Filtering and sampling device and testing device

Abstract

A filter assembly (2224, 2324) is provided that includes a tubular container (2030, 2330) shaped to define a proximal container opening (2036) for receiving a liquid sample sample (22). The plunger (1730, 2340) includes a plunger head (1742, 2342) and a plunger rod (1782, 2382) and is insertable into the tubular container (2030, 2330) via the proximal container opening (2036). The filter support (1662, 2362) is shaped to define a support surface (1659, 2359) on which the filter (60) is removably disposed and a plurality of filtrate passage openings (1668) through the filter support (1662, 2362) into the waste fluid receptacle (1656, 2356). The filter assembly (2224, 2324) is configured such that when the liquid sample sample (22) is contained in the tubular container (2030, 2330) and the filter (60) is disposed on the support surface (1659, 2359), energy release of the preloaded energy storage element (2202) urges at least a portion of the liquid sample sample (22) through the filter (60) and the filtrate passage opening (1668) and into the waste liquid receptacle (1656, 2356). Other embodiments are also described.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application:

[0003] (a) claims priority from international application PCT / IL2023 / 050014 filed on January 5, 2023, and is a continuation-in-part of that international application; and

[0004] (b) Claims the benefit of U.S. Provisional Application No. 63 / 388,851, filed on July 13, 2022, and U.S. Provisional Application No. 63 / 432,231, filed on December 13, 2022.

[0005] All of the above-referenced applications are assigned to the assignee of the present application and are incorporated herein by reference. Technical Field

[0006] Applications of the invention relate to the sampling of biological fluids. Background Art

[0007] There are many technologies used to test for the presence of bacteria and viruses to aid in disease diagnosis. For example, testing for influenza virus includes molecular-based detection methods, viral culture methods, and immunoassay methods. Influenza virus testing includes testing of nasal swabs, nasopharyngeal swabs, nasal aspirates, nasopharyngeal aspirates, nasal washes, nasopharyngeal washes, throat swabs, and combinations of specimens.

[0008] PCT Publication WO 2018 / 158768 by Fruchter et al. describes, inter alia, a method for testing for the presence of particles selected from a group comprising: microorganisms, fungi, bacteria, spores, viruses, mites, biological cells, biological antigens, proteins, protein antigens, and carbohydrate antigens. The method comprises (a) collecting a fluid that may contain particles in a tube, (b) using a plunger to push the fluid through a filter that is removably disposed at a distal portion of the tube or at the distal end of the plunger, and then, (c) while the filter is inside the tube, determining whether any particles are captured by the filter by applying a particle presence test promoting solution to the filter.

[0009] PCT publication WO 2020 / 049569 by Fruchter et al. describes, inter alia, a test device for testing the presence of particles in a liquid. The test device includes: a liquid container for containing a liquid; a filter disposed in or downstream of the liquid container; a liquid pressure source arranged to apply pressure to drive the liquid contained in the liquid container through the filter; and a filter chamber (a) disposed downstream of the liquid container, (b) shaped to define an inlet, and (c) in fluid communication with the filter.

[0010] PCT Publication WO 2022 / 149135 by Feldman et al. describes, inter alia, a sampling device for concentrating a liquid test sample, the sampling device comprising a filter assembly comprising a tubular container and a plunger. The plunger comprises a plunger head and a plunger rod, the plunger rod being shaped to define an internal plunger space having a plunger space proximal opening through the proximal end of the plunger rod. The sampling device is configured so that the filter can be removed from the tubular container via the plunger space proximal opening when the plunger head is in the tubular container.

[0011] U.S. Patent Application Publication 2011 / 0318814 to Kshirsagar et al. describes, inter alia, a method for separating microorganisms from a sample comprising a sample matrix and microorganisms, the method comprising the steps of providing a receiving portion configured to allow filtering of the sample and to reversibly contain the sample and a concentrator; adding the sample to the receiving portion, wherein a composition with microorganisms bound thereto is formed in the receiving portion, the composition with microorganisms bound thereto comprising the microorganisms bound thereto and the sample matrix; and filtering the composition with microorganisms bound thereto through a filter to collect the microorganisms bound thereto on the filter. The average pore size of the filter is greater than the average size of the microorganisms. Kits and systems are also described.

[0012] Guirguis' U.S. Patent No. 5,077,012 describes a device for collecting biological fluids and preserving samples extracted from biological fluids for qualitative and quantitative testing. The device includes a tubular container open at two ends, wherein a quantitative test storage unit is removably fixed to one of the ends of the tubular container. The quantitative test storage unit has an open end, a cytological membrane installed in the storage unit, and a retaining rib. A reciprocating assembly is slidably installed in the tubular container, the reciprocating assembly including a cylindrical hollow piston defining a chamber, a thumb-shaped cover covering one end of the piston and a fluid flow orifice formed in the piston, and a qualitative sample container assembly removably fixed to the piston. The qualitative sample container assembly includes a clamping membrane assembly, which includes a membrane containing fixed antibodies and a filter housing mounted to the clamping membrane assembly. The filter housing is suitable for being seated in the quantitative test storage unit after being slidably transported along the tubular container by the piston.

[0013] U.S. Patent 8,322,539 to Ellis et al. describes a filter bottle for separating biological fluids and chemical fluids, the filter bottle having a cylindrical sidewall with an open top and a closed bottom. A projection extends upward from the middle of the bottom to form an annular recess. A tubular plunger has an open bottom end, to which an annular cup having an outer sidewall sized to fit into the bottle and seal against the sidewall of the bottle is fastened. The inner sidewall of the annular cup holds the filter above the opening at the bottom of the plunger and forms a shaped cavity leading to the filter. The annular cup on the plunger fits into the annular recess in the bottle to force the fluid from the bottle through the filter and into the plunger.

[0014] U.S. Patent Application Publication 2015 / 0076069 to Ellis et al. describes a filter bottle and piston wherein the bottle has a cylindrical wall having a closed bottom and an open top and a hollow tubular piston therein. The piston has a position stop positioned and configured to abut a mating position stop on the bottle to limit relative movement of the piston and the bottle. The position stop is positioned to stop the distal end of the piston at a distance of about 10% to 30% of the height of the bottle from the bottom of the bottle. A material is dissolved in a liquid in the bottle and undesirable molecules are removed from the liquid in a manner such that the piston forces the liquid through the filter but does not squeeze a slurry of the material to force the slurry into the filter. Summary of the invention

[0015] Some applications of the present invention provide sampling devices for concentrating a liquid sample. Some of the sampling devices include a filter assembly, which includes a tubular container for receiving the liquid sample, a plunger, and a filter disposed in the tubular container. The filter assembly is configured so that when the liquid sample is contained in the tubular container and the filter is disposed in the tubular container, movement of the plunger head in the tubular container pushes at least a portion of the liquid sample through the filter.

[0016] In some configurations, the sampling device includes a mechanical energy storage element. The filter assembly is configured so that when the liquid sample sample is contained in the tubular container and the filter is arranged on the support surface, the movement of the plunger head in the tubular container additionally stores mechanical energy in the mechanical energy storage element. In some configurations in these configurations, the filter assembly is configured to push more parts of the liquid sample sample through the filter when at least a portion of the mechanical energy stored in the mechanical energy storage element is released. For example, the filter assembly can be configured so that the release of at least a portion of the mechanical energy causes the tubular container to move toward the proximal end relative to the plunger head, thereby pushing the additional portion of the liquid sample sample through the filter.

[0017] In other configurations, the sampling device includes a preloaded energy storage element. The filter assembly is configured such that when a liquid sample is contained in the tubular container and the filter is disposed on a support surface, the energy release of the preloaded energy storage element pushes at least a portion of the liquid sample through the filter and the filtrate passage opening and into the waste liquid receiving portion. For some applications, the preloaded energy storage element includes a gas source. In some of these configurations, the gas source includes a substance that releases gas when combined with a liquid, and in other of these applications, the gas source includes a compressed gas container.

[0018] Therefore, according to the application of the present invention, a sampling device for concentrating a liquid test sample is provided, the sampling device comprising a filter assembly, the filter assembly comprising:

[0019] a tubular container shaped to define an interior wall and a proximal container opening for receiving a liquid test sample;

[0020] a plunger (i) comprising a plunger head and a plunger rod, the plunger rod having a distal end portion coupled to the plunger head, and (ii) insertable into the tubular container through the proximal container opening such that a lateral surface of the plunger head forms a movable fluid tight seal with an inner wall of the tubular container;

[0021] A waste liquid receiving part;

[0022] Filters;

[0023] a filter support shaped to define (a) a support surface on which the filter is removably disposed, and (b) a plurality of filtrate passage openings through the filter support into the waste receiving portion; and

[0024] Preload the energy storage element,

[0025] Therein, the filter assembly is configured such that when a liquid sample is contained in a tubular container and a filter is disposed on a support surface, the release of energy from the preloaded energy storage element pushes at least a portion of the liquid sample through the filter and the filtrate passage opening and into the waste liquid receiving portion.

[0026] For some applications, the pre-loading energy storage element includes a gas source.

[0027] For some applications, the gas source includes one or more substances that generate a gas.

[0028] For some applications, the gas source includes a compressed gas container.

[0029] For some applications, the filter assembly is configured such that movement of the plunger head within the tubular container causes the gas source to provide gas by releasing or generating gas.

[0030] For some applications:

[0031] This motion is non-rotational.

[0032] The sampling device also includes a container housing, and

[0033] The filter assembly also includes a plunger support that is (a) coupled to the proximal end portion of the plunger and (b) hingedly attached to the container housing.

[0034] For some applications:

[0035] The plunger rod is shaped to define a waste receiving portion within the plunger rod, and

[0036] The plunger head includes a filter support.

[0037] For some applications:

[0038] The sampling device also includes a container housing,

[0039] The tubular container is at least partially disposed within the container housing such that the tubular container is movable relative to the container housing, and

[0040] The filtration assembly is configured such that release of energy of the preloaded energy storage element causes the tubular container to move proximally relative to the plunger head, thereby pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste receptacle.

[0041] For some applications:

[0042] The preload energy storage element includes a gas source configured to provide gas by releasing or generating gas into a space defined between (a) a proximal-facing inner surface of the container shell and (b) an outer surface of the tubular container defined by a distal end of the tubular container, and

[0043] The filter assembly is configured such that providing gas to the space increases the pressure in the space, thereby causing the tubular container to move proximally relative to the plunger head.

[0044] For some applications, the distal bottom surface of the tubular container includes a filter support.

[0045] For some applications:

[0046] The filtering components also include:

[0047] a housing including a tubular container; and

[0048] a plunger support that is coupleable to the housing and includes a plunger tube in which the plunger rod is at least partially disposed so as to be axially movable relative to the plunger tube, and

[0049] The filter assembly is configured such that release of energy of the preloaded energy storage element causes the plunger rod to move distally relative to the plunger tube, thereby pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste receptacle.

[0050] For some applications:

[0051] The preload energy storage element includes a gas source configured to provide gas by releasing or generating gas into a space defined between (a) a proximal surface of the plunger rod and (b) a distally facing inner surface of the plunger support, and

[0052] The filter assembly is configured such that providing gas to the space increases the pressure in the space, thereby causing the plunger rod to move distally relative to the plunger tube.

[0053] For some applications:

[0054] The pre-loaded energy storage element includes a gas source, and

[0055] The filter assembly is configured such that coupling of the plunger support to the housing causes proximal movement of the plunger rod within the plunger support, which causes the gas source to provide gas by releasing or generating gas.

[0056] For some applications:

[0057] The pre-loaded energy storage element includes a gas source configured to provide gas to a space defined within the filter assembly by releasing or generating gas,

[0058] The filter assembly is shaped to define an energy storage element chamber that is in fluid communication with the space only through one or more narrow openings having a total area of ​​75 square microns to 8,000 square microns, and

[0059] A preloaded energy storage element is disposed in the energy storage element chamber.

