Sample collection device and method

Abstract

The present disclosure provides a sample collection device comprising: a mouthpiece configured to engage with at least a portion of a subject's mouth; an expandable member located on one side of the mouthpiece in a longitudinal direction thereof, the expandable member having a first state and a second state, wherein the first state has a first size and the second state has a second size that is larger than the first size; and a drive member coupled to the expandable member and configured to change the expandable member from the first state to the second state. When in the second state, at least a portion of the expandable member contacts a collection site of the subject and collects a biological sample from the collection site.

Description

Technical Field

[0001] The present disclosure relates to a device and method for sampling a sample, and in particular to a device and method that can be used by a subject for self-sampling. Background Art

[0002] Typically, a swab is used to sample the biological sample at the oropharynx of an experimenter, and then the swab head with the biological sample of the experimenter is broken off and the sampling head is placed in a reaction tube, and then the biological sample in the reaction tube is processed, such as nucleic acid amplification and detection. Nucleic acid amplification methods can selectively amplify and identify nucleic acid of interest from a complex mixture (e.g., biological sample). In order to detect the nucleic acid in a biological sample, typically the biological sample is processed to isolate nucleic acid from other components of the biological sample and other substances that may interfere with nucleic acid and / or amplification. After isolating the nucleic acid of interest from the biological sample, the nucleic acid of interest can be amplified by, for example, amplification methods known in the art, such as based on thermal cycling methods (e.g., polymerase chain reaction (PCR)). After amplifying the nucleic acid of interest, the amplified product can be detected, and the test result is interpreted by the end user. Summary of the Invention

[0003] In one aspect, the present disclosure provides a sample collection device. In some embodiments, the sample collection device may include a mouthpiece configured to engage with at least a portion of a subject's mouth; an expandable member located on one side of the mouthpiece in a longitudinal direction thereof, the expandable member having a first state and a second state, wherein the expandable member has a first size in the first state and a second size in the second state that is larger than the first size; and an actuator coupled to the expandable member and configured to change the expandable member from the first state to the second state. In some cases, the expandable member is configured such that, when in the second state, at least a portion of the expandable member contacts a collection site of the subject and collects a biological sample from the collection site.

[0004] In another aspect, the present disclosure provides a method for collecting a biological sample from a subject. In some embodiments, the method may include: (a) providing a sample collection device comprising: (i) a mouthpiece; (ii) an expandable member located on one side of the mouthpiece in a longitudinal direction of the mouthpiece, the expandable member being in a first state having a first size; and (iii) an actuator coupled to the expandable member, wherein the mouthpiece engages at least a portion of the subject's mouth; (b) with the mouthpiece engaged with the at least a portion of the subject's mouth, expanding the expandable member under the action of the actuator such that the expandable member changes from the first state to a second state, wherein the expandable member has a second size larger than the first size in the second state, wherein in the second state, at least a portion of the expandable member contacts a collection site of the subject to collect the biological sample from the subject; and (c) removing the mouthpiece from the subject's mouth.

[0005] In another aspect, the present disclosure provides a method for collecting a sample. In some embodiments, the method may include: (a) providing a sample collection device comprising: (i) a mouthpiece configured to engage at least a portion of a subject's mouth; (ii) an expandable member located on one side of the mouthpiece in a longitudinal direction of the mouthpiece, the expandable member having a first state and a second state, wherein the expandable member has a first size in the first state and a second size in the second state that is larger than the first size; and (iii) an actuator coupled to the expandable member and configured to change the expandable member from the first state to the second state, wherein the expandable member is configured such that, when in the second state, at least a portion of the expandable member contacts a collection site of the subject and collects a biological sample from the collection site; (b) removing the expandable member from the sample collection device; and (c) placing the expandable member in a container.

[0006] In another aspect, the present disclosure provides a kit. In some embodiments, the kit may include: a sample collection device as provided in the present disclosure; and optionally, instructions for guiding a user to use the sample collection device to collect a biological sample from a subject.

[0007] Other aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. It will be appreciated that the present disclosure is capable of other and different embodiments, and that its several details are capable of modification in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative rather than restrictive.

[0008] Incorporation by reference

[0009] All publications, patents, and patent applications mentioned in this specification are herein incorporated 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The novel features of the present disclosure are particularly set forth in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by referring to the following detailed description and accompanying drawings which illustrate illustrative embodiments in which the principles of the present disclosure are utilized, in which:

[0011] Figure 1 is a schematic diagram depicting an exemplary sample acquisition device of the present disclosure.

[0012] Figure 2 and Figure 3 sectional views depicting an expandable member of an exemplary sample acquisition device of the present disclosure in a first state and a second state, respectively.

[0013] Figure 4 and Figure 5 FIG2 is a partial enlarged cross-sectional view illustrating an expandable member of an exemplary sample acquisition device of the present disclosure in a first state and a second state, respectively.

[0014] Figure 6 is a flow chart depicting an exemplary method for collecting a biological sample from a subject using a sample collection device of the present disclosure.

[0015] Figure 7 is a flow chart depicting an exemplary method of collecting a sample using a sample collection device of the present disclosure. DETAILED DESCRIPTION

[0016] Although various embodiments of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that these embodiments are provided by way of example only. Many variations, changes, and substitutions can be envisioned by those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein may be employed.

[0017] As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, the term "a cell" includes a plurality of cells, including mixtures thereof.

[0018] As used herein, the term "amplification" generally refers to the production of one or more copies of a nucleic acid or an "amplification product." The term "DNA amplification" generally refers to the production of one or more copies of a DNA molecule or an "amplified DNA product." The term "reverse transcription amplification" generally refers to the production of deoxyribonucleic acid (DNA) from a ribonucleic acid (RNA) template via the action of the enzyme reverse transcriptase.

[0019] As used herein, the term "denaturation" generally refers to the complete or partial unwinding of the helical structure of a double-stranded nucleic acid, and in some cases refers to the unwinding of the secondary structure of a single-stranded nucleic acid. Denaturation can include the inactivation of pathogen cell walls or viral coats, as well as the inactivation of inhibitor proteins. The conditions under which denaturation may occur include a "denaturation temperature" and a "denaturation duration." The "denaturation temperature" generally refers to the temperature that allows denaturation to occur, and the "denaturation duration" generally refers to the amount of time allotted for denaturation to occur.

