found that a metered sample between about 1 gram and 15 grams can be used. To test for more or different analytes in feces, or to test other materials (e.g., food, environmental samples, industrial samples, etc.), it may be preferable to collect less or more sample. The volume of the internal void (9) of the sampling head (8) of the present technique is not limited to any particular size and can be designed to accommodate 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 or more grams of sample, including any intermediate fractions thereof, e.g., 0.1 grams, 0.01 grams, 0.001 grams or multiples thereof.

[0249] In a preferred embodiment, the metered sample is discharged from the sampling head (8) into a volume of solution, preferably a stabilizing solution, in the collection tube (3). The volume of solution for the volumetric metering of the sample is preferably chosen to be large enough to sufficiently stabilize the metered sample, but small enough to avoid over-diluting the metered sample. In some embodiments, the volume of solution in the collection tube (3) is at least 5 mL, preferably between about 5 mL and 300 mL, including any intermediate number of mL or fraction thereof, preferably between about 5 mL and 300 mL, preferably between about 10 mL and 100 mL, including 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and 99.999 mL, including any intermediate fraction thereof.

[0250] In a preferred embodiment, the ratio (v:v) of the volume of the metered sample to the volume of solution (e.g., in the collection tube), or the ratio (w:v) of the mass of the metered sample to the volume of solution, is at least about 1:2, preferably between 1:2 and 1:300, preferably between 1:2 and 1:100, preferably between 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:5. In embodiments of the present technology, the volume of solution in the collection tube is provided as a solution in a premixed form; while in some embodiments, the volume of solution is provided as, for example, a dry active agent to be dissolved or resuspended by the user of the device, for example, by adding a measured amount of water.

[0251] In some embodiments, the cap (5) and the sampling head (8) have a substantially circular cross-section. In a preferred embodiment, the rod (4) also has a circular cross-section over at least a portion of its length, and the centers of the circular cross-sections of the cap (5), the rod (4) and the sampling head (8) are aligned on the central axis (23) of the device (1), as Figure 1 illustrated. In some embodiments, the rod (4) and / or the sampling head (8) have a central axis that is not the same as the central axis (23) of the entire device (1).

[0252] In a preferred embodiment, the cap (5) is adapted to mate with the collection tube (3) and seal the collection tube at the top edge (18) of the collection tube (discussed below). In a preferred embodiment, mating threads on the cap (5) and the collection tube (3) engage with each other, for example by rotating the cap relative to the collection tube, thereby sealing the device (1). In some contemplated embodiments, the device (1) is sealed by using one or more of a snap closure, a bayonet closure, or a friction seal to effect the engagement of the cap with the collection tube, or by any other closure mechanism by which the cap securely closes the container to seal the contents inside the container. In a preferred embodiment, the mating threads on the cap (5) and the collection tube (3) provide for fastening the sampling rod (2) to the collection tube (3) by a half-turn helical fit. For example, as shown in FIGS. 4 and Figure 12A As illustrated, in some embodiments, the device (1) includes a gasket (25) to seal the junction between the cap (5) and the collection tube (3).

[0253] In some embodiments, the device (1) is configured to allow the user to separate the sampling head (8) from the cap (5), for example after the sampling rod (2) containing the collected sample is mated with the collection tube (3) to seal the device. For example, in some embodiments, the sampling rod (2) is configured to have a detachment feature such that manipulation of the sampling rod (2) or the sealing device (1) detaches the detachable sampling head (8) from the sampling rod (2). For example, in some embodiments, the rod (4) includes a break point or a disassembly point at which separation occurs, for example when the cap (5) is loosened or further rotated relative to the collection tube. In some embodiments, all or part of the rod (4) remains attached to the detached sampling head (8), while in some embodiments, all or part of the rod (4) detaches from the detached sampling head (8). In some embodiments, the engagement features of the sampling head (8) are configured to interact with the engagement features of the collection tube (3), such as on the bottom wall (20) of the collection tube (3) and / or on the displacement member (21), such that the sampling head (8) can be reversibly or irreversibly attached to the collection tube (3), for example when sealing the device. The engagement of the sampling head (8) with the collection tube (3) can be configured to facilitate the separation of the sampling head (8) from the cap (5), for example by promoting the breakage or detachment of the sampling head (8) from the cap (5).

[0254] In some embodiments, the device further includes an ejector movably attached to or incorporated in the sampling rod (2), for example in the cap (5), wherein manipulation of the ejector (such as pressing or sliding a button, pulling a tab, rotating a portion of the cap, etc.) detaches the sampling head (8) from the cap (5).

[0255] As Figure 12Band Figure 12C As illustrated, in some embodiments, the device (1) includes a gasketless seal at the junction between the cap (5) and the collection tube (3). For example, a precision molding process can be used such that the contact between the surfaces on the cap (5) and the collection tube (3) becomes a direct contact to form a sealed joint (27) between the cap and the collection tube. Figure 12B A detailed illustration of an embodiment is shown, where the sealed joint (27) is formed by the contact between the flange portion (4a) of the rod member (4) of the sampling rod (2) and the top edge (18) of the collection tube (3), and Figure 12C An embodiment is shown where the sealed joint (27) is formed by the contact between the sealing lip (28) on the cap (5) and the sealing surface (29) on the inner sidewall (30) of the collection tube (3). In a preferred embodiment, the sealing lip (28) is an integral part of the cap (5), for example, it is formed during the molding process to form part of the sampling rod (2), for example, the molding portion of the cap (5) or the rod member (4).

