Biological sample collection system with torsion activated valve for sample release

Abstract

A biological sample collection system is provided that includes a sealed container and a sample collection assembly coupled thereto. The assembly includes a sample collector in threaded engagement with a sample collection container, the sample collection container having a sample receiving region for receiving the biological sample from the sample collector. The collector includes a valve stem that includes a valve face, and the collection container includes a complementary valve seat. The valve stem and the valve seat form a valve that includes a closed configuration in which the threaded connection members of the collector and the collection container are fully engaged, and an open configuration in which the threaded connection members are not fully engaged. In the closed configuration, the valve face forms a sealing engagement with the valve seat. In the open configuration, the valve face is spaced apart from the valve seat to cause the sealed container, the collection container, and the collector to be in fluid communication with each other.

Description

Technical Field

[0001] The present invention relates to a biological sample collection system. More particularly, the present invention relates to a biological sample collection system having a twist-activated valve for sample release. Background Art

[0002] On-site collection of biological samples (such as saliva or sputum) can provide invaluable information about patients or donors. It may be inconvenient to require patients / donors to go to biological sample collection sites or laboratories. Similarly, it may be difficult and expensive for laboratory personnel to directly contact patients / donors for sample collection, especially if the sample size is large and / or geographically different. In addition, patients / donors are usually inexperienced first-time donors, so it is crucial that biological sample collection systems are easy for novice users to operate or manipulate. The desired collection system does not require professional / clinicians, facilities and equipment when collecting, transporting and storing biological samples.

[0003] At ambient temperatures, nucleic acids and other biomolecules (e.g., metabolites) in biological samples degrade rapidly and must often be stored at refrigerated temperatures to remain stable. This problem is magnified when biological samples are collected at remote field locations or at a significant distance from a laboratory or doctor's office, and especially when electricity and refrigeration are nonexistent or inconsistent. In addition, transporting biological samples with dry ice or ice packs is expensive, complicated, and impractical, and may result in worker exposure to infectious agents or pathogens. Therefore, there is a need for a safe collection, transportation, and storage system that can maintain the integrity of the collected biomolecules in biological samples under ambient conditions for further molecular analysis or diagnostic testing.

[0004] An improved reservoir system for releasably and reliably storing a substance is needed. It is often desirable to store a substance (e.g., a liquid, solid, slurry, gas, mixtures thereof, etc.) in a reservoir or compartment prior to mixing the contents of the reservoir with another material. For example, prior to combining one or more compounds with another material, it may be desirable to package and store the compounds in a reservoir for transport and / or safe storage and handling.

[0005] Before toxic compounds are combined with detoxification materials or reagents, it may be desirable to package and store such toxic compounds in a reservoir. Similarly, it is generally desirable to separate concentrated active ingredients from diluents until just before use. The reservoir system with a separate sealed compartment / chamber for sample preservatives protects patients / sample donors from contact, ingestion and / or spilling preservatives. Toxic compounds or preservatives are safely confined in a separate compartment of a sample collection device or system to allow the use of more effective chemicals or preservatives (e.g., denaturants), to stabilize biomarkers / biomolecules, e.g., nucleic acids and metabolites, contained in the collected sample. Only after closing the device or system containing the biological sample with a lid or cap, the compartment for the preservative will be opened, and the biological sample is allowed to mix with the preservative.

[0006] There are various reservoirs / systems for containing substances in a manner that allows a user to seal the closure to combine the substances. Typically, these reservoirs are dual compartment systems in which the substances are stored separately and the substances are combined by the user applying the reservoir / system closure. There are many ways to design the two compartment / chamber system. In particular, there is a need for a patient-friendly sample collection device or system that allows Safety Collection at home followed by leak-proof transport and storage at ambient or room temperature. A two compartment / chamber system is ideal for protecting the donor / patient from preservatives required to preserve the sample or analyte of interest until analysis. Ideally, the method or instructions involve a minimum number of steps for use.

[0007] Biological sample collection systems are needed to facilitate sample collection.

[0008] The purpose of providing this background information is to make known information that the applicant believes may be relevant to the present invention. It is not necessary to admit, nor should it be construed, that any of the foregoing information constitutes prior art to the present invention. Summary of the invention

[0009] In one aspect, a biological sample collection system is provided. The system comprises a sealed container, the sealed container comprising a first open end, the first open end for receiving a biological sample, a second end, the second end comprising a sample storage chamber, and a connecting member, the connecting member being disposed at the first open end; and a sample collection assembly, the sample collection assembly being configured to be connected to the first open end of the sealed container when collecting the biological sample. The sample collection assembly comprises a sample collector, the sample collector comprising a proximal open end, the proximal open end for receiving a biological sample, a distal open end, the distal open end being in fluid communication with the proximal open end; a valve stem; and a threaded connection member, the threaded connection member being disposed at the distal open end of the sample collector. The valve stem comprises a first rod end, the first rod end extending from an inner portion of the sample collector, the inner portion being disposed proximal to the distal open end of the sample collector; and an opposite second rod end, the second rod end comprising a valve face, the valve stem extending along the longitudinal axis of the sample collector and in a direction away from the proximal open end of the sample collector. The sample collection assembly further comprises a sample collection container, the sample collection container being configured to be in fluid communication with the sample collector when collecting the biological sample, the sample collection container comprising a proximal open end, the proximal open end being used to receive the biological sample from the sample collector, a distal open end, the distal open end being configured to be in fluid communication with the proximal open end, one or more walls, the one or more walls defining a sample receiving area and a valve seat, wherein the valve seat is complementary to the valve face of the sample collector. The sample collection assembly further comprises a threaded connection member disposed at the proximal open end, wherein the threaded connection member is complementary to the threaded connection member of the sample collector and is configured to engage therewith, and a connecting member disposed at the distal open end, wherein the connecting member is complementary to the connecting member of the sealed container and is configured to engage therewith. The valve stem and the valve seat form a valve, which includes: a closed configuration, wherein the threaded connection components of the sample collector and the sample collection container are fully engaged, wherein when the valve is in the closed configuration, the valve face forms a sealed engagement with the valve seat; and an open configuration, wherein the threaded connection components of the sample collector and the sample collection container are not fully engaged, wherein when the valve is in the open configuration, the valve face is spaced apart from the valve seat, so that the sealed container, the sample collection container and the sample collector are fluidically connected to each other.

