Sample collection device

Abstract

Apparatus for collecting quantifiable samples from specimen materials, particularly soft or semi-solid materials such as feces, food, soil, environmental materials, and / or industrial materials, as well as methods and kits for using techniques for collecting quantifiable samples of materials for analysis.

Description

Technical Field

[0001] This application claims priority to U.S. Provisional Application No. 63 / 381,031, filed Oct. 26, 2022, and Design Application No., filed Apr. 26, 2023, current International Registration No. DM / 231747, the contents of each of which are incorporated herein by reference.

[0002] This specification provides techniques related to collecting and preparing samples. For example, the techniques relate in particular, but not limited to, to devices, systems, and kits that enable the collection and preparation of samples of soft material compositions, such as feces, for analysis, and methods of using the devices.

Background Art

[0003] Generating a sample of a defined volume or mass for subsequent testing is an important initial step in many environments, such as in the food industry, for environmental testing, in medicine, etc. For example, in a medical environment, clinical testing of soft material compositions, such as fecal samples, is an important element of some diagnoses. In a food testing environment, taking a soft material composition may involve taking processed foods such as canned entrees, nut butters, cheeses, yogurts, pastes, etc. that can be spread or eaten with a spoon, and in an environmental testing environment, the soft material composition taken may include wet soil, clay, sludge, etc.

[0004] Diagnostic tests often require separating and analyzing biomolecules from specimens (e.g., tissues, body fluids, feces) collected from a subject. Biomolecules for analysis include, for example, nucleic acids, proteins, fats, or other molecules present in the specimen.

[0005] Test stool samples are preferably collected at home by the subject at their convenience. For reliability and compliance, the equipment used for home sample collection by untrained persons (i.e., persons not trained in medical sample collection) is preferably easy to use and can be securely sealed for delivery to a medical facility. For samples that some subjects may find uncomfortable to handle, such as stool samples, the equipment is preferably configured to minimize the subject's exposure to the sample material. Sample integrity and reproducibility of sample size are also crucial for subsequent processing and testing steps.

[0006] The equipment available for collecting stool samples at home is typically either too large or too small to collect a sufficient amount of stool for nucleic acid analysis, particularly for analyzing human nucleic acids in the sample (e.g., free nucleic acids, nucleic acids in colorectal cells from the human subject who produced the stool sample). Larger kits configured to collect the entire stool from a subject for nucleic acid testing are usually more expensive to manufacture and ship. Furthermore, all collected samples and equipment used must be discarded after testing and treated and disposed of as hazardous waste. Therefore, collecting larger samples results in a greater discharge of hazardous waste. Additionally, only a portion of the entire stool sample is needed to produce a sufficient amount of human nucleic acid or other analytes for analysis, typically less than 10 grams, whereas a whole stool sample collected using a large container may provide several hundred grams of material.

[0007] Furthermore, collecting whole stool samples results in significant variations in the ratio of the stool sample to the stabilizing buffer added by the subject at home before returning the collected sample. For example, whole stool samples collected at home can vary in mass from 1 to 1000 grams. However, subjects are usually provided with a certain amount of stabilizing buffer to stabilize whole stool samples after collection and during transport. If the sample is small, the amount of buffer may over-dilute the sample, resulting in a lower yield of nucleic acids or other analytes. If the sample is large, the stabilizing buffer may be insufficient to adequately stabilize the nucleic acids or other analytes in the sample. Moreover, processing whole stool samples in large collection containers, such as homogenizing the sample in buffer before nucleic acid extraction, requires larger and more specialized laboratory equipment.

[0008] The smaller devices available are typically configured for immunoassays of blood proteins (fecal immunochemistry tests, or "FIT"), which require very small amounts of stool, usually a few milligrams, and can be collected from the entire stool using, for example, a small spoon, paddle, brush, or cotton swab. Therefore, devices configured to collect stool samples for FIT tests typically do not collect enough stool to analyze human nucleic acids in the sample.

[0009] For example, there are several intermediate-sized instruments typically used for analyzing non-human nucleic acids and other materials, such as bacteria or viruses from non-human sources, or for analyzing infectious diseases or the gut microbiome. These types of instruments usually use a spoon-like instrument to collect small portions of stool, typically less than 1 gram. The amount of microbial nucleic acid present in a stool sample is usually far greater than the amount of human nucleic acid in the same stool sample. Therefore, samples of less than 1 gram are usually insufficient for analyzing nucleic acids from humans that produce the stool sample, but are suitable for microbial analysis. [Overview of the Initiative]

[0010] This specification provides techniques for collecting samples of soft material compositions, wherein the samples have a specified size or are within a size range acceptable for the analysis of analytes in the sample. In particular, the techniques provide apparatus, kits, and methods for collecting measurable samples from soft material compositions, such as stool samples. Embodiments of the techniques include, but are not limited to, the following:

[0011] 1. Apparatus for collecting and storing a sample for weighing, wherein the apparatus includes a sampler wand containing a sampler head, and the sampler head is i) The sampler head sidewall includes a plurality of ports passing through the sampler head sidewall, ii) The closed end of the sampler head, iii) A sampler head opening surrounded by the distal edge, Includes, The sampler head sidewall, the sampler head closed end, and the sampler head opening define and accommodate the internal void of the sampler head having an internal volume. The aforementioned device.

[0012] 2. The apparatus according to Embodiment 1, wherein the sampler head opening lies on a plane defined by the distal edge.

[0013] 3. The apparatus according to Embodiment 1, wherein the sampler head has a central axis of the sampler head, and the sample head opening has a center point on the central axis of the sampler head.

[0014] 4. The apparatus according to any one of Embodiments 1 to 3, wherein the sampler wand includes a cap.

[0015] 5. The apparatus according to Embodiment 4, wherein the cap is attached to the sampler head, preferably the closed end of the sampler head, by a stem.

[0016] 6. The apparatus according to Embodiment 4 or Embodiment 5, wherein the cap has a center point on the cap's central axis, and the sampler wand has a wand central axis defined by the center point of the cap and the center point of the sampler head opening.

[0017] 7. The apparatus according to any one of embodiments 1 to 6, wherein the distal edge of the sampler head includes one or more teeth.

[0018] 8. The apparatus according to any one of Embodiments 1 to 7, wherein the internal void of the sampler head is sized to accommodate a sample material of about 0.1 grams to about 50 grams, preferably a fecal sample material.

[0019] 9. The apparatus according to Embodiment 8, wherein the internal void of the sampler head is sized to accommodate approximately 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 of sample material (including any intermediate fractions thereof), preferably fecal sample material.

[0020] 10. The apparatus according to Embodiment 9, wherein the internal void of the sampler head is sized to accommodate approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 grams of sample material, preferably fecal sample material, including any intermediate portion thereof.

[0021] 11. The apparatus according to any one of embodiments 4 to 10, further comprising a collection tube including a bottom wall joined to the tube wall, wherein the upper end of the collection tube defines a tube opening.

[0022] 12. The apparatus according to Embodiment 11, wherein the cap includes a cap engagement portion and the collection tube includes an engagement portion into which it is fitted.

[0023] 13. The apparatus according to embodiment 12, wherein the cap engaging portion includes a cap screw and the engaged engaging portion includes a tube screw.

[0024] 14. The apparatus according to embodiment 12 or embodiment 13, wherein when the cap engaging portion and the engaged engaging portion are engaged, the sampler wand and the collection tube form a sealed apparatus.

[0025] 15. The collection tube has an internal void surrounded by a plane defined by the tube wall, the bottom wall, and the upper end, and the internal void of the tube is at least 5 mL, preferably between about 5 mL and 250 mL (including any intermediate mL number or fraction thereof), preferably 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 portion thereof), and has a maximum volume of the internal void between about 10 mL and 100 mL. The apparatus according to embodiment 14.

[0026] 16. The apparatus 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.

[0027] 17. The collection tube has a tube central axis defined by the center point of the collection tube opening and the center point of the displacement member, the cap has a center point on the cap central axis, and the sampler wand has a wand central axis defined by the center point of the cap and the center point of the sampler head opening. The apparatus according to embodiment 16.

[0028] 18. The apparatus according to Embodiment 17, wherein the cap has a center point on the cap's central axis, the sampler wand has a wand central axis defined by the center point of the cap and the center point of the sampler head opening, and when the sampler wand and the collection tube are sealed together, the wand central axis and the tube central axis are on the same line.

[0029] 19. The apparatus according to any one of embodiments 16 to 18, wherein when the sampler wand and the collection tube are sealed together, the displacement member of the collection tube is positioned inside the sampler head and fills at least a portion of the internal void of the sampler head.

[0030] 20. The apparatus according to Embodiment 19, wherein when the sampler wand and the collection tube are sealed together, the displacement member of the collection tube fills at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, and 99% of the internal volume of the internal void of the sampler head.

[0031] 21. The apparatus according to Embodiment 20, wherein the displacement member of the sampling tube fills substantially all of the internal void of the sampler head.

[0032] 22. The apparatus according to any one of embodiments 16 to 21, wherein the apparatus has a primary residual volume of the internal void of the collection tube that is equal to the maximum volume of the internal void obtained by subtracting the internal void volume displaced by the sampler head and sampler system.

[0033] 23. The apparatus according to Embodiment 22, wherein the ratio (v:v) of the primary residual volume of the internal void of the sampler head to 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.

[0034] 24. The apparatus according to any one of embodiments 16 to 23, wherein the apparatus further comprises a certain amount of solution contained in the collection tube.

[0035] 25. The apparatus according to Embodiment 24, wherein the ratio (v:v) of the internal void of the sampler head to the fixed amount of 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.

[0036] 26. The above solution, i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and, viii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants, xi) Nuclease inhibitors and xii) Protease inhibitors, xiii) Chelating agents, xiv) Chaotropic salt and, xv) Inhibitor conjugates, The apparatus according to Embodiment 24 or Embodiment 25, comprising one or more agents selected from the group consisting of the following.

[0037] 27. The apparatus according to any one of embodiments 16 to 23, wherein the apparatus further comprises at least one drying agent contained in the collection tube.

[0038] 28. The at least one drying agent is i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and, viii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants, xi) Nuclease inhibitors and xii) Protease inhibitors, xiii) Chelating agents, xiv) Chaotropic salt and, xv) Inhibitor conjugates, xvi) Desiccant, The apparatus according to Embodiment 27, comprising one or more agents selected from the group consisting of the following.