[0020] As used herein, the term "extension" generally refers to the incorporation of nucleotides into a nucleic acid in a template-directed manner. Extension can occur with the aid of an enzyme such as, for example, a polymerase or a reverse transcriptase. Conditions under which extension can occur include an "extension temperature," which generally refers to the temperature that allows extension to occur, and an "extension duration," which generally refers to the amount of time allotted for extension to occur.

[0021] As used herein, the term "nucleic acid" generally refers to a polymeric form of nucleotides (deoxyribonucleotides (dNTPs) or ribonucleotides (rNTPs)) of any length or their analogs. Nucleic acids can have any three-dimensional structure and can perform any known or unknown function. Non-limiting examples of nucleic acids include DNA, RNA, coding or non-coding regions of genes or gene fragments, one or more loci determined by linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA), ribozymes, cDNA, recombinant nucleic acids, branched nucleic acids, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes and primers. Nucleic acids may contain one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure can be performed before or after nucleic acid assembly. The nucleotide sequence of a nucleic acid can be interrupted by non-nucleotide components. Nucleic acids can be further modified after polymerization, for example by coupling or binding to a reporter agent.

[0022] As used herein, the term "primer extension reaction" generally refers to denaturation of double-stranded nucleic acid, binding of primers to one or both strands of the denatured nucleic acid, and subsequent extension of the primers.

[0023] As used herein, the term "reaction mixture" generally refers to a composition comprising reagents necessary to perform nucleic acid amplification (e.g., DNA amplification, RNA amplification), non-limiting examples of which include a primer set specific for the target RNA or target DNA, DNA produced by reverse transcription of RNA, DNA polymerase, reverse transcriptase (e.g., for reverse transcription of RNA), a suitable buffer (including a zwitterionic buffer), cofactors (e.g., divalent and monovalent cations), dNTPs, and other enzymes (e.g., uracil-DNA glycosylase (UNG)). In some cases, the reaction mixture may further include one or more reporter agents.

[0024] As used herein, the term "target nucleic acid" generally refers to a nucleic acid molecule in a starting population of nucleic acid molecules, with a certain nucleotide sequence, the presence, amount and / or sequence of which or one or more variations thereof need to be measured. Target nucleic acid can be any type of nucleic acid, including DNA, RNA and their analogs. As used herein, "target ribonucleic acid (RNA)" generally refers to a target nucleic acid as RNA. As used herein, "target deoxyribonucleic acid (DNA)" generally refers to a target nucleic acid as DNA.

[0025] As used herein, the term "subject" generally refers to an entity or medium having testable or detectable genetic information. A subject can be a human or an individual. A subject can be a vertebrate, such as a mammal. Non-limiting examples of mammals include mice, monkeys, humans, livestock, sport animals, and pets. Other examples of subjects include food, plants, soil, and water.

[0026] As used herein, the term "biological sample" generally refers to any specimen taken from a target location in a subject. Non-limiting examples of biological samples include blood (or components of blood—e.g., white blood cells, red blood cells, platelets) obtained from any anatomical location of a subject (e.g., tissue, circulatory system, bone marrow), cells obtained from any anatomical location of a subject, skin, heart, lung, kidney, exhaled breath, bone marrow, stool, semen, vaginal fluid, tissue fluid from tumor tissue, breast, pancreas, cerebrospinal fluid, tissue, throat swab, biopsy, placental fluid, amniotic fluid, liver, muscle, smooth muscle, bladder, gall bladder, colon, intestine, brain, cavity fluid, sputum, pus, micropiota, meconium, breast milk, prostate, esophagus, thyroid, serum, saliva, urine, gastric and digestive fluids, tears, ocular fluids, sweat, mucus, earwax, oils, glandular secretions, spinal fluid, hair, nails, skin cells, plasma, nasal swab or nasopharyngeal wash, spinal fluid, umbilical cord blood, and / or other excreta or body tissues.

[0027] As used herein, the term "oropharynx" is also called the middle pharynx or oropharynx, and generally refers to the part located between the free edge of the velum palatine and the upper edge of the epiglottis of the subject, which communicates with the oral cavity through the pharyngeal isthmus, continues with the nasopharynx above, and connects to the laryngopharynx below.

[0028] Figure 1 is a schematic diagram depicting an exemplary sample collection device of the present disclosure. The sample collection device of the present disclosure may include a mouthpiece 102 and an expandable component 103 located on one side of the longitudinal axis of the mouthpiece. The side of the longitudinal axis of the mouthpiece may be the distal side relative to the mouthpiece (i.e., the side closer to the subject). During use of the sample collection device of the present disclosure, the expandable component is placed in the mouth of the subject. The sample collection device of the present disclosure may also include a handle 101, which may be located on the side opposite to the expandable component in the longitudinal direction of the mouthpiece (i.e., the side away from the subject). The handle may facilitate the subject to hold the sample collection device.

[0029] The mouthpiece 102 of the sample collection device is configured to engage with at least a portion of a subject's mouth. In some cases, during use of the sample collection device of the present disclosure, at least a portion of the mouthpiece is located outside of at least a portion of the subject's mouth. In some cases, during use of the sample collection device of the present disclosure, at least a portion of the mouthpiece is located within at least a portion of the subject's mouth. The at least a portion of the subject's mouth may include lips or teeth. The shape and size of the mouthpiece are set to be suitable for closely fitting with the subject's lips or teeth. The shape of the mouthpiece may be circular, oval, or irregular. In some cases, the mouthpiece may be made of a resilient material (e.g., silicone). In other cases, the mouthpiece may be made of a substantially rigid material (e.g., plastic). In other cases, the mouthpiece may include stacked layers of material, such as a stack of layers of resilient material and layers of substantially rigid material.