[0060] According to the application of the present invention, there is also provided a method for concentrating a liquid test sample, the method comprising:

[0061] placing a liquid test sample into a tubular container of a filter assembly of a sampling device through a proximal container opening;

[0062] inserting a plunger head of a plunger of the filter assembly into the tubular container through the proximal container opening of the tubular container so that a lateral surface of the plunger head forms a movable fluid tight seal with an inner wall of the tubular container, wherein the plunger further comprises a plunger rod having a distal end portion coupled to the plunger head; and

[0063] A preloaded energy storage element of the filter assembly is caused to release energy, thereby pushing at least a portion of a liquid test sample through a filter removably disposed on a support surface of a filter support portion in a tubular container, wherein the filter support portion is shaped to define a plurality of filtrate passage openings that pass through the filter support portion and into a waste liquid receiving portion of the filter assembly.

[0064] For some applications, the pre-loading energy storage element includes a gas source.

[0065] For some applications, the gas source includes one or more substances that generate a gas.

[0066] For some applications, the gas source includes a compressed gas container.

[0067] For some applications, releasing the energy of the preloaded energy storage element includes moving the plunger head within the tubular container to cause the gas source to provide gas by releasing or generating gas.

[0068] For some applications:

[0069] The sampling device also includes a container housing,

[0070] The filter assembly further includes a plunger support (a) coupled to the proximal end portion of the plunger and (b) hingedly attached to the container housing, and

[0071] Moving the plunger head within the tubular container includes non-rotationally moving the plunger head within the tubular container.

[0072] For some applications:

[0073] The plunger rod is shaped to define a waste receiving portion within the plunger rod, and

[0074] The plunger head includes a filter support.

[0075] For some applications:

[0076] The sampling device also includes a container housing,

[0077] The tubular container is at least partially disposed within the container housing such that the tubular container is movable relative to the container housing, and

[0078] Releasing the preloaded energy storage element causes the tubular container to move proximally relative to the plunger head, thereby pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste receiving portion.

[0079] For some applications:

[0080] The pre-loaded energy storage element includes a gas source, and

[0081] Causing the preloaded energy storage element to release energy includes causing a gas source to provide gas to a space by releasing or generating gas - the space being defined between (a) an inner surface of the container shell facing the proximal end and (b) an outer surface of the tubular container defined by the distal end of the tubular container - thereby increasing the pressure in the space, thereby causing the tubular container to move proximally relative to the plunger head.

[0082] For some applications, the distal bottom surface of the tubular container includes a filter support.

[0083] For some applications:

[0084] The filtering components also include:

[0085] a housing including a tubular container; and

[0086] a plunger support that is coupleable to the housing and includes a plunger tube in which the plunger rod is at least partially disposed so as to be axially movable relative to the plunger tube, and

[0087] Releasing the preloaded energy storage element causes the plunger rod to move distally relative to the plunger tube, thereby pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste receptacle.

[0088] For some applications:

[0089] The preload energy storage element includes a gas source configured to provide gas by releasing or generating gas into a space defined between (a) a proximal surface of the plunger rod and (b) a distally facing inner surface of the plunger support, and

[0090] Causing the preloaded energy storage element to release energy includes causing a gas source to provide gas into the space to increase a pressure in the space, thereby causing the plunger rod to move distally relative to the plunger tube.

[0091] For some applications:

[0092] The pre-loaded energy storage element includes a gas source, and

[0093] Releasing the energy of the preloaded energy storage element includes coupling the plunger support to the housing to move the plunger rod proximally within the plunger support, which causes the gas source to provide gas by releasing or generating gas.

[0094] For some applications:

[0095] The pre-loaded energy storage element includes a gas source configured to provide gas to a space defined within the filter assembly by releasing or generating gas,

[0096] The filter assembly is shaped to define an energy storage element chamber that is in fluid communication with the space only through one or more narrow openings having a total area of ​​75 square microns to 8,000 square microns, and

[0097] A preloaded energy storage element is disposed in the energy storage element chamber.

[0098] For some applications, the method further includes detecting the presence of biological particles captured by the filter after the filter has been removed from the tubular container.

[0099] For some applications, detecting the presence of the biological particle captured by the filter includes using a lateral flow test strip to detect the presence of the biological particle captured by the filter.

[0100] For some applications, the biological particle is selected from the group consisting of viruses, bacteria, microorganisms, fungi, spores, mites, biological cells, biological antigens, proteins, protein antigens, and carbohydrate antigens.

[0101] For some applications, the liquid test sample includes a mouthwash fluid.

[0102] According to the application of the present invention, there is also provided a sampling device for concentrating a liquid test sample, the sampling device comprising a filter assembly, the filter assembly comprising:

[0103] a tubular container shaped to define an interior wall and a proximal container opening for receiving a liquid test sample;

[0104] a plunger (i) comprising a plunger head and a plunger rod, the plunger rod (a) having a distal end portion coupled to the plunger head and (b) shaped to define a waste receiving portion within the plunger rod, and the plunger (ii) being insertable into the tubular container through the proximal container opening such that a lateral surface of the plunger head forms a movable fluid tight seal with the inner wall;

[0105] Filters; and

[0106] Mechanical energy storage elements,

[0107] wherein the plunger head includes a filter support portion shaped to define (a) a support surface on which the filter is removably disposed, and (b) a plurality of filtrate passage openings extending through the filter support portion into the waste receiving portion, and

[0108] wherein the filter assembly is configured such that when a liquid sample is contained in the tubular container and the filter is disposed on a support surface, movement of the plunger head within the tubular container:

[0109] pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste receiving portion, and

[0110] The mechanical energy is stored in the mechanical energy storage element.

[0111] For some applications:

[0112] The sampling device also includes a container housing,

[0113] The tubular container is at least partially disposed within the container housing such that the tubular container is movable relative to the container housing, and

[0114] The mechanical energy storage element is arranged inside the container shell, outside the tubular container and directly or indirectly contacts the outer surface of the tubular container, so that the movement of the plunger head in the tubular container causes the tubular container to move relative to the container shell, thereby storing mechanical energy in the mechanical energy storage element.

[0115] For some applications, the filter assembly is configured to push a greater portion of the liquid sample through the filter when at least a portion of the mechanical energy stored in the mechanical energy storage element is released.

[0116] For some applications, the filter assembly is configured such that release of at least a portion of the mechanical energy causes the tubular container to move proximally relative to the plunger head, thereby pushing a greater portion of the liquid test sample through the filter.

[0117] For some applications:

[0118] The outer wall of the container shell is shaped to define an optical window,

[0119] The filter assembly also includes a visual indicator, and

[0120] The filter assembly is constructed so that the visual indicator:

[0121] The tubular container is not visible through the optical window when the tubular container is located at a first plurality of distal axial positions within the filter assembly where the visual indicator is not axially aligned with the optical window, and

[0122] The tubular container is visible through the optical window when the tubular container is in a second proximal axial position within the filter assembly, where the visual indicator is axially aligned with the optical window.

[0123] For some applications, the mechanical energy storage element includes a resilient element configured to store mechanical energy.

[0124] For some applications, the elastic element includes a spring.

[0125] For some applications, the spring is partially preloaded with mechanical energy in a pre-insertion state of the sampling device in which the plunger head is not within the tubular container.

[0126] For some applications:

[0127] The sampling device also includes a container housing,

[0128] The tubular container is at least partially disposed within the container housing such that the tubular container is movable relative to the container housing,

[0129] A mechanical energy storage element is disposed within the container housing, outside the tubular container, and in direct or indirect contact with an outer surface of the tubular container defined by a distal end of the tubular container, such that movement of the plunger head within the tubular container moves the tubular container relative to the container housing, thereby storing mechanical energy in the mechanical energy storage element, and

[0130] The spring is disposed between an outer surface of the tubular container and a proximally facing inner surface of the container housing.

[0131] For some applications, the spring is positioned around at least a longitudinal portion of the tubular container.

[0132] For some applications, the spring is disposed along at least a longitudinal portion of the tubular container.

[0133] For some applications, the mechanical energy storage element includes a plurality of springs disposed along at least a longitudinal portion of the tubular container.

[0134] For some applications, the mechanical energy storage element is disposed within the tubular container.

[0135] For some applications, the mechanical energy storage element includes a flexible container containing a gas.

[0136] According to the application of the present invention, there is also provided a method for concentrating a liquid test sample, the method comprising:

[0137] placing a liquid test sample in a tubular container of a filter assembly of a sampling device;

[0138] inserting a plunger head of a plunger of a filter assembly into the tubular container through the proximal container opening of the tubular container so that a lateral surface of the plunger head forms a movable fluid tight seal with an inner wall of the tubular container, wherein the plunger further comprises a plunger rod (a) having a distal end portion coupled to the plunger head and (b) shaped to define a waste receiving portion within the plunger rod; and

[0139] Advance the plunger tip distally within the tubular container to:

[0140] driving at least a portion of a liquid test sample through a filter removably disposed on a support surface of a filter support in the tubular container, wherein the filter support is shaped to define a plurality of filtrate passage openings through the filter support into a waste receiving portion, and

[0141] The mechanical energy is stored in a mechanical energy storage element of the filter assembly.

[0142] For some applications:

[0143] The sampling device also includes a container housing,

[0144] The tubular container is at least partially disposed within the container housing such that the tubular container is movable relative to the container housing,

[0145] The energy storage element is disposed within the container housing, outside the tubular container and in direct or indirect contact with the outer surface of the tubular container, and

[0146] Advancing the plunger tip distally within the tubular container includes advancing the plunger tip distally within the tubular container to move the tubular container relative to the container housing, thereby storing energy in the energy storage element.

[0147] For some applications, the filter assembly is configured to push a greater portion of the liquid sample through the filter when at least a portion of the mechanical energy stored in the mechanical energy storage element is released.

[0148] For some applications, the filter assembly is configured such that release of at least a portion of the mechanical energy causes the tubular container to move proximally relative to the plunger head, thereby pushing a greater portion of the liquid test sample through the filter.

[0149] For some applications:

[0150] The outer wall of the container shell is shaped to define an optical window,

[0151] The filter assembly also includes a visual indicator, and

[0152] The filter assembly is constructed so that the visual indicator:

[0153] The tubular container is not visible through the optical window when the tubular container is located at a first plurality of distal axial positions within the filter assembly where the visual indicator is not axially aligned with the optical window, and

[0154] The tubular container is visible through the optical window when the tubular container is in a second proximal axial position within the filter assembly, where the visual indicator is axially aligned with the optical window.

[0155] For some applications, the mechanical energy storage element includes a resilient element configured to store mechanical energy.

[0156] For some applications, the elastic element includes a spring.

[0157] For some applications, the spring is partially preloaded with energy in a pre-insertion state of the sampling device in which the plunger tip is not within the tubular container.

[0158] For some applications:

[0159] The tubular container is at least partially disposed within the container housing such that the tubular container is movable relative to the container housing,

[0160] A mechanical energy storage element is disposed within the container housing, outside the tubular container, and in direct or indirect contact with an outer surface of the tubular container defined by a distal end of the tubular container, such that movement of the plunger head within the tubular container moves the tubular container relative to the container housing, thereby storing mechanical energy in the mechanical energy storage element, and

[0161] The spring is disposed between an outer surface of the tubular container and a proximally facing inner surface of the container housing.

[0162] For some applications, the spring is positioned around at least a longitudinal portion of the tubular container.

[0163] For some applications, the spring is disposed along at least a longitudinal portion of the tubular container.

[0164] For some applications, the mechanical energy storage element includes a plurality of springs disposed along at least a longitudinal portion of the tubular container.

[0165] For some applications, the energy storage element is disposed within the tubular container.

[0166] For some applications, the energy storage element includes a flexible container containing a gas.

[0167] For some applications, the method further includes detecting the presence of biological particles captured by the filter after the filter has been removed from the tubular container.

[0168] For some applications, detecting the presence of the biological particle captured by the filter includes using a lateral flow test strip to detect the presence of the biological particle captured by the filter.

[0169] For some applications, the biological particle is selected from the group consisting of viruses, bacteria, microorganisms, fungi, spores, mites, biological cells, biological antigens, proteins, protein antigens, and carbohydrate antigens.