[0039] 29. The apparatus according to any one of embodiments 22 to 28, wherein the apparatus has a secondary residual volume of the internal void of the sampling tube that is equal to the maximum volume of the internal void of the sampling tube, obtained by subtracting the volume displaced by the sampler head and sampler system, and subtracting the volume of the internal void of the sampler head.

[0040] 30. The apparatus according to Embodiment 29, wherein the ratio (v:v) of the secondary residual volume of the internal void of the sampler head to 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.

[0041] 31. A method for collecting a sample for measurement of materials, a) To provide an apparatus including a sampler wand including a sampler head, wherein the sampler head is i) The sampler head sidewall includes a plurality of ports passing through the sampler head sidewall, ii) The closed end of the sampler head, iii) A sampler head opening surrounded by the distal edge, Includes, The sampler head side wall, the sampler head closed end, and the sampler head opening define and accommodate an internal void of the sampler head having an internal volume, and to provide, b) Collecting a certain amount of the material from the internal void of the sampler head, The method, including the method described above.

[0042] 32. The method according to Embodiment 31, wherein the sampler head opening lies on a plane defined by the distal edge.

[0043] 33. The method according to Embodiment 31 or Embodiment 32, wherein the sampler wand is equipped with a cap.

[0044] 34. The method according to embodiment 33, wherein the cap is attached to the sampler head, preferably the closed end of the sampler head, by a stem.

[0045] 35. The method according to Embodiment 33 or Embodiment 34, wherein the cap has a center point on the cap's central axis, and the sampler wand has a wand central axis defined by the center point of the cap and the center point of the sampler head opening.

[0046] 36. The method according to any one of embodiments 31 to 35, wherein the distal edge of the sampler head includes one or more teeth.

[0047] 37. The method according to any one of embodiments 31 to 36, wherein the internal void of the sampler head is sized to accommodate a sample material of about 0.1 grams to about 50 grams, preferably a fecal sample material.

[0048] 38. The method according to Embodiment 37, wherein the internal void of the sampler head is sized to accommodate approximately 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 of sample material (including any intermediate fractions thereof), preferably fecal sample material.

[0049] 39. The method according to Embodiment 37, wherein the internal void of the sampler head is sized to accommodate approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 grams of sample material (including any intermediate fractions thereof), preferably fecal sample material.

[0050] 40. The apparatus according to any one of embodiments 33 to 39, wherein the apparatus further includes a collection tube having a bottom wall joined to the tube wall, and the upper end of the collection tube defines a tube opening.

[0051] 41. The method according to Embodiment 40, wherein the cap includes a cap engagement portion and the collection tube includes an engagement portion into which it is fitted.

[0052] 42. The method according to embodiment 41, wherein the cap engagement portion includes a cap screw and the fitted engagement portion includes a pipe thread.

[0053] 43. The method according to Embodiment 41 or Embodiment 42, wherein when the cap engagement portion and the fitted engagement portion are engaged, the sampler wand and the collection tube form a sealed device.

[0054] 44.c) Inserting the sampler head into the collection tube, The method according to any one of embodiments 33 to 43, further including the method described above.

[0055] 45. The collection tube has an internal void surrounded by a plane defined by the tube wall, the bottom wall, and the upper end, and 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 fraction therebetween), preferably 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, The method according to Embodiment 44, having a maximum volume between approximately 10 mL and 100 mL, including 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).

[0056] 46. ​​The method according to any one of embodiments 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.

[0057] 47. The method according to embodiment 46, wherein the collection tube has a tube central axis defined by the center point of the opening of the collection tube and the center point of the displacement member.

[0058] 48. The method according to Embodiment 47, wherein the cap has a center point on the cap's central axis, the sampler wand has a wand central axis defined by the center point of the cap and the center point of the sampler head opening, and when the sampler wand and the collection tube are sealed together, the wand central axis and the tube central axis are on the same line.

[0059] 49. When the sample wand and the collection tube form a sealed apparatus, the displacement member of the collection tube is positioned inside the sampler head, filling at least a portion of the internal void of the sampler head, thereby discharging at least a portion of the amount of material collected inside the internal void of the sampler head through the port inside the sampler head into the collection tube, and the weighed sample of the material is, The amount of the material contained within the internal void of the sampler head, The amount of the material discharged from the internal void of the sampler head, A method according to any one of embodiments 46 to 48, selected from the above.

[0060] 50. The apparatus according to Embodiment 49, wherein the apparatus further comprises a certain amount of solution contained in the collection tube.

[0061] 51. The method according to Embodiment 50, wherein the ratio (v:v) of the volume of the sample to the fixed amount of solution in the collection tube, or the ratio (w:v) of the mass of the sample to the fixed amount of 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.

[0062] 52. The above solution, i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and, viii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants, xi) Nuclease inhibitors and xii) Protease inhibitors, xiii) Chelating agents, xiv) Chaotropic salt and, xv) Inhibitor conjugates, The method according to Embodiment 50 or Embodiment 51, comprising one or more reagents selected from the group consisting of the following.

[0063] 53. A kit for collecting samples for measurement of materials, i) The apparatus described in any one of Embodiments 1 to 30, ii) Solution and, Desiccant and Drugs selected from, The kit includes the above.

[0064] 54. The kit according to embodiment 53, wherein the apparatus is a sealed apparatus for containing the drug.

[0065] 55. The aforementioned drug, i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and, viii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants, xi) Nuclease inhibitors and xii) Protease inhibitors, xiii) Chelating agents, xiv) Chaotropic salt and, xv) Inhibitor conjugates, The kit according to Embodiment 53 or Embodiment 54, which is a solution comprising one or more reagents from the group consisting of the following.

[0066] 56. The aforementioned drug, i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and, viii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants, xi) Nuclease inhibitors and xii) Protease inhibitors, xiii) Chelating agents, xiv) Chaotropic salt and, xv) Inhibitor conjugates, xvi) Desiccant, The kit according to Embodiment 53 or Embodiment 54, which is a dried drug comprising one or more reagents from the group consisting of the following.

[0067] 57.a) Packaging for shipping, storing, or mailing the above-mentioned device, b) Printed instructions for collecting a sample for measurement using the apparatus, c) A collection system for holding the sample material while collecting a weighing sample, d) A holder for holding an unsealed device for collecting a weighing sample from the specimen, e) A holder for securing sealed equipment inside the shipping container, A kit according to any one of embodiments 53 to 56, further comprising one or more of the above.

[0068] This embodiment of the technology further includes the following: 58. A method for processing a stool sample, a) Obtaining a stool sample by the method described in any one of claims 31 to 52, b) Testing the stool sample for the quantity and / or presence of the analyte, wherein the analyte is i) Nucleic acids and, ii) Proteins and, iii) Lipids and, iv) Carbohydrates and, v) Metabolites and, The tests include one or more of the following: The method, including the method described above.

[0069] definition To facilitate understanding of this technology, several terms and phrases are defined below. Further definitions are provided throughout the descriptions of the modes for carrying out the invention.

[0070] As used herein, "a," "an," or "the" can mean one or more things. For example, "a part" may mean one part or more parts.

[0071] As used herein, the term “measured” means having a measured quantity that is reproducible and has an acceptable range of variation.

[0072] As used herein, the term “analyte” is broadly interpreted as any compound, molecule, element, ion, or other substance of interest that is detected, identified, or characterized.

[0073] As used herein, the terms “subject” and “patient” refer to the animal, preferably a human, from which a stool sample is collected. In some examples, the subject is also the “user” (and therefore the user is also the subject or patient).

[0074] When used herein, the transitional phrase “essentially consists of” used in reference to a composition, step, or other feature should be interpreted as “consisting of” a specified material, step, or feature, with only unavoidable additional elements that do not substantially affect the basic and novel features of the material, method, step, or other feature, such as unavoidable contaminants or unavoidable steps.

[0075] As used herein, the term “comprising” is used interchangeably with “including,” “containing,” “having,” and “characterized by,” and is comprehensive or non-restrictive, not excluding additional undescribed elements, features, or method steps. The term “comprising” means that the specified elements are essential, but other elements may be added and may form a construct within the scope of the claims.

[0076] The transitional phrase "consisting essentially of" limits the claims to those that do not substantially affect the specified materials or steps, or the basic and novel features of the claimed invention.

[0077] The transitional clause "consists of" excludes elements, steps, or components not specified in the claims.

[0078] As used herein, the terms “sample” and “specimen” are used interchangeably in the broadest sense. In a sense, a sample is intended to include specimens or cultures obtained from any source, as well as biological and environmental samples. Biological samples may be obtained from animals (including humans) and include fluids, solids, tissues, and gases. Biological samples include blood products such as plasma, serum, feces, and urine. Environmental samples include environmental materials such as surface materials, soil, mud, sludge, biofilms, water, and crystals, as well as industrial samples. However, such examples should not be construed as limiting the types of samples to which the present invention is applicable.

[0079] As used herein, the term “soft material composition” is used without limitation to refer to any material or specimen of a soft composition, preferably non-liquid, encompassing soft solids and semi-solids, such as feces, pastes, gels, greases, butters, foams, sludges, clays, and tissues.

[0080] As used herein, the term "non-liquid" as used with respect to the viscosity of a sampled soft material composition or material refers to a soft material that does not exhibit the properties of a liquid, such as lacking the characteristic speed to flow and conform its shape to the shape of a container, and lacking the ability to maintain a certain shape in the absence of a container.

[0081] As used herein, the term “measurable sample” refers to a sample having a measured quantity that is reproducible within an acceptable range of variation, such as within an acceptable range of variation for the purpose for which the measurable sample is produced.

[0082] As used herein, the term “essential” when describing a part or feature of a component refers to a feature or part that is formed from the same material as part of the process of forming the component (e.g., by molding, sculpting, or machining). Features formed as an essential part of a component are distinguished from features that are added to the component after it has been formed, for example, by using fasteners or adhesives.

[0083] As used herein, the term “port” means an opening or hole through an element or feature of the apparatus, preferably a hole through the side wall (10) of the sampler head, thereby exposing material (e.g., air, fluid, sample material) inside the sampler head (8) to the environment outside the sampler head (8), thereby allowing such material inside the sampler head (8) to pass between the internal void (9) of the sampler head and the environment outside the sampler head (8), or vice versa.