[0030] In some cases, the mouthpiece may include a feature portion, such as a groove or a protrusion. The shape and size of the feature portion are set to be different from the portion outside the feature portion and are particularly suitable for fitting closely with the lips or teeth of the subject, so that the subject can tactilely know that at least a part of their mouth should be positioned on the feature portion. In one example, the feature portion of the mouthpiece may include a raised flange; when sampling, the subject's lips rest on the flange, thereby achieving positioning of the subject's mouth. In another example, the feature portion of the mouthpiece may include a groove; when sampling, the subject's teeth enter the groove, thereby achieving positioning of the subject's mouth.

[0031] The expandable component of the sample collection device of the present disclosure may include a balloon. The balloon is expandable under the action of a positive pressure exceeding a preset threshold, and is collapsible when the positive pressure decreases or disappears. The expandable component can therefore have a first state and a second state. In the first state (e.g., the collapsed state), the expandable component can have a first size (e.g., volume, or length along its longitudinal direction), and in the second state (e.g., the expanded state), the expandable component can have a second size that is larger than the first size. In some examples, the length of the expandable member along its longitudinal direction may change by at least 0.1 centimeters (cm), 0.2 cm, 0.4 cm, 0.6 cm, 0.8 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3.0 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4.0 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, 5.0 cm, 5.2 cm, 5.4 cm, 5.6 cm, 5.8 cm, 6.0 cm, 6.2 cm, 6.4 cm, 6.6 cm, 6.8 cm, 7.0 cm, 7.2 cm, 7.4 cm, 7.6 cm, 7.8 cm, 8.0 cm, 8.2 cm, 8.4 cm, 8.6 cm, 8.8 cm, 9.0 cm, 9.2 cm, 9.4 cm, 9.6 cm, 9.8 cm, 10.0 cm, 10.2 cm, 10. 4cm, 5.6cm, 5.8cm, 6.0cm, 6.2cm, 6.4cm, 6.6cm, 6.8cm, 7.0cm, 7.2cm, 7.4cm, 7.6cm, 7.8cm, 8.0cm, 8.2cm, 8.4cm, 8.6cm, 8.8cm, 9.0cm, 9.2cm, 9.4cm, 9.6cm, 9.8cm, 10.0cm, 10.5cm, 11.0cm, 11.5cm, 12.0cm, 12.5cm, 13.0cm, 13.5cm, 14.0cm, 14.5cm or 15.0cm. The length of the expandable component along its longitudinal direction may vary by a value greater than or less than any of the above-mentioned preset values. The length of the expandable component along its longitudinal direction may vary by a value between any two of the above-mentioned preset values. Multiple models of expandable components can be provided, and the size change values ​​of the expandable components when they are converted from the first state to the second state are different, so as to be suitable for use by subjects of different ages, genders, and oral cavity sizes.

[0032] In some cases, the change in the size of the expandable component of the sample collection device of the present disclosure (e.g., the length along its longitudinal direction) may occur in a direction substantially along its longitudinal axis. In other cases, the change in the size of the expandable component may occur in a direction deviating from its longitudinal axis. The direction of the change in the size of the expandable component can be achieved by controlling the shape and / or material of the expandable component. For example, the direction of the change in the length of the expandable component can be controlled by controlling the initial shape, material, or a combination thereof of the expandable component. In one example, the materials of various parts of the expandable component may be different. When a pressure medium of injected gas or liquid is injected into the interior of the expandable component, the length of the part made of a material with smaller deformation properties changes less, resulting in the change in the length of the expandable component occurring in a direction deviating from the longitudinal axis of the expandable component.

[0033] During use of the sample collection device disclosed herein, the expandable component is located in the mouth of a subject and transitions therein from a first state to a second state. When the expandable component is in the first state, it is not in contact with the subject's predetermined collection site (e.g., the oropharyngeal site). When the expandable component is in the second state, at least a portion of it contacts the subject's predetermined collection site and collects a biological sample from the collection site. The at least a portion of the expandable component may be its distal portion, i.e., the end proximal to the subject. In some instances, the expandable component may have a sampling portion at least at its distal end. The sampling portion may retain a biological sample collected from the subject's collection site. The sampling portion may include a material suitable for transferring a biological sample (e.g., saliva, oropharyngeal secretions, nasopharyngeal secretions) from the subject's predetermined collection site to the sampling portion and for retention by the sampling portion. Exemplary materials may include, but are not limited to, cotton, polyester, dacron, or rayon, etc. In one instance, these materials may be formed by winding, spraying, flocking, or the like to be fixed to the distal end of the expandable component. Examples of the sampling portion include bristles fixed to the distal end of the expandable component. In some embodiments, the expandable component is removable from the sample collection device. For example, the expandable component is disposable. A temporary locking device, such as a buckle or elastic ring, can be used to temporarily secure the expandable component to the sample collection device. After sampling is complete, the expandable component can be removed and placed in a container (e.g., a sample storage device or a sample processing device).

[0034] The sample collection device of the present disclosure may further include a drive component. The drive component may be configured to inject a pressure medium, such as a gas or liquid, into the expandable component, thereby achieving a transition of the expandable component from the first state to the second state. Under the action of the drive component, the time to complete the transition from the first state to the second state of the expandable component may be less than 60 seconds, 55 seconds, 50 seconds, 45 seconds, 40 seconds, 35 seconds, 30 seconds, 25 seconds, 20 seconds, 19 seconds, 18 seconds, 17 seconds, 16 seconds, 15 seconds, 14 seconds, 13 seconds, 12 seconds, 11 seconds, 10 seconds, 9 seconds, 8 seconds, 7 seconds, 6 seconds, 5 seconds, 4 seconds, 3 seconds, 2 seconds, or 1 second. The time to complete the transition from the first state to the second state of the expandable component may be greater than or less than any of the above values. The time to complete the transition from the first state to the second state of the expandable component may be a value between any two of the above values.