[0170] For some applications, the liquid test sample includes a mouthwash fluid.

[0171] According to the application of the present invention, a container assembly is further provided, the container assembly comprising:

[0172] (a) an extraction tube shaped to define:

[0173] an inner wider proximal portion shaped to define a proximal opening of the extraction tube, and

[0174] An inner narrower distal portion shaped to limit the extraction

[0175] a closed distal end of the tube;

[0176] (b) an elongated sealing insert removably coupled to the extraction tube and comprising:

[0177] a shaft including a distal shaft portion that is narrower than the inner narrower distal portion of the extraction tube and that is removably disposed at least partially within the inner narrower distal portion of the extraction tube;

[0178] one or more distal plugs located along or at the distal end of the distal shaft portion and removably disposed within the inner, narrower distal portion of the extraction tube; and

[0179] One or more proximal plugs positioned along the shaft

[0180] at a proximal end of one or more distal plugs;

[0181] (c) a first substance contained within the inner narrower distal portion of the extraction tube at a distal end of the one or more distal plugs such that the one or more distal plugs seal the first substance within the inner narrower distal portion of the extraction tube; and

[0182] (d) a second substance, isolated from and different from the first substance, the second substance being contained within the extraction tube distal to the one or more proximal plugs and proximal to the one or more distal plugs such that:

[0183] One or more proximal plugs seal the second substance within the extraction tube, and

[0184] one or more distal plugs sealingly isolating the second substance from the first substance,

[0185] The container assembly is configured such that the one or more distal plugs are proximally withdrawn from within the inner narrower distal portion to the inner wider proximal portion by proximal withdrawal of the shaft to place the second substance in fluid communication with the first substance.

[0186] For some applications, both the first substance and the second substance include liquids.

[0187] For some applications, one of the first substance and the second substance comprises a liquid and the other of the first substance and the second substance comprises a solid.

[0188] For some applications, the one or more proximal plugs include a proximal plug positioned along the distal shaft portion and removably disposed within an interior narrower distal portion of the extraction tube.

[0189] For some applications, the one or more proximal plugs include a proximal plug that removably plugs a proximal opening of the extraction tube.

[0190] For some applications, the one or more proximal plugs include:

[0191] a first proximal plug located along the distal shaft portion and removably disposed within the inner narrower distal portion of the extraction tube, and

[0192] A second proximal plug removably blocks the proximal opening of the extraction tube.

[0193] For some applications:

[0194] The container assembly further includes a third substance contained within the extraction tube proximal to the first proximal plug and distal to the second proximal plug such that:

[0195] The second proximal plug seals the third substance within the extraction tube, and

[0196] The first proximal plug sealingly isolates the third substance from the second substance, and

[0197] The container component is constructed as:

[0198] The first proximal plug is proximally withdrawn from the inner narrower distal portion to the inner wider proximal portion by axial proximal withdrawal to place the third substance in fluid communication with the second substance, and

[0199] The one or more distal plugs are further proximally withdrawn through the shaft from within the inner narrower distal portion to the inner wider proximal portion, placing the second and third substances in fluid communication with the first substance.

[0200] For some applications, the kit also includes a filter assembly comprising:

[0201] Filters;

[0202] Bottles; and

[0203] A filter shaft, the filter shaft comprising:

[0204] a proximal portion slidably disposed through a shaft passage hole extending through an end of the bottle opposite the bottle opening; and

[0205] a distal portion coupled to the filter,

[0206] The kit is configured such that the bottle can be at least partially inserted into the extraction tube and can be advanced distally within the extraction tube until the filter is positioned adjacent the closed distal end of the extraction tube, and

[0207] The extraction tube is shaped to prevent the bottle from reaching the closed distal end of the extraction tube so that the bottle slides upward along a portion of the filter extraction axis when the filter is positioned near the closed distal end, thereby pushing the filter out of the bottle opening and exposing the filter to the first substance and the second substance in the inner narrower distal portion of the extraction tube.

[0208] According to the application of the present invention, a method is also provided, the method comprising:

[0209] orienting the container assembly so that the proximal opening of the extraction tube of the container assembly is above the closed distal end of the extraction tube relative to the ground,

[0210] Among them, the extraction tube is shaped as defined by:

[0211] an inner wider proximal portion shaped to define a proximal opening of the extraction tube, and

[0212] an inner narrower distal portion shaped to define a closed distal end of the extraction tube;

[0213] The container assembly further comprises an elongated sealing insert, which can be

[0214] The elongated sealing insert is connected to the extraction tube in a removable manner and comprises:

[0215] a shaft including a distal shaft portion that is narrower than the inner narrower distal portion of the extraction tube and that is removably disposed at least partially within the inner narrower distal portion of the extraction tube;

[0216] one or more distal plugs located along or at the distal end of the distal shaft portion and removably disposed within the interior narrower distal portion of the extraction tube; and

[0217] one or more proximal plugs positioned along the shaft proximal to the one or more distal plugs;

[0218] The container component also includes:

[0219] a first substance received within the inner narrower distal portion of the extraction tube at a distal end of the one or more distal plugs such that the one or more distal plugs seal the first substance within the inner narrower distal portion of the extraction tube; and

[0220] a second substance, isolated from and distinct from the first substance, the second substance being contained within the extraction tube distal to the one or more proximal plugs and proximal to the one or more distal plugs such that (a) the one or more proximal plugs seal the second substance within the extraction tube and (b) the one or more distal plugs sealingly isolate the second substance from the first substance; and

[0221] The one or more distal plugs are proximally withdrawn from within the inner narrower distal portion to the inner wider proximal portion by axial proximal withdrawal, thereby placing the second substance in fluid communication with the first substance.

[0222] For some applications, both the first substance and the second substance include liquids.

[0223] For some applications, one of the first substance and the second substance comprises a liquid and the other of the first substance and the second substance comprises a solid.

[0224] For some applications, the one or more proximal plugs include a proximal plug positioned along the distal shaft portion and removably disposed within an interior narrower distal portion of the extraction tube.

[0225] For some applications, the one or more proximal plugs include a proximal plug that removably plugs a proximal opening of the extraction tube.

[0226] For some applications, the one or more proximal plugs include:

[0227] a first proximal plug located along the distal shaft portion and removably disposed within the inner narrower distal portion of the extraction tube, and

[0228] A second proximal plug removably blocks the proximal opening of the extraction tube.

[0229] For some applications:

[0230] The container assembly further includes a third substance contained within the extraction tube proximal to the first proximal plug and distal to the second proximal plug such that:

[0231] The second proximal plug seals the third substance within the extraction tube, and

[0232] The first proximal plug sealingly isolates the third substance from the second substance, and

[0233] The method further includes, prior to proximally withdrawing the one or more distal plugs from within the inner narrower distal portion to the inner wider proximal portion:

[0234] withdrawing the first proximal plug proximally from within the inner narrower distal portion to the inner wider proximal portion by axial proximal withdrawal, thereby placing the third substance in fluid communication with the second substance, and

[0235] Proximally withdrawing the one or more distal plugs includes proximally withdrawing the one or more distal plugs from within the inner narrower distal portion to the inner wider proximal portion by further withdrawing the shaft proximally, thereby placing the second substance and the third substance in fluid communication with the first substance.

[0236] For some applications, the method further includes, after proximally withdrawing the one or more distal plugs from within the inner narrower distal portion to the inner wider proximal portion:

[0237] inserting the bottle of the filter assembly at least partially into the extraction tube and advancing the bottle distally within the extraction tube until the filter of the filter assembly is positioned adjacent the closed distal end of the extraction tube, wherein the filter assembly further comprises a filter shaft comprising (a) a proximal portion slidably disposed through a shaft passage hole extending through an end of the bottle opposite the bottle opening; and (b) a distal portion coupled to the filter,

[0238] The extraction tube is shaped to prevent the bottle from reaching the closed distal end of the extraction tube so that the bottle slides upward along a portion of the filter extraction axis when the filter is positioned near the closed distal end, thereby pushing the filter out of the bottle opening and exposing the filter to the first substance and the second substance in the inner narrower distal portion of the extraction tube.

[0239] The present invention will be more fully understood through the following detailed description of embodiments of the present invention taken in conjunction with the accompanying drawings, in which: BRIEF DESCRIPTION OF THE DRAWINGS

[0240] Figure 1A to Figure 1B Schematic diagrams of a sampling device for concentrating a liquid test sample and a part of the sampling device according to the application of the present invention, respectively;

[0241] FIG. 2A to FIG. 2D According to the corresponding application of the present invention Figure 1A to Figure 1B A schematic diagram of a sampling device and a method of using the sampling device;

[0242] FIG. 3A to FIG. 3I According to the corresponding application of the present invention Figure 1A to Figure 1B A schematic cross-sectional view of a sampling device and a method of using the sampling device;

[0243] Figure 3J to Figure 3K is the use of the application according to the invention Figure 1A to Figure 1B A schematic diagram of another method of a sampling device;

[0244] Figure 4 According to the application of the present invention Figure 1A to Figure 1B An enlarged schematic diagram of a portion of a sampling device;

[0245] FIG. 5A to FIG. 5B Schematic diagrams of another sampling device for concentrating a liquid test sample and a part of the sampling device according to the application of the present invention, respectively;

[0246] FIG. 6A to FIG. 6E According to the corresponding application of the present invention FIG. 5A to FIG. 5B A schematic diagram of a sampling device and a method of using the sampling device;

[0247] 7A to 7E According to the corresponding application of the present invention FIG. 5A to FIG. 5B A schematic cross-sectional view of a sampling device and a method of using the sampling device;

[0248] FIG. 8A to FIG. 8B Schematic diagrams of a further sampling device for concentrating a liquid test sample and a part of the sampling device, respectively, according to the application of the present invention;

[0249] 9A to 9E According to the corresponding application of the present invention FIG. 8A to FIG. 8B A schematic diagram of a sampling device and a method of using the sampling device;

[0250] FIG. 10A to FIG. 10E According to the corresponding application of the present invention FIG. 8A to FIG. 8B A schematic cross-sectional view of a sampling device and a method of using the sampling device;

[0251] FIG. 11A to FIG. 11D is a schematic diagram of another sampling device and a method for using the sampling device according to the corresponding application of the present invention;

[0252] FIG. 12A to FIG. 12C is a schematic cross-sectional view of yet another sampling device and a method of using the sampling device according to a corresponding application of the present invention;

[0253] FIG. 13A to FIG. 13D is a schematic cross-sectional view of yet another sampling device and a method of using the sampling device according to a corresponding application of the present invention;

[0254] FIG. 14A to FIG. 14E is a schematic cross-sectional view of another sampling device and a method using the sampling device according to a corresponding application of the present invention;

[0255] FIG. 15A to FIG. 15B is a schematic diagram of another sampling device and a method for using the sampling device according to corresponding applications of the present invention;

[0256] FIG. 16A to FIG. 16D According to the corresponding application of the present invention FIG. 15A to FIG. 15B A schematic cross-sectional view of a sampling device and a method of using the sampling device;

[0257] FIG. 17A to FIG. 17D is a schematic diagram of another sampling device and a method for using the sampling device according to corresponding applications of the present invention;

[0258] 18A to 18D According to the corresponding application of the present invention FIG. 17A to FIG. 17D A schematic cross-sectional view of a configuration of a sampling device and a method of using the sampling device;

[0259] 19A to 19D According to the corresponding application of the present invention FIG. 17A to FIG. 17D A schematic cross-sectional view of another configuration of a sampling device and a method of using the sampling device;

[0260] FIG. 20A to FIG. 20D According to the corresponding application of the present invention FIG. 17A to FIG. 17D A schematic cross-sectional view of another configuration of a sampling device and a method of using the sampling device;

[0261] FIG. 21A to FIG. 21Cis a schematic diagram of another sampling device and a method for using the sampling device according to corresponding applications of the present invention;

[0262] FIG. 22A to FIG. 22F is a schematic cross-sectional view of a sampling device for concentrating a liquid test sample and a method for using the sampling device according to a corresponding application of the present invention;

[0263] FIG. 23A to FIG. 23E is a schematic diagram of another sampling device and a method for using the sampling device according to the corresponding application of the present invention;

[0264] FIG. 24A to FIG. 24E According to the corresponding application of the present invention FIG. 23A to FIG. 23E A schematic cross-sectional view of a sampling device and a method of using the sampling device;

[0265] Fig.25 is a schematic diagram of a kit for use according to the present invention;

[0266] Fig.26 is a schematic diagram of a test kit for use according to the present invention; and

[0267] FIG. 27A to FIG. 27E is a schematic cross-sectional view of a container assembly according to the application of the present invention and a method of using the container assembly. DETAILED DESCRIPTION

[0268] Figure 1A to Figure 1B Schematic diagram of a sampling device 1620 and a part of the sampling device for concentrating a liquid test sample 22 according to an application of the present invention.