[0010] On the other hand, a method for preserving biological molecules in a biological sample and / or neutralizing one or more inhibitors in the biological sample is provided, the method comprising: a) obtaining a biological sample; b) obtaining the above-mentioned biological sample collection system, wherein the valve is in a closed configuration; c) placing the biological sample in a sample collector, the sample collector being in fluid communication with a sample collection container, so that the biological sample is received in a sample receiving area of ​​the sample collection container; d) rotating the sample collector relative to the sample collection container in a first direction (e.g., counterclockwise) to move the valve from the closed configuration to an open configuration, so that the sealed container, The sample collection container and the sample collector are fluidically connected to each other, and the biological sample is received in the sample storage chamber of the sealed container; e) optionally, rotating the sample collector in a second direction (e.g., clockwise) relative to the sample collection container to return the valve to the closed configuration, wherein the second direction is opposite to the first direction; and f) mixing the biological sample received in the sample storage chamber of the sealed container with a stabilizing composition, preservative and / or neutralizer in the sealed container to preserve the biological molecules in the biological sample and / or neutralize one or more inhibitors in the biological sample. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] For a better understanding of the present invention, including the development process to obtain the final product, reference is made to the following description used in conjunction with the accompanying drawings, in which:

[0012] Figure 1 A perspective exploded view of a biological sample collection system 100 according to one embodiment of the present application is shown.

[0013] Figure 2a Shown Figure 1 1 is a side exploded view of the biological sample collection system 100 in FIG. Figure 2b It is along Figure 2a Simplified cross-sectional view taken along line CC.

[0014] Figure 3a Shown Figure 1 1 is a side view of the assembled biological sample collection system 100. Figure 3b Shown along Figure 3a A simplified cross-sectional view taken along line AA.

[0015] Figure 4a Shown Figure 1 1 is a perspective view of a sample collector 114 of a biological sample collection system 100. Figure 4b Shown Figure 4a A top view of the sample collector 114 is shown.

[0016] Figure 5A side view of an alternative embodiment of a sample collector 114 that may be used with the biological sample collection system 100 of the present application is shown.

[0017] Figure 6a -d show various views of alternative embodiments of the sample collector 114 that can be used with the biological sample collection system 100 of the present application. Figure 6a A perspective view showing an alternative embodiment of a sample collector 114 is shown. Figure 6b shows a second perspective view thereof, and 6c shows a side view thereof, and Figure 6d A top view is shown.

[0018] Figure 7a -d shows Figure 1 Various views of the sample collection container 114 of the biological sample collection system 100. Figure 7a is a side view, Figure 7b It is along Figure 7a A simplified cross-sectional view taken along line BB of Figure 7c is a perspective view, and Figure 7d It is a top view.

[0019] Figure 8a and 8b Shown Figure 1 A simplified cross-sectional view of the biological sample collection system 100 in operation, showing the closed configuration ( Figure 8a ) and the open configuration ( Figure 8b ) valve.

[0020] Figure 9a , 9b 9c illustrate a simplified partial cross-sectional view of a biological sample collection system 100a having an alternative embodiment of a sample collector (designated 114a). DETAILED DESCRIPTION

[0021] definition

[0022] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0023] As used in the specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0024] The term "comprising" as used herein will be understood to mean that the following list is non-exhaustive and may or may not include any other additional suitable items, such as one or more additional features, components, ingredients and / or elements, as the case may be.

[0025] As used herein, terms of degree such as "substantially", "about" and "approximately" refer to a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be interpreted as including a deviation of at least ±10% of the modified term if this deviation does not negate the meaning of the word modified by the term.

[0026] As used herein, the term "biological sample" will be understood to mean any biological sample that may contain substances of interest, particularly nucleic acids, and optionally proteins or other biomolecules of interest, or a composition comprising such a biological sample (e.g., where the biological sample has been pretreated with a stabilizer / preservative). A biological sample may include a body fluid (e.g., sputum or saliva) or a composition comprising a body fluid. In one embodiment, the biological sample is a liquid biological sample.

[0027] The term "body fluid" as used herein will be understood to mean naturally occurring fluids from humans or animals and includes, but is not limited to, urine; saliva; sputum; serum; plasma; blood; pharyngeal, nasal / nasopharyngeal and sinus secretions; mucus; gastric juice; pancreatic juice; bone marrow aspirate; cerebrospinal fluid; feces; semen; products of lactation or menstruation; cervical secretions; vaginal fluid; tears or lymph fluid. In one embodiment, the body fluid is selected from sputum or saliva.

[0028] The term "ambient temperature" as used herein refers to a range of temperatures that may be encountered by a biological sample collection system as described herein, starting from the point of collection, during transportation (which may involve relatively extreme temperatures, although typically for a short period of time (e.g., <5 days)), and during prolonged storage prior to analysis, wherein the biological sample collection system may contain a mixture of body fluids (e.g., saliva samples) and a stabilizing composition / preservative / neutralizer. In one embodiment, the ambient temperature is in the range of about -20°C to about 50°C. In another embodiment, the ambient temperature is room temperature (RT) and is in the range of about 15°C to about 25°C.

[0029] As described above, a two compartment / chamber system is ideal for protecting the donor / patient from preservatives required to preserve the sample or analyte of interest until analysis.One mechanism for separating the two compartments within a collection system is to utilize a valve.

[0030] As outlined in further detail below, the system as described herein is a two compartment / chamber system that utilizes a valve to separate a sample collection container from a sample storage chamber, wherein after collection of a biological sample, the valve is moved to an open position.