[0035] In some instances, the driving component may include a push-type balloon pump. The push-type balloon pump may include a cavity made of an elastic material and having a certain volume. The push-type balloon pump is connected to the expandable component through a pipeline. The subject presses the push-type balloon pump with his hand to inject a pressure medium into the expandable component, thereby converting the expandable component from a collapsed state to an expanded state. In some cases, the push-type balloon pump may have a one-way valve that opens in one direction toward its interior, so that after one press by the subject, external air can be inhaled through the one-way valve, thereby allowing the subject to press again to continuously inject air into the expandable component. In some instances, the driving component may include a pump. The pump is connected to the expandable component through a pipeline and injects a pressure medium into the expandable component, thereby realizing the conversion of the expandable component from a collapsed state to an expanded state.

[0036] In some examples, the drive component may include a motor and a plunger coupled to the motor. Figure 2 and Figure 3, which are cross-sectional views of an exemplary sample collection device of the present disclosure in a first state and a second state, respectively, wherein the motor 112 can drive the plunger 113 to perform linear motion in the pipe 115. For example, an external thread can be provided on the outer circumference of the plunger, which engages with a gear driven by the motor or a nut with an internal thread, thereby converting the rotation of the motor into the linear motion of the plunger. The length of the plunger can be at least 0.1 cm, 0.2 cm, 0.4 cm, 0.6 cm, 0.8 cm, 1.0 cm, 1.2 cm, 1.4 cm, 1.6 cm, 1.8 cm, 2.0 cm, 2.2 cm, 2.4 cm, 2.6 cm, 2.8 cm, 3.0 cm, 3.2 cm, 3.4 cm, 3.6 cm, 3.8 cm, 4.0 cm, 4.2 cm, 4.4 cm, 4.6 cm, 4.8 cm, 5.0 cm, 5.2 cm, 5.4 cm, 5.6 cm, 5.8 cm, 6.0 cm, 7.0 cm, 8.0 cm, 9.0 cm, 10.0 cm, 11.0 cm, 12 cm, 14 cm, 16 cm, 18 cm, 19 cm, 20 cm, 21 cm, 22 cm, 23 cm, 24 cm, 25 cm, 26 cm, 27 cm, 28 cm, 29 cm, 30 cm, 31 cm, 32 cm, 33 cm, 34 cm, 35 cm, 36 cm, 37 cm, 38 cm, 39 cm, 40 cm, 41 cm, 42 cm, 43 cm, 44 cm, 45 cm, 46 cm, 47 cm, 58 cm The length of the plunger can be greater than or less than any of the above values. The length of the plunger can be a value between any two of the above values. Multiple models of sample collection devices can be provided with different lengths of plungers in the drive components to accommodate subjects of different ages, genders, and oral cavity sizes. The conduit 115 is in communication with the expandable component 103. The plunger may have a piston head 114 at its distal end that fits tightly against the inner wall of the pipe 115, so that the movement of the piston head toward the expandable component transfers the pressure medium such as gas or liquid in the pipe to the interior of the expandable component, thereby changing the expandable component from the first state to the second state. Figure 2 The position shown is moved away from the expandable member to Figure 3 During the process of approaching the expandable component as shown, the pressure medium such as gas or liquid originally existing in the pipeline 115 is pressed into the interior of the expandable component, applying positive pressure to the expandable component, thereby changing the expandable component from the collapsed state to the expanded state.

[0037] Example sample collection devices of the present disclosure may further include a power source configured to power at least the drive component. The power source may be disposed within the interior space of the handle. In some cases, the power source may be a replaceable battery that is removable from the sample collection device. In some cases, the power source may be a rechargeable battery, such as a lithium battery or a nickel-metal hydride battery. Example sample collection devices of the present disclosure may further include a switch configured to turn at least the drive component on and off. The switch may be disposed in a location convenient for operation by the subject, such as on the handle.

[0038] Figure 4 and Figure 5 The figures depict enlarged partial cross-sectional views of an exemplary sample collection device of the present disclosure in a first state and a second state, respectively. In some embodiments, the sample collection device of the present disclosure may include a recovery component configured to change the expandable component from the second state to the first state. In one example, the recovery component may include a pressure release component configured to release at least a portion of the pressure medium within the expandable component to reduce the pressure within the expandable component when the expandable component is in the second state (e.g., the expanded state) and sampling is completed, thereby converting the expandable component to the first state (e.g., the collapsed state). In one example, the pressure release component may include a one-way valve 117 located in the conduit 115 between the piston head 114 of the plunger 115 and the expandable component 103. The one-way valve only allows the pressure medium to pass in a direction toward the expandable component and prevents the pressure medium from passing in a direction away from the expandable component. In addition, the one-way valve 117 is movable within the conduit 115 under the action of the pressure medium.

[0039] like Figure 4 As shown, during the process of the piston head of the plunger moving toward the expandable component, thereby transferring the pressure medium in the pipeline 115 toward the expandable component, the one-way valve abuts against the blocking member 119 under the action of the pressure from the pressure medium, while allowing the pressure medium to flow through it toward the expandable component. The blocking member 119 can be a blocking plate set in the pipeline 115 or a diameter reduction portion of the pipeline, which is used to block the one-way valve from further moving toward the expandable component. Figure 4 In the state shown, the one-way valve closes the release outlet 118 provided on the pipeline, so that no pressure medium flows from the release outlet into the release channel 121 connected to the release outlet.

[0040] like Figure 5As shown, when the expandable component 103 is in the second state, contacting the subject's predetermined collection site (e.g., the oropharynx), as the pressure medium continues to flow into the expandable component and further contact the collection site, the subject's collection site exerts a reaction force F on the expandable component, generally toward the mouthpiece. This reaction force compresses the expandable portion, causing a portion of the pressure medium within the expandable component to flow toward the one-way valve. Because the one-way valve does not allow the pressure medium to pass away from the expandable component, the pressure medium from the expandable component exerts a force on the one-way valve, forcing the one-way valve to move within the conduit 115 toward the piston head of the plunger. This movement of the one-way valve causes it to no longer block the release outlet 118 provided in the conduit, allowing the pressure medium from the expandable component to flow from the release outlet into a release channel connected to the release outlet. In some cases, the release channel may include a through-hole connected to the ambient air. The release of pressure medium from the expandable component causes the expandable component to transition from the expanded state to the collapsed state. The subject can then remove the collapsed expandable component from the oral cavity, completing the sampling procedure.