[0269] Also refer to FIG. 2A to FIG. 2D , FIG. 2A to FIG. 2D is a schematic diagram of a sampling device 1620 and a method of using the sampling device 1620 according to corresponding applications of the present invention.

[0270] Also refer to FIG. 3A to FIG. 3I , FIG. 3A to FIG. 3I 1 is a schematic cross-sectional view of a sampling device 1620 and a method of using the sampling device 1620 according to the corresponding application of the present invention. Figure 3J to Figure 3K , Figure 3J to Figure 3K is a schematic diagram of another method of using a sampling device 1620 according to an application of the present invention.

[0271] Further references Figure 4 , Figure 4 is the application according to the present invention Figure 2D and Figure 3D An enlarged schematic diagram of a portion of the sampling device 1620 in the state shown in FIG.

[0272] Sampling device 1620 includes a filter assembly 1624 and a collection bottle 1650. With necessary modifications, the features of sampling device 1620 - including but not limited to collection bottle 1650 - can be implemented in any of the other sampling devices described below. Similarly, sampling device 1620 can be implemented in combination with any of the features of the other sampling devices described below, including, by way of example and not limitation, the reversible filter clamping technology of sampling device 1820 or 1920 described in international application PCT / IL2023 / 050014 filed on January 5, 2023, which is assigned to the assignee of the present application and is referenced thereto, respectively. Fig.11A To Figure 13F and Fig.14A to Figure 16E are incorporated herein by reference.

[0273] The filter assembly 1624 includes a tubular container 1630, a plunger 1640 (in Figure 3A ) and filter 60.

[0274] The tubular container 1630 is shaped to define a proximal container opening 1632 (at Figure 2A The proximal container opening 1632 is used to receive the liquid sample 22 after or during the collection of the liquid sample 22 from the subject. The tubular container 1630 is also shaped to define an inner wall 1634 (at Figure 3A At least a portion of the tubular container 1630, such as the distal end portion, may define a syringe barrel.

[0275] As in Figure 2A and Figure 3A As shown in FIG. 1 , the plunger 1640 includes a plunger head 1642 and a plunger rod 1682. The plunger 1640 can be inserted into the tubular container 1630 via the proximal container opening 1632 so that the lateral surface 1646 (at Figure 3A ) forms a movable fluid-tight seal with the inner wall 1634. To this end, the lateral surface 1646 may include an elastomeric material, such as natural rubber, synthetic rubber, a thermoplastic elastomer, or a combination thereof. Optionally, the filter assembly 1624 also includes a plunger support 1658, which is connected to the proximal portion of the plunger 1640. The plunger support 1658 can be configured to be connected to the tubular container 1630. A portion of the plunger support 1658 can be used as a handle to easily manipulate the plunger 1640, including inserting the plunger 1640 into the tubular container 1630. Optionally, a portion of the plunger support 1658 surrounds the plunger 1640.

[0276] For some of these applications, the plunger rod 1682 is shaped to define an internal plunger space 1686 (in Figure 3D For some of these applications, the proximal end of the plunger rod 1682 is shaped to define a plunger space proximal opening 1690 of the internal plunger space 1686. The plunger head 1642 is shaped to define a plunger head opening 1644 (at Figure 3C (marked in).

[0277] Typically, the collection bottle 1650 is at least partially disposed within the internal plunger space 1686 in a removable manner.

[0278] Typically, the collection bottle 1650 is positioned proximate to the plunger head 1642.

[0279] Reference Figure 2A and Figure 3A . Optionally, the proximal container opening 1632 is shaped as a funnel to facilitate receiving the liquid sample sample 22 during the collection of the liquid sample sample. For example, the liquid sample sample 22 can be squeezed (e.g., spit out) from the mouth of the subject into the tubular container 1630, or transferred from the collection container to the tubular container 1630. Optionally, the funnel shape of the proximal container opening 1632 is similar to the funnel-shaped proximal opening 36 shown in FIG. 1 of U.S. Patent Application Publication 2019 / 0381498 of Fruchter et al., which is incorporated herein by reference. As shown, the tubular container 1630 can be cylindrical, or can alternatively have another non-circular cross-sectional shape. Alternatively or additionally, the tubular container 1630 can have different cross-sectional shapes along corresponding different longitudinal portions of the tubular container; optionally, one or more of the cross-sectional shapes is circular.

[0280] Typically, the tubular container 1630 has an internal volume of at least 0.5 ml (e.g., at least 1 ml, such as at least 5 ml), no more than 500 ml (e.g., no more than 70 ml) and / or 0.5 ml (e.g., 1 ml or 5 ml) to 500 ml (e.g., 70 ml).

[0281] For some applications, tubular container 1630 does not include a Luer lock or any other type of needle coupling mechanism.

[0282] As in Figure 2D , Figure 3C and Figure 3D As shown in FIG. 1 , the collection bottle 1650 is generally shaped to define a bottle opening 1652 .

[0283] For some applications, the collection bottle 1650 has a volume of at least 1 ml, no more than 50 ml, and / or 1 ml to 50 ml, such as at least 2 ml, no more than 20 ml, and / or 2 ml to 20 ml, such as at least 3 ml (e.g., at least 5 ml), no more than 15 ml, and / or 3 ml (e.g., 5 ml) to 15 ml. For some applications, the collection bottle 1650 has a maximum inner diameter of no more than 35 mm, such as no more than 20 mm, such as no more than 15 mm, or no more than 10 mm.

[0284] The collection bottle 1650 typically has a maximum outer diameter that is smaller than the inner diameter of the axial portion of the tubular container 1630 in which the plunger head 1642 can be advanced distally (e.g., less than 80% of the inner diameter, such as less than 70% of the inner diameter).

[0285] Collection bottle 1650 is generally amorphous so as to define any pressure relief openings and does not include any pressure relief valve.

[0286] Reference FIG. 3B to FIG. 3D Typically, the filter assembly 1624 also includes a waste receiving portion 1656 for receiving the filtrate 61. For some of these applications, the plunger rod 1682 is shaped to define the waste receiving portion 1656 therein. Typically, the waste receiving portion 1656 partially or completely surrounds the internal plunger space 1686, such as shown.

[0287] For some applications, plunger head 1642 is shaped to define a filter support portion 1662 (at Figure 3A ), the filter support portion 1662 is shaped to define:

[0288] a bearing surface 1659 which may be perpendicular to the central longitudinal axis of the plunger head 1642 (as shown) or may be angled relative to the central longitudinal axis (configuration not shown),

[0289] a plurality of filtrate passage openings 1668 extending through the filter support portion 1662 into the waste receiving portion 1656, and

[0290] A central opening defining a plunger head opening 1644 (at Figure 3C and Figure 3D (marked in).

[0291] The filter 60 is (removably) disposed on the support surface 1659 , typically on the upstream side of the support surface 1659 (in the configuration of the sampling device 1620 , the upstream side of the support surface 1659 is the distal side of the support surface 1659 ).

[0292] Reference FIG. 2A to FIG. 2B as well as FIG. 3A to FIG. 3B The filter assembly 1624 is configured such that when the liquid sample 22 is contained in the tubular container 1630 and the filter 60 is disposed in the tubular container 1630, the movement of the plunger head 1642 within the tubular container 1630 (typically, the distal advancement) pushes at least a portion of the liquid sample 22 through the filter 60. The filter 60 is configured to concentrate at least a portion of the liquid sample 22 onto the filter 60 while allowing the filtrate 61 to pass through the filter 60. Typically, the distal advancement of the plunger 1640 within the tubular container 1630 applies pressure to drive (e.g., push) at least a portion of the liquid sample 22 contained in the tubular container 1630 through the filter 60, such as in Figure 2A and Figure 2B between and in Figure 3A and Figure 3B The transition between is shown.

[0293] The filter assembly 1624 is configured such that when a liquid sample 22 is contained in the tubular container 1630 and the filter 60 is disposed in the tubular container 1630, movement of the plunger head 1642 within the tubular container 1630 pushes at least a portion of the liquid sample sample 22 through the filter 60 and the filtrate passage opening 1668 and into the waste liquid receiving portion 1656.

[0294] Optionally, the waste receiving portion 1656 is shaped to define an opening through the outer wall of the waste receiving portion 1656 to release the displaced air. For example, the opening can be located on the proximal portion of the outer wall, generally above the highest level of the filtrate 61 expected to reach during normal use of the device. For some applications, the waste receiving portion 1656 includes an air filter (e.g., an N98 filter) that is configured to filter air that exits from the waste receiving portion 1656 through the opening. Alternatively or additionally, for some applications, the waste receiving portion 1656 includes a one-way pressure-sensitive valve disposed in the opening.

[0295] Filter 60 includes, for example, synthetic or natural materials formed into a matrix, membrane, fabric, bead, or other configuration. For some applications, filter 60 includes a mechanical filter configured to mechanically filter particles from liquid sample 22 by size-based filtration. Optionally, filter 60 includes a depth filter.

[0296] Alternatively or additionally, for some applications, filter 60 includes immobilized antibodies configured to capture particles (eg, free viral particles) by affinity-based filtration.

[0297] For some applications, for example, when the filter 60 is used to capture free viruses, virus particles or virus particles by size-based filtration, the filter 60 can have a pore size of 0.01 micron to 0.3 micron and / or a molecular weight cut-off of 10 kDa to 500 kDa. For some applications, for example, when the filter 60 is used to capture bacteria by size-based filtration, the filter 60 has a pore size of 0.2 micron to 5.0 micron, such as 0.2 micron to 2.0 micron (e.g., 0.8 micron to 1.5 micron, such as 1.2 micron).

[0298] For some applications, filter 60 comprises a polyethersulfone (PES) membrane filter.

[0299] Alternatively or additionally, for some applications, filter 60 has a nominal pore size of 30 microns to 1.5 mm, which represents the pore size of the filter when containing spherical particles. 2 O The minimum spherical particle size necessary for the filter to retain 85% of the spherical particles when passing through the filter at 20 degrees Celsius under a pressure provided by a 10 cm water column. For these applications, the filter 60 can implement the technology described in U.S. Provisional Application 63 / 117,294 filed on November 23, 2020 and / or in PCT Publication WO 2021 / 224925 to Levitz et al., which is assigned to the assignee of the present application and is incorporated herein by reference, and the PCT publication is incorporated herein by reference.

[0300] For example, the nominal pore size can be at least 40 microns, such as at least 60 microns, such as at least 100 microns, at least 120 microns, at least 150 microns, at least 200 microns or at least 500 microns. Alternatively or additionally, for example, the nominal pore size can be less than 1 mm, such as less than 750 microns, less than 500 microns or less than 250 microns.

[0301] For some applications, filter assembly 1624 includes multiple filters, such as those described in PCT publication WO2022 / 149135 by Feldman et al. FIG. 10A to FIG. 10B As described in the PCT publication assigned to the assignee of the present application and incorporated herein by reference. Optionally, two or more of the plurality of filters are in contact with each other, such as disclosed in '024 FIG. 10A to FIG. 10B, or separated from each other by one or more thin spacers (configuration not shown) having a thickness of, for example, at least 0.05 mm, no more than 1 mm, and / or 0.05 mm to 1 mm. Alternatively or additionally, two or more of the multiple filters are spaced apart from each other, in which case the filter assembly 1624 optionally includes a corresponding number of filter supports 1662, some or all of which may have some or all of the features of the filter supports 1662 (configuration not shown). In addition, alternatively or additionally, the filter assembly 1624 includes one or more additional filters (configuration not shown) located downstream of the filter 60.