[0084] As used herein, the term “engaging feature” refers to a first feature of the apparatus (1) configured to interact with a feature of a second element of the apparatus, for example, to reversibly or irreversibly attach a first element to a second element. For example, in some embodiments, the engaging features of a cap and a sampling tube are configured to interact with each other to seal the apparatus (1). In some embodiments, the engaging feature of a sampler head (8) is configured to interact with the engaging feature of the sampling tube (3) on the bottom wall (20) and / or displacement member (21) of the sampling tube (3), for example, so that the sampler head (8) can be reversibly or irreversibly attached to the sampling tube (3), for example, when the apparatus is sealed. In some embodiments, some part, such as a cap (5), has an engaging feature, and another part, such as a sampling tube (3), has a fitted engaging feature selected for effective engagement with the engaging feature of the cap. For example, in some embodiments, the cap (5) and the collection tube (3) have threaded features, so that the cap (5) engages with the collection tube (3) by rotation, that is, by "screwing" the cap onto the collection tube. Other engagement features include, but are not limited to, bayonet mounting elements, snap fasteners, and parts that form friction seals.

[0085] As used herein, the term “sealed device” means a device (1) having a cap (5) and a sampling tube (3), wherein the engaging features on the cap and sampling tube engage to the extent necessary to prevent, for example, fluid from passing from the sealed device (1) inside to the outside of the device (1).

[0086] As used herein, the term “substantially” in relation to the quality or quantity of a component or feature means that a certain degree of variation is permissible, and that the variation does not substantially affect the component or feature, or the basic and novel features of the claimed embodiment.

[0087] As used herein, the term "analyte" refers to any component of the sample being analyzed. Non-limiting examples of analytes include biomolecules, e.g., nucleic acids, proteins, carbohydrates, lipids, metabolites, organic compounds and inorganic compounds; eukaryotic cells, such as human cells or cellular components (e.g., tumor-associated cells, tissue cells, blood cells, etc.); bacterial cells or cellular components; plant cells or cellular components; fungal cells or cellular components; and, for each of the aforementioned cells and cell types, whole cells, nucleic acids, organelles, membranes, proteins, small molecules, metabolites, and viral components, including any molecules, substances, or materials produced within or associated with cells or cellular components as a result of recombinant engineering, conjugation, transfection, transformation, and / or infection; whole viruses, viral nucleic acids, viral proteins, organic compounds, inorganic compounds, etc., including, for example, capsid proteins and viral proteins produced by infected cells; and any molecules, substances, or materials produced within or associated with viruses or viral components as a result of recombinant engineering, conjugation, transfection, transformation, and / or infection.

[0088] As used herein, “kit” refers to any delivery system for delivering materials. In the context of a sample collection system, such a delivery system includes a system that enables the storage, transport, or delivery of a sample collected by an apparatus or sample collection system (e.g., in a suitable container, e.g., buffer, stabilizer, preservative, etc.) and / or supporting materials (e.g., written instructions for performing the procedure) from one location to another. For example, a kit includes one or more enclosures (e.g., a box) that house the associated sampling device and the supporting materials. As used herein, the term “fragmented kit” refers to a delivery system that includes two or more separate containers, each containing a portion of the entire kit components. The containers may be delivered together or separately to the intended recipient. For example, a first container may contain the materials for sample collection and a buffer, while a second container contains the sampling device, separate shipping materials, etc. The term “fragmented kit” is intended to encompass, but is not limited to, kits containing analyte-specific reagents (ASRs) regulated under Section 520(e) of the Federal Food, Drug, and Cosmetic Act. In practice, any delivery system containing two or more separate containers, each containing a portion of the entire kit components, falls under the term “fragmented kit.” In contrast, “combined kit” refers to a delivery system that contains all components in a single container (e.g., a single box containing each of the desired components). The term “kit” encompasses both fragmented and combined kits.

[0089] As used herein, the term “system” refers to a collection of articles for use in a particular purpose. In some embodiments, the articles include instructions for use, such as information provided on the articles, on paper, or on a recordable medium (e.g., a CD, flash drive, etc.). In some embodiments, the instructions direct the user to an online location, such as a website or a remote server of a service provider.

[0090] As used herein, the term “central axis” as used with respect to an apparatus or component of an apparatus refers to an axis around which the apparatus has rotational symmetry with at least one element. For example, in the apparatus (1) shown in Figures 1 and 2, the central axis (23) is shown by a dashed line and is defined by the line between a point at the center of the bottom of the sampling tube (3) and a point at the center of the top of the cap (5) when the cap is engaged with the sampling tube. In the illustrated embodiment, when the apparatus is not assembled, the central axis of the sampler wand (2) is defined by a point at the center of the sampler head opening (14) and the center of the top of the cap (5), while the central axis of the sampling tube (3) is defined by the line between a point at the center of the tube opening (19) and a point at the center of the bottom wall (20) of the sampling tube (3) and / or the center of the displacement member (21). Embodiments may include asymmetric features, such as a sampler wand stem (4) or sampler head (8), which may include one or more protrusions, indentations, depressions, grooves, or other protruding or recessed elements that differ from one another in size, shape, and / or distribution, and as a result are not symmetrical. In such embodiments, the basic or fundamental shape of the device component, such as the sampler wand stem (4) or sampler head (8) (or other components of the sampler wand or collection tube), may be considered separately from such features. For example, the basic conical or tubular shape of the stem (4), or the bell shape of the sampler head (8), as in the embodiments shown in Figures 1 and 7A, respectively, may define a central axis even if such a stem and / or sampler head further include elements that are not symmetrical with respect to a central axis. [Brief explanation of the drawing]

[0091] [Figure 1] This is a diagram of an embodiment of the apparatus provided herein, showing a sample wand (2) and a collection tube (3), with the sample wand detached from the collection tube. [Figure 2]This is a side view of one embodiment provided herein, showing the apparatus (1) in a sealed state with the cap (5) of the sampler wand (2) fixed to the collection tube (3). The stem (4) and sampler head (8) are visible inside the collection tube (3). [Figure 3A] Figure 3B shows a side view of a sampler wand (2) and a collection tube (3) of one embodiment of the apparatus provided herein, with dimensions indicated in inches (Figure 3A) or millimeters (Figure 3B). [Figure 3B] Figure 3B shows a side view of a sampler wand (2) and a collection tube (3) of one embodiment of the apparatus provided herein, with dimensions indicated in inches (Figure 3A) or millimeters (Figure 3B). [Figure 4A] The illustrated embodiment shows a side view and a cross-sectional view of one embodiment of the apparatus provided herein, in which the cap (5) engages with the collection tube (3) to provide a sealed apparatus. The illustrated embodiment includes a gasket (25) that provides a seal between the cap (5) and the upper end (18) of the collection tube (3). [Figure 4B] An exploded view of one embodiment of a sampler wand (2) is shown, which includes a cover (6), a gripping ring (5a), a stem (4) to which a sampler head (8) is attached, and a gasket (25). [Figure 5A] A top view of one embodiment of the apparatus (1) is shown. [Figure 5B] A side view of one embodiment of the apparatus (1) is shown, with exemplary dimensions (in inches). [Figure 5C] The bottom view of one embodiment of the apparatus (1) is shown, and the recess (26) inside the bottom wall (20) of the collection tube (3) is shown. [Figure 5D] A cross-sectional view of the apparatus at position AA is shown in Figure 5A. [Figure 5E] A side view of one embodiment of the apparatus (1) is shown, with exemplary dimensions (in millimeters). [Figure 6]An example of the internal volume of one embodiment of the device is shown. A) The maximum volume of the internal void (22) of the sampling tube (3) when empty, B) The primary remaining volume of the internal void (22) of the sampling tube (3) when displaced by the stem (4) having the sampler head (8), C) The volume of the internal void (9) of the sampler head (8). [Figure 7A] Embodiments of the apparatus having different arrangements, patterns, and distances of raised or recessed features (16) (e.g., bumps, ridges, grooves, depressions, etc.) on the external surface of an exemplary cap are shown. The upper panel shows four sealed apparatuses including a sampler wand and a collection tube, while the lower panel shows only four exemplary sampler wands. Different embodiments of the cap and different embodiments of the sampler head are shown. [Figure 7B] Different embodiments of a stem (4), shown as dashed lines illustrating exemplary silhouettes of three-dimensional stems of different shapes and dimensions, are shown. Embodiments of the Art are not limited to any particular stem shape or size. Stems may have a round cross-section, or their cross-section may have different shapes, such as elliptical or oblong, regular polygons or irregular polygons (e.g., squares, rectangles, triangles, hexagons, preferably convex polygons). Different parts of a single stem may have different cross-sectional shapes. Stems may include one or more ridges, indentations, depressions, grooves, or other protruding or recessed elements, and may include holes or ports through the stem, as schematically illustrated by the two smaller ellipses in Embodiment VI of Figure 7B. [Figure 8A] Different embodiments of the sampler head are shown. [Figure 8B] An embodiment of a sampler head (8) including a slit (32) between teeth (13) is shown. [Figure 9] Figure A shows, for example, the positioning of the sampling tip (e.g., a pipette device) relative to the displacement member (21) inside the sampling tube (3) so that the displacement member does not prevent the sampling tip from approaching the bottom of the sampling tube. Figure B (a detailed view of Figure 9A) shows, for example, the positioning of the sampling tip (e.g., a pipette device) relative to the displacement member (21) inside the sampling tube (3) so that the displacement member does not prevent the sampling tip from approaching the bottom of the sampling tube. [Figure 10] An embodiment of a sealed, vertically oriented device (with a cap on top) for holding different volumes (40, 45, or 50 mL) of fluid is shown. The arrow indicates the liquid level covering the sampler head (8). [Figure 11] An embodiment of a sealed device oriented horizontally and containing different volumes (40, 45, or 50 mL) of fluid is shown. Arrows indicate the liquid level partially or completely covering the sampler head (8). [Figure 12A] A detailed view of the joint between the flange portion (4a) (see Figure 4B) of the stem (4) of the sampler wand (2) and the upper end (18) of the collection tube (3), which is sealed by a gasket (25) when the cap screw (7) is engaged with the pipe thread (24). [Figure 12B] A detailed view of the sealed joint (27) between the flange portion (4a) of the stem (4) of the sampler wand (2) (see Figure 4B) and the upper end (18) of the collection tube (3), which is sealed without a gasket. [Figure 12C] A detailed view of the sealed joint (27) between the sealing lip (28) on the cap (5) and the sealing surface (29) on the inner side wall (30) of the collection tube (3), which is sealed without a gasket, is shown. In some embodiments, the sealing lip (28) is molded as an integral part of the cap (5). [Modes for carrying out the invention]

[0092] Embodiments of the present invention are described in the modes for carrying out this invention and the outline of the invention, and are incorporated herein by reference. Although the present invention has been described in relation to specific embodiments, it should be understood that the claimed invention should not be excessively limited to such specific embodiments. Those skilled in the art who are studying this disclosure will readily understand that many modifications are possible (e.g., changes in the size, dimensions, structure, shape, and proportions of various elements, parameter values, mounting arrangement, use of materials, orientation, etc.) without substantially departing from the novel teachings and advantages of the subject matter of the present art. Accordingly, all such modifications are intended to fall within the scope of the present invention as defined in the appended claims. In particular, the features of the present art have been described herein by particular reference to fecal samples, but the art is not limited to fecal samples and can be applied to any soft material composition from which a quantifiable sample can be taken.