[0031] In one embodiment, a biological sample collection system is provided. The system includes a sealed container, the sealed container including a first open end, the first open end for receiving a biological sample, a second end, the second end including a sample storage chamber, and a connecting member, the connecting member being disposed at the first open end; and a sample collection assembly, the sample collection assembly being configured to be connected to the first open end of the sealed container when collecting the biological sample. The sample collection assembly includes a sample collector, the sample collector including a proximal open end, the proximal open end for receiving a biological sample, a distal open end, the distal open end being in fluid communication with the proximal open end; a valve stem; and a threaded connection member, the threaded connection member being disposed at the distal open end of the sample collector. The valve stem includes a first rod end, the first rod end extending from an inner portion of the sample collector, the inner portion being disposed proximal to the distal open end of the sample collector; and an opposite second rod end, the second rod end including a valve face, the valve stem extending along the longitudinal axis of the sample collector and in a direction away from the proximal open end of the sample collector. The sample collection assembly further comprises a sample collection container, the sample collection container being configured to be in fluid communication with the sample collector when collecting the biological sample, the sample collection container comprising a proximal open end, the proximal open end being used to receive the biological sample from the sample collector, a distal open end, the distal open end being configured to be in fluid communication with the proximal open end, one or more walls, the one or more walls defining a sample receiving area and a valve seat, wherein the valve seat is complementary to the valve face of the sample collector. The sample collection assembly further comprises a threaded connection member disposed at the proximal open end, wherein the threaded connection member is complementary to the threaded connection member of the sample collector and is configured to engage therewith, and a connecting member disposed at the distal open end, wherein the connecting member is complementary to the connecting member of the sealed container and is configured to engage therewith. The valve stem and the valve seat form a valve, the valve comprising: a closed configuration, wherein the threaded connection members of the sample collector and the sample collection container are fully engaged, wherein when the valve is in the closed configuration, the valve face forms a sealing engagement with the valve seat; and an open configuration, wherein the threaded connection members of the sample collector and the sample collection container are not fully engaged, wherein when the valve is in the open configuration, the valve face is spaced apart from the valve seat, so that the sealed container, the sample collection container and the sample collector are in fluid communication with each other. In one embodiment, the valve seat is disposed toward the distal open end of the sample collection container.

[0032] In another embodiment, the valve stem extends centrally from the distal open end of the sample collector, the inner portion of the sample collector is centrally disposed within the sample collector, and the inner portion of the sample collector is connected to an inner surface of the sample collector via at least one attachment; the inner surface of the sample collector, the inner portion of the sample collector and the at least one attachment together define at least one opening to provide fluid communication between the distal open end of the sample collector and the proximal open end of the sample collection container when collecting the biological sample.

[0033] In another embodiment, the sealing engagement between the valve face and the valve seat is fluid-tight.

[0034] In yet another embodiment, the sample collector is funnel-shaped.

[0035] In still yet another embodiment, at least a portion of the sample collector extending from the proximal open end comprises a flexible material.

[0036] In another embodiment, the flexible material comprises silicone or rubber.

[0037] In yet another embodiment, the connection member disposed at the first open end of the sealed container and the connection member disposed at the distal open end of the specimen collection container comprise a threaded connection.

[0038] In another embodiment, the opposing second rod end extends beyond the distal open end of the sample collector.

[0039] In another embodiment, the capacity of the sample receiving area of ​​the sample collection container is about 0.1 mL to about 10 mL of sample.

[0040] In yet another embodiment, the sample storage chamber of the sealed container comprises a stabilizing composition, a preservative and / or a neutralizing agent. Suitable stabilizing compositions, preservatives and neutralizing agents are well known to those skilled in the art. In another embodiment, the preservative may be a single component or a composition. In another embodiment, the neutralizing agent may be a single component or may be a composition. In another embodiment, the neutralizing agent neutralizes one or more inhibitors in a biological sample, such as nucleases, including deoxyribonucleases and ribonucleases. In another embodiment, the stabilizing composition, preservative and / or neutralizing agent may include, for example, a composition described in U.S. Patent Nos. 7,482,116, 10,000,795 or 8,158,357.

[0041] In yet another embodiment, the valve is configured to move from the closed configuration to the open configuration by rotating the sample collector relative to the sample collection container in a first direction (e.g., counterclockwise) such that the threaded connection members of the sample collector and the sample collection container are not fully engaged. In another embodiment, rotating the sample collector relative to the sample collection container in the first direction comprises about a quarter turn of rotation.

[0042] In another embodiment, the valve can be returned from the open configuration to the closed configuration by rotating the sample collector relative to the sample collection container in a second direction (e.g., clockwise) to fully engage the threaded connection members of the sample collector and the sample collection container, wherein the second direction is opposite to the first direction. In yet another embodiment, rotating the sample collector relative to the sample collection container in the second direction comprises about a quarter turn.

[0043] In another embodiment, a method for preserving biomolecules in a biological sample and / or neutralizing one or more inhibitors in the biological sample is provided, the method comprising: a) obtaining a biological sample; b) obtaining a biological sample collection system as described herein, wherein the valve is in a closed configuration; c) placing the biological sample in a sample collector, the sample collector being in fluid communication with a sample collection container so that the biological sample is received in a sample receiving area of ​​the sample collection container; d) rotating the sample collector relative to the sample collection container in a first direction (e.g., counterclockwise) to move the valve from the closed configuration to an open configuration so that the seal is released. The sealing container, the sample collection container and the sample collector are fluidly connected to each other, and the biological sample is received in the sample storage chamber of the sealed container; e) optionally, rotating the sample collector in a second direction (e.g., clockwise) relative to the sample collection container to return the valve to the closed configuration, wherein the second direction is opposite to the first direction; and f) mixing the biological sample received in the sample storage chamber of the sealed container with a stabilizing composition, a preservative and / or a neutralizer in the sealed container to preserve the biological molecules in the biological sample and / or neutralize one or more inhibitors in the biological sample.

[0044] In another embodiment, rotating the sample collector relative to the sample collection container in the first direction comprises about a quarter turn of rotation. In another embodiment, rotating the sample collector relative to the sample collection container in the second direction comprises about a quarter turn of rotation.

[0045] Figure 1 , 2a-b, 3-b, 4a-b, 7a-d and 8a-b show a biological sample collection system 100 and its components according to an embodiment of the present application. System 100 includes a sealed container shown as a tube 102, which in the illustrated embodiment is generally cylindrical in shape. Any suitable sealed container can be used, such as a common sample collection tube known in the art or other vials / tubes / reservoirs / containers having the properties described herein. Tube 102 includes a first open end 104, which is used to receive a biological sample, such as a body fluid (e.g., sputum or saliva); a second end 106, which includes a sample storage chamber 108 defined by a wall 107. Tube 102 further includes a connecting member 110 disposed at the first open end 104, which in the illustrated embodiment is an external helical thread located on the outer surface of the wall 107 of tube 102. As will be appreciated by those skilled in the art, in alternative embodiments, an internal helical thread (not shown) may be present.