[0041] In some embodiments, after the expandable member is converted from the expanded state to the collapsed state, the drive member (e.g., a motor) may stop operating. In other embodiments, after the expandable member is converted from the expanded state to the collapsed state, the drive member (e.g., a motor) may move the plunger in the direction away from the expandable member within the conduit, such as Figure 2 The initial state shown in FIG2 is shown, and a second operation of converting the expandable component from the collapsed state to the expanded state is performed. In this way, the sampling site of the subject can be sampled multiple times, thereby ensuring that an effective amount of biological sample is collected from the sampling site of the subject.

[0042] Figure 6 6 is a flow chart depicting an exemplary method of collecting a biological sample from a subject according to the present disclosure. In process 601, a sample collection device is provided. In process 602, an expandable member of the sample collection device is caused to change from a first state to a second state, thereby collecting a biological sample from a collection site of the subject. In process 603, the sample collection device is removed from the subject's mouth.

[0043] In process 601, the sample collection device provided may be the one described above. Figure 1-Figure 5 An exemplary embodiment of a sample collection device is described. In one example, the sample collection device may include a mouthpiece, an expandable component, and a drive component. In step 601, at least the expandable component of the sample collection device may be optionally placed in the oral cavity of a subject. The expandable component is in a first state (e.g., a collapsed state), and the mouthpiece engages at least a portion of the subject's mouth (e.g., lips).

[0044] In process 602, with the mouthpiece engaged with at least a portion of the subject's mouth, an expandable component is caused to change from a first state to a second state (e.g., an expanded state) under the action of a drive component. In the second state, the expandable component has a second length along its longitudinal axis that is greater than its first length along its longitudinal axis when in the first state. When the expandable component reaches its second state, a distal end of the expandable component contacts a collection site of the subject to collect a biological sample (e.g., saliva, oropharyngeal secretions, etc. containing nucleic acids) from the subject from the collection site. In the second state of the expandable component, as pressure medium continues to flow into the expandable component, causing the expandable component to further contact the collection site, the collection site of the subject exerts a reaction force on the expandable component that is substantially toward the mouthpiece. Under the action of this reaction force, the expandable portion is compressed, causing a portion of the pressure medium within the expandable component to flow toward the one-way valve, forcing the one-way valve to move within the conduit toward the piston head of the plunger. This movement of the one-way valve causes it to no longer block the release outlet provided on the conduit, so that the pressure medium from the expandable component flows from the release outlet into the release channel connected to the release outlet, causing the expandable component to transition from an expanded state to a collapsed state. In process 603, the subject can remove the expandable component in the collapsed state from the oral cavity and complete the sampling operation. In some cases, process 602 can be performed more than once, so that the distal end of the expandable component contacts the subject's collection site multiple times, thereby ensuring that an effective amount of biological sample is collected from the subject's collection site.

[0045] Figure 7 7 is a flow chart depicting an exemplary method of collecting a biological sample from a subject according to the present disclosure. In process 701, a sample collection device is provided, and a biological sample is collected from a collection site of a subject. In process 702, an expandable member is removed from the sample collection device. In process 703, the expandable member is placed in a container.

[0046] In process 701, the sample collection device provided may be the one described above. Figure 1-Figure 5A sample collection device of an exemplary embodiment is described. In one example, the sample collection device may include a mouthpiece, an expandable component, and a drive component. The expandable component in a first state (e.g., a collapsed state) may be placed in the oral cavity of a subject. With the mouthpiece engaged with at least a portion of the subject's mouth, the expandable component is caused to change from the first state to a second state (e.g., an expanded state) under the action of the drive component, such that at least the distal end of the expandable component contacts a collection site of the subject to collect a biological sample. In the second state of the expandable component, the expandable component may automatically transition from the expanded state to the collapsed state, as described above. In some cases, the biological sample collection process of changing the expandable component from the first state to the second state and from the second state to the first state of process 701 may be performed more than once, such that the distal end of the expandable component contacts the collection site of the subject multiple times, thereby ensuring that an effective amount of the biological sample is collected from the collection site of the subject.

[0047] In process 702, the subject can remove the expandable component in the collapsed state from the oral cavity and remove the expandable component from the sample collection device. As described above, the expandable component can be temporarily fixed to the sample collection device by a temporary locking device such as a lock buckle or an elastic ring. In process 703, the expandable component removed from the sample collection device is placed in a container. The container can be a sample storage device or a sample processing device. The sample storage device or the sample processing device can be pre-loaded with a sample processing liquid. The sample processing liquid is mixed with the biological sample in proportion to obtain a processed sample.

[0048] In some instances, the sample preservation device or the sample processing device can be configured to pre-store therein at least one reagent necessary for preserving and / or processing a biological sample. In some instances, at least one reagent includes all reagents necessary for completing sample preservation, sample processing, nucleic acid amplification (e.g., DNA amplification, RNA amplification). The reagent necessary for processing a biological sample includes reagents necessary for reverse transcription and nucleic acid amplification (e.g., reverse transcriptase, DNA polymerase, dNTP, cofactor, primer, suitable buffer, etc.) and a reporter (e.g., an oligonucleotide probe comprising a FAM dye). After adding the biological sample collected from the subject, all processing of the sample required for nucleic acid amplification can be completed in the sample preservation device or the sample processing device. The biological sample processed via the sample processing device ultimately forms a reaction mixture. The reaction mixture can be transferred to a reaction vessel and undergoes, for example, nucleic acid amplification reaction in the reaction vessel. In one example, the sample processing device can operate together with a thermal cycler (e.g., a PCR thermal cycler) to amplify the nucleic acid of interest in the sample and detect the amplified product.

[0049] The present disclosure also provides a kit comprising the sample collection device of the present disclosure. The kit may optionally further comprise instructions for guiding a user to use the sample collection device to collect a biological sample from a subject.