[0093] This specification provides a sampling device used when collecting samples, such as stool samples, in a suitable sample volume for the analyte (e.g., human nucleic acids, proteins, etc.) contained in the sample, and of a appropriately regenerative size. The device is particularly used when collecting weighable samples for disease screening, such as nucleic acid-based or protein-based screening for inflammation of the digestive system and / or cancer, such as colorectal cancer, in a subject.

[0094] In addition to facilitating the collection of samples with a regenerative volume or mass by subjects, the apparatus provided herein actively discharges the collected sample material into a stabilizing buffer within the apparatus to enhance the stabilization of analytes (cells, proteins, nucleic acids, etc.) within the sample material, and / or reduces the loss of sample material by, for example, allowing the collected sample to adhere to the apparatus.

[0095] This specification provides an embodiment of a sampling device (1) adapted to include one or more of the following features: 1. For example, collect a weighable sample from a soft sample such as a stool sample whose viscosity changes. 2. To maximize the possibility of collecting analytes associated with conditions such as inflammation or cancer, for example, cells, nucleic acids, proteins, lipids, etc., if present, weighing samples are collected from the outer and inner regions of the stool sample, and optionally from multiple locations within the sample. 3. Collect enough sample material to obtain a sufficient amount of nucleic acid for nucleic acid analysis (e.g., methylation assay, gene expression assay). 4. Actively disperse the sample to be measured in the stabilizing buffer solution within the instrument. 5. The buffer solution should be placed in the device before the sample is collected, so that the user does not need to transfer the buffer solution from a separate container to the device. 6. Regardless of whether the apparatus is vertical or horizontal, it should contain enough buffer solution to cover the collected sample to be weighed.

[0096] In contrast to tubular sampling devices configured for FIT testing, the apparatus of this technology can capture a sufficient amount of sample material, particularly stool sample material, for the analysis of target analytes, such as nucleic acids, including 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 amount therebetween). In a preferred embodiment, the apparatus of this technology provides a sufficient sample for at least two independent measurements of an analyte or panel of analytes, such as a target nucleic acid or a panel of target nucleic acids. In contrast to all-stool bucket type home sampling devices, this technology provides a sampling device that uses substantially less material for manufacture, is substantially less cumbersome to package, ship, and process, and generates substantially less downstream waste, including hazardous medical waste for disposal.

[0097] Device As shown in Figures 1 to 12, the apparatus (1) includes a sampler wand (2) and a collection tube (3) as its main components. Embodiments of the apparatus are described below, in particular with respect to the interactions of these components and other components.

[0098] Sanpla Wand The apparatus includes a sampler wand (2) as a first component. In the embodiment shown in Figure 1, the sampler wand (2) includes a proximal portion adapted for contact with and operation by the user, and a distal portion adapted for capturing the sample to be measured.

[0099] In the embodiment shown in Figure 1, the sampler wand (2) includes a stem (4) between the proximal and distal portions of the wand. In the illustrated embodiment, the stem (4) connects a cap (5) on the proximal portion to a sampler head (8) on the distal portion. In some embodiments, the sampler wand (2) includes a cap, while in some embodiments, the sampler wand (2) does not include a cap.

[0100] cap In the embodiment shown in Figure 1, a cap (5) is provided. The cap (5) provides a component for gripping or manipulating the sampler wand (2) by, for example, a user or a robotic device. The cap (5) more preferably includes a cap engagement feature, such as a cap screw (7), configured to engage with a fitted engagement feature, such as a pipe thread (24) on the sampling tube, and when the cap engagement feature engages with the fitted engagement feature, the cap and tube form a sealed device. In some embodiments, the cap (5) includes raised or textured features, such as bumps and / or ridges, as shown in Figure 7A, which are useful when gripping and manipulating the sampler wand (2) by a user.

[0101] Sample Head The distal portion of the sampler wand (2) includes a sampler head (8) adapted to capture the sample to be measured. For example, in the embodiment shown in Figure 1, the sampler head (8) includes a side wall (10) defining a sampler head opening (14) at the distal end of the sampler wand (2). In certain preferred embodiments, the side wall (10) includes a distal edge (12) at the distal end of the sampler wand (2). In some embodiments, the distal edge (12) includes a plurality of teeth (13). The teeth (13) of the distal edge (12) are not limited to a particular shape or end cross-section. For example, the teeth (13) may be sharp or pointed as shown in Figure 8, and the end cross-section of the teeth may be angular, blunt, and / or rounded, or a combination thereof, as shown in Figures 1 and 3, for example. The distal margin may contain 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 or more teeth. In some embodiments, the teeth (13) are the same length, and in some embodiments, some teeth are longer or shorter than adjacent teeth. In some embodiments, all teeth (13) on the sampler head (8) are substantially the same width, but in some embodiments, one or more teeth are wider or narrower than other teeth on the same sampler head (8). Furthermore, in some embodiments, multiple teeth (13) are evenly distributed so that each is equidistant from adjacent teeth, while in some embodiments, at least some teeth are unevenly arranged so that not all teeth are equidistant from adjacent teeth.

[0102] In a preferred embodiment, the sampler head opening (14) is defined circumferentially by the sampler head sidewall (10), resulting in a circular sampler head opening (14). In the embodiment shown in Figure 1, the sampler head (8) includes a closed end (15) at the end of the sampler head attached to the stem (4). The sampler head (8) includes an internal void (9) enclosed by a plane defined by the sidewall (10), the closed end (15), and the distal edge (12) of the sampler head (8). In embodiments where the distal edge (12) includes multiple teeth (13), the plane defined by the distal edge (12) is defined by the points of the ends of the teeth, preferably three or more of the longest teeth, if the teeth are not all 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 sampler head sidewall (10) defines a sampler head opening (14) that is not circular but has a different shape, such as elliptical or oblong, or a regular polygon or an irregular polygon (e.g., square, rectangle, triangle, hexagon, preferably convex polygon).

[0103] The sampler head sidewall (10) of the sampler head (8) includes at least one port (11), preferably a plurality of ports (11) that provide a connection between the internal void (9) and the outside of the sampler head (8). In a preferred embodiment, the sampler head sidewall (10) includes a plurality of ports preferably distributed at different locations on the sampler head (8), for example, in some embodiments the plurality of ports are distributed radially around the central axis of the sampler head (8). An example of additional suitable arrangements of ports (11) on the sampler head is provided in Figure 8. In other embodiments, the sampler head (8) includes a plurality of ports (11) irregularly or asymmetrically arranged on the sampler head (8). The ports (11) are not limited to any particular shape and may include, for example, circular, elliptical, rectangular, or irregular or other suitable shapes in any combination or arrangement. As shown in Figure 8B, in some embodiments the teeth (13) of the sampler head (8) are not connected to each other around the outer circumference of the sampler head sidewall (10). For example, in some embodiments, the sampler head sidewall (10) includes a gap (32) between, for example, at least one pair of teeth (13) connecting the port (11) and the distal edge (12), or between multiple pairs of teeth (13), or between all of the teeth (13). In some embodiments, adjacent teeth are in contact at the gap (32), while in some embodiments, the gap (32) provides a gap between adjacent teeth.

[0104] stem In a preferred embodiment, the sampler head (8) is attached to the cap (5) by a stem (4). In some embodiments, the stem (4) has a diameter that changes along its length. In some embodiments, the stem (4) tapers along its length. For example, in the embodiment shown in Figure 1, the stem (4) has a large diameter at its proximal end and gradually narrows between the proximal and distal portions of the sampler wand (2), forming a frustoconical shape.

[0105] In some embodiments, the shape of the stem (4) is selected to provide a specific ratio between the internal volume of the collection tube (3) and the volume of the internal void (9) of the sampler head, or a specific ratio between the solution and the sample being measured when the apparatus (1) is in use. In some embodiments, for example, the shape of the stem (4) is selected to maximize the amount of internal volume of the collection tube that the stem (4) displaces within the sealed apparatus (1), resulting in less solution being required, for example, to fill the remaining internal volume of the collection tube (3) and / or to cover the sampler head (8). For example, the tapered stem (4) shown in Figures 1 and 2 displaces more of the internal volume of the collection tube (3) than a slim cylindrical stem, for example, as illustrated in the embodiment shown in Figure 7A. The stem (4) may be larger than those in these exemplary embodiments. For example, the stem (4) may be further thicker between the cap (5) and the sampler head (8), and may have, for example, convexly curved or bulging sides.

[0106] The stem (4) of the device is not limited to any particular shape. As shown in Figure 7B, which illustrates an exemplary silhouette of an embodiment of the stem (4), any number of shapes can be used in embodiments of the device, as long as the stem positions the sampler head (8) at a desired position within the collection tube (3).

[0107] As will be described in more detail below, in certain embodiments, the use of the apparatus (1) involves, for example, when the cap (5) is screwed onto the collection tube (3) or otherwise sealed to the collection tube (3), discharging the metering sample from the internal void (9) of the sampler head (8) through the port (11) while the apparatus is closed. Thus, in some embodiments, the shape(s) and / or distribution of the ports (11) on the sampler head (8) are generally selected to suit the expected range of texture or plastic properties (e.g., hardness, stiffness, tackiness, etc.) of the material being sampled using the apparatus. For example, if the type of metering sample is very hard, it may be preferable to use a larger port, as pushing such a sample through a very small port may require an unacceptable amount of pressure. Conversely, if the material is very soft, it may be preferable to use a smaller port, for example, to improve containment of the metering sample and / or to reduce or prevent leakage or loss of the metering sample through the port before the sampler wand (2) can be inserted into the collection tube (3).