[0046] The tube 102 can have any desired width, length or thickness as desired and is made of an inert durable material such as polyethylene, polypropylene, polystyrene or related plastics. The tube 102 is ideally self-supporting. Optionally, a base (not shown) can be provided for the tube 102 to prevent the system 100 from tipping over. The sample storage chamber 108 is suitable for containing substances such as liquids, solids, semi-solids, slurries, suspensions, powders, colloids, gels, gases, mixtures thereof, etc. The sample storage chamber 108 should have sufficient void volume to accommodate the biological sample, plus any desired composition or agent for mixing with the sample.

[0047] The wall 107 of the tube 102 should ideally be transparent or translucent to allow the sample to be viewed once collected. The wall 107 may be free of any markings or other indicia, and should be adapted to be comfortably held by a user. However, if desired, the wall may be decorated, and / or have handles or raised textures on its outer surface for ease of holding, or graduated markings indicating volume.

[0048] The system 100 further includes a sample collection assembly 112 connected to the first open end 104 of the tube 102. The sample collection assembly 112 includes a sample collector 114. The sample collector 114 includes a proximal open end 116 for receiving a biological sample 118 and a distal open end 120 in fluid communication with the proximal open end 116. In one embodiment, the sample collector 114 tapers from the proximal open end 116 to the distal open end 120. Figure 1 , 2aIn the embodiments shown in Figures 1-b, 3-b, 4a-b and 8a-b, the sample collector 114 is funnel-shaped. The sample collector 114 further includes a valve stem 122 and an opposite second stem end 128, wherein the valve stem includes a first stem end 124 extending from an inner portion 126 of the sample collector 114 (see Figure 2b and 3b ,as well as Figure 4a -b), the inner portion 126 is disposed proximal to the distal open end 120 of the sample collector 114, the opposite second stem end includes a valve face 130, and the valve stem 122 extends along the longitudinal axis (L) of the sample collector 114 and in a direction away from the proximal open end 116 of the sample collector 114 (see specifically Figure 2b In the illustrated embodiment, the opposing second rod end 128 extends beyond the distal open end 120 of the sample collector 114. The sample collector 114 further includes a threaded connection member 132 disposed at the distal open end 120 of the sample collector 114.

[0049] If you can Figure 4a and 4b As seen in FIG. 1 , the valve stem 122 extends centrally from the distal open end 120 of the sample collector 114 , and an interior portion 126 of the sample collector 114 is centrally disposed within the sample collector 114 , the interior portion 126 of the sample collector 114 being connected to an interior surface 150 of the sample collector by at least one attachment 152 . Figure 4b The illustrated embodiment has three such attachments 152. The inner surface 150 of the sample collector 114, the interior portion 126 of the sample collector 114, and the at least one attachment 152 collectively define at least one opening 154 to provide fluid communication between the distal open end 120 of the sample collector 114 and the proximal open end 136 of the sample collection container 134. Figure 4b The illustrated embodiment has three such openings 154 .

[0050] Figure 5 and 6a -d shows an alternative embodiment of the sample collector 114, which is similar in shape to Figure 4a - The embodiment shown in b is different. Figure 6a -d The example shown is similar to Figure 4a -b embodiment, because the sample collector 114 is funnel-shaped; however, although Figure 4a -b embodiment, the proximal open end 116 is circular in top view, but Figure 6a The proximal open end 116 of the -d embodiment has a more rectangular shape in top view (eg, stadium or pill shape), which may be beneficial for shipping purposes. Figure 5An alternative embodiment is shown in which the sample collector 114 has a more cylindrical shape.

[0051] The sample collector 114 can have any desired width, length, or thickness as desired, and can be made of an inert durable material such as polyethylene, polypropylene, polystyrene, or related plastics or glass. The collector 114 can be formed from a one-piece mold, or, alternatively, the collector 114 can be formed from separate components that are assembled to form this portion of the sample collection system 100. Alternatively, in any of the embodiments of the sample collector 114, at least a portion of the sample collector 114 extending from the proximal open end 116 can include a flexible material, such as silicone or rubber, to allow this portion of the sample collector 114 to be compressed during shipping, while maintaining a more rigid, more durable plastic material in the portion of the sample collector 114 where the valve stem 122 extends and the portion where the threaded connection member 132 is located.

[0052] The sample collection assembly 112 further includes a sample collection container 134 in fluid communication with the sample collector 114. The sample collection container 134 includes a proximal open end 136 for receiving the biological sample 118 from the sample collector 114 and a distal open end 138 configured to be in fluid communication with the proximal open end 136. The sample collection container 134 has one or more walls 140 defining a sample receiving area 142 and a valve seat 144 (see in detail). Figure 2b and 7b ), wherein the valve seat 144 is complementary to the valve face 130 of the sample collector 114. In one embodiment, the sample receiving area 142 of the sample collection container 134 is volumetric and / or contains a mark line or fill-to-line so that the donor delivers the correct amount of biological sample for subsequent mixing with the stabilizing composition, preservative and / or neutralizer. As will be appreciated by those skilled in the art, the capacity can be extended to any desired volume. In an embodiment in which the biological sample is saliva / sputum, the capacity of the sample receiving area can be in the range of 1-2 mL. In an embodiment in which the biological sample is urine, the capacity of the sample receiving area can be in the range of 1-50 mL. In one embodiment, the capacity of the sample receiving area 142 can be about 0.1 mL to about 10 mL of sample.

[0053] In one embodiment, the valve face 130 and / or the valve seat 144 can be made of a flexible material or over-mould (e.g., silicone or rubber). For example, if one surface is hard and the other surface is soft, the corresponding surfaces can "bite" to each other and form a good seal.