[0302] Reference Figure 2D and Figure 3D The sampling device 1620 is generally configured so that the filter 60 can be removed from the tubular container 1630 via the plunger space proximal opening 1690 while the plunger head 1642 of the plunger 1640 (and typically the filter support 1662) remains within the tubular container 1630 (if the plunger head 1642 has been removed from the tubular container 1630, the filter 60 can also be removed from the tubular container 1630 via the plunger space proximal opening 1690). As described above, the plunger head 1642 is shaped to define a plunger head opening 1644 that passes through the plunger head 1642 and enters the internal plunger space 1686 of the plunger 1640.

[0303] The sampling device 1620 is configured such that the filter 60 can be advanced into (e.g., fully into) the collection bottle 1650 through the bottle opening 1652 when the collection bottle 1650 is releasably coupled to the filter assembly 1624, such as in Figure 2C and Figure 3C As shown in .

[0304] Reference Figure 2C and Figure 3C For some applications, sampling device 1620 is configured so that filter 60 can be advanced into collection bottle 1650 through bottle opening 1652 while plunger head 1642 (and typically filter support 1662) is retained within tubular container 1630, such as in Figure 2C and Figure 3C For some of these applications, the sampling device 1620 is configured so that the filter 60 can be advanced into the collection bottle 1650 through the bottle opening 1652 when the plunger head 1642 is advanced as far as possible within the tubular container 1630, such as Figure 2C and Figure 3CAlternatively or additionally, for some applications, the sampling device 1620 is configured so that the filter 60 can be advanced into the collection bottle 1650 through the bottle opening 1652 without any proximal withdrawal of the plunger head 1642 within the tubular container 1630, such as Figure 2C and Figure 3C As shown in .

[0305] Reference Figure 2D and Figure 3D For some applications, sampling device 1620 is configured such that collection bottle 1650 can be disconnected from filter assembly 1624, typically but not necessarily via the proximal end of plunger 1640, while plunger head 1642 remains within tubular container 1630, such as Figure 2D and Figure 3D For some of these applications, the sampling device 1620 is configured so that the collection bottle 1650 can be disconnected from the filter assembly 1624 when the plunger head 1642 is pushed as far as possible in the tubular container 1630, such as Figure 2D and Figure 3D Alternatively or additionally, for some applications, the sampling device 1620 is configured so that the collection bottle 1650 can be disconnected from the filter assembly 1624 without any proximal withdrawal of the plunger head 1642 within the tubular container 1630, such as Figure 2D and Figure 3D As shown in .

[0306] The collection bottle 1650 is releasably coupled to the filter assembly 1624. Once the collection bottle 1650 has been disconnected from the filter assembly 1624, diagnostic testing can be performed on the presence of particles captured by the filter 60, which are now located in the collection bottle 1650. For some applications, such as applications for transporting the collection bottle 1650 to a remote diagnostic laboratory, the sampling device 1620 also includes a collection bottle cap configured to seal the bottle opening 1652.

[0307] For some applications, collection bottle 1650 is releasably coupled to plunger 1640. Once collection bottle 1650 has been removed from plunger 1640, for example as described below, a diagnostic test can be performed for the presence of particles captured by filter 60, which are now located in collection bottle 1650. For some applications, such as applications for transporting collection bottle 1650 to a remote diagnostic laboratory, sampling device 1620 also includes a collection bottle cap configured to seal bottle opening 1652.

[0308] Still refer to Figures 1A to 4 For some applications, such as FIG. 3A to FIG. 4As shown in FIG. 1 , the sampling device 1620 includes an extractor 1692 including a filter extraction shaft 1672. The filter extraction shaft 1672:

[0309] partially disposed within the collection bottle 1650 within the internal plunger space 1686,

[0310] · includes a proximal portion 1687 that is slidably disposed through an axis passage hole 1609 that passes through an end 1604 of the collection bottle 1650 opposite the bottle opening 1652 (at Figure 4 ), and

[0311] · Includes distal portion 1608 (at Figure 4 ), the distal portion 1608 is typically connected to the filter 60 or capable of being connected to the filter 60 via an end 1604 of the collection bottle 1650 opposite to the bottle opening 1652 (directly or indirectly).

[0312] The sampling device 1620 is configured such that while the plunger head 1642 (and typically the filter support 1662) is retained within the tubular container 1630, proximal movement (e.g., extraction) of the filter extraction shaft 1672 causes the filter 60 to be collected in the collection bottle 1650 (e.g., in the presence of a filter) by at least partially pulling the filter 60 into (e.g., completely pulling the filter 60 into) the collection bottle 1650 through the plunger head opening 1644 (as described above, the plunger head opening 1644 is defined by the central opening of the filter support 1662), through the bottle opening 1652, and into the collection bottle 1650. Figure 2B and Figure 2C between and in Figure 3B and Figure 3C 16 and 16. At least a portion of the filter 60 is typically gathered from the initial flat shape of the filter when disposed on the filter support 1662 within the collection bottle 1650, such as into a flower-like arrangement.

[0313] Typically, the sampling device 1620 is configured such that while the plunger head 1642 (and typically the filter support 1662) remains within the tubular container 1630, further proximal withdrawal of the filter withdrawal shaft 1672 from the internal plunger space 1686 pulls the collection bottle 1650 out of the internal plunger space 1686 through the proximal opening 1690 of the plunger space (e.g., Figure 2C and Figure 2D between and in Figure 3C and Figure 3D It should be noted that, as shown in Figure 2D and Figure 3DAs shown in FIG. 1 , the filter extraction shaft 1672 of the sampling device 1620 is not an element of the filter assembly 1624 , but is removable from the filter assembly 1624 .

[0314] For some applications, the distal portion 1608 of the filter extraction shaft 1672 is coupled to the filter 60 prior to use of the filter 60 (typically during manufacture), while for other applications, the distal portion 1608 of the filter extraction shaft 1672 can be coupled to the filter 60 during use of the filter 60, such as by way of example and not limitation, as described in the above-mentioned International Application PCT / IL2023 / 050014. Fig.25 A to Fig.25 E and Fig.26 A to Fig.26 Described by E.

[0315] For some applications, sampling device 1620 includes distal plate 1671 (at Figure 3A ), the distal plate 1671 is arranged to contact the distal surface of the filter 60 and is connected (directly or indirectly) to the filter extraction shaft 1672 passing through the end 1604 of the collection bottle 1650. For example, the distal plate 1671 can be circular, i.e., shaped as a disk or any other shape. The distal plate 1671 can be flexible, for example, including silicone, or can be rigid, for example, including metal or polymer.

[0316] For some applications, extractor 1692 also includes a shaft handle 1605 coupled to a proximal portion of filter extraction shaft 1672. Optionally, shaft handle 1605 is shaped as a butterfly nut.

[0317] For some applications, filter assembly 1624 (e.g., plunger space proximal opening 1690 and / or plunger support 1658) and extractor 1692 (shaft handle 1605 or filter extraction shaft 1672) are shaped to define corresponding threads 1623A and 1623B (e.g., female threads 1623A and male threads 1623B), respectively (in Figure 3D ), the threads 1623A and 1623B (a) removably couple the filter extraction shaft 1672 to the plunger rod 1682 when the filter extraction shaft 1672 is arranged to pass through the internal plunger space 1686, such as in Figure 3B , and (b) prevent premature proximal withdrawal of the filter withdrawal shaft 1672 from the internal plunger space 1686. The sampling device 1620 is configured such that rotation of the filter withdrawal shaft 1672 and the proximal opening 1690 of the plunger space relative to each other (a) causes at least an initial portion of the proximal withdrawal of the filter withdrawal shaft 1672 from the internal plunger space 1686, such as during Figure 3B and Figure 3C and (b) disconnecting the female thread 1623A and the male thread 1623B from each other, thereby allowing the filter extraction shaft 1672 to continue to be extracted proximally from the internal plunger space 1686, such as at FIG. 3C to FIG. 3D Alternatively, shaft handle 1605 may be shaped to define threads 1623B, such as described below with respect to shaft handle 1805 and extractor 1892, mutatis mutandis.

[0318] Optionally, in a configuration in which the plunger support 1658 and / or the plunger 1640 and the tubular container 1630 are threadedly connected to each other, the threads between (a) the proximal opening 1690 of the plunger space and the filter extraction shaft 1672 or the shaft handle 1603 and (b) the threads between the plunger 1640 and the tubular container 1630 have opposite handedness.

[0319] For other applications, the filter assembly 1624 and the filter extraction shaft 1672 are not threadedly coupled together, and the plunger space proximal opening 1690 and the shaft handle 1605 are not threadedly coupled together.

[0320] Reference Figure 2D , FIG. 3A to FIG. 3F as well as Figure 4 For some applications, sampling device 1620 also includes a seal 1614 that inhibits fluid leakage between proximal end portion 1687 of filter extraction shaft 1672 and shaft passage hole 1609 .

[0321] Optionally, when most or all of the filter withdrawal shaft 1672 is withdrawn proximally from the collection bottle 1650, the inner portion of the seal 1614 can snap into the outer circumferential groove of the proximal portion 1687 of the filter withdrawal shaft 1672, such as at Figure 4 As shown in .

[0322] Refer again Figures 1A to 4 As described above, filter extraction shaft 1672 includes distal portion 1608 that is directly or indirectly coupled to filter 60. Exemplary ways in which the distal portion of the filter extraction shaft may be directly or indirectly coupled to filter 60 include, but are not limited to:

[0323] The distal portion of the filter extraction shaft 1672 may be secured to the distal end of the distal portion of the filter extraction shaft 1672, for example, by adhesive and / or by a distal plate 1671 that may be secured, for example, by staples (in Figure 3A ) is directly connected to the filter 60, such as Figure 4 In these configurations, the distal end portion of the filter extraction shaft passes through the end of the collection bottle opposite to the bottle opening; and

[0324] The distal end portion of the filter extraction shaft 1672 can be extended, for example, by a rod 1679 ( Figure 4 ) - the rod 1679 is (a) fixed to the distal end of the distal portion of the filter extraction shaft 1672 and (b) extends through the end of the collection bottle opposite the bottle opening - indirectly connected to the filter, such as at Figure 4 As shown in FIG. 16 , and optionally, can also be indirectly coupled to the filter via an adhesive and / or via a distal plate 1671 that can be integral with or fixed to the rod 1679 .

[0325] Those skilled in the art who read this application will appreciate that the distal portion of the filter extraction shaft 1672 may be coupled to the filter directly or indirectly in additional ways, all of which are within the scope of the present invention.

[0326] Optionally, the filter is withdrawn from the shaft 1672 for reference hereinafter. Fig.25 and Fig.26 The described manner couples to the filter 60 .

[0327] Now refer to FIG. 3E to FIG. 3I For some applications, the method optionally continues as FIG. 3E to FIG. 3I By way of example and not limitation, FIG. 3E to FIG. 3I The collection bottle 1650 shown in Figures 1A to 3D The collecting bottle shown in FIG. 1 is shorter. In actual use, the collecting bottle has the same length during its entire use, i.e. Figures 1A to 3D The length of FIG. 3E to FIG. 3I If the collection bottle is longer than Figures 1A to 3D If the collection bottle shown in FIG. 16 is shorter, the collection bottle only occupies the proximal portion of the internal plunger space 1686 .

[0328] like FIG. 3E to FIG. 3F , the collection bottle 1650 is at least partially inserted into the extraction tube 1718 and advanced distally within the extraction tube 1718 until the gathered filter 60 is positioned near the distal end 1751 of the extraction tube 1718 opposite the proximal end opening 1721. The extraction tube 1718 is shaped to prevent the collection bottle 1650 from reaching the distal end 1751 of the extraction tube 1718, so that the collection bottle 1650 slides upward along a portion of the filter extraction shaft 1672 when the gathered filter 60 is positioned near the distal end 1751, thereby pushing the gathered filter 60 out of the bottle opening 1652 of the collection bottle 1650 and exposing the gathered filter 60 to the liquid 1030, such as described below, within the distal portion of the extraction tube 1718.