[0108] In some embodiments, for example, to prepare weighing samples from stool samples, the internal cavity (9) of the sampler head (8) is sized to allow at least two tests to be performed, preferably to collect an appropriate amount of sample based on the requirements of the test(s) to be performed. In a non-limiting example, for human DNA testing, weighing samples between approximately 1 gram and 15 grams are used. When testing stool for more or different analytes, or when testing other materials (e.g., food, environmental samples, industrial samples, etc.), it may be preferable to collect either smaller or larger samples. The volume of the internal void (9) of the sampler head (8) of this technology is not limited to any particular size, and can be sized to accommodate samples of 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 grams or more (including any intermediate fractions thereof).

[0109] In a preferred embodiment, the metering sample is discharged from the sampler head (8) into a fixed volume of solution, preferably a stabilizing solution, in a collection tube (3). The fixed volume of solution used for volumetric metering is preferably selected to be large enough to sufficiently stabilize the metering sample, but small enough to avoid over-diluting the metering sample. In some embodiments, the fixed 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 fractions therebetween), preferably between about 5 mL and 300 mL, preferably 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 The amount is between approximately 10 mL and 100 mL, including 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).

[0110] In preferred embodiments, for example, the ratio of the volume of the sample to the volume of the solution in the collection tube (v:v), or the ratio of the mass of the sample to the volume of the solution (w:v), 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, a certain amount of solution in the collection tube is provided in a pre-mixed form as a solution, while in some embodiments, a certain amount of solution is provided as a dry agent that is dissolved or resuspended by the user of the apparatus, for example, by adding a measured amount of water.

[0111] In some embodiments, the cross-sections of the cap (5) and sampler head (8) are essentially circular. In preferred embodiments, the stem (4) also has a circular cross-section in at least a portion of its length, and the centers of the circular cross-sections of the cap (5), stem (4), and sampler head (8) are aligned on the central axis (23) of the device (1), as shown in Figure 1. In some embodiments, the stem (4) and / or sampler head (8) have a central axis that is not the same as the central axis (23) of the entire device (1).

[0112] In a preferred embodiment, the cap (5) is fitted to the upper end (18) of the collection tube (3) (as described below) and is adapted to seal the collection tube (3). In a preferred embodiment, the fitting threads of 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 intended embodiments, the device (1) is sealed by the engagement of the cap and the collection tube using one or more of a snap fastener, a bayonet fastener, or a friction seal, or by any other closing mechanism in which the cap tightly closes the container and seals the contents inside the container. In a preferred embodiment, the fitting threads of the cap (5) and the collection tube (3) secure the sampler wand (2) with a half-turn screw fitted into the collection tube (3). For example, as shown in Figures 4 and 12A, in some embodiments, the device (1) includes a gasket (25) to seal the joint between the cap (5) and the collection tube (3).

[0113] In some embodiments, the apparatus (1) is configured to allow the user to separate the sampler head (8) from the cap (5) after, for example, the sampler wand (2) containing the collected sample is engaged with the collection tube (3) to seal the apparatus. For example, in some embodiments, the sampler wand (2) is configured to have a detachment feature so that the removable sampler head (8) is removed from the sampler wand (2) by manipulating the sampler wand (2) or the sealed apparatus (1). For example, in some embodiments, the stem (4) includes a cut point or detachment point so that, for example, the cap (5) is loosened from the collection tube (3) or rotated further relative to the collection tube (3) and separation occurs. In some embodiments, all or part of the stem (4) remains attached to the removed sampler head (8), while in some embodiments, all or part of the stem (4) detaches from the removed sampler head (8). In some embodiments, the engagement features of the sampler head (8) are configured to interact with the engagement features of the sampling tube (3) on, for example, the bottom wall (20) and / or displacement member (21) of the sampling tube (3), so that the sampler head (8) can be reversibly or irreversibly attached to the sampling tube (3), for example, when the device is sealed. The engagement of the sampler head (8) and the sampling tube (3) may be configured to facilitate the separation of the sampler head (8) from the cap (5), for example, by facilitating the cutting or detachment of the sampler head (8) from the cap (5).

[0114] In some embodiments, the device further includes, for example, an ejector that is movably mounted on or incorporated within the sampler wand (2) within the cap (5), and the sampler head (8) is removed from the cap (5) by operating the ejector (for example, by pressing or sliding a button, pulling a tab, rotating a part of the cap, etc.).

[0115] As shown in Figures 12B and 12C, in some embodiments, the apparatus (1) includes a gasketless seal at the joint between the cap (5) and the sampling tube (3). For example, a precision molding process may be used to create a sealed joint (27) between the cap and the sampling tube, where the contact between the surfaces of the cap (5) and the sampling tube (3) is direct. Figure 12B shows a detailed description of one embodiment in which the sealed joint (27) is made by contact between the flange portion (4a) of the stem (4) of the sampler wand (2) and the upper end (18) of the sampling tube (3), and Figure 12C shows one embodiment in which the sealed joint (27) is made by contact between the sealing lip (28) of the cap (5) and the sealing surface (29) on the inner side wall (30) of the sampling tube (3). In a preferred embodiment, the sealing lip (28) is an integral part of the cap (5), and for example, the sealing lip (28) is formed during a molding process that manufactures a part of the sampler wand (2), such as molding the cap (5) or the stem (4).

[0116] collection tube This technology provides an apparatus (1) including a collection tube (3). In some embodiments, the collection tube (3) has an overall tubular or cylindrical shape. However, the collection tube may have a non-circular cross-section, such as elliptical, hexagonal, or square. In a preferred embodiment, for example, as shown in Figure 1, the collection tube (3) using a threaded closure has a circular cross-section in 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 usually a projection from the bottom wall (20) of the collection tube (3) into the internal void (22) of the collection tube (3). See, for example, Figures 1 and 3. The displacement member (21) may be hollow or solid and may be formed from the same material as the collection tube (3), and may be formed when the tube is formed, or may be added to the flat bottom wall (20) of the collection tube after the body of the collection tube has been formed separately. In a preferred embodiment, the displacement member (21) is formed as an integral part of the collection tube (3) and is formed simultaneously with the collection tube (3) and from the same material as the collection tube (3). For example, Figure 4A provides a cross-sectional view of the apparatus (1) showing the displacement member (21) formed by a recess (26) formed in the bottom wall (20) of the collection tube (3), and the side wall (17), bottom wall (20), and displacement member (21) of the collection tube are formed as a continuous part, for example, from plastic. In some embodiments, the recess (26) is used as a method for engaging the collection tube (3) to engage the collection tube (with or without other components of the apparatus (1)) with a holder, rack, conveyor, mixer, gripper, rotor, etc.

[0117] In some embodiments, the displacement member (21) has an essentially circular cross-section, preferably centered on the central axis of the sampling tube (3). In a preferred embodiment, for example, in the closed or sealed device (1) shown in Figure 2, the central axis of the displacement member (21) is aligned with the centers of the cap (5), stem (4), and sampler head (8) on the central axis (23) of the device (1), as shown in Figures 1 and 2.

[0118] The purpose of the displacement member (21) is to occupy part or all of the internal void (9) of the sampler head (8) of the sampler wand (2). Therefore, in a preferred embodiment, the displacement member (21) is made to match the internal dimensions of the sampler head (8), as shown in Figure 4A. Furthermore, the displacement member (21) is positioned at the bottom of the collection tube (3) so that when the sampler wand (2) is fully inserted into the collection tube (3) (for example, when the cap (5) on the sampler wand (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 sampler head (8). Therefore, while being used to collect weighable samples, the material in the sampler head (4) is discharged from the sampler head through one or more ports (11) as the displacement member (21) displaces the material. The displacement member does not need to discharge all of the sample material from the sampler head, and the amount discharged can be determined by, for example, what percentage of the volume of the internal void (9) of the sampler head (8) is filled by the displacement member (21) when the device is sealed. In preferred embodiments, the displacement member of the collection tube fills at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the internal volume of the sampler head. In some embodiments, the collection tube (3) includes a movable displacement member (21), which may be positioned, for example, fully or partially withdrawn from the sampler head (8) when the sampler wand (2) is fully inserted into the collection tube (3), and may be moved in appropriate locations, such as extending into the internal void (9) of the sampler head (8), thereby displacing some or all of the material in the sampler head.

[0119] As shown in Figure 6A, the collection tube (3) has the maximum volume of its internal void (22) when empty. In this specification, the terms "mL" (milliliter) and "cc" (cubic centimeter) are used alternately with respect to the maximum volume of the collection tube, where 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., 1 mL, 0.01 mL, 0.001 mL, or multiples thereof). In a preferred embodiment, the collection tube (3) is arranged as follows: 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, 6 It has a maximum volume between approximately 10 mL and 100 mL, including 7, 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)).

[0120] As shown in Figure 6B, the primary residual volume of the internal void (22) of the sampling tube (3) is the maximum volume obtained by subtracting the volume of displacement caused by the stem (4) having the sampler head (8). Figure 6C shows the volume of the internal void (9) of the sampler head (8). In a preferred embodiment, the secondary residual volume of the internal void (22) when the stem and sampler head (8) are inserted is the maximum volume obtained by subtracting the volume of displacement caused by the stem (4) having the sampler head (8) and then subtracting the volume of the internal void (9) of the sampler head (8). The secondary residual volume is preferably at least twice (2X) the volume of the internal void (9) of the sampler head (8), preferably at least 3X, preferably at least 4X, preferably at least 5X, 6X, 7X, 8X, 9X, or 10X, or an intermediate fraction thereof (e.g., 4.1X, 4.2X, 4.3X, 4.4X, etc.). In other embodiments, the secondary residual volume of the internal void (22) is the same as or less than the internal volume (9) of the sampler head (8).

[0121] As shown in Figures 10 and 11, in a preferred embodiment, the remaining internal volume is preferably large enough to hold a certain amount of solution, such as a stabilizing solution or buffer solution, that at least partially, preferably mostly, covers the sampler head (8), and more preferably completely covers the sampler head (8). Preferably, the sampler head (8) is partially or completely covered when the sealed device containing the sample to be measured is horizontal, such as when it is lying on its side, as shown in Figure 11. Preferably, the ratio (v:v) of the internal void (9) of the sampler head (8) to a certain amount of solution in the collection tube 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), regardless of whether the solution is provided as a pre-filled solution or as a solution reconstituted from dried reagents.