[0054] The sample collection container 134 also has a threaded connection member 146 disposed at the proximal open end 136, wherein the threaded connection member 146 is complementary to and configured to engage with the threaded connection member 132 of the sample collector 114. The sample collection container 134 further has a connection member 148 disposed at the distal open end 138, wherein the connection member 148 is complementary to and configured to engage with the connection member 110 of the tube 102. In the embodiment shown in the figures, the connection member 110 disposed at the first open end 104 of the tube 102 and the connection member 148 disposed at the distal open end 138 of the sample collection container 134 include a threaded connection; however, other connection members known to those skilled in the art, such as a snap-fit ​​or press-fit arrangement, may also be used.

[0055] The sample collection container 134 may have any desired width, length, or thickness as desired, and may be made of an inert, durable material such as polyethylene, polypropylene, polystyrene, or related plastics, or glass.

[0056] If you can Figure 8a -b, the valve stem 122 including the valve face 130 forms a valve with the valve seat 144, the valve comprising: (a) a closed configuration, wherein the threaded connection member 132 of the sample collector 114 and the threaded connection member 146 of the sample collection container 134 are fully engaged, wherein when the valve is in the closed configuration, the valve face 130 forms a sealing engagement with the valve seat 144 ( Figure 8a ); and (b) an open configuration, wherein the threaded connection member 132 of the sample collector 114 and the threaded connection member 146 of the sample collection container 134 are not fully engaged, wherein when the valve is in the open configuration, the valve face 130 is spaced apart from the valve seat 144, so that the tube 102, the sample collection container 134 and the sample collector 114 are in fluid communication with each other ( Figure 8b ). In one embodiment, a "click" may be felt by the user and / or labels may be displayed on the sample collector 114 and the sample collection container 134 to indicate to the user when the open configuration of the valve is achieved. In one embodiment, the sealing engagement between the valve face 130 and the valve seat 144 in the closed configuration is fluid-tight.

[0057] like Figure 8a As shown in Figure 1-b, the sample storage chamber 108 of the tube 102 can contain a stabilizing composition, a preservative and / or a neutralizing agent 156.

[0058] exist Figure 8aIn the embodiment shown in Figure 1-b, the valve is configured to move from a closed configuration to an open configuration by rotating the sample collector 114 relative to the sample collection container 134 in a first direction (e.g., counterclockwise) such that the threaded connection members (132, 146) of the sample collector 114 and the sample collection container 134 are not fully engaged. In one embodiment, rotating the sample collector 114 relative to the sample collection container 134 in the first direction involves approximately a quarter turn of rotation.

[0059] The valve can then be returned from the open configuration to the closed configuration by rotating the sample collector 114 relative to the sample collection container 134 in a second direction (e.g., clockwise) to fully engage the threaded connection members (132, 146) of the sample collector 114 and the sample collection container 134, wherein the second direction is opposite to the first direction. In one embodiment, rotating the sample collector 114 relative to the sample collection container 134 in the second direction comprises approximately a quarter turn.

[0060] Thus, in one embodiment, a method for preserving biomolecules in a biological sample and / or neutralizing one or more inhibitors in the biological sample is provided, the method comprising: a) obtaining a biological sample 118; b) obtaining a biological sample collection system 100 as described herein, wherein the valve is in a closed configuration; c) placing the biological sample 118 in a sample collector 114, the sample collector 114 being in fluid communication with a sample collection container 134, such that the biological sample 118 is received in a sample receiving area 142 of the sample collection container 134 (see Figure 8a ) d) rotating the sample collector 114 relative to the sample collection container 134 in a first direction (e.g., counterclockwise) to move the valve from the closed configuration to the open configuration, so that the tube 102, the sample collection container 134 and the sample collector 114 are fluidically connected to each other, and the biological sample 118 is received in the sample storage chamber 108 of the tube 102; e) optionally, rotating the sample collector 114 relative to the sample collection container 134 in a second direction (e.g., clockwise) to return the valve to the closed configuration, wherein the second direction is opposite to the first direction; and f) mixing the biological sample 118 received in the sample storage chamber 108 of the tube 102 with the stabilizing composition, preservative and / or neutralizer 156 in the tube 102 to preserve the biological molecules in the biological sample 118 and / or neutralize one or more inhibitors in the biological sample.

[0061] In the case where the biological sample is saliva / sputum, the biological sample 118 may be placed in the sample collector 114 by expectorating the sputum from the oral cavity of the user / sample donor.

[0062] In one embodiment, rotating the sample collector 114 in a first direction relative to the sample collection container 134 comprises approximately a quarter turn rotation. In another embodiment, rotating the sample collector 114 in a second direction relative to the sample collection container 134 comprises approximately a quarter turn rotation.

[0063] The biological sample collection system 100 can be shipped to the user / sample donor with the valve in a closed configuration to preserve the stabilizing composition, preservative, and / or neutralizer 156 contained in the tube 102 from contamination thereof and to protect the patient / sample donor from contact, ingestion, and / or spillage of the stabilizing composition / preservative / neutralizer. After sample collection, the biological sample collection system 100 can be shipped to a laboratory for analysis, again with the valve in a closed configuration to preserve the mixture of the stabilizing composition / preservative / neutralizer 156 contained in the tube 102 and the biological sample 118 and to preserve the mixture from contamination prior to analysis.

[0064] In an alternative embodiment of the sample collection system, the valve stem is a first valve stem and the valve is a first valve, and the sample collection system further comprises a second valve stem, the second valve stem comprising: a proximal end extending from and releasably engaging with an opposite second stem end of the first valve stem; and a distal end comprising a second valve face. The second valve stem extends along a longitudinal axis (L) of the sample collector in a direction away from a proximal open end of the sample collector and through an opening defined by a valve seat. The second valve face is configured to engage with the valve seat at an angle relative to engagement of the valve seat with the valve face of the first valve stem. The second valve stem and the valve seat form a second valve, and the second valve includes: a second valve opening configuration corresponding to the opening configuration of the first valve, wherein the threaded connection components of the sample collector and the sample collection container are not fully engaged, wherein the second valve face is spaced apart from the valve seat, so that the sealed container, the sample collection container and the sample collector are in fluid communication with each other; a second valve closing configuration, wherein the threaded connection components of the sample collector and the sample collection container are fully disengaged, thereby causing the sample collector to disengage from the sample collection container, and the proximal end of the second valve stem is disengaged from the opposite second stem end of the first valve stem, wherein when the second valve is in the second valve closing configuration, the second valve face forms a sealing engagement with the valve seat.