[0256] Collection tube

[0257] The present technology provides a device (1) including a collection tube (3). In some embodiments, the collection tube (3) has an integral tubular or cylindrical shape. However, the collection tube can have a non-circular cross-section, such as oval, hexagonal, square, etc. In a preferred embodiment, a threaded closure collection tube (3) (e.g., as Figure 1 illustrated) has a circular cross-section on at least the portion of the collection tube including the pipe thread (24). In a preferred embodiment, the collection tube (3) includes a displacement member (21), which is typically a protrusion protruding from the bottom wall (20) of the collection tube (3) into the internal void (22) of the collection tube. See, for example, Figure 1 and FIG. 3. The displacement member (21) can be hollow or solid, can be formed of the same material as the collection tube (3), and can be formed during tube formation, or can be added to the flat bottom wall (20) of the collection tube after the body of the collection tube is formed separately. In a preferred embodiment, the displacement member (21) is formed as an integral part of the collection tube (3), formed simultaneously with the collection tube (3) and formed of the same material as the collection tube. For example, Figure 4AA cross-sectional view of the device (1) is provided, which shows a displacement member (21) formed by a notch (26) formed in the bottom wall (20) of the collection tube (3), wherein the collection tube side wall (17), the bottom wall (20) and the displacement member (21) are formed as a continuous piece of, for example, plastic. In some embodiments, the notch (26) serves as a way to engage the collection tube (3), for example, to engage the collection tube (with or without other components of the device (1)) with a holder, a bracket, a transfer device, a mixer, a gripper, a rotator, etc.

[0258] In some embodiments, the displacement member (21) has a substantially circular cross-section and is preferably centered on the central axis of the collection tube (3). In a preferred embodiment, the central axis of the displacement member (21) in the device (1) is aligned with the centers of the cap (5), the rod (4) and the sampling head (8) on the central axis (23) of the device (1) in a closed or sealed state (e.g., as Figure 2 illustrated), as Figure 1 and Figure 2 illustrated.

[0259] The purpose of the displacement member (21) is to occupy some or all of the internal void (9) of the sampling head (8) of the sampling rod (2). Therefore, in a preferred embodiment, the size of the displacement member (21) is designed to match the internal dimensions of the sampling head (8), as Figure 4AAs shown). In addition, the displacement member (21) is positioned inside the bottom of the collection tube (3) such that when the sampling rod (2) is fully inserted into the collection tube (3) (e.g., when the cap (5) on the sampling rod (2) is screwed into place to seal the collection tube (3)), the displacement member (21) fills most or all of the internal void (9) of the sampling head (8). Thus, during use when collecting a measured fecal sample, when the displacement member (21) displaces the material, the material inside the sampling head (4) is discharged from the sampling head through one or more orifices (11). The displacement member does not need to discharge all of the sample material from the sampling head, and the amount discharged can be determined according to the volume (e.g., what percentage of the volume) of the internal void (9) of the sampling head (8) filled by the displacement member (21) when the device is sealed. In a preferred embodiment, the displacement member of the collection tube fills at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% of the internal volume of the sampling head. In some embodiments, the collection tube (3) includes a movable displacement member (21), e.g., when the sampling rod (2) is fully inserted into the collection tube (3), the movable displacement member can be positioned in a fully or partially retracted position relative to the sampling head (8) and can be moved to an appropriate position, e.g., extended into the internal void (9) of the sampling head (8) to displace some or all of the material in the sampling head.

[0260] As Figure 6AAs illustrated, the collection tube (3) has a maximum volume of the internal void (22) of the collection tube (3) when empty. As used herein, when referring to the maximum volume of the collection tube, the terms "mL" (milliliter) and "cc" (cubic centimeter) are used interchangeably, and 1 cc is equivalent to 1 mL. In a preferred embodiment, the maximum volume of the collection tube (3) is at least 5 mL, preferably between about 5 mL and 250 mL, including any intermediate number of mL or fractions thereof (e.g., 0.1 mL, 0.01 mL, 0.001 mL or multiples thereof). In a preferred embodiment, the maximum volume of the collection tube (3) is between about 10 mL and 100 mL, including 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 560, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and 99.999 mL, including any intermediate fractions thereof (e.g., 0.1 mL, 0.01 mL, 0.001 mL or multiples thereof).

[0261] As Figure 6B illustrated, the once remaining volume of the internal void (22) of the collection tube (3) is the maximum volume minus the displacement volume achieved by the rod (4) and the sampling head (8). Figure 6C The volume of the internal void (9) of the sampling head (8) is illustrated. In a preferred embodiment, the twice remaining volume of the internal void (22) after inserting the rod and the sampling head (8) is the maximum volume minus the displacement volume achieved by the rod (4) and the sampling head (8), minus the volume of the internal void (9) of the sampling head (8). The twice remaining volume is preferably at least 2 times (2X) the volume of the internal void (9) of the sampling head (8), preferably at least 3X, preferably at least 4X, preferably at least 5, 6, 7, 8, 9 or 10X the volume of the internal void (9) of the sampling head (8), or any intermediate fraction thereof (e.g., 4.1X, 4.2X, 4.3X, 4.4X, etc.). In other embodiments, the twice remaining volume of the internal void (22) is the same as or less than the internal void of the sampling head (8).

[0262] As Figure 10 and Figure 11As illustrated, in a preferred embodiment, the remaining internal volume is preferably large enough to hold a volume of solution, such as a stabilizing solution or buffer, that at least partially covers the sampling head (8), preferably covers most of the sampling head (8), and more preferably completely covers the sampling head (8). Preferably, when the sealed device containing the metered sample is in a horizontal position, e.g., side placed as shown in Figure 11 , the sampling head (8) is partially or completely covered. Preferably, the ratio of the volume of the internal void (9) of the sampling head (8) to the volume of the solution in the collection tube (whether provided as a pre-filled solution or as a solution reconstituted from a dried active reagent) is at least about 1:2 (v:v), preferably between 1:2 and 1:300 (v:v), preferably between 1:2 and 1:100 (v:v), preferably between 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:5 (v:v).

[0263] In a preferred embodiment, during use, when the sampling rod (2) is inserted into the collection tube (3), e.g., when the cap (5) is engaged to the collection tube (3) to form the sealed device, some or all of the material in the sampling head (8) is expelled into the surrounding fluid (e.g., stabilizing buffer) in the collection tube (3).