[0329] This technique can facilitate the insertion of the clustered filter 60 into the extraction tube 1718. The collection bottle 1650 is easily inserted into the extraction tube 1718, thereby inserting the clustered filter 60 into the extraction tube 1718 when the clustered filter is initially located within the collection bottle 1650. The collection bottle 1650 can also be used to cover and / or shield the clustered filter 60 when the filter 60 is exposed to the environment, such as before being inserted into the extraction tube 1718 and / or after being optionally removed from the extraction tube 1718, such as described below with reference to Figure 3J 32G and 34D thereof; in this sense, the collecting bottle 1650 can also be used as a sleeve to cover and / or shield the gathered filter 60.

[0330] Optionally, as in FIG. 3E to FIG. 3H As shown in FIG. 1 , the extraction tube 1718 may include a twist-off distal tip cap 1749 that removably seals a distal end 1751 of the extraction tube 1718 opposite the proximal end opening 1721. The liquid within the extraction tube 1718 may be discharged (e.g., squeezed out or dripped out) from the extraction tube 1718, such as described below with reference to Fig. 3I as described in, or as referred to in, the above-mentioned international application PCT / IL2023 / 050014 FIG. 9C to FIG. 9D As described.

[0331] For some applications, such as Figure 3G , when the gathered filter 60 is exposed to the liquid 1030 in the extraction tube 1718, the filter 60 is squeezed (e.g., by squeezing the flexible extraction tube 1718) at least once without any of the liquid 1030 being expelled from the extraction tube 1718. Then, the twist-off distal tip cap 1749, if provided, is removed from the extraction tube 1718, such as in Figure 3H As shown in .

[0332] For some applications, extraction tube 1718 is oriented horizontally (rather than vertically) during exposure of gathered filters 60 to liquid 1030 in extraction tube 1718, either fully or partially. For example, filters 60 may be rotated in extraction tube 1718 while optionally only partially immersed in liquid 1030.

[0333] As in Fig. 3IAs shown in the figure, the liquid 1030 in the extraction tube 1718 is discharged (e.g., squeezed out or dripped out) from the extraction tube 1718, such as discharged onto the sample pad 1797 of the lateral flow test strip 1799, such as a lateral flow immunoassay test strip. Alternatively, the lateral flow test strip 1799 may include another type of lateral flow test strip, such as a CRISPR / Cas9-based lateral flow assay. Optionally, the liquid 1030 is discharged from the extraction tube 1718 by squeezing the extraction tube 1718 at least once to both squeeze a portion of the liquid 1030 from the filter 60 and discharge the portion of the liquid from the extraction tube. Fig. 3I In the technique illustrated in , liquid 1030 within extraction tube 1718 is discharged from extraction tube 1718 while filter 60 remains within extraction tube 1718 .

[0334] Figure 3E , Figure 3F , Figure 3G , Figure 3H and / or Fig. 3I The techniques of may optionally be implemented in combination with the techniques of any of the sampling devices described herein.

[0335] For some applications, collection bottle 1650 is flexible. As described above, gathered filter 60 is exposed to liquid 1030 in extraction tube 1718. Then, by moving filter shaft 1672 proximally relative to collection bottle 1650, gathered filter is withdrawn from extraction tube 1718 and at least partially pulled into collection bottle 1650 through bottle opening 1652. Thereafter, the gathered portion of filter 60 is squeezed by squeezing collection bottle 1650 while at least a portion of gathered filter 60 is covered and / or shielded by collection bottle 1650 to squeeze a portion of liquid 1030 from filter 60 (configuration not shown).

[0336] Reference Figure 3J to Figure 3K . Figure 3J The steps illustrated in the figure may optionally be performed in Figure 3F After the steps shown in the figure or after Figure 3G 1718) (i.e., with or without squeezing the filter 60 when it is in the extraction tube 1718). After the gathered filter 60 has been exposed to the liquid 1030 in the extraction tube 1718 (typically immersed in the liquid 1030 for a certain period of time), the filter extraction shaft 1672 is extracted from the extraction tube 1718. This proximal movement of the filter extraction shaft 1672 relative to the collection bottle 1650 pulls the filter 60 at least partially (e.g., completely) into the collection bottle 1650 via the bottle opening 1652.

[0337] For some applications, the gathered filter 60 is removed from the extraction tube 1718 while the extraction tube 1718 is being squeezed. For example, the extraction tube 1718 can be squeezed before removing the gathered filter 60, such as Figure 3G , and the extraction tube 718 can continue to be squeezed during removal of the gathered filter 60 from the extraction tube 1718.

[0338] For some applications, after filter 60 is removed from extraction tube 1718, liquid 1030 is tested for the presence of a target analyte released into liquid 1030 from particles captured by filter 60. For example, a lateral flow test strip, such as a lateral flow immunoassay test strip, which may be optionally implemented as a dipstick 1757, may be inserted into liquid 1030 in extraction tube 1718, such as in Figure 3K As shown in .

[0339] Alternatively, in Figure 3J The steps illustrated in the figure may be followed by the techniques of Figures 32H to 32K, Figures 34E to 34F, or Figures 35A to 35D of the above-mentioned international application PCT / IL2023 / 050014.

[0340] Figure 3J and / or Figure 3K The techniques of may optionally be implemented in combination with the techniques of any of the sampling devices described herein.

[0341] Alternatively, such as described in the above-mentioned International Application PCT / IL2023 / 050014 with reference to its Figures 32H to 32K or Figures 34E to 34F, after the gathered filter 60 is exposed to the liquid 1030 in the extraction tube 1718 (usually immersed in the liquid 1030 for a certain period of time), the collection bottle 1650 is removed from the extraction tube 1718 and the filter 60 is squeezed to partially release a portion of the liquid 1030 from the filter 60, such as onto the sample pad 1797 of the lateral flow test strip 1799, such as a lateral flow immunoassay test strip. Alternatively, the filter 60 is squeezed by squeezing the flexible collection bottle 1650 (configuration not shown).

[0342] Refer again Figure 3J For some applications, after the gathered filter 60 is immersed in the liquid 1030 in the extraction tube (and optionally squeezed in the extraction tube 1718), the portion of the liquid 1030 is discarded, such as by draining the portion of the liquid 1030 from the extraction tube 1718. For example, the extraction tube 1718 can have the FIG. 3E to FIG. 3H The configuration described, and the unscrewed distal tip cap 1749 can be removed from the extraction tube 1718, such as Figure 3H, so that this portion of the liquid 1030 is discarded.

[0343] For some applications, liquid sample sample 22 is received from the mouth of a subject. For some applications, liquid sample sample 22 comprises a rinse fluid, i.e., a rinse fluid that a subject has swished in his or her mouth and possibly spit out with some saliva. In this application, including in the claims and inventive concepts, "rinse fluid" means a "rinse fluid" that has been swished by a subject. Typically, the rinse fluid includes water, carbonated water, saline (e.g., phosphate buffered saline), geranium extract, tannic acid, platycodon, berberine sulfate, S-carboxymethylcysteine, curcumin, colorants, flavorings, detergents (such as polysorbate 20 (e.g., )) or any combination thereof. In some applications, the mouthwash fluid is carbonated. Alternatively or additionally, for some applications, a detergent, such as polysorbate 20 (e.g., ) is added to the mouthwash fluid after being rinsed by the subject. Alternatively, the liquid test sample 22 may include another type of biological fluid, such as blood (e.g., diluted blood), urine, feces (e.g., diluted feces), gastrointestinal (GI) fluid, or bronchoalveolar lavage fluid.

[0344] Alternatively, liquid specimen sample 22 includes saliva that has not been swabbed from the subject's throat (i.e., saliva is collected without swabbing the subject's throat). (Note the distinction between "swab" as a verb and as a noun. "Swab" (as a noun) can be used to obtain saliva without "swabbing" (as a verb) the subject's throat. For example, the subject can suck on the swab, or the swab can be dipped into a container that has been placed with a rinse fluid or saliva.) In contrast, in a common practice technique for testing for Streptococcus, the tonsils are swabbed. Also alternatively, liquid specimen sample 22 includes liquid from a culture medium containing a biological sample that has been incubated within tubular container 30 or incubated separately from the device and then added to tubular container 30.

[0345] The liquid test sample 22 (e.g., saliva) can be directly spit into the tubular container 30 by the subject, or transferred by a healthcare provider from another container into which the subject spits. Alternatively, in the case of saliva, saliva can be collected from the subject's mouth by having the subject suck on a swab or other absorbent collection element, such as a flocked swab or cotton roll.

[0346] For some applications where the method does not include swabbing the subject's throat, the liquid sample sample 22 is collected by drawing the liquid sample sample 22 from the subject's oral cavity through the anterior opening of the oral cavity by contacting one or more portions of the oral cavity with an absorbent material (e.g., at the tip of the collector shaft), such as flocking or a cotton swab or sponge, without swabbing the subject's oropharynx. (For example, a collector shaft may be used Saliva collection device (DNAGenotek, Inc., a subsidiary of OraSure Technologies, Inc., Bethlehem, Pennsylvania, USA). ) Optionally, an absorbent material is located on the tip of the collector shaft, and by inserting the tip of the collector shaft into the oral cavity, the liquid sample sample 22 is extracted from the oral cavity through the front opening of the oral cavity using the absorbent material. For some of these applications, the liquid sample sample 22 is extracted from the oral cavity through the front opening of the oral cavity using the absorbent material by the subject sucking the absorbent material. For example, one or more parts of the oral cavity may include one or more of the buccal mucosa, the tongue (e.g., under the tongue), the gums (e.g., the lower gums), and / or the palatal mucosa. For example, to wipe the lower gums, the absorbent material (e.g., at the tip of the collector shaft) can be rubbed back and forth along the lower gums several times. (The front opening of the oral cavity is the opening of the mouth between the lips, between the outside of the oral cavity and the inside of the oral cavity.)

[0347] Alternatively, the liquid test sample 22 comprises an incubation medium containing a biological sample.

[0348] Still refer to Figures 1A to 4 In some applications of the present invention, a method for concentrating a liquid test sample 22 is provided. The method comprises:

[0349] Place the liquid sample 22 in the tubular container 1630 of the filter assembly 1624, such as Figure 2A and Figure 3A As shown in;

[0350] Insert the plunger head 1642 of the plunger 1640 into the tubular container 1630 via the proximal container opening 1632 of the tubular container 1630, such as in Figure 2A and Figure 2B between and in Figure 3A and Figure 3B The transition between is shown in;

[0351] · Advance the plunger head 1642 distally within the tubular container 1630 to drive at least a portion of the liquid sample 22 through the filter 60 disposed in the tubular container 1630, such as Figure 2B and Figure 3B1630 (note that in this configuration, the filter 60 is not initially disposed in the tubular container 1630 when the liquid test sample 22 is placed in the tubular container 1630, and is inserted into the tubular container 1630 when the plunger head 1642 is inserted into the tubular container); and

[0352] • Remove the filter 60 from the tubular container 1630 via the plunger space proximal opening 1690 while the plunger head 1642 and the filter support 1662 remain within the tubular container 1630, as in Figure 2C to Figure 2D and in FIG. 3C to FIG. 3D As shown in .

[0353] For some applications, liquid test sample 22 may be obtained and / or may have any of the characteristics described above.

[0354] For some applications, the method further includes sealing collection bottle opening 1652 with a collection bottle cap after filter 60 has been advanced into collection bottle 1650 .

[0355] For some applications, the method further includes detecting the presence of biological particles captured by filter 60 after filter 60 has been removed from tubular container 1630. For example, the biological particles can be selected from the group consisting of viruses, bacteria, microorganisms, fungi, spores, mites, biological cells, biological antigens, proteins, protein antigens, and carbohydrate antigens.