[0065] In another aspect of the alternative embodiment, the proximal end of the second valve stem frictionally engages the opposing second stem end of the first valve stem within an opening defined by the opposing second stem end of the first valve stem.

[0066] In another embodiment, a method for preserving biological molecules in a biological sample and / or neutralizing one or more inhibitors in the biological sample is provided, the method comprising: a) obtaining a biological sample; b) obtaining an alternative embodiment of the above-mentioned biological sample collection system, wherein the first valve is in a closed configuration; c) placing the biological sample in a sample collector, the sample collector being in fluid communication with a sample collection container so that the biological sample is received in a sample receiving area of ​​the sample collection container; d) rotating the sample collector relative to the sample collection container in a first direction (e.g., counterclockwise) to move the first valve from the closed configuration to an open configuration and the second valve to a second valve open configuration, so that the sealed container, the sample collection container, and the sample collection container are sealed. The container and the sample collector are in fluid communication with each other, and the biological sample is received in the sample storage chamber of the sealed container; e) further rotating the sample collector relative to the sample collection container in the first direction to move the second valve to a second valve closed configuration, thereby disengaging the sample collector from the sample collection container and disengaging the proximal end of the second valve stem from the second stem end opposite to the first valve stem, so that the second valve face forms a sealing engagement with the valve seat; and f) mixing the biological sample received in the sample storage chamber of the sealed container with a stabilizing composition, a preservative and / or a neutralizing agent in the sealed container to preserve the biological molecules in the biological sample and / or neutralize one or more inhibitors in the biological sample. In another embodiment, rotating the sample collector relative to the sample collection container in the first direction in step (d) comprises a rotation of about a quarter turn.

[0067] Figure 9a-9cA partial view of an alternative embodiment of a biological sample collection system 100a having a sample collector (designated 114a) is shown, wherein elements having the same structure and function as the previously described biological sample collection system 100 and sample collector 114 are given the same reference numerals, and for the sake of brevity, the same details will not be described again herein. The system 100a includes a sample collection assembly 112a connected to the first open end 104 of the tube 102. The sample collection assembly 112a includes the sample collector 114a as described above. The sample collector 114a includes a proximal open end 116 for receiving a biological sample (not shown) and a distal open end 120 in fluid communication with the proximal open end 116. The sample collector 114a further includes a valve stem 122a and an opposite second stem end 128a, the valve stem including a first stem end 124 extending from an inner portion 126 of the sample collector 114a, the inner portion 126 being disposed proximal to the distal open end 120 of the sample collector 114a, the opposite second stem end including a valve face 130a, the valve stem 122a extending along a longitudinal axis (L) of the sample collector 114a and in a direction away from the proximal open end 116 of the sample collector 114. In the illustrated embodiment, the opposite second stem end 128a extends beyond the distal open end 120 of the sample collector 114a. The sample collector 114a further includes a threaded connection member 132 disposed at the distal open end 120 of the sample collector 114a.

[0068] The valve stem 122a extends centrally from the distal open end 120 of the sample collector 114a, and the inner portion 126 of the sample collector 114a is centrally disposed within the sample collector 114a, and the inner portion 126 of the sample collector 114a is connected to the inner surface of the sample collector by at least one attachment (not shown). As with the embodiment of the sample collector 114, the inner surface of the sample collector 114a, the inner portion 126 of the sample collector 114a, and the at least one attachment collectively define at least one opening 154 to provide fluid communication between the distal open end 120 of the sample collector 114a and the proximal open end 136 of the sample collection container 134.

[0069] The sample collector 114a can have any desired width, length, or thickness as desired, and can be made of an inert durable material such as polyethylene, polypropylene, polystyrene, or related plastics or glass. The collector 114a can be formed from a one-piece mold, or, alternatively, the collector 114a can be formed from separate components that are assembled to form this portion of the sample collection system 100a. Alternatively, in any of the embodiments of the sample collector 114a, at least a portion of the sample collector 114a extending from the proximal open end 116 can include a flexible material, such as silicone or rubber, to allow this portion of the sample collector 114a to be compressed during shipping, while maintaining a more rigid, more durable plastic material in the portion of the sample collector 114a where the valve stem 122a extends and the portion where the threaded connection member 132 is located.

[0070] The sample collection assembly 112a further includes a sample collection container 134 in fluid communication with the sample collector 114a. The sample collection container 134 includes a proximal open end 136 for receiving a biological sample (not shown) from the sample collector 114a and a distal open end 138 configured to be in fluid communication with the proximal open end 136. The sample collection container 134 has one or more walls 140 defining a sample receiving area 142 and a valve seat 144a, wherein the valve seat 144a is complementary to the valve face 130a of the sample collector 114a.

[0071] The sample collection container 134 also has a threaded connection member 146 disposed at the proximal open end 136, wherein the threaded connection member 146 is complementary to and configured to engage with the threaded connection member 132 of the sample collector 114a. The sample collection container 134 further has a connection member 148 disposed at the distal open end 138, wherein the connection member 148 is complementary to and configured to engage with the connection member 110 of the tube 102. In the embodiment shown in the figures, the connection member 110 disposed at the first open end 104 of the tube 102 and the connection member 148 disposed at the distal open end 138 of the sample collection container 134 include a threaded connection; however, other connection members known to those skilled in the art may also be used.

[0072] The valve stem 122a including the valve face 130a and the valve seat 144a form a valve, wherein the valve comprises: (a) a closed configuration ( Figure 9a ), wherein the threaded connection member 132 of the sample collector 114a and the threaded connection member 146 of the sample collection container 134 are fully engaged, wherein when the valve is in the closed configuration, the valve face 130a forms a sealing engagement with the valve seat 144a; and (b) an open configuration ( Figure 9b), wherein the threaded connection member 132 of the sample collector 114a and the threaded connection member 146 of the sample collection container 134 are not fully engaged, wherein when the valve is in the open configuration, the valve face 130a is spaced apart from the valve seat 144a, so that the tube 102, the sample collection container 134 and the sample collector 114a are in fluid communication with each other. In one embodiment, a user may feel a "click" sound and / or labels may be displayed on the sample collector 114a and the sample collection container 134 to indicate to the user when the open configuration of the valve is achieved. In one embodiment, the sealing engagement between the valve face 130a and the valve seat 144a in the closed configuration is fluid-tight.