[0122] In a preferred embodiment, when the sampler wand (2) is inserted into the collection tube (3), for example when the cap (5) engages with the collection tube (3) to form a sealed device, some or all of the material in the sampler head (8) is discharged into the ambient fluid, such as a stabilizing buffer in the collection tube (3).

[0123] For example, by filling the sampler head (8) with a material such as feces using a twisting, scooping, pushing, or scraping motion, a sample is provided having a volume or mass mainly determined by the volume of the internal void of the sampler head (8). When the sample is discharged through multiple ports (11), the sample is decomposed and dispersed in the buffer, enhancing the stabilizing effect of the buffer.

[0124] material Some embodiments have the advantage of constructing the apparatus from various types of materials, such as disposable materials, recyclable materials, reusable materials, sterilizable materials, autoclavable materials, chemically inert materials, and biodegradable materials. Components of apparatus (1) can be made from any material that provides structural integrity to the apparatus used for its intended purpose and is chemically and biochemically compatible with measured samples and solutions, such as stabilized buffers, which may come into contact with the apparatus.

[0125] The components of the apparatus may all be made of the same material, or different components may be made of different materials. For example, in a preferred embodiment, components of the apparatus (1) exposed to the metrological 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 may lead to the loss of the bound material. The materials are also typically 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. For example, the materials may be selected to avoid altering the composition of the sample components by releasing, leaching, and / or migrating materials such as plasticizers, coatings, or by-products of manufacturing (e.g., bisphenol A (BPA), phthalates, perfluoroalkyl compounds, and polyfluoroalkyl compounds (PFAS), fine particles such as talc powder, surfactants, dyes, etc.) into the sample.

[0126] In some embodiments, one or more elements of the apparatus are made from plastics such as polypropylene, polyethylene, polystyrene, or polytetrafluoroethylene. In some embodiments, the collection tube (3) is made from a transparent plastic such as polypropylene (PP) or polyethylene (PE), while in some embodiments, the collection tube may contain or consist of a non-transparent material to limit exposure to the sample contained within, for example. Different materials may be suitable for different applications and types of samples. Embodiments of the apparatus include, for example, silicone, glass, ceramic materials and / or crystalline materials (e.g., alumina, hydroxyapatite, zirconia, diamond, graphite), metallic materials (e.g., platinum, gold, cobalt-chromium alloys, stainless steel, titanium and titanium alloys, etc.), and / or polymers (e.g., acetal (ACL), cyclic olefin copolymer (COC), ethylene chlorotrifluoroethylene (ECTFE), ethylene propylene diene monomer rubber (EPDM), ethylene propylene rubber (EPR), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), fluorinated high-density polyethylene (FLPE), high-density polyethylene (HDPE)). This may include one or more of the following materials: 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 difluoride (PVDF), tetrafluoroethylene (PTFE / TFE), thermoplastic elastomer (TPE), trimethyl carbonate (TMC), TMC-NAD-lactide, etc. In some embodiments, the components of the sample wand (2) and the collection tube (3) are made from the same material.For example, in certain embodiments, the same material, such as polypropylene, polyethylene, or one of the polymers mentioned above, is used for multiple parts, but one or more parts may be of different colors or have different levels of transparency. For example, in some embodiments, the sampling tube (3) is made of transparent polypropylene, and parts of the sampler wand (2) (e.g., the cap (5), stem (4), and / or sampler head (8)) are made of opaque polypropylene, such as white polypropylene.

[0127] In some embodiments, the components of the sampler wand (2) and the collection tube (3) are made from different materials. For example, in some embodiments, the collection tube (3) is made of transparent polypropylene, and the parts of the sampler wand (2) (e.g., the cap (5), stem (4), and / or sampler head (8)) are made of opaque polyethylene, such as white polyethylene. On the other hand, 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 view or light, and the parts of the sampler wand (2) (e.g., the cap (5), stem (4), and / or sampler head (8)) are made of a transparent material, such as transparent polypropylene, polymethylpentene, or polycarbonate.

[0128] In some embodiments, the sampler wand (2) comprises a mixture of different materials. For example, in some embodiments, the cap (5) is made from one material, and the stem (4) and / or sampler head (8) are made from one or more different materials.

[0129] The materials used in the apparatus (1) are not limited to any particular selection or combination of suitable materials used in parts of the apparatus. In some embodiments, the materials and compositions are selected to give the apparatus a shelf life of at least two years. In some embodiments, the materials of the apparatus are selected to block light and / or ultraviolet light. For example, amber or opaque materials may be selected. In some embodiments, the materials may be selected to allow the sample contained therein to be examined, for example, optically or under different lighting conditions. Thus, in some embodiments, the materials may be selected for their optical properties, e.g., transparency under different lighting conditions, such as light in the sunlight spectrum and / or ultraviolet illumination. For example, in some embodiments, the materials may be selected to fluoresce or not fluoresce under ultraviolet light.

[0130] For example, as shown in Figures 4 and 12A, in some embodiments, the apparatus (1) includes a gasket (25) to seal the joint between the cap (5) and the collection tube (3). Any suitable material, usually a polymer material, may be used. In some embodiments, the gasket includes low-density polyethylene (LDPE), silicone, nitrile, EPDM (ethylene propylene diene monomer) rubber, vinylidenediene fluoride rubber (VITONO), etc. In certain preferred embodiments, the gasket comprises 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, Blauvert, NY).

[0131] In some embodiments, the material of the sampler head (8) may be selected to provide a certain degree of friction to the sample to hold the sample material, such as stool, during the collection process. In some embodiments, the inner surface of the sampler head (8) may provide friction to hold the weighing sample, for example, during the removal of the weighing sample from the stool sample. For example, in some embodiments, the number and arrangement of the ports (11) may be selected to enhance the holding of very soft samples, such as semi-liquid samples, within the internal sampler head (8).

[0132] In some embodiments, one or more materials or surfaces on materials within the apparatus (1) may be selected to provide a smooth surface to enhance the release of sample material from the sampler head (8), for example, and the collection tube (3) and / or stem (4) may have a smooth surface and / or a treated surface to enhance the release of material. In some embodiments, one or more of the apparatus surfaces include a non-sticky or hydrophobic layer or coating.

[0133] In some embodiments, the material of the cap (5) may be selected to enhance grip. For example, in some embodiments, the components of the cap (5) may include a thermoplastic vulcanized material (TPV), such as Santoprene® TPV (Celanese Corp.), to have a rubber-like grip and feel. Santoprene® TPV is an EPDM (ethylene propylene diene monomer) rubber that is fully dynamic vulcanized in a thermoplastic matrix of polypropylene (PP). In preferred embodiments, for example, as shown in Figure 2, the raised features (16) of the cap (5) are formed entirely or partially from the TPV.

[0134] In some embodiments, the cap (5) and / or the collection tube (3) are configured to facilitate automated processes such as opening, closing, and / or transporting the device by mechanical or robotic means. For example, in some embodiments, the cap (5) includes one or more features configured to engage with a cap driver device, such as a raised ridge or groove on the side of the cap (5) and / or the collection tube (3), a raised element and / or recessed feature(s) on the top of the cap (5) (e.g., a ridge, blade, cross-shaped, hexagonal, square, or star-shaped element), for rotating the cap (5) automatically or by robot using a cap driver.

[0135] solution In some embodiments, the apparatus includes a solution in a collection tube (3), and in some embodiments, the apparatus includes reagents in the form of, for example, one or more dry reagents, such as a powder, cake, or coating, or as an encapsulated composition that can be dissolved, suspended, or otherwise broken down in a fluid to provide the solution in the collection tube (3). In some embodiments, the solution (provided as a solution or in dry form to form the solution) is a stabilizing buffer that provides a buffer and one or more salts, such as sodium chloride. In certain embodiments, the stabilizing solution includes, for example, a Tris buffer and EDTA such as 500 mM Tris, pH 9.0, 150 mM EDTA, and 10 mM NaCl. In some embodiments, other salts may be used, such as Hanks Balanced Salt Solution (HBBS). HBSS: CaCl2 dihydrate 0.185g / L MgSO4 (anhydrous) 0.09767g / L KCl 0.4g / L KH2PO4 (anhydrous) 0.06g / L NaHCO3 0.35g / L NaCl 8.0g / L Na2PO4 (anhydrous) 0.04788g / L D-Glucose 1.0g / L pH 7.4 ± 0.2

[0136] In some embodiments, the stabilizing solution may comprise a protoporphyrin, a polyvalent cation, a sugar or polysaccharide, and optionally a polyvalent cation, osmolyte, and horseradish peroxidase (HRP) stabilizing component, and optionally a reagent selected from, for example, the polyvalent cations described in WO2019 / 190787, which is incorporated herein by reference for all purposes. For example, one such exemplary solution may comprise a buffer and Cr 3+ or Co 3- It contains a protoporphyrin that forms a complex with Cr 3+ The concentration of protoporphyrin that formed a complex with Co was 1.25-5 μM. 3+ The concentration of protoporphyrin that forms a complex with the compound is 2.5–10 μM.

[0137] In some embodiments, the stabilizing solution may comprise one or more surfactants (e.g., Tween-20) and nuclease inhibitors (e.g., RNase inhibitors, proteinase K, chelating agents). In some embodiments, the solution may comprise one or more sarcosyl and chaotropic salts (e.g., guanidine thiocyanates).

[0138] The solution contains components for breaking down, solubilizing, and / or suspending the quantified sample so that, when a portion of the mixture is drawn, a fixed amount suitable for analysis is provided. Furthermore, the solution contains components for stabilizing, preserving, and / or protecting the resulting suspension so that the analyte being tested (e.g., cells, RNA, DNA, proteins) does not degrade or become damaged between the time the sample is taken and the time it is tested. Thus, the solution helps ensure that the analysis of the quantified sample accurately reflects the analytes (e.g., RNA, DNA, proteins) present in the sample when the sample was taken. The solution or drying agent may contain components for neutralizing or binding to substances that may inhibit downstream assays, such as polyvinylpyrrolidone and / or polyvinylpolypyrrolidone, which bind to phenolic substances. In some embodiments, one or more reagents, such as polyvinylpolypyrrolidone, are provided in an insoluble form in the solution. In some embodiments, preferably, the apparatus houses a drying agent, in embodiments where the apparatus houses a drying reagent. This technology is intended to provide any solution that is useful for storing or preparing metrological samples, for example, for specific types of analysis.