[0264] For example, filling the sampling head (8) with a material such as feces using a twisting, coring, piercing or scraping action provides a sample whose volume or mass depends to a large extent on the volume of the internal void of the sampling head (8). Expelling the metered sample through the plurality of orifices (11) fragments the metered sample and disperses it into the buffer, thereby enhancing the stabilizing effect of the buffer.

[0265] Material

[0266] Some embodiments find advantages in constructing the device from various types of materials, e.g., disposable materials, recyclable materials, reusable materials, sterilizable materials, autoclaveable materials, chemically inert materials, biodegradable materials, etc. The components of the device (1) can be made of any material that provides structural integrity to the device when the device is used for its intended purpose and is chemically and biochemically compatible with the metered sample and solution (e.g., stabilizing buffer) that can contact the device.

[0267] The components of the device can all be made of the same material, or different components can be made of different materials. For example, in a preferred embodiment, the components of the device (1) that are exposed to the metered sample are typically selected to minimize or prevent the binding of analytes (e.g., nucleic acids, proteins, cells) to the surfaces of these components during use, which can result in the loss of bound material. Additionally, the materials are typically also selected to minimize or prevent changes in the sample components, such as molecular degradation, changes in the viability or stability of human cells, bacteria, or viruses, etc. For example, the materials can be selected to avoid altering the composition of the sample components by releasing, leaching, and / or transferring materials such as plasticizers, coatings, or production by-products (e.g., bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), fine particles such as talc, surfactants, dyes, etc.) into the sample.

[0268] In some embodiments, one or more elements of the device are made of plastic, such as, for example, polypropylene, polyethylene, polystyrene, and polytetrafluoroethylene. In some embodiments, the collection tube (3) is made of a transparent plastic, such as polypropylene (PP) or polyethylene (PE), while in some embodiments, the collection tube may comprise or consist of an opaque material, for example to limit light exposure to the contained sample. Different materials may be suitable for different applications and sample types. Embodiments of the device may comprise, for example, one or more of the following: silicone, glass, ceramic, and / or crystalline materials (e.g., alumina, hydroxyapatite, zirconia, diamond, graphite), metallic materials (e.g., platinum, gold, cobalt-chromium alloy, stainless steel, titanium, and titanium alloys, etc.), and / or polymers (e.g., acetal (ACL), cycloolefin copolymer (COC), ethylene-chlorotrifluoroethylene (ECTFE), ethylene propylene diene monomer (EPDM), ethylene propylene rubber (EPR), ethylene-tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), fluorinated high density polyethylene (FLPE), high density polyethylene (HDPE), high impact polystyrene (HIPS), low density polyethylene (LDPE), polycarbonate (PC), polyetherimide (PEI), polyethylene terephthalate (PET), polyethylene terephthalate copolymer (PETG), polymethyl methacrylate (PMMA), polymethylpentene (PMP), polypropylene (PP), polypropylene copolymer (PPCO), modified polyphenylene ether (PPE), polystyrene (PS), polysulfone (PSF), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE / TFE), thermoplastic elastomer (TPE), trimethyl carbonate (TMC), TMC / NAD-lactide, etc.). In some embodiments, the components of the sampling rod (2) and the collection tube (3) are made of the same material. For example, in certain embodiments, the same material (e.g., polypropylene, polyethylene, or one of the polymers discussed above) is used for multiple components, but one or more components are differently colored or have different transparency levels. For example, in some embodiments, the collection tube (3) is made of transparent polypropylene, and the components of the sampling rod (2) (e.g., the cap (5), the rod (4), and / or the sampling head (8)) consist of opaque polypropylene (e.g., white polypropylene).

[0269] In some embodiments, the components of the sampling rod (2) and the collection tube (3) are made of different materials. For example, in some embodiments, the collection tube (3) is made of transparent polypropylene, and the components of the sampling rod (2) (e.g., the cap (5), the rod (4), and / or the sampling head (8)) are made of opaque polyethylene (e.g., white polyethylene). In some embodiments, the collection tube (3) is made of an opaque material, such as white, amber, brown, or black polyethylene or polypropylene, for example to shield the contents of the collection tube (3) from sight or light, and the components of the sampling rod (2) (e.g., the cap (5), the rod (4), and / or the sampling head (8)) are made of a transparent material, such as transparent polypropylene, polymethylpentene, or polycarbonate.

[0270] In some embodiments, the sampling rod (2) comprises a mixture of different materials. For example, in some embodiments, the cap (5) is made of one material, and the rod (4) and / or the sampling head (8) are made of one or more different materials.

[0271] The materials that can be used in the device (1) are not limited to any specific selection or combination of suitable materials for the device components. In some embodiments, the materials and compositions are selected to provide a shelf life of at least 2 years for the device. In some embodiments, the materials used for the device are selected to block light and / or ultraviolet radiation. For example, an amber or opaque material can be selected. In some embodiments, the materials can be selected to allow inspection of the sample contained therein, for example optically or under different lighting conditions. Thus, in some embodiments, the materials can be selected for their optical properties, for example transparency under different lighting conditions, such as light within the daylight spectrum, and / or under UV illumination. For example, in some embodiments, the materials can be selected to fluoresce or not fluoresce under UV light.

[0272] For example, as illustrated in FIG. 4 and Figure 12A As exemplified, in some embodiments, the device (1) includes a gasket (25) to seal the junction between the cap (5) and the collection tube (3). Any suitable material can be used, typically a polymeric material. In some embodiments, the gasket comprises low density polyethylene (LDPE), silicone, nitrile, EPDM (ethylene propylene diene monomer rubber), Viton, etc. In certain preferred embodiments, the gasket includes multiple layers. For example, in some embodiments, the gasket is a three-layer co-extruded material consisting of a foamed LDPE core sandwiched between two layers of solid LDPE, such as TRISEAL F-217® (Tri-Seal, Blauvelt, NY).