[0073] exist Figure 9a-9c In the illustrated embodiment, the second valve stem 158a extends centrally from the opposite second stem end 128a of the valve stem 122a within the opening 159a defined by the opposite second stem end 128a of the valve stem 122a and frictionally engages with the opposite second stem end at its proximal end 161a in one embodiment, wherein the second valve stem 158a extends through the opening 160a defined by the valve seat 144a. Other means for releasably engaging the second valve stem 158a with the opposite second stem end 128a of the valve stem 122a will be known to those skilled in the art. The second valve stem 158a extends along the longitudinal axis (L) of the sample collector 114a and in a direction away from the proximal open end 116 of the sample collector 114. The second valve stem 158a has a second valve face 162a at its distal end 164a, which is configured to engage the valve seat 144a at an angle relative to the engagement of the valve seat 144a with the valve face 130a. The engagement of the second valve face 162a of the second valve stem 158a with the valve seat 144a then closes the valve, and continued twisting of the sample collector 114a disengages the second valve stem 158a from the opposite second stem end 128a of the valve stem 122a. The sample collector 114a can then be disengaged from the sample collection container 134. When the downward force exerted by the valve seat 144a on the second valve face 162a exceeds the friction force maintaining the engagement of the second valve stem 158a with the opposite second stem end 128a of the valve stem 122a, the second valve stem 158a will disengage from the opposite second stem end 128a of the valve stem 122a, thereby forming a seal. After the sample collector 114a is removed from the sample collection container 134, a cap (not shown) can also be used to engage with the threaded connection member 146 of the sample collection container 134 to provide an additional member to retain the mixture of the biological sample with the stabilizing composition, preservative and / or neutralizer (not shown) contained in the tube 102.

[0074] In one embodiment, the valve face 130a / 162a and / or the valve seat 144a can be made of a flexible material or over-molded (e.g., silicone or rubber). For example, if one surface is hard and the other surface is soft, the corresponding surfaces can "snap" into each other and form a good seal.

[0075] In one embodiment, the biological sample collection system 100a is pre-assembled for the user. To assemble the biological sample collection system 100a, the sample collection container 134 is first attached to the sample collector 114a (by the engagement of the connecting members 132 and 146) without the second valve stem 158a. Then, the second valve stem 158a is engaged in the opening 159a defined by the opposite second stem end 128a of the valve stem 122a by inserting through the opening 160a defined by the valve seat 144a. Subsequently, the tube 102 is connected to the sample collection container 134 by the engagement of the connecting members 148 and 110.

[0076] The biological sample collection system 100 / 100a described herein is particularly advantageous because it can be provided to the user / sample donor completely assembled as a whole, thereby avoiding any loose parts. In addition, the sample collection system 100 / 100a requires only slight manipulation by the user / sample donor to operate (a simple untwisting / twisting action between the sample collector 114 / 114a and the sample collection container 134 after collecting the biological sample), which provides a user-friendly and simplified method of use for the user / sample donor.

[0077] By detaching the sample collection assembly 112 / 112a from the tube 102 , the biological sample can be recovered from the biological sample collection system 100 / 100a in a laboratory setting.

[0078] List of elements and reference numerals

[0079]

[0080]

[0081] All publications, patents, and patent applications mentioned in this specification are indicative of the levels of skill of those skilled in the art to which this invention pertains and are incorporated herein by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0082] Having thus described the invention, it will be apparent that the invention may be varied in many ways. Such variations should not be regarded as departing from the spirit and scope of the invention, and all such modifications apparent to those skilled in the art are intended to be included within the scope of the following claims. The scope of the claims should not be limited to the preferred embodiments set forth for the specification, but should be given the broadest interpretation consistent with the specification as a whole.

Claims

1. A biological sample collection system, the system comprising: A sealed container, the sealed container comprising: a first open end, the first open end being used to receive a biological sample, a second end, the second end comprising a sample storage chamber, and a connecting member disposed at the first open end; A sample collection assembly configured to be connected to the first open end of the sealed container when collecting the biological sample, the sample collection assembly comprising: A sample collector, the sample collector comprising: a proximal open end, the proximal open end being used to receive a biological sample; a distal open end, the distal open end being in fluid communication with the proximal open end; A valve stem, the valve stem comprising: a first rod end extending from an interior portion of the sample collector, the interior portion being disposed proximal to the distal open end of the sample collector, and an opposing second rod end, the second rod end including a valve face, The valve stem extends along the longitudinal axis of the sample collector and in a direction away from the proximal open end of the sample collector; as well as a threaded connection member disposed at the distal open end of the sample collector; as well as A sample collection container, the sample collection container being configured to be in fluid communication with the sample collector when collecting the biological sample, the sample collection container comprising: a proximal open end, the proximal open end being used to receive the biological sample from the sample collector; a distal open end configured to be in fluid communication with the proximal open end; one or more walls defining a sample receiving area and a valve seat, wherein the valve seat is complementary to the valve face of the sample collector; a threaded connection member disposed at the proximal open end, wherein the threaded connection member is complementary to and configured to engage the threaded connection member of the sample collector; and a connecting member disposed at the distal open end, wherein the connecting member is complementary to the connecting member of the sealed container and is configured to engage therewith; wherein the valve stem and the valve seat form a valve, the valve comprising: a closed configuration wherein the threaded connection members of the sample collector and the sample collection container are fully engaged, wherein the valve face forms a sealing engagement with the valve seat when the valve is in the closed configuration; as well as An open configuration, wherein the threaded connection components of the sample collector and the sample collection container are not fully engaged, wherein when the valve is in the open configuration, the valve face is spaced apart from the valve seat, so that the sealed container, the sample collection container and the sample collector are in fluid communication with each other.

2. The sample collection system of claim 1, wherein the valve stem extends centrally from the distal open end of the sample collector, the interior portion of the sample collector is centrally disposed within the sample collector, and the interior portion of the sample collector is connected to an interior surface of the sample collector by at least one attachment; The inner surface of the sample collector, the interior portion of the sample collector and the at least one attachment together define at least one opening to provide fluid communication between the distal open end of the sample collector and the proximal open end of the sample collection container when collecting the biological sample.