[0139] Use of the device The apparatus is designed to provide a simple method for easily collecting and preparing fecal samples for analysis. Therefore, the apparatus is designed for use by both sample providers and sample testers. Since sample providers may, in some applications of the apparatus, be individuals without medical or clinical training, the apparatus is designed to be easy for such general users to use when acquiring samples. Thus, the apparatus is particularly suitable for remote use, such as at home or within a residential facility, or somewhere outside a clinic or laboratory, or for field use, such as collecting environmental or industrial samples. Therefore, in some embodiments, the collection tube (3) is made of an opaque material or covered with, for example, a label, so that the internal components (e.g., the stem and head of the sampler wand) are substantially hidden from the user's view, for example, to avoid confusion regarding the proper use of the apparatus.

[0140] At the same time, the apparatus is designed to allow for precise and accurate analysis of samples by human testers or mechanical testing equipment within appropriate tolerances. Generally, the apparatus is provided to the sample provider in an assembled form, for example, the collection tube (3) is pre-filled with a certain amount of solution, and the cap (5) of the sampler wand (2) is secured to the collection tube so that the apparatus (1) is sealed.

[0141] Once the stool sample is produced, the sample provider removes the sample wand (2) from the collection tube (3) and positions the distal edge (12) of the sample head (8) onto the site on the stool sample. Using a twisting motion, the sample provider inserts the distal edge (12) of the sample head (8) into the sample, preferably capturing a substantially cylindrical portion of the sample within the internal cavity (9) of the sample head (8). Preferably, the sample provider collects enough stool material to fill the internal cavity (9) of the sample head (8) by collecting it from a single location on the sample or by successively collecting it from multiple different locations on the sample. In some embodiments, teeth (13) on the sample head (8) may also be used to loosen the sample material and / or collect the sample material by scraping, for example, scraping off the entire sample, in order to obtain samples from multiple locations. In a preferred embodiment, when the sampler head is removed from the sample by a twisting motion, the sampler head (8) is released from the sample with minimal excess fecal material on the outside of the sampler head (8).

[0142] The sample wand (2) is then reinserted into the collection tube (3), the cap screw (7) engages with the pipe thread (24), and the cap (5) is rotated relative to the collection tube (3) until it can no longer be rotated, so that the device (1) is completely sealed and no fluid can leak out.

[0143] Once the cap (5) is returned to the collection tube (3) and secured to it, the displacement member (21) aligns with the sampler head (8) and is pushed into the sampler head (8) through the sampler head opening (14). The displacement member (21) then pushes the stool material from the sampler head (8) through the port (11) into a solution, such as a buffer solution, contained in the collection tube (3). Pushing the sample material through the port can finer and reduce the particle size of the sample, and the solution then works to further finen, solubilize, and / or suspend the sample to be weighed. In addition, the solution usually contains components to stabilize, preserve, and / or protect the suspension. In some embodiments, the sample provider further mixes the solution and the sample to be weighed by, for example, shaking, rotating, or otherwise stirring the sealed device. The sample provider then returns the sealed device (1) containing the sample to a laboratory, clinic, or other location for analysis. In some embodiments, the device is designed to be suitable for return via mail or delivery service.

[0144] Next, the testing facility takes out a portion of the stool suspension for analysis. In some embodiments, the sealed container is shaken, rotated, or vortexed to ensure that the sample is completely dispersed or homogenized in the solution. The user or machine takes out a portion of the suspension (e.g., by a needle or pipette tip) for further processing and testing to collect a certain volume of the suspension. As shown in Figure 9, the sampler wand (2) is removed from the collection tube (3) to access the mixture of buffer and stool in the collection tube (3). As illustrated, embodiments of the collection tube (3) are configured to allow the pipette tip to reach the bottom of the collection tube without obstruction, facilitating the withdrawal of a certain volume or essentially all of the suspension material. In some embodiments, the suspension is removed from the collection tube (3) without removing the sampler wand (2). For example, in some embodiments, the cap (5) or collection tube (3) includes an openable and closable port that provides access to the fluid or suspension contained within the apparatus. In some embodiments, the apparatus may be punctured, for example, with a needle or cannula, to access the fluid or suspension contained within the apparatus. In some embodiments, the apparatus (1) includes a pierceable seal from which a portion of the suspension is obtained. In some embodiments, it is specified that the seal is made of foil. However, other materials are suitable for the apparatus as long as the material seals the sample collection chamber while being pierceable (for example, by a pipette tip or a hypodermic needle) so that a person or machine can obtain a portion of the sealed contents within the apparatus (1). Non-limiting examples of materials provided in various embodiments include, for example, foil paper in layered or laminated forms, rubber, wax, plastic, and combinations thereof.

[0145] In some embodiments, a cap with an attached sampler wand is replaced, for example, after the sample is discharged from the sampler head into the solution in the collection tube. Such a replacement cap is preferably one that engages with the collection tube (3) to form a sealed container, but does not have a sampler wand attached, thereby facilitating or simplifying additional processing steps, such as centrifugation and obtaining a supernatant or pelletized sample using the original collection tube (3).

[0146] In some embodiments, part or all of the suspension is poured from the collection tube (3) into another container or apparatus for further processing steps. After a certain amount of the required suspension has been drawn, the apparatus may be resealed, and any remaining stool sample suspension may be stored (e.g., heated, at room temperature, refrigerated, or frozen) as needed, used in another process, or discarded as needed.

[0147] Although the use of the apparatus for collecting stool samples is described as one embodiment, the apparatus (1) is applicable to collecting any type of similar soft material, such as food, environmental samples (e.g., soil or biological materials), waste, or industrial materials.

[0148] Systems and kits This technology is used in embodiments of the apparatus described, and in some embodiments, in kits that include optional components such as instructions for use (e.g., providing relevant method steps) and relevant packaging for storage, shipping, etc. Embodiments of a kit may include, for example, one or more solutions containing a collected metrological sample and the analytes contained therein, and stabilizing reagents, buffers, salts, or preservatives for use (e.g., for processing, homogenization, preservation, or storage).

[0149] The kit may also include other components useful for capturing stool samples, such as a collection system for use with a toilet or urinal to conveniently secure stool samples produced by the subject during defecation, and as a result, the weighing sample may be collected from the sample using this technique. Many different suitable toilet sample collectors, such as paper or plastic bowls, slings, webs, bags, or other containers that fit into a toilet or urinal, are available through medical supply suppliers, pharmacies, scientific supply companies, or directly from manufacturers such as Therepak Corp., Zymo Research, Alpha Labs, Excretas, HyStool, Abexx, Ability Building Community, or Takahashi Keisei Corp. Stool sample containers, U.S. Patent No. 10,265,054, are also suitable for use.

[0150] The kit may also provide other products to facilitate the use, pre- and post-use shipping, and handling of the device. For example, the kit may provide a holder or rack for holding the device during use (e.g., to stably hold the collection tube in a vertical position, to prevent spills when the device is not sealed) and / or to secure the sealed device in the shipping container.

[0151] Aspects of this technology are shown in U.S. Provisional Application No. 63 / 381,031 filed on 26 October 2022, U.S. Design Application No. 29 / 867,482 filed on 26 October 2022, and WIPO 132201 / 970181898 filed on 26 April 2023, now International Registration No. DM / 231747, each of which is incorporated herein by reference in whole for all purposes.

[0152] experiment As described above, the present invention aims to overcome the challenge of providing a sample collection device that can be reliably used by any subject in a diverse subject population to collect weighable samples of materials, such as stool, in a stable manner suitable for transport, for example, from a subject's home to a medical laboratory, using standard commercial shipping methods or public mail. Exemplary embodiments of the device of the present invention are shown in Figures 1 to 12.

[0153] Example 1 Collection of weighing samples Using one embodiment of the sample collection apparatus shown in Figures 3A and 3B, fecal material was collected from the surface and interior of 20 different fecal samples with varying viscosities. The mass of each weighed sample collected from each fecal sample was measured to determine the range of sample sizes generated using the apparatus, and the results are shown in the table below. [Table 1]

[0154] These data indicate that the average mass of stool samples collected from different specimens was 10.8 grams per specimen, which is within a suitable range for use in processing and testing methods for stool samples (for example, the method described by DA Ablquist, et al., Gastroenterology 2012, 142.248-256, which is incorporated herein by reference in its entirety for all purposes).

[0155] Example 2 Nucleic acid capture and testing from collected weighing samples. Fecal material was collected from 10 stool samples (five samples from subjects in a state associated with specific target nucleic acids in their stool ("cases"), and five control samples) using one embodiment of the sample collection apparatus shown in Figures 3A and 3B. The sample wand containing the collected samples was inserted into a collection tube containing 40 mL of buffer. The mixture of collected weighed samples and buffer was processed, and the nucleic acids were isolated from the stool supernatant by directly capturing the target sequences by hybridization using oligonucleotide probes as described above by D.A. Ahlquist, et al. Three human target nucleic acids (A, B, and C) and one human reference nucleic acid (R) were isolated from each sample. The nucleic acids were analyzed using a PCR flap assay, for example, as described in WO2021 / 041726 to S. Morris, et al., which is incorporated herein by reference as a whole for all purposes. An increase in the amount of at least one of nucleic acids A, B, or C was interpreted as indicating a positive state of the subject (indicated as "POS" in the assay call column). The assay results are summarized in the table below. [Table 2]

[0156] From each weighed sample, sufficient stool supernatant was obtained to analyze the panel of the four nucleic acids listed above at least twice. These data demonstrate that the sample collection device of this technology was used to obtain sufficient stool volume to quantitatively analyze specific human target nucleic acids with sufficient sensitivity and specificity for diagnostic purposes.

[0157] All documents and similar materials cited in this application, including but not limited to patents, patent applications, articles, books, papers, manufacturer's publications and product documents, and internet web pages, are 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 those skilled in the art to which the various embodiments described herein belong. If there is any difference between the definition of a term in an incorporated reference and the definition given herein, the definition given herein shall prevail.

[0158] The scope of this disclosure is not intended to be limited by any specific disclosure of preferred embodiments in this section or elsewhere in this specification, but may be defined by claims presented or hereafter presented in this section or elsewhere in this specification. The wording of the claims shall be interpreted broadly on the basis of the wording used in the claims, and shall not be limited to the examples described herein or at the time of filing, and such examples shall be interpreted as non-exclusive.