[0050] Exemplary embodiments of the present disclosure include, but are not limited to, the following:

[0051] 1. A sample collection device comprising:

[0052] a mouthpiece configured to engage at least a portion of a subject's mouth;

[0053] an expandable member located on one side of the mouthpiece in a longitudinal direction of the mouthpiece, the expandable member having a first state and a second state, wherein in the first state, the expandable member has a first size, and in the second state, the expandable member has a second size, the second size being larger than the first size; and

[0054] an actuation member coupled to the expandable member and configured to change the expandable member from the first state to the second state,

[0055] The expandable member is configured such that, when in the second state, at least a portion of the expandable member contacts a collection site of the subject and collects a biological sample from the collection site.

[0056] 2. The sample acquisition device of embodiment 1, wherein the expandable component comprises a balloon.

[0057] 3. The sample collection device of embodiment 2, wherein the balloon is expandable under the action of positive pressure from the drive component.

[0058] 4. The sample collection device according to embodiment 3, wherein the positive pressure is generated by gas or liquid driven by the driving component.

[0059] 5. The sample collection device of embodiment 1, wherein the expandable member comprises a sampling member at a distal end thereof, the sampling member being configured to retain the biological sample collected from the collection site of the subject.

[0060] 6. The sample acquisition device of embodiment 1, wherein the expandable member is removable relative to the mouthpiece.

[0061] 7. The sample acquisition device of embodiment 6, wherein the expandable member is disposable.

[0062] 8. The sample collection device of embodiment 1, wherein the drive component comprises a pump.

[0063] 9. The sample collection device of embodiment 1, wherein the driving component comprises a motor.

[0064] 10. The sample collection device of embodiment 9, wherein the electrode drives a plunger that fits snugly within a tube coupled to the expandable member.

[0065] 11. The sample acquisition device of embodiment 1, further comprising a recovery component configured to change the expandable component from the second state to the first state.

[0066] 12. The sample acquisition device of embodiment 11, wherein the recovery component comprises a pressure release component configured to release pressure within the expandable component when the expandable component is in the second state.

[0067] 13. The sample acquisition device of embodiment 12, wherein the pressure relief member comprises a one-way valve configured to (i) only allow pressure medium to flow toward the expandable member, and (ii) be movable relative to the expandable member.

[0068] 14. The sample acquisition device of embodiment 13, wherein the pressure release component comprises a release outlet through which the pressure medium is released from the expandable portion.

[0069] 15. The sample collection device of embodiment 14, wherein the release outlet is in communication with a release channel.

[0070] 16. The sample acquisition device of embodiment 1, wherein at least a portion of the mouthpiece is configured to reside outside of the at least a portion of the subject's mouth.

[0071] 17. The sample acquisition device of embodiment 1, wherein at least a portion of the mouthpiece is configured to reside within the at least a portion of the subject's mouth.

[0072] 18. The sample acquisition device of embodiment 16 or 17, wherein the at least a portion of the mouth comprises the lips of the subject.

[0073] 19. The sample acquisition device of embodiment 18, wherein the mouthpiece is sized to abut the lips when the expandable member is positioned within the mouth of the subject.

[0074] 20. The sample collection device of embodiment 1, further comprising a handle coupled to a side of the mouthpiece opposite the expandable member in the longitudinal direction of the mouthpiece.

[0075] 21. The sample collection device of embodiment 1, further comprising a power supply configured to supply power to at least the driving component.

[0076] 22. The sample collection device of embodiment 1, further comprising a switch configured to turn at least the driving component on and off.

[0077] 23. The sample collection device of embodiment 1, wherein the collection site of the subject comprises an oropharyngeal area.

[0078] 24. A method for collecting a biological sample from a subject, comprising:

[0079] (a) providing a sample collection device comprising (i) a mouthpiece, (ii) an expandable member located on one side of the mouthpiece in a longitudinal direction of the mouthpiece, the expandable member being in a first state having a first size, and (iii) an actuation member coupled to the expandable member, wherein the mouthpiece engages at least a portion of a mouth of a subject;

[0080] (b) with the mouthpiece engaged with the at least a portion of the subject's mouth, expanding the expandable member under the action of the drive member so that the expandable member changes from the first state to a second state, wherein in the second state the expandable member has a second size that is larger than the first size, wherein in the second state of the expandable member, at least a portion of the expandable member contacts the collection site of the subject to collect the biological sample of the subject from the collection site; and

[0081] (c) removing the mouthpiece from the subject's mouth.

[0082] 25. The method of embodiment 24, wherein the expandable member comprises a balloon.

[0083] 26. The method of embodiment 25, wherein the balloon is expandable under positive pressure from the drive component.

[0084] 27. The method of embodiment 26, wherein the positive pressure is generated by a gas or liquid driven by the driving component.

[0085] 28. The method of embodiment 24, wherein the expandable member comprises a sampling member at its distal end, the sampling member configured to retain the biological sample collected from the collection site of the subject.

[0086] 29. The method of embodiment 24, wherein the expandable member is removable relative to the mouthpiece.

[0087] 30. The method of embodiment 29, wherein the expandable member is disposable.

[0088] 31. The method of embodiment 24, wherein the drive component comprises a pump.

[0089] 32. The method of embodiment 24, wherein the drive component comprises a motor.

[0090] 33. The method of embodiment 32, wherein the electrode drives a plunger that fits snugly within a tube coupled to the expandable member.

[0091] 34. The method of embodiment 33, further comprising a recovery component configured to change the expandable component from the second state to the first state.

[0092] 35. The method of embodiment 34, wherein the recovery component comprises a pressure release component configured to release pressure within the expandable component when the expandable component is in the second state.

[0093] 36. The method of embodiment 35, wherein the pressure relief member comprises a one-way valve configured to (i) only allow the pressure medium to flow toward the expandable member, and (ii) be movable relative to the expandable member.

[0094] 37. The method of embodiment 36, wherein the pressure release component includes a release outlet through which the pressure medium is released from the expandable portion.

[0095] 38. The method of embodiment 37, wherein the release outlet is in communication with a release channel.

[0096] 39. The method of embodiment 24, wherein at least a portion of the mouthpiece is configured to be positioned outside of the at least a portion of the subject's mouth.

[0097] 40. The method of embodiment 24, wherein at least a portion of the mouthpiece is configured to reside within the at least a portion of the subject's mouth.