[0356] For some applications, such as Fig. 3I and Figure 3K , detecting the presence of biological particles captured by the filter 60 includes using a lateral flow test strip 1799 (e.g., a lateral flow immunoassay test strip) to detect the presence of biological particles captured by the filter 60. The lateral flow test strip is optionally housed in a housing 1710 (e.g., including a cartridge 1789 (also referred to as a cassette) or card 3294, such as described below with reference to FIGS. 34E to 34F of the above-mentioned International Application PCT / IL2023 / 050014), or is implemented as a dipstick 1757 as is known in the lateral flow art, such as in Figure 3K As shown in .

[0357] For some applications, the filter extraction shaft 1672 is not pre-coupled to the filter 60 (configuration not shown, but alternatively may be similar to that described below with reference to the above-mentioned International Application PCT / IL2023 / 050014, mutatis mutandis). Fig.26 A to Fig.26E). Instead, the filter extraction shaft is advanced within (and optionally inserted into) the internal plunger space 1686 and coupled to the filter 60 after the plunger 1640 has been inserted into the tubular container 1630 (and optionally has been moved within the tubular container 1630 to push at least a portion of the liquid test sample 22 through the filter 60).

[0358] For some applications, the method further includes immersing filter 60 with liquid 1030 in collection bottle 1650 (or extraction tube 1718, if provided) after filter 60 has been advanced into collection bottle 1650 (and into extraction tube 1718, if provided). For example, liquid 1030 can be selected from the group consisting of: a lysis buffer, an extraction buffer, a saline solution, a transport medium, and one or more reagents, such as one or more reagents for use in a lateral flow test.

[0359] In any of the applications of the present invention described herein, the liquid 1030 may include two or more liquids that are combined (and optionally mixed together), a solid (e.g., a powder) and a liquid that are combined (and optionally mixed together), or two solids (e.g., two powders) that are combined (and optionally mixed together), typically during a testing procedure, such as described below with reference to FIG. 27A to FIG. 27C 32B and 34A thereof. In any of the applications of the present invention described herein, liquid 1030 may include one or more liquids that are typically combined (and optionally mixed together) with a solid, such as a powder, during a testing procedure; for example, the powder may be arranged to be contained in one of the tubes described herein, such as one of the extraction tubes described herein.

[0360] Now refer to FIG. 5A to FIG. 5B , FIG. 5A to FIG. 5B Schematic diagram of a sampling device 1720 and a part of a sampling device for concentrating a liquid test sample 22 according to an application of the present invention, respectively.

[0361] Also refer to FIG. 6A to FIG. 6E , FIG. 6A to FIG. 6E is a schematic diagram of a sampling device 1720 and a method of using the sampling device 1720 according to corresponding applications of the present invention.

[0362] Also refer to 7A to 7E , 7A to 7E is a schematic cross-sectional view of a sampling device 1720 and a method of using the sampling device 1720 according to corresponding applications of the present invention.

[0363] The sampling device 1720 is generally similar to the one described above with reference to Figures 1A to 4 The sampling device 1620 described herein may implement any of the features of the sampling device 1620 mutatis mutandis. Like reference numerals refer to like parts.

[0364] Similar to sampling device 1620, sampling device 1720 generally includes a filter assembly 1724, which can have any of the characteristics described above. Filter assembly 1724 includes a tubular container 1630, a plunger 1740, and a filter 60, which can have any of the characteristics described above with reference to Figures 1A to 4 However, the sampling device 1720 does not include a collection bottle constructed or arranged in a manner similar to the collection bottle 1650. However, the sampling device 1720 may optionally include an extraction tube 1718, such as described below with reference to Fig. 6E and Fig. 7E as described.

[0365] The plunger head 1742 is shaped to define a plunger head opening 1744 through the plunger head 1742 and into the interior plunger space 1786 of the plunger rod 1782. The proximal end of the plunger rod 1782 is shaped to define a plunger space proximal opening 1790 of the interior plunger space 1786.

[0366] The sampling device 1720 includes an extractor 1792 including a filter extraction shaft 1772 including a distal portion directly or indirectly coupled to the filter 60, and the filter extraction shaft 1772 is disposed through the internal plunger space 1786. Exemplary ways in which the distal portion 1708 of the filter extraction shaft 1772 can be directly or indirectly coupled to the filter 60 include, but are not limited to:

[0367] The distal portion 1708 of the filter extraction shaft 1772 may be directly coupled to the filter 60, such as by an adhesive and / or by a distal plate 1671 that is fixed, such as stapled, to the distal end of the distal portion of the filter extraction shaft, such as at Figure 4 as shown in; and

[0368] The distal portion 1708 of the filter extraction shaft 1772 may be coupled to the filter 60 indirectly, such as by a rod secured to the distal end of the distal portion of the filter extraction shaft and optionally also by an adhesive and / or by a distal plate 1671 which may be integral with or secured to the rod, such as at Figure 4 The filter extraction shaft 1672 is shown in FIG.

[0369] Those skilled in the art who read this application will appreciate that the distal portion of the filter extraction shaft may be coupled to the filter directly or indirectly in other ways, all of which are within the scope of the present invention.

[0370] For some applications, extractor 1792 also includes a shaft handle 1705 coupled to a proximal portion of filter extraction shaft 1772. Optionally, shaft handle 1705 is shaped as a wing nut.

[0371] The sampling device 1720 is configured such that the filter extraction shaft 1772 is proximally extracted from the internal plunger space 1786 while the plunger head 1742 and the filter support 1662 remain within the tubular container 1630, thereby pulling the filter 60 into the internal plunger space 1786 via the plunger head opening 1744 (the plunger head opening 1744 is defined by the central opening of the filter support 1662), and pulling the filter 60 out of the internal plunger space 1786 via the plunger space proximal opening 1790, and removing the filter extraction shaft 1772 and the filter 60 from the filter assembly 1724. At least a portion of the filter 60 is typically gathered from the initial flat shape of the filter when it is disposed on the filter support 1662, such as gathered into a flower-like arrangement.

[0372] Note that, as in FIG. 6D to FIG. 6E and in FIG. 7D to FIG. 7E As shown in FIG. 1 , the filter extraction shaft 1772 of the sampling device 1720 is not an element of the filter assembly 1724 , but is removable from the filter assembly 1724 .

[0373] Typically, but not necessarily, after the filter extraction shaft 1772 and filter 60 have been removed from the filter assembly 1724, the filter 60 and a portion of the filter extraction shaft 1772 are inserted into the extraction tube 1718, such as at Fig. 6E and Fig. 7E As described below, bunching of at least a portion of filter 60 can help facilitate this insertion; in some aspects, the bunched filter can be used somewhat similar to a conventional swab. As is known in the diagnostic testing art, one or more reagents can also be placed in extraction tube 1718 before or after insertion into filter 60. Optionally, extraction tube 1718 implements the method described above with reference to PCT publication WO 2022 / 149135 of Feldman et al., mutatis mutandis. FIG. 16A to FIG. 16C All or part of the described techniques.

[0374] For some applications, sampling device 1720 includes filter receiver 1714 that is slidably coupled to a distal end portion of filter extraction shaft 1772 and is shaped to define a distal receiver opening 1716. Sampling device 1720 is configured such that filter extraction shaft 1772 is proximally extracted from internal plunger space 1786 while plunger head 1742 remains within tubular container 1630, thereby pulling a portion of filter 60 into filter receiver 1714 via distal receiver opening 1716. For example, the portion of filter 60 may include a central portion (as viewed when filter 60 is flat). When the filter 60 is disposed on the filter support 1662, pulling that portion of the filter 60 into the filter receiving portion 1714 typically causes the remainder of the filter 60 to be gathered, such as gathered into a flower-like arrangement, from the initial flat shape of the filter when disposed on the filter support 1662, and at least partially disposed outside of the filter receiving portion 1714. The gathered filter can be used somewhat similar to a conventional swab, and because of the reduced diameter due to the gathering, the gathered filter can be easily inserted into an extraction tube 1718, such as described above and in Fig. 6E and Fig. 7E As shown in .

[0375] Now refer to FIG. 8A to FIG. 8B , FIG. 8A to FIG. 8B Schematic diagram of a sampling device 2120 and a part of a sampling device, respectively, for concentrating a liquid test sample 22 according to an application of the present invention.

[0376] Also refer to 9A to 9E , 9A to 9E is a schematic diagram of a sampling device 2120 and a method of using the sampling device 2120 according to corresponding applications of the present invention.

[0377] Further references FIG. 10A to FIG. 10E , FIG. 10A to FIG. 10E is a schematic cross-sectional view of a sampling device 2120, 2120A and a method of using the sampling device 2120, 2120A according to respective applications of the present invention.

[0378] Still further reference FIG. 11A to FIG. 11D , FIG. 11A to FIG. 11D 21 is a schematic diagram of a sampling device 2120, 2120B and a method of using the sampling device 2120, 2120B according to corresponding applications of the present invention.

[0379] See also FIG. 12A to FIG. 12C , FIG. 12A to FIG. 12C is a schematic cross-sectional view of a sampling device 2120, 2120C and a method of using the sampling device 2120, 2120C according to respective applications of the present invention.

[0380] Also refer to FIG. 13A to FIG. 13D , FIG. 13A to FIG. 13D 21 is a schematic cross-sectional view of a sampling device 2120 , 2120D and a method of using the sampling device 2120 , 2120D according to respective applications of the present invention.

[0381] Also refer to FIG. 14A to FIG. 14E , FIG. 14A to FIG. 14E is a schematic cross-sectional view of a sampling device 2120, 2120E and a method of using the sampling device 2120, 2120E according to respective applications of the present invention.

[0382] In all of the above configurations, the sampling device 2120 is substantially similar to that described above with reference to FIG. 5A to FIG. 7E The sampling device 1720 described herein may be implemented with the same reference numerals as those in the above description, and any of the features of the sampling device 1720 may be implemented mutatis mutandis. Like reference numerals refer to like parts. Alternatively or additionally, the features of the sampling device 2120 may be implemented in combination with any of the other sampling devices described herein, including but not limited to those described above with reference to Figures 1A to 4 The sampling device 1620 described and / or referred to above FIG. 5A to FIG. 7E The described sampling device 1720. For example, as in FIG. 11A to FIG. 11C , FIG. 12A to FIG. 12C as well as FIG. 13A to FIG. 13D As shown in FIG. 1 , the sampling device 2120 may optionally include a collection bottle 1650, and the sampling device 2120 may be configured such that the filter 60 can be advanced into (e.g., fully into) the collection bottle 1650 through the bottle opening 1652, while the collection bottle 1650 is connected to the filter assembly in a removable manner, such as described above with reference to FIG. Figure 2C and Figure 3C As described.

[0383] The sampling device 2120 includes a filter assembly 2124, which includes a container housing 2022, which is shaped to define a cylindrical space 2023 within the container housing 2022. Optionally, the container housing 2022 is also shaped to define one or more first threads 2025A. Typically, the threads are configured to provide 1 to 2 turns, such as 1 to 1.5 turns.

[0384] The filter assembly 2124 includes a tubular container 2030, instead of the tubular container 1630, which is shaped to define an inner wall 2033 and a proximal container opening 2036 for receiving the liquid test sample 22. The inner wall 2033 is generally not threaded to form a good seal with the plunger head 1742; alternatively, the inner wall is threaded. The tubular container 2030 is at least partially disposed within the cylindrical space 2023 of the container housing 2022. The tubular container 2030 can be rotatable or non-rotatable relative to the cylindrical space 2023. As shown, the tubular container 2030 can be cylindrical, or can alternatively have another non-circular cross-sectional shape.

[0385] The filter assembly 2124 also includes a plunger support 2058 that is coupled to the proximal portion of the plunger 1740 and is shaped to define one or more second threads 2025B that are shaped to engage with one or more first threads 2025A. The one or more first threads 2025A and / or the one or more second threads 2025B can each be a single complete thread, or a plurality of thread segments that include or do not include a complete turn, such as, for example, described in the above-mentioned International Application PCT / IL2023 / 050014 with reference to FIG. 38 thereof. A portion of the plunger support 2058 can be used as a handle to enable easy manipulation of the plunger 1740, including inserting the plunger 1740 into the tubular container 2030. Optionally, the one or more first threads 2025A define 1 to 2 turns, such as 1 to 1.5 turns.