[0273] In some embodiments, the material of the sampling head (8) can be selected to provide a specific degree of friction relative to the sample, for example to hold sample material such as feces during the sampling process. In some embodiments, the inner surface of the sampling head (8) provides friction to hold a metered sample, for example, during removal of a metered sample from a fecal sample. For example, in some embodiments, the number and arrangement of the orifices (11) are selected to enhance the retention of a very soft sample (e.g., a semi-liquid sample) within the inner sampling head (8).

[0274] In some embodiments, one or more of the materials or material surfaces in the device (1) can be selected to provide a smooth surface, for example to enhance the release of sample material from the sampling head (8), and the collection tube (3) and / or the rod (4) can have a smooth surface and / or a treated surface to enhance the release of the material. In some embodiments, one or more of the device surfaces include a non-stick or hydrophobic layer or coating.

[0275] In some embodiments, the material of the cap (5) can be selected to enhance the gripping force. For example, in some embodiments, the components of the cap (5) can comprise thermoplastic vulcanizate (TPV), such as Santoprene™ TPV (Celanese Corp.), to have a rubber-like gripping force and feel. Santoprene™ TPV is a fully dynamically vulcanized EPDM (ethylene propylene diene monomer) rubber in a thermoplastic polypropylene (PP) matrix. In a preferred embodiment, the raised features (16) of the cap (5) (e.g., as Figure 2 shown) are formed, in whole or in part, of TPV.

[0276] In some embodiments, the cap (5) and / or the collection tube (3) are configured to facilitate automated processing, such as opening, closing, and / or transferring the device by mechanical or robotic means. For example, in some embodiments, the cap (5) includes one or more features configured to engage a cap drive device, e.g., ridges or grooves on the side of the cap (5) and / or the collection tube (3); raised elements and / or recessed features (e.g., ridge-shaped, blade-shaped, cross-shaped, hexagonal, square, or star-shaped elements, etc.) on the top of the cap (5), e.g., for rotating the cap (5) relative to the collection tube (3) in an automated manner or by a robot using, for example, a cap driver.

[0277] Solution

[0278] In some embodiments, the device comprises a solution in a collection tube (3), and in some embodiments, the device comprises a reagent in some form, e.g., one or more dried reagents, e.g., as a powder, cake, or coating, or as an encapsulated composition that can be dissolved, suspended, or otherwise dispersed in a fluid to provide a solution in the collection tube (3). In some embodiments, the solution (provided as a solution or provided in dried form to form a solution) is a stable buffer that provides a buffer and one or more salts (e.g., sodium chloride). In certain embodiments, the stable solution comprises Tris buffer and EDTA, e.g., 500 mM Tris, pH 9.0, 150 mM EDTA, and 10 mM NaCl. In some embodiments, other salts may be used, e.g., Hank's balanced salt solution (HBBS).

[0279] HBSS:

[0280]

[0281] In some embodiments, the stable solution may comprise a reagent selected from the following: protoporphyrin; polyvalent cations; sugars or polysaccharides and optionally polyvalent cations; osmolytes; and horseradish peroxidase (HRP) stabilizing components and optionally polyvalent cations, e.g., as described in WO 2019 / 190787, which is incorporated herein by reference for all purposes. For example, one such exemplary solution may comprise a buffer and protoporphyrin complexed with Cr 3+ or Co 3- wherein the concentration of protoporphyrin complexed with Cr 3+ is 1.25 - 5 μM, and the concentration of protoporphyrin complexed with Co 3+ is 2.5 - 10 μM.

[0282] In some embodiments, the stable solution may comprise one or more of a surfactant (e.g., Tween-20) and a nuclease inhibitor (e.g., RNase inhibitor, proteinase K, chelating agent). In some embodiments, the solution comprises one or more of sarcosyl and a chaotropic salt (e.g., guanidine thiocyanate).

[0283] The solution contains components that fragment, dissolve, and / or suspend a metered sample such that taking a portion of the aspirated mixture provides an aliquot suitable for analysis. Additionally, the solution contains components that stabilize, preserve, and / or protect the resulting suspension such that the analyte to be tested (e.g., cells, RNA, DNA, proteins) does not degrade or become damaged between the time the sample is collected and the time the sample is tested. Accordingly, the solution helps to ensure that the analysis of the metered sample accurately reflects the analyte (e.g., RNA, DNA, proteins) present in the sample at the time the sample was collected. The solution or the dry active agent may also contain components that neutralize or bind substances that can inhibit downstream assays, such as polyvinylpyrrolidone and / or polyvinylpolypyrrolidone that bind phenolic substances. In some embodiments, one or more of the reagents (e.g., polyvinylpolypyrrolidone) are provided in a form that is insoluble in the solution. In some embodiments, preferably in embodiments where the device contains a dry active reagent, the device contains a desiccant. The present technology contemplates any solution that can be used to preserve or prepare a metered sample, e.g., for a particular type of analysis.

[0284] Use of the device

[0285] The device is designed to provide a simple way to collect and generate a fecal sample for analysis. Accordingly, it is designed for use by both the sample provider and the sample tester. In some uses of the device, the sample provider can be a person who has not received medical or clinical training, and thus the device can be readily used by such non-professional users to collect a sample. Accordingly, the device is particularly suitable for remote use, e.g., at home or in a residential facility, or anywhere outside of a medical clinic or laboratory, or for on-site use, e.g., for collecting environmental or industrial samples. Accordingly, in some embodiments, the collection tube (3) is composed of an opaque material or is covered, for example, with a label such that the internal components (e.g., the shaft and sampling head of the sampling swab) are substantially blocked from the user's view, e.g., to avoid confusion regarding the proper use of the device.

[0286] At the same time, the device is designed within appropriate tolerances and in a design that allows for precise and accurate analysis of the sample by a human tester or a machine tester. Generally, the device will be provided to the sample provider in an assembled form – e.g., the collection tube (3) is pre-filled with a certain volume of solution and the cap (5) of the sampling swab (2) is fastened to the collection tube such that the device (1) is sealed.