[0098] 41. The method of embodiment 39 or 40, wherein the at least a portion of the mouth comprises the lips of the subject.

[0099] 42. The method of embodiment 41, wherein the mouthpiece is sized to abut the lips when the expandable member is positioned within the mouth of the subject.

[0100] 43. The method of embodiment 24, wherein the collection site of the subject comprises an oropharyngeal site.

[0101] 44. A method for collecting a sample, comprising:

[0102] (a) A sample collection device is provided, the sample collection device comprising (i) a mouthpiece configured to engage with at least a portion of a mouth of a subject, (ii) an expandable member located on one side of the mouthpiece in a longitudinal direction of the mouthpiece, the expandable member having a first state and a second state, wherein in the first state, the expandable member has a first size, and in the second state, the expandable member has a second size, the second size being larger than the first size, and (iii) an actuation member coupled to the expandable member and configured to change the expandable member from the first state to the second state, wherein the expandable member is configured such that, when in the second state, at least a portion of the expandable member contacts a collection site of the subject and collects a biological sample from the collection site;

[0103] (b) removing the expandable member from the sample collection device; and

[0104] (c) placing the expandable member in a container.

[0105] 45. The method of embodiment 44, wherein the expandable member comprises a balloon.

[0106] 46. ​​The method of embodiment 45, wherein the balloon is expandable under positive pressure from the drive component.

[0107] 47. The method of embodiment 46, wherein the positive pressure is generated by a gas or liquid driven by the driving component.

[0108] 48. The method of embodiment 44, wherein the expandable member comprises a sampling member at its distal end, the sampling member configured to retain the biological sample collected from the collection site of the subject.

[0109] 49. The method of embodiment 44, wherein the expandable member is removable relative to the mouthpiece.

[0110] 50. The method of embodiment 49, wherein the expandable member is disposable.

[0111] 51. The method of embodiment 44, wherein the drive component comprises a pump.

[0112] 52. The method of embodiment 44, wherein the drive component comprises a motor.

[0113] 53. The method of embodiment 52, wherein the electrode drives a plunger that fits snugly within a tube coupled to the expandable member.

[0114] 54. The method of embodiment 44, further comprising a recovery component configured to change the expandable component from the second state to the first state.

[0115] 55. The method of embodiment 54, wherein the recovery component comprises a pressure release component configured to release pressure within the expandable component when the expandable component is in the second state.

[0116] 56. The method of embodiment 55, wherein the pressure relief member comprises a one-way valve configured to (i) only allow the pressure medium to flow toward the expandable member, and (ii) be movable relative to the expandable member.

[0117] 57. The method of embodiment 56, wherein the pressure release component includes a release outlet through which the pressure medium is released from the expandable portion.

[0118] 58. The method of embodiment 57, wherein the release outlet is in communication with a release channel.

[0119] 59. The method of embodiment 44, wherein at least a portion of the mouthpiece is configured to be positioned outside of the at least a portion of the subject's mouth.

[0120] 60. The method of embodiment 44, wherein at least a portion of the mouthpiece is configured to reside within the at least a portion of the subject's mouth.

[0121] 61. The method of embodiment 59 or 60, wherein the at least a portion of the mouth comprises the lips of the subject.

[0122] 62. The method of embodiment 61, wherein the mouthpiece is sized to abut the lips when the expandable member is positioned within the mouth of the subject.

[0123] 63. The method of embodiment 44, wherein the collection site of the subject comprises the oropharynx.

[0124] 64. A kit comprising:

[0125] The sample collection device according to embodiment 1; and

[0126] Optionally, instructions directing a user to use the sample collection device to collect a biological sample from a subject.

[0127] Although preferred embodiments of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that these embodiments are provided by way of example only. Numerous variations, modifications, and substitutions will now occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein may be used to practice the present disclosure. It is intended that the scope of the present disclosure be defined by the following claims, and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. A sample collection device comprising: a mouthpiece configured to engage at least a portion of a subject's mouth; an expandable member, the expandable member being located on one side of the mouthpiece in a longitudinal direction of the mouthpiece, the expandable member having a first state and a second state, wherein in the first state, the expandable member has a first size, and in the second state, the expandable member has a second size, the second size being larger than the first size; a drive component coupled to the expandable component and configured to change the expandable component from the first state to the second state, wherein the drive component comprises a pump or a motor; as well as a recovery component configured to change the expandable component from the second state to the first state, wherein the recovery component includes a pressure release component configured to release pressure within the expandable component when the expandable component is in the second state, The expandable member is configured such that, when in the second state, at least a portion of the expandable member contacts a collection site of the subject and collects a biological sample from the collection site.

2. The sample collection device of claim 1, wherein the expandable member comprises a balloon.

3. The sample collection device of claim 2, wherein the balloon is expandable under the action of positive pressure from the drive component.

4. The sample collection device of claim 3, wherein the positive pressure is generated by gas or liquid driven by the driving component.

5. The sample collection device of claim 1, wherein the expandable member comprises a sampling member at a distal end thereof, the sampling member configured to retain the biological sample collected from the collection site of the subject.

6. The sample collection device of claim 1, wherein the expandable member is removable relative to the mouthpiece.

7. The sample collection device of claim 6, wherein the expandable member is disposable.

8. The sample collection device of claim 1, wherein the drive member comprises a motor, wherein the motor drives a plunger that fits snugly within a tube coupled to the expandable member.

9. The sample acquisition device of claim 1, wherein the pressure relief member comprises a one-way valve configured to (i) only allow pressure medium to flow toward the expandable member, and (ii) be movable relative to the expandable member.

10. The sample acquisition device of claim 9, wherein the pressure release member includes a release outlet through which the pressure medium is released from the expandable member. The sample collection device of claim 10 , wherein the release outlet is in communication with a release channel.

12. The sample acquisition device of claim 1, wherein at least a portion of the mouthpiece is configured to be positioned outside of the at least a portion of the subject's mouth.

13. The sample acquisition device of claim 1, wherein at least a portion of the mouthpiece is configured to be positioned within the at least a portion of the subject's mouth.