3. A sample collection system according to claim 1 or 2, wherein the sealing joint between the valve face and the valve seat is fluid-tight.

4. The sample collection system according to any one of claims 1 to 3, wherein the sample collector is funnel-shaped.

5. The sample collection system of any one of claims 1 to 4, wherein at least a portion of the sample collector extending from the proximal open end comprises a flexible material. The sample collection system of claim 5 , wherein the flexible material comprises silicone or rubber.

7. The sample collection system according to any one of claims 1 to 6, wherein the connection member disposed at the first open end of the sealed container and the connection member disposed at the distal open end of the sample collection container include a threaded connection.

8. The sample collection system of any one of claims 1 to 7, wherein the opposing second rod end extends beyond the distal open end of the sample collector.

9. The sample collection system of any one of claims 1 to 8, wherein the capacity of the sample receiving area of ​​the sample collection container is about 0.1 mL to about 10 mL of sample.

10. The sample collection system according to any one of claims 1 to 9, wherein the sample storage chamber of the sealed container comprises a stabilizing composition, a preservative and / or a neutralizing agent.

11. A sample collection system according to any one of claims 1 to 10, wherein the valve is configured to move from the closed configuration to the open configuration by rotating the sample collector relative to the sample collection container in a first direction (e.g., counterclockwise) so that the threaded connection components of the sample collector and the sample collection container are not fully engaged.

12. The sample collection system of claim 11, wherein rotating the sample collector relative to the sample collection container in the first direction comprises approximately a quarter turn rotation.

13. A sample collection system according to claim 11 or 12, wherein the valve can be returned from the open configuration to the closed configuration by rotating the sample collector relative to the sample collection container in a second direction (e.g., clockwise) to fully engage the threaded connection members of the sample collector and the sample collection container, The second direction is opposite to the first direction.

14. The sample collection system of claim 13, wherein rotating the sample collector relative to the sample collection container in the second direction comprises approximately a quarter turn rotation.

15. The sample collection system according to any one of claims 1 to 14, wherein the valve stem is a first valve stem and the valve is a first valve, the sample collection system further comprising: A second valve stem, the second valve stem comprising: a proximal end extending from and releasably engaging the opposing second stem end of the first valve stem, and a distal end, the distal end comprising a second valve face; The second valve stem extends along the longitudinal axis (L) of the sample collector in a direction away from the proximal open end of the sample collector and through an opening defined by the valve seat, wherein the second valve face is configured to engage the valve seat at an angle relative to engagement of the valve seat with the valve face of the first valve stem, The second valve stem and the valve seat form a second valve, and the second valve comprises: a second valve open configuration corresponding to the open configuration of the first valve, wherein the threaded connection members of the sample collector and the sample collection container are not fully engaged, wherein the second valve face is spaced apart from the valve seat such that the sealed container, the sample collection container, and the sample collector are in fluid communication with one another; A second valve closing configuration, wherein the threaded connection components of the sample collector and the sample collection container are completely disengaged, thereby causing the sample collector to be disengaged from the sample collection container, and the proximal end of the second valve stem to be disengaged from the opposite second stem end of the first valve stem, wherein when the second valve is in the second valve closing configuration, the second valve face forms a sealing engagement with the valve seat.

16. The sample collection system of claim 15, wherein the proximal end of the second valve stem frictionally engages the opposing second stem end of the first valve stem within an opening defined by the opposing second stem end of the first valve stem.

17. A method for preserving biomolecules in a biological sample and / or neutralizing one or more inhibitors in the biological sample, the method comprising: a) obtaining a biological sample; b) obtaining the biological sample collection system according to any one of claims 1 to 10, wherein the valve is in a closed configuration; c) placing the biological sample in a sample collector that is in fluid communication with a sample collection container such that the biological sample is received in a sample receiving area of ​​the sample collection container; d) rotating the sample collector relative to the sample collection container in a first direction (e.g., counterclockwise) to move the valve from the closed configuration to the open configuration, so that the sealed container, the sample collection container, and the sample collector are in fluid communication with each other, and the biological sample is received in the sample storage chamber of the sealed container; e) optionally, rotating the sample collector relative to the sample collection container in a second direction (e.g., clockwise) to return the valve to the closed configuration, wherein the second direction is opposite to the first direction; and f) mixing the biological sample received in the sample storage chamber of the sealed container with a stabilizing composition, a preservative and / or a neutralizing agent in the sealed container to preserve the biomolecules in the biological sample and / or neutralize one or more inhibitors in the biological sample.

18. The method of claim 17, wherein rotating the sample collector relative to the sample collection container in the first direction comprises approximately a quarter turn rotation.

19. The method of claim 17 or 18, wherein rotating the sample collector relative to the sample collection container in the second direction comprises approximately a quarter turn rotation.

20. A method for preserving biomolecules in a biological sample and / or neutralizing one or more inhibitors in the biological sample, the method comprising: a) obtaining a biological sample; b) obtaining the biological sample collection system according to claim 15 or 16, wherein the first valve is in a closed configuration; c) placing the biological sample in a sample collector that is in fluid communication with a sample collection container such that the biological sample is received in a sample receiving area of ​​the sample collection container; d) rotating the sample collector relative to the sample collection container in a first direction (e.g., counterclockwise) to move the first valve from the closed configuration to the open configuration and the second valve to the second valve open configuration, so that the sealed container, the sample collection container, and the sample collector are in fluid communication with each other, and the biological sample is received in the sample storage chamber of the sealed container; e) further rotating the sample collector relative to the sample collection container in the first direction to move the second valve to a second valve closed configuration, thereby disengaging the sample collector from the sample collection container and disengaging the proximal end of the second valve stem from the opposite second stem end of the first valve stem, so that the second valve face forms a sealing engagement with the valve seat; as well as f) mixing the biological sample received in the sample storage chamber of the sealed container with a stabilizing composition, a preservative and / or a neutralizing agent in the sealed container to preserve the biomolecules in the biological sample and / or neutralize one or more inhibitors in the biological sample.

21. The method of claim 20, wherein rotating the sample collector relative to the sample collection container in the first direction in step (d) comprises approximately a quarter turn of rotation.

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