[0287] After defecation, the sample provider removes the sampling stick (2) from the collection tube (3) and places the distal edge (12) of the sampling head (8) at a location on the fecal sample. Using a twisting motion, the sample provider cuts the distal edge (12) of the sampling head (8) into the sample, preferably capturing a generally cylindrical portion of the sample within the internal void (9) of the sampling head (8) in a "core sampling" manner. Preferably, the sample provider collects sufficient fecal material to fill the internal void (9) of the sampling head (8) at a single site on the sample or by successive core sampling at multiple different sites on the sample. In some embodiments, the teeth (13) on the sampling head (8) may also be used to loosen the sample material and / or collect sample material by scraping, e.g., scraping across the sample to obtain sample from multiple locations. In a preferred embodiment, removing the sampling head from the sample using a twisting motion causes the sampling head (8) to release from the sample while having a minimal amount of excess fecal material outside the sampling head (8).

[0288] The sampling stick (2) is then reinserted into the collection tube (3), the cap thread (7) is engaged with the tube thread (24), and the cap (5) is rotated relative to the collection tube (3) until the cap can no longer be turned, such that the device (1) is fully sealed and fluid cannot escape.

[0289] When the cap (5) is replaced and tightened onto the collection tube (3), the displacement member (21) aligns with the sampling head (8) and is forced through the sampling head opening (14) into the sampling head (8). The displacement member (21) then presses the fecal material out of the sampling head (8) through the orifice (11) into a solution, e.g., a buffer contained in the collection tube (3). Forcing the sample material through the orifice serves to fragment the sample and reduce the particle size of the sample, and then the solution acts to further fragment, dissolve, and / or suspend the metered sample. Additionally, the solution typically contains components that stabilize, preserve, and / or protect the suspension. In some embodiments, the sample provider further mixes the solution and the metered sample, e.g., by shaking, rotating, or otherwise agitating the sealed device. The sample provider then returns the sealed device (1) containing the metered sample to a laboratory, clinic, or other location for analysis. In some embodiments, the device is designed to be suitable for return by mail or shipping service.

[0290] Next, the testing agency removes a portion of the fecal suspension for analysis. In some embodiments, the sealed container is shaken, rotated, or vortexed to ensure that the metered sample is fully dispersed or homogenized in the solution. A user or machine aspirates a portion of the suspension (e.g., through a syringe needle or pipette tip) to collect an aliquot of the suspension for further processing and testing. As illustrated in FIG. 9, the sampling rod (2) is removed from the collection tube (3) to contact the buffer and fecal mixture in the collection tube (3). As shown, the embodiment of the collection tube (3) is configured to allow the pipette tip to reach the bottom of the collection tube unobstructed, thereby facilitating the aspiration of an aliquot or substantially all of the suspended material. In some embodiments, the suspension is removed from the collection tube (3) without removing the sampling rod (2). For example, in some embodiments, the cap (5) or the collection tube (3) includes an openable orifice that provides access to the fluid or suspension contained in the device. In some embodiments, the device can be pierced, e.g., with a needle or cannula, to obtain the fluid or suspension contained in the device. In some embodiments, the device (1) includes a penetrable seal through which a portion of the suspension is obtained. Some embodiments provide that the seal is made of foil. However, other materials are also suitable for the device, as long as the material can seal the sample collection chamber while being penetrable (e.g., by a pipette tip or by a syringe needle) such that a human or machine can obtain a portion of the sealed contents within the device (1). Some non-limiting examples of materials provided in various embodiments include foil, rubber, wax, and plastic, and combinations thereof, such as combinations in the form of laminates or layers.

[0291] In some embodiments, for example, after discharging the sample from the sampling head into the solution in the collection tube, the cap with the attached sampling rod is replaced with a different cap. This replacement cap is preferably one that engages with the collection tube (3) to form a sealed container but does not attach the sampling rod, thereby facilitating or simplifying additional processing steps, such as centrifugation and supernatant or pellet sample collection, using the original collection tube (3).

[0292] In some embodiments, some or all of the suspension is poured from the collection tube (3) into a different container or device for further processing steps. After aspirating the desired aliquot of the suspension, the device can be resealed and any remaining fecal sample suspension can then be stored as appropriate (e.g., heated, at room temperature, refrigerated, or frozen) or used for another process, or discarded.

[0293] Although the use of the device in fecal sample collection has been described as one embodiment, the device (1) can also be applied to sampling any type of similar soft material, such as food, environmental samples (e.g., soil or biological materials), waste, or industrial materials, etc.

[0294] Systems and kits

[0295] The present technology can be used in kits that include embodiments of the described device and, in some embodiments, include optional components such as, for example, instructions for use (e.g., providing steps of the relevant method) and associated packaging for storage, transportation, etc. Embodiments of the kit can include one or more solutions that, for example, contain stabilizing reagents, buffers, salts, or preservatives for use with the collected metered sample and the analytes contained therein (e.g., for processing, homogenizing, preserving, or storing).

[0296] The kit can also include other components that can be used to capture fecal samples, such as collection systems for use with a toilet or flush toilet to facilitate securing the fecal sample excreted by a subject during defecation such that a metered sample can be collected from the sample using the present technology. Many different suitable toilet sample collectors, such as paper bowls or plastic bowls, slings, meshes, bags, or other reservoirs suitable for a toilet or flush toilet, can be obtained through medical suppliers, pharmacies, and scientific supply companies or directly from manufacturers (e.g., Therepak Corp., Zymo Research; Alpha Labs; Excretas, HyStool; Abexx; Ability Building Community; or Takahashi Keisei Corp.). The fecal sample container of U.S. Patent No. 10,265,054 is also suitable for use.