14. The sample acquisition device of claim 12 or 13, wherein the at least a portion of the mouth comprises the lips of the subject.

15. The sample acquisition device of claim 14, wherein the mouthpiece is sized to abut the lips when the expandable member is positioned within the mouth of the subject.

16. The sample collection device of claim 1, further comprising a handle coupled to a side of the mouthpiece opposite the expandable member in the longitudinal direction of the mouthpiece.

17. The sample acquisition device of claim 1, further comprising a power source configured to power at least the drive component.

18. The sample collection device of claim 1, further comprising a switch configured to at least turn the drive component on and at least turn off.

19. The sample collection device of claim 1, wherein the collection site of the subject comprises the oropharynx.

20. A method for collecting a biological sample from a subject, the method comprising: (a) providing a sample collection device comprising (i) a mouthpiece, (ii) an expandable member located on one side of the mouthpiece in a longitudinal direction of the mouthpiece, the expandable member being in a first state having a first size, and (iii) an actuation member coupled to the expandable member, wherein the mouthpiece engages at least a portion of a mouth of a subject; (b) with the mouthpiece engaged with the at least a portion of the subject's mouth, expanding the expandable member under the action of the drive member such that the expandable member changes from the first state to a second state, wherein in the second state the expandable member has a second size that is larger than the first size, wherein in the second state of the expandable member, at least a portion of the expandable member contacts a collection site of the subject to collect the biological sample from the collection site; as well as (c) removing the mouthpiece from the subject's mouth, wherein the driving component comprises a pump or a motor, and The sample collection device further comprises a recovery component configured to change the expandable component from the second state to the first state, wherein the recovery component comprises a pressure release component configured to release pressure within the expandable component when the expandable component is in the second state.

21. The method of claim 20, wherein the expandable member comprises a balloon.

22. The method of claim 21, wherein the balloon is inflatable under positive pressure from the drive member.

23. The method of claim 22, wherein the positive pressure is generated by a gas or liquid driven by the driving member.

24. The method of claim 20, wherein the expandable member comprises a sampling member at a distal end thereof, the sampling member configured to retain the biological sample collected from the collection site of the subject.

25. The method of claim 20, wherein the expandable member is removable relative to the mouthpiece.

26. The method of claim 25, wherein the expandable member is disposable.

27. The method of claim 20, wherein the drive member comprises a motor, wherein the motor drives a plunger that fits snugly within a tube coupled to the expandable member.

28. The method of claim 20, wherein the pressure relief member comprises a one-way valve configured to (i) only allow pressure medium to flow toward the expandable member, and (ii) be movable relative to the expandable member.

29. The method of claim 28, wherein the pressure relief member includes a release outlet through which the pressure medium is released from the expandable member.

30. The method of claim 29, wherein the release outlet is in communication with a release passage.

31. The method of claim 20, wherein at least a portion of the mouthpiece is configured to be positioned outside of the at least a portion of the subject's mouth.

32. The method of claim 20, wherein at least a portion of the mouthpiece is configured to be positioned within the at least a portion of the subject's mouth.

33. The method of claim 31 or 32, wherein the at least a portion of the mouth comprises the subject's lips.

34. The method of claim 33, wherein the mouthpiece is sized to abut the lips when the expandable member is positioned within the mouth of the subject.

35. The method of claim 20, wherein the collection site of the subject comprises an oropharyngeal site.

36. A method for collecting a sample, comprising: (a) A sample collection device is provided, comprising: (i) a mouthpiece configured to engage with at least a portion of a mouth of a subject, (ii) an expandable member located on one side of the mouthpiece in a longitudinal direction, the expandable member having a first state and a second state, wherein in the first state, the expandable member has a first size, and in the second state, the expandable member has a second size that is larger than the first size, and (iii) an actuation member coupled to the expandable member and configured to change the expandable member from the first state to the second state, wherein the expandable member is configured such that: when in the second state, at least a portion of the expandable member contacts a collection site of the subject and collects a biological sample from the collection site; (b) removing the expandable member from the sample acquisition device; and (c) placing the expandable member in a container, wherein the driving component comprises a pump or a motor, and The sample collection device further comprises a recovery component configured to change the expandable component from the second state to the first state, wherein the recovery component comprises a pressure release component configured to release pressure within the expandable component when the expandable component is in the second state.

37. The method of claim 36, wherein the expandable member comprises a balloon.

38. The method of claim 37, wherein the balloon is inflatable under positive pressure from the drive member.

39. The method of claim 38, wherein the positive pressure is generated by a gas or liquid driven by the driving member.

40. The method of claim 36, wherein the expandable member comprises a sampling member at a distal end thereof, the sampling member configured to retain the biological sample collected from the collection site of the subject.

41. The method of claim 36, wherein the expandable member is removable relative to the mouthpiece.

42. The method of claim 41, wherein the expandable member is disposable.

43. The method of claim 36, wherein the drive member comprises a motor, wherein the motor drives a plunger that fits snugly within a tube coupled to the expandable member.

44. The method of claim 36, wherein the pressure relief member comprises a one-way valve configured to (i) only allow pressure medium to flow toward the expandable member, and (ii) be movable relative to the expandable member.

45. The method of claim 44, wherein the pressure relief member includes a release outlet through which the pressure medium is released from the expandable member.

46. ​​The method of claim 45, wherein the release outlet is in communication with a release passage.

47. The method of claim 36, wherein at least a portion of the mouthpiece is configured to be positioned outside of the at least a portion of the subject's mouth.

48. The method of claim 36, wherein at least a portion of the mouthpiece is configured to be positioned within the at least a portion of the subject's mouth.

49. The method of claim 47 or 48, wherein the at least a portion of the mouth comprises the subject's lips.

50. The method of claim 49, wherein the mouthpiece is sized to abut the lips when the expandable member is positioned within the mouth of the subject.

51. The method of claim 36, wherein the collection site of the subject comprises the oropharynx.

52. A kit comprising: The sample collection device according to claim 1; as well as Instructions directing a user to use the sample collection device to collect a biological sample from a subject.

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