[0159] Features, materials, characteristics, or groups described in conjunction with a particular aspect, embodiment, or example should be understood to be applicable to any other aspect, embodiment, or example described elsewhere in this section or specification, unless inconsistent with such other aspects, embodiments, or examples. All features disclosed herein (including any appended claims, abstracts, and drawings) and / or all steps of any method or process disclosed herein may be combined in any combination, except for any combination in which at least some of such features and / or steps are mutually exclusive. This protection is not limited to the details of any of the embodiments described above. The protected subject matter extends to any novel one or any novel combination of features disclosed herein (including any appended claims, abstracts, and drawings), or any novel one or any novel combination of any steps of any method or process disclosed herein.

[0160] Furthermore, certain features described in this disclosure in relation to separate embodiments can be combined to be implemented in a single embodiment. Conversely, various features described in relation to a single embodiment can be implemented separately in multiple embodiments or in any preferred partial combination. Furthermore, although features may be described above as working in a particular combination, one or more features from the claimed combination can, in some cases, be removed from that combination, and the combination can be claimed as a partial combination or a variation of a partial combination.

Claims

1. An apparatus for collecting and storing a sample for weighing, wherein the apparatus comprises a sampler wand equipped with a sampler head, and the sampler head is i) The sampler head side wall having multiple ports passing through the sampler head side wall, ii) The closed end of the sampler head, iii) Sampler head opening surrounded by distal edge, Equipped with, The sampler head sidewall, the sampler head closed end, and the sampler head opening define and accommodate the internal void of the sampler head having an internal volume. The aforementioned device.

2. The apparatus according to claim 1, wherein the sampler head opening lies on a plane defined by the distal edge.

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

4. The apparatus according to any one of claims 1 to 3, wherein the sample wand is equipped with a cap.

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

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

7. The apparatus according to any one of claims 1 to 6, wherein the distal edge of the sampler head is provided with one or more teeth.

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

9. The apparatus according to claim 8, wherein the internal void of the sampler head is sized to accommodate approximately 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 of sample material (including any intermediate fractions thereof), preferably fecal sample material.

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

11. The apparatus according to any one of claims 4 to 10, further comprising a collection tube having a bottom wall joined to the tube wall, wherein the upper end of the collection tube defines the opening of the tube.

12. The apparatus according to claim 11, wherein the cap has a cap engagement portion and the collection tube has an engagement portion into which it is fitted.

13. The apparatus according to claim 12, wherein the cap engagement portion is provided with a cap screw and the fitted engagement portion is provided with a pipe screw.

14. The apparatus according to claim 12 or claim 13, wherein when the cap engagement portion and the fitted engagement portion are engaged, the sampler wand and the collection tube form a sealed apparatus.

15. The collection tube has an internal void surrounded by a plane defined by the tube wall, the bottom wall, and the upper end, and 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 fraction therebetween), preferably between about 10 mL and 100 mL, 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, The apparatus according to claim 14, having a maximum internal void volume including 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).

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

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

18. The apparatus according to claim 17, wherein the cap has a center point on the cap's central axis, the sampler wand has a wand central axis defined by the center point of the cap and the center point of the sampler head opening, and when the sampler wand and the collection tube are sealed together, the wand central axis and the tube central axis are on the same line.

19. The apparatus according to any one of claims 16 to 18, wherein when the sampler wand and the collection tube are sealed together, the displacement member of the collection tube is positioned inside the sampler head and fills at least a portion of the internal void of the sampler head.

20. The apparatus according to claim 19, wherein when the sampler wand and the collection tube are sealed together, the displacement member of the collection tube fills at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, and 99% of the internal volume of the internal void of the sampler head.

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

22. The apparatus according to any one of claims 16 to 21, wherein the apparatus has a primary residual volume of the internal void of the collection tube that is equal to the maximum volume of the internal void obtained by subtracting the volume of the internal void that is displaced by the sampler head and the sampler system.

23. The apparatus according to claim 22, wherein the ratio (v:v) of the primary residual volume of the internal void of the sampler head to 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 apparatus according to any one of claims 16 to 23, wherein the apparatus further comprises a certain amount of solution contained in the collection tube.

25. The apparatus according to claim 24, wherein the ratio (v:v) of the volume of the internal void of the sampler 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 aforementioned solution i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and viiii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants and, xi) Nuclease inhibitors, xi) Protease inhibitors, xiiii) Chelating agent, xiv) Chaotropic salt and, xv) Inhibitor conjugate, The apparatus according to claim 24 or claim 25, comprising one or more agents selected from the group consisting of the following.

27. The apparatus according to any one of claims 16 to 23, further comprising at least one drying agent contained in the collection tube.

28. The at least one drying agent is i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and viiii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants and, xi) Nuclease inhibitors, xi) Protease inhibitors, xiiii) Chelating agent, xiv) Chaotropic salt and, xv) Inhibitor conjugate, xvi) Desiccant, The apparatus according to claim 27, comprising one or more agents selected from the group consisting of the following.

29. The apparatus according to any one of claims 22 to 28, wherein the apparatus has a secondary residual volume of the internal void of the sampling tube that is equal to the maximum volume of the internal void of the sampling tube, obtained by subtracting the volume displaced by the sampler head and sampler system, and subtracting the volume of the internal void of the sampler head.

30. The apparatus according to claim 29, wherein the ratio (v:v) of the secondary residual volume of the internal void of the sampler head to 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 for collecting a sample for measurement of materials, a) To provide an apparatus comprising a sampler wand equipped with a sampler head, wherein the sampler head is i) The sampler head side wall having multiple ports passing through the sampler head side wall, ii) The closed end of the sampler head, iii) Sampler head opening surrounded by distal edge, Equipped with, The sampler head side wall, the sampler head closed end, and the sampler head opening define and accommodate an internal void of the sampler head having an internal volume, and to provide, b) Collecting a certain amount of the material from the internal void of the sampler head, The method, including the method described above.

32. The method according to claim 31, wherein the sampler head opening lies on a plane defined by the distal edge.

33. The method according to claim 31 or claim 32, wherein the sample wand is equipped with a cap.

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

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

36. The method according to any one of claims 31 to 35, wherein the distal edge of the sampler head is provided with one or more teeth.

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

38. The method according to claim 37, wherein the internal void of the sampler head is sized 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 of sample material (including any intermediate fractions thereof), preferably fecal sample material.

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

40. The apparatus according to any one of claims 33 to 39, wherein the apparatus further comprises a collection tube having a bottom wall joined to the tube wall, and the upper end of the collection tube defines a tube opening.

41. The method according to claim 40, wherein the cap has a cap engagement portion and the collection tube has an engagement portion into which it is fitted.

42. The method according to claim 41, wherein the cap engagement portion is provided with a cap screw and the fitted engagement portion is provided with a pipe screw.

43. The method according to claim 41 or claim 42, wherein when the cap engagement portion and the fitted engagement portion are engaged, the sampler wand and the collection tube form a sealed device.

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

45. The collection tube has an internal void surrounded by a plane defined by the tube wall, the bottom wall, and the upper end, and the internal void of the tube is at least 5 mL, preferably between about 5 mL and 250 mL (including any intermediate number or amount in mL), preferably 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, 4 The method according to claim 44, having a maximum volume between approximately 10 mL and 100 mL, comprising 7, 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).

46. The method according to any one of claims 40 to 45, wherein the bottom wall of the collection tube is provided with 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 central axis defined by the center point of the opening of the collection tube 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's central axis, the sampler wand has a wand central axis defined by the center point of the cap and the center point of the sampler head opening, and when the sampler wand and the collection tube form a sealed device, the wand central axis and the tube central axis are on the same line.

49. When the sampler wand and the collection tube form a sealed device, the displacement member of the collection tube is positioned inside the sampler head and fills at least a portion of the internal void of the sampler head, thereby at least a portion of the amount of material collected in the internal void of the sampler head is discharged from the internal void of the sampler head through the port inside the sampler head into the collection tube, and the measured sample of the material is, The amount of the material contained within the internal void of the sampler head, The amount of the material discharged from the internal void of the sampler head, The method according to any one of claims 46 to 48, selected from the following.

50. The apparatus according to claim 49, wherein the apparatus further comprises a certain amount of solution contained in the collection tube.

51. The method according to claim 50, wherein the ratio (v:v) of the volume of the sample to the fixed amount of solution in the collection tube, or the ratio (w:v) of the mass of the sample to the fixed amount of 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 aforementioned solution i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and viiii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants and, xi) Nuclease inhibitors, xi) Protease inhibitors, xiiii) Chelating agent, xiv) Chaotropic salt and, xv) Inhibitor conjugate, The method according to claim 50 or claim 51, comprising one or more reagents selected from the group consisting of the following.

53. A kit for collecting samples for weighing materials, i) The apparatus according to any one of claims 1 to 30, ii) Solution and, Desiccant and Drugs selected from, The kit comprising the above.

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

55. The aforementioned drug, i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and viiii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants and, xi) Nuclease inhibitors, xi) Protease inhibitors, xiiii) Chelating agent, xiv) Chaotropic salt and, xv) Inhibitor conjugate, The kit according to claim 53 or claim 54, which is a solution comprising one or more reagents from the group consisting of the following.

56. The aforementioned drug, i) Buffer solution, ii) Salt and, iii) Preservatives and, iv) Detergent and, v) Sugars or polysaccharides, vi) Protoporphyrin and, vii) Polyvalent cations and viiii) Osmolite and, ix) Horseradish peroxidase (HRP) stabilizing component, x) Surfactants and, xi) Nuclease inhibitors, xi) Protease inhibitors, xiiii) Chelating agent, xiv) Chaotropic salt and, xv) Inhibitor conjugate, xvi) Desiccant, The kit according to claim 53 or claim 54, which is a dried drug comprising one or more reagents from the group consisting of the following.

57. a) Packaging for shipping, storing, or mailing the device, b) A printed instruction manual for collecting a sample for measurement using the apparatus, c) A collection system for holding the sample material while collecting a sample for weighing, d) A holder for holding an unsealed device during the collection of weighing samples from a specimen, e) A holder for securing the sealed device inside the shipping container, The kit according to any one of claims 53 to 56, further comprising one or more of the above.

58. A method for processing stool samples, a) Obtaining a stool sample by the method described in any one of claims 31 to 52, b) Testing the stool sample for the amount and / or presence of one or more analytes, wherein the analytes are i) Nucleic acids and, ii) Proteins and, iii) Lipids and, iv) Carbohydrates, v) Metabolites and, The testing includes one or more of the following: The method, including the method described above.

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