[0297] The kit can also provide other items to assist in using the device or for transporting and disposing of the device before or after use. For example, the kit can provide a holder or stand to hold the device during use (e.g., to stably hold the collection tube in a vertical position to avoid spillage when the device is unsealed) and / or to secure the sealing device in a transport container.

[0298] Aspects of the present technology are illustrated in U.S. Provisional Application Serial No. 63 / 381,031, filed October 26, 2022, U.S. Design Application Serial No. 29 / 867,482, filed October 26, 2022, and International Design Application Serial No. WIPO132201 / 970181898, filed April 26, 2023, now International Registration No. DM / 231747, each of which is incorporated herein by reference in its entirety for all purposes.

[0299] Experiment

[0300] As discussed above, the technology herein aims to overcome the challenge of providing a sample collection device that can be reliably used by any subject in different subject populations to collect a measured sample of material (e.g., feces) in a stable manner suitable for transportation, e.g., from the subject's home to a medical laboratory using standard commercial shipping methods or public mail. Figures 1 to 1 An exemplary embodiment of the device of the technology is shown in 2.

[0301] Example 1

[0302] Collection of Measured Samples

[0303] As Figure 3A and Figure 3B The depicted embodiment of the sample collection device was used to collect fecal material from the surface and interior of 20 different fecal samples of different consistencies. The mass of each measured sample collected from each fecal sample was measured to determine the range of sample sizes produced using the device, where the results are shown in the table below:

[0304]

[0305] These data show that the mass of feces collected from different samples averaged 10.8 grams per sample, which is within the appropriate range for use in fecal sample processing and testing methods (e.g., methods such as those described by D Ahlquist et al. Gastroenterology 2012;142:248–256, which are hereby incorporated by reference in their entirety for all purposes).

[0306] Example 2

[0307] Nucleic Acid Capture and Testing in the Collected Measured Samples

[0308] As Figure 3A and Figure 3BThe described embodiment of the sample collection device is used to collect fecal material from 10 fecal samples (5 samples from subjects suffering from a disorder associated with a specific target nucleic acid in feces ("cases"), and 5 samples are control samples). The sampling stick including the collected samples is inserted into a collection tube containing 40 mL of buffer. The mixture of the collected and measured samples and buffer is processed, and nucleic acids are isolated from the fecal supernatant by directly capturing the target sequences via hybridization with oligonucleotide probes, as described by D Ahlquist et al. (ibid.). Three human target nucleic acids (A, B, and C) and one human reference nucleic acid (R) are isolated from each sample. The nucleic acids are assayed using a PCR-flap assay, as described, for example, in WO 2021 / 041726 by S. Morris et al., which is hereby incorporated by reference in its entirety for all purposes. An elevated amount of at least one of nucleic acids A, B, or C is considered to positively indicate the presence of the disorder in the subject (indicated as "positive" in the assay interpretation column). The assay results are summarized in the following table:

[0309]

[0310] Each measured sample yielded sufficient fecal supernatant for at least two assays of the group of 4 nucleic acids listed above. These data demonstrate that sufficient amounts of feces were obtained using the sample collection device of the present technique to quantitatively assay specific human target nucleic acids with sufficient sensitivity and specificity for diagnostic applications.

[0311] All documents and similar materials cited in this application, including but not limited to patents, patent applications, articles, books, theses, manufacturer publications and product literature, and Internet web pages are hereby expressly incorporated by reference in their entirety for any purpose. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the various embodiments described herein belong. When the definition of a term in the incorporated reference seems to be different from the definition provided in this teaching, the definition provided in this teaching shall prevail.

[0312] The scope of the present disclosure is not intended to be limited by the specific disclosure of the preferred embodiments in this section or elsewhere in this specification, and may be defined by the claims set forth in this section or elsewhere in this specification or in claims to be filed in the future. The language of the claims should be interpreted broadly based on the language employed in the claims, and not limited to the examples described in this specification or during the examination of the application, which examples should be construed as non-exclusive.

[0313] Features, materials, characteristics or groups described in connection with a particular aspect, embodiment or example are to be understood as applicable to any other aspect, embodiment or example described in this section or elsewhere in this specification, unless incompatible therewith. All features disclosed in this specification (including any appended claims, abstract and drawings) and / or all steps of any method or process so disclosed may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The protection is not limited to the details of any foregoing embodiment. The protection extends to any novel feature or any novel combination of features disclosed in this specification (including any appended claims, abstract and drawings), or to any novel step or any novel combination of steps of any method or process so disclosed.

[0314] In addition, certain features that are described in the context of separate implementations in this disclosure may also be implemented in combination in a single implementation. Conversely, the various features that are described in the context of a single implementation may also be implemented separately or in any suitable sub-combination in multiple implementations. Further, although features may have been described above as acting in certain combinations, in some cases, one or more features of a claimed combination may be deleted from the combination, and the combination may be claimed as a sub-combination or a variation of a sub-combination.

Claims

1. An apparatus for collecting and containing a metered sample, the apparatus comprising a sampling rod including a sampling head, wherein the sampling head comprises: i) a sampling head sidewall including a plurality of apertures therethrough; ii) a sampling head closed end; and iii) a sampling head opening defined by a distal edge; wherein the sampling head sidewall, the sampling head closed end and the sampling head opening define and enclose a sampling head internal void having an internal volume.

2. The apparatus according to claim 1, wherein the sampling head opening is in a plane defined by the distal edge.

3. The apparatus according to claim 1, wherein the sampling head has a sampling head central axis, wherein the sampling head opening has a center point on the sampling head central axis.

4. The apparatus according to any one of claims 1 to 3, wherein the sampling rod comprises a cap.

5. The apparatus according to claim 4, wherein the cap is attached to the sampling head by a rod, preferably attached to the sampling head closed end.

6. The apparatus according to claim 4 or claim 5, wherein the cap has a center point on a cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening.

7. The apparatus according to any one of claims 1 to 6, wherein the distal edge of the sampling head comprises one or more teeth.

8. The apparatus according to any one of claims 1 to 7, wherein the size of the sampling head internal void is designed to accommodate from about 0.1 grams to about 50 grams of sample material, preferably fecal sample material.

9. The apparatus according to claim 8, wherein the size of the sampling head internal void is designed to accommodate about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 grams, including any intermediate fraction thereof, of sample material, preferably fecal sample material.

10. The apparatus according to claim 9, wherein the size of the sampling head internal void is designed to accommodate about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 grams, including any intermediate fraction thereof, of sample material, preferably fecal sample material.

11. The apparatus according to any one of claims 4 to 10, further comprising a collection tube, the collection tube comprising a bottom wall connected to a tube wall, wherein a top edge of the collection tube defines a tube opening.

12. The apparatus according to claim 11, wherein the cap comprises a cap engagement portion and the collection tube comprises a mating engagement portion.

13. The device according to claim 12, wherein the cap engaging portion includes cap threads, and wherein the mating engaging portion includes pipe threads.

14. The device according to claim 12 or claim 13, wherein the cap engaging portion and the mating engaging portion are engaged, and the sampling rod and the collection tube form a sealing device.

15. The device according to claim 14, wherein the collection tube has an internal void defined by the tube wall, the bottom wall, and a plane defined by the top edge, and the maximum volume of the internal void of the tube internal void is at least 5 mL, preferably between about 5 mL and 250 mL, including any intermediate number of mL or fractions thereof, preferably between about 10 mL and 100 mL, including 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, and 99.999 mL, including any intermediate fraction thereof.

16. The device according to claim 14 or claim 15, wherein the bottom wall of the collection tube includes a displacement member that protrudes into the internal void of the collection tube.

17. The device according to claim 16, wherein the collection tube has a tube central axis defined by the collection tube opening and the center point of the displacement member, and wherein the cap has a center point on the cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening.

18. The device according to claim 17, wherein the cap has a center point on the cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening, and wherein when the sampling rod and the collection tube form a sealing device, the rod central axis and the tube central axis are collinear.

19. The device according to any one of claims 16 to 18, wherein when the sampling rod and the collection tube form a sealing device, the displacement member of the collection tube is positioned within the sampling head and fills at least a portion of the internal void of the sampling head.

20. The device according to claim 19, wherein when the sampling rod and the collection tube form a sealing device, the displacement member of the collection tube fills at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% of the internal volume of the internal void of the sampling head.

21. The device according to claim 20, wherein the displacement member of the collection tube fills substantially all of the internal void of the sampling head.

22. The device according to any one of claims 16 to 21, wherein the device has a primary remaining volume of the internal void of the collection tube, and the primary remaining volume is equal to the maximum volume of the internal void minus the volume of the internal void displaced by the sampling head and the sampling rod.

23. The device according to claim 22, wherein the ratio (v:v) of the internal void of the sampling head to the primary remaining volume of the internal void of the collection tube is at least about 1:2, preferably between about 1:2 and 1:300, preferably between about 1:2 and 1:100, preferably between about 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:

5.

24. The device according to any one of claims 16 to 23, wherein the device further comprises a certain volume of solution contained in the collection tube.

25. The device according to claim 24, wherein the ratio (v:v) of the volume of the internal void of the sampling head to the volume of the solution in the collection tube is at least about 1:2, preferably between 1:2 and 1:300, preferably between 1:2 and 1:100, preferably between 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:

5.

26. The device according to claim 24 or claim 25, wherein the solution comprises one or more agents selected from the group consisting of: i) Buffer ii) Salt; iii) Preservative; iv) Detergent; v) Sugar or polysaccharide; vi) Protoporphyrin; vii) Polyvalent cation; viii) Osmotic agent; ix) Horseradish peroxidase (HRP) stabilizing component; x) Surfactant; xi) Nuclease inhibitor; xii) Protease inhibitor xiii) Chelating agent; xiv) Chaotropic salt; and xv) Inhibitor binder.

27. The device according to any one of claims 16 to 23, wherein the device further comprises at least one dry active agent contained in the collection tube.

28. The device according to claim 27, wherein the at least one dry active agent comprises one or more reagents selected from the group consisting of: i) Buffer ii) Salt; iii) Preservative; iv) Detergent; v) Sugar or polysaccharide; vi) Protoporphyrin; vii) Polyvalent cation; viii) Osmotic agent; ix) Horseradish peroxidase (HRP) stabilizing component; x) Surfactant; xi) nuclease inhibitors; xii) protease inhibitors xiii) chelating agents; xiv) chaotropic salts; xv) inhibitor binders; and xvi) desiccants.

29. The device according to any one of claims 22 to 28, wherein the device has a secondary residual volume of the internal void of the collection tube, the secondary residual volume being equal to the maximum volume of the internal void of the collection tube minus the volume displaced by the sampling head and the sampling rod, minus the volume of the internal void of the sampling head.

30. The device according to claim 29, wherein the ratio (v:v) of the internal void of the sampling head to the secondary residual volume of the internal void of the collection tube is at least about 1:2, preferably between about 1:2 and 1:300, preferably between about 1:2 and 1:100, preferably between about 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:

5.

31. A method of metering a sample of a material, comprising: a) providing a device comprising a sampling rod having a sampling head, wherein the sampling head comprises: i) a sampling head sidewall comprising a plurality of apertures therethrough; ii) a sampling head closed end; and iii) a sampling head opening defined by a distal edge; wherein the sampling head sidewall, the sampling head closed end and the sampling head opening define and enclose an internal void of the sampling head having an internal volume; and b) collecting an amount of the material within the internal void of the sampling head.

32. The method according to claim 31, wherein the sampling head opening is in a plane defined by the distal edge.

33. The method according to claim 31 or claim 32, wherein the sampling rod comprises a cap.

34. The method according to claim 33, wherein the cap is attached to the sampling head by a rod, preferably attached to the sampling head closed end.

35. The method according to claim 33 or claim 34, wherein the cap has a center point on a cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening.

36. The method according to any one of claims 31 to 35, wherein the distal edge of the sampling head comprises one or more teeth.

37. The method according to any one of claims 31 to 36, wherein the internal void of the sampling head is sized to accommodate from about 0.1 grams to about 50 grams of sample material, preferably fecal sample material.

38. The method according to claim 37, wherein the size of the internal void of the sampling head is designed to accommodate a sample material of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 grams, including any intermediate fraction thereof, preferably a fecal sample material.

39. The method according to claim 37, wherein the size of the internal void of the sampling head is designed to accommodate a sample material of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 grams, including any intermediate fraction thereof, preferably a fecal sample material.

40. The method according to any one of claims 33 to 39, wherein the device further comprises a collection tube, the collection tube comprising a bottom wall connected to the tube wall, wherein the top edge of the collection tube defines a tube opening.

41. The method according to claim 40, wherein the cap comprises a cap engaging portion and the collection tube comprises a mating engaging portion.

42. The method according to claim 41, wherein the cap engaging portion comprises a cap thread, and wherein the mating engaging portion comprises a tube thread.

43. The method according to claim 41 or claim 42, wherein the cap engaging portion and the mating engaging portion are engaged, and the sampling rod and the collection tube form a sealing device.

44. The method according to any one of claims 40 to 43, further comprising: c) inserting the sampling head into the collection tube.

45. The method according to claim 44, wherein the collection tube has an internal void defined by the tube wall, the bottom wall, and a plane defined by the top edge, and the maximum volume of the internal void of the tube is at least 5 mL, preferably between about 5 mL and 250 mL, including any intermediate number of mL or fractions thereof, preferably between about 10 mL and 100 mL, including 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, and 99.999 mL, including any intermediate fraction thereof.

46. The method according to any one of claims 40 to 45, wherein the bottom wall of the collection tube includes a displacement member that protrudes into the internal void of the collection tube.

47. The method according to claim 46, wherein the collection tube has a tube central axis defined by the collection tube opening and the center point of the displacement member.

48. The method according to claim 47, wherein the cap has a center point on the cap central axis, and wherein the sampling rod has a rod central axis defined by the center point of the cap and the center point of the sampling head opening, and wherein when the sampling rod and the collection tube form a sealing device, the rod central axis and the tube central axis are collinear.

49. The method according to any one of claims 46 to 48, wherein when the sampling rod and the collection tube form a sealing device, the displacement member of the collection tube is positioned within the sampling head and fills at least a portion of the internal void of the sampling head, whereby at least a portion of the amount of material collected in the internal void of the sampling head is discharged from the internal void of the sampling head through an orifice in the sampling head and into the collection tube, wherein the metered sample of the material is selected from: - the amount of material contained in the internal void of the sampling head; and - the amount of material discharged from the internal void of the sampling head.

50. The method according to claim 49, wherein the device further includes a certain volume of solution contained in the collection tube.

51. The method according to claim 50, wherein the ratio (v:v) of the volume of the metered sample to the volume of the solution in the collection tube, or the ratio (w:v) of the mass of the metered sample to the volume of the solution in the collection tube, is at least about 1:2, preferably between 1:2 and 1:300, preferably between 1:2 and 1:100, preferably between 1:2 and 1:75, 1:50, 1:40, 1:30, 1:20, 1:10 or 1:

5.

52. The method according to claim 50 or claim 51, wherein the solution comprises one or more reagents selected from the group consisting of: i) a buffer ii) a salt; iii) a preservative; iv) a detergent; v) a sugar or a polysaccharide; vi) protoporphyrin; vii) a multivalent cation; viii) a penetrant; ix) a horseradish peroxidase (HRP) stabilizing component; x) a surfactant; xi) a nuclease inhibitor; xii) a protease inhibitor xiii) a chelating agent; xiv) a chaotropic salt; and xv) an inhibitor binder.

53. A kit for collecting a metered sample of a material, comprising: i) a device according to any one of claims 1 to 30; and ii) an agent selected from: - a solution, and - a dry active agent.

54. The kit according to claim 53, wherein the device is a sealed device containing the agent.

55. The kit according to claim 53 or claim 54, wherein the agent is a solution comprising one or more reagents selected from the group consisting of: i) a buffer ii) a salt; iii) a preservative; iv) a detergent; v) a sugar or a polysaccharide; vi) protoporphyrin; vii) a multivalent cation; viii) a penetrant; ix) a horseradish peroxidase (HRP) stabilizing component; x) a surfactant; xi) a nuclease inhibitor; xii) a protease inhibitor xiii) a chelating agent; xiv) a chaotropic salt; and xv) an inhibitor binder.

56. The kit according to claim 53 or claim 54, wherein the agent is a dry active agent comprising one or more reagents selected from the group consisting of: i) a buffer ii) a salt; iii) a preservative; iv) a detergent; v) a sugar or a polysaccharide; vi) protoporphyrin; vii) a multivalent cation; viii) a penetrant; ix) a horseradish peroxidase (HRP) stabilizing component; x) a surfactant; xi) a nuclease inhibitor; xii) a protease inhibitor xiii) a chelating agent; xiv) a chaotropic salt; xv) an inhibitor binder; and xvi) a desiccant.

57. The kit according to any one of claims 53 to 56, further comprising one or more of the following: a) a packaging for transporting, storing or mailing the device; b) printed instructions for using the device to collect a metered sample; c) A collection system for holding the sample material during collection of a metered sample; d) A holder for holding an unsealed device during collection of a metered sample from the sample; and e) A holder for securing a sealing device in a transport container.

58. A method of processing a fecal sample, the method comprising, a) obtaining a fecal sample by the method according to any one of claims 31 to 52; b) testing the fecal sample for the amount and / or presence of one or more analytes, wherein the analytes include one or more of the following: i) nucleic acid ii) protein iii) lipid iv) carbohydrate, and v) metabolite.

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