[0386] The plunger 1740 can be inserted into the tubular container 2030 via the proximal container opening 2036 so that the lateral surface of the plunger head 1742 forms a movable fluid-tight seal with the inner wall 2033. To this end, the lateral surface of the plunger head 1742 can include an elastomeric material, such as natural rubber, synthetic rubber, thermoplastic elastomer, or a combination thereof, for example, at or near the distal end of the lateral surface. For example, the plunger head 1742 can be shaped to define a radial protrusion 1741 including an elastomeric material, such as at FIG. 10A to FIG. 10D and in FIG. 14A to FIG. 14D and / or may include an O-ring 1743 comprising an elastomeric material, such as in FIG. 11A to FIG. 11C , Fig. 12A To Figure 12D and in FIG. 13A to FIG. 13D As shown in (and described below in FIG. 16A to FIG. 16D , 18A to 18D , 19A to 19D , FIG. 20A to FIG. 20D and in FIG. 21A to FIG. 21C ).

[0387] The plunger 1740 is connected to the plunger support 2058 so that when one or more second threads 2025B engage with one or more first threads 2025A, rotation of the plunger support 2058 relative to the container housing 2022 causes the plunger support 2058 to be advanced distally relative to the container housing 2022 and thus the plunger 1740 is located within the tubular container 2030 when the tubular container 2030 rotates relative to the container housing 2022.

[0388] The filter assembly 2124 is configured such that when a liquid sample 22 is contained in the tubular container 2030 and the filter 60 is disposed in the tubular container 2030 , movement of the plunger head 1742 within the tubular container 2030 pushes at least a portion of the liquid sample 22 through the filter 60 and into the waste liquid receiving portion 1656 .

[0389] For some applications, one or more first threads 2025A face radially outward, and one or more second threads 2025B face radially inward, such as shown in the figure. For other applications, one or more first threads 2025A face radially inward, and one or more second threads 2025B face radially outward (configuration not shown).

[0390] Optionally, the proximal container opening 2036 is shaped as a funnel, such as shown.

[0391] Optionally, the container housing 2022 includes a proximal portion 2041 located proximal to the cylindrical space 2023, having a maximum inner diameter greater than the inner diameter of the cylindrical space 2023, and shaped to define a funnel-shaped portion, such as shown. For example, the distal end of the funnel-shaped portion can be within 2 cm, such as within 1 cm, of the cylindrical space 2023 measured along the central longitudinal axis of the cylindrical space 2023.

[0392] The sampling device 2120 also includes an energy storage element 2102. The filter assembly 2124 of the sampling device 2120 is configured so that when the liquid sample 22 is contained in the tubular container 2030 and the filter 60 is disposed on the support surface 1659 (at Figure 3A The markings in the figure are for the sampling device 1620), the movement of the plunger head 1742 in the tubular container 2030:

[0393] Pushing at least a portion of the liquid test sample 22 through the filter 60 and the filtrate passage opening 1668 and into the waste receiving portion 1656, and

[0394] • Store energy in energy storage element 2102.

[0395] The energy storage element 2102 can act as a shock absorber in the event that the plunger 1740 is advanced within the tubular container 2030 faster than the liquid sample 22 can pass through the filter 60. The energy storage element 2102 causes the pressure exerted on the filter by the liquid sample 22 to be momentarily reduced. Without this technique, excessive accumulation of pressure of the liquid sample 22 in the tubular container could clog or tear the filter (which could include delicate material), and / or the liquid sample 22 could escape the tubular container 2030 without passing through the filter 60 using the fluid escape techniques described herein.

[0396] For some applications, the above-mentioned movement of the plunger head 1742 within the tubular container 2030 to store energy in the energy storage element 2102 may be only a minimal movement of the plunger head 1742 within the tubular container 2030, such as a movement just enough to engage the plunger head with the tubular container and move the tubular container slightly.

[0397] For some applications, the energy storage element 2102 can alternatively or additionally release energy to push at least a portion of the liquid sample 22 through the filter 60 and into the waste receiving portion 1656, such as in FIG. 11A to FIG. 11C , FIG. 12A to FIG. 12C as well as FIG. 13A to FIG. 13D In these applications, the filter assembly 2124 is generally configured to push the liquid test sample 22 through the filter 60 at a rate that falls within a predetermined range and is not overly sensitive to the rate at which the plunger head 1742 is advanced within the tubular container 2030 by a user of the filter unit.

[0398] The energy released by the energy storage element 2102 can:

[0399] · completely stored in the energy storage element 2102 during advancement of the plunger head 1742 within the tubular container 2030, such as described below with reference to FIG. 12A to FIG. 12C as well as FIG. 13A to FIG. 13D as described;

[0400] Partially pre-stored in the energy storage element 2102 prior to advancement of the plunger head 1742 within the tubular container 2030 and partially stored in the energy storage element 2102 during advancement of the plunger head 1742 within the tubular container 2030, such as described below with reference to FIG. 11A to FIG. 11D described; or

[0401] · completely pre-stored in the energy storage element 2102 prior to advancement of the plunger head 1742 within the tubular container 2030, such as described below with reference to FIG. 15A to FIG. 15B , FIG. 16A to FIG. 16D , FIG. 17A to FIG. 17D , 18A to 18D, 19A to 19D , FIG. 20A to FIG. 20D as well as FIG. 21A to FIG. 21C as described.

[0402] Reference FIG. 10A to FIG. 10E , FIG. 11A to FIG. 11D , FIG. 12A to FIG. 12C , FIG. 13A to FIG. 13D as well as FIG. 14A to FIG. 14E In these configurations, the sampling device 2120 also includes a container housing 2022, and the tubular container 2030 is at least partially disposed within the container housing 2022, such that the tubular container 2030 is movable relative to the container housing 2022, for example, axially and / or rotationally movable relative to the container housing 2022. The energy storage element 2102 is disposed within the container housing 2022, outside the tubular container 2030, and in direct or indirect contact with an outer surface 2106 of the tubular container 2030, such that movement of the plunger head 1742 within the tubular container 2030 causes the tubular container 2030 to move relative to the container housing 2022, thereby storing energy in the energy storage element 2102. Typically, when the plunger head 1742 contacts the liquid sample 22, the tubular container 2030 begins to move relative to the container housing 2022.

[0403] For some applications, energy storage element 2102 includes a mechanical storage element including an elastic element 2126, such as a spring 2103 (e.g., FIG. 10A to FIG. 10E , FIG. 11A to FIG. 11D , FIG. 12A to FIG. 12C and in FIG. 13A to FIG. 13D ), a balloon (configuration not shown), or a soft bead (eg, comprising silicone) (configuration not shown).

[0404] Reference FIG. 10A to FIG. 10E , FIG. 11A to FIG. 11D , FIG. 12A to FIG. 12C as well as FIG. 13A to FIG. 13D In these configurations, the mechanical energy storage element 2102 includes a spring 2103, as shown below.

[0405] exist FIG. 10A to FIG. 10E and FIG. 11A to FIG. 11D In the configuration shown in FIG. 1 , the mechanical energy storage element 2102, 2102A includes a spring 2103, 2103A. The outer surface 2106, 2106A of the tubular container 2030 is defined by the distal end 2107 of the tubular container 2030. (The distal end 2107 can be substantially flat, such as at FIG. 10A to FIG. 10D or may have a three-dimensional shape, such as in FIG. 11A to FIG. 11C , FIG. 12A to FIG. 12C , FIG. 13A to FIG. 13D , FIG. 16A to FIG. 16D , 18A to 18D , 19A to 19D , FIG. 20A to FIG. 20D and in FIG. 21A to FIG. 21C ) The spring 2103, 2103A is disposed between the outer surface 2106, 2106A of the tubular container 2030 and the inner surface 2108 of the container housing 2022 facing the proximal end. The spring 2103, 2103A may directly contact the outer surface 2106, 2106A, such as in FIG. 10A to FIG. 10E , or may indirectly contact the outer surface 2106, 2106A, such as via the support 2105, such as in FIG. 11A to FIG. 11D The springs 2103, 2103A may directly contact the inner surface 2108 facing the proximal end, such as in FIG. 10A to FIG. 10E and FIG. 11A to FIG. 11D , or indirectly contacting the proximal-facing inner surface 2108 (configuration not shown).

[0406] For some applications, such as Fig.11A As shown in FIG. 1 , the mechanical energy storage element 2102, 2102A is preloaded, such as slightly preloaded with energy, in a pre-insertion state of the sampling device 2120, 2120B, wherein the plunger head 1741 is not within the tubular container 2030 (and / or before the movement of the plunger head 1742 within the tubular container 2030 stores energy in the spring). For example, in a configuration in which the mechanical energy storage element 2102, 2102A includes a spring 2103, 2103A, the spring may include a compression spring that is partially compressed prior to the movement of the plunger head 1742 within the tubular container 2030. For example, the container housing 2022 may include a retaining ring 2026 that acts as a stopper to prevent the tubular container 2030 from moving proximally, thereby keeping the spring 2103, 2103A partially compressed.

[0407] Slightly preloading the spring 2103, 2103A results in the spring still being slightly compressed when it finishes pushing the liquid sample sample 22 through the filter 60. The final stages of pushing the liquid sample sample 22 through the filter 60 typically require the greatest pressure because the filter 60 typically becomes progressively more clogged during filtration.

[0408] Optionally, the sampling device 2120 also includes an absorbent material 2109 that absorbs the liquid filtrate to inhibit spillage and / or inhibit the liquid filtrate from returning through the filter 60. For example, the absorbent material 2109 may include sodium polyacrylate. Optionally, the absorbent material 2109 is sandwiched between two layers of material, such as polyester, that can be separated and allowed to swell when liquid is absorbed by the absorbent material 2109.

[0409] exist FIG. 12A to FIG. 12CIn the configuration shown in , the mechanical energy storage element 2102, 2102B includes a spring 2103, 2103B, which is arranged to surround at least a longitudinal portion of the tubular container 2030. For example, the outer surface 2106, 2106B of the tubular container 2030 can be defined by the proximal lip 2110 of the tubular container 2030, such as shown. Alternatively, the tubular container 2030 can be shaped to define one or more protrusions that protrude radially outward from the lateral outer surface 2106 of the tubular container 2030 and engage with the spring 2103, 2103B, in which case the spring 2103, 2103B is in indirect contact with the outer surface 2106 of the tubular container 2030.

[0410] In Figures 13 to Fig.13D In the configuration shown in FIG. 2 , the mechanical energy storage element 2102, 2102C includes a spring 2103, 2103C disposed beside at least a longitudinal portion of the tubular container 2030. Optionally, the mechanical energy storage element 2102, 2102C includes a plurality of springs 2103, 2103C disposed beside at least a longitudinal portion of the tubular container 2030, such as shown; alternatively, the mechanical energy storage element 2102, 2102C includes exactly one spring 2103, 2103C disposed beside at least a longitudinal portion of the tubular container 2030 (configuration not shown). For example, the outer surface 2106, 2106B of the tubular container 2030 can be defined by a proximal lip 2110 of the tubular container 2030, such as shown. Alternatively, the tubular container 2030 can be shaped to define one or more protrusions that protrude radially outward from the lateral outer surface 2106 of the tubular container 2030 and engage with the springs 2103, 2103C, in which case the springs 2103, 2103C are in indirect contact with the outer surface 2106 of the tubular container 2030.

[0411] Reference FIG. 12A to FIG. 12C as well as FIG. 13A to FIG. 13D As described above, for some applications, the energy storage element 2102 may alternatively or additionally release energy to push at least a portion of the liquid sample 22 through the filter 60 and into the waste receiving portion 1656. FIG. 12A to FIG. 12C as well as FIG. 13A to FIG. 13D In the configuration shown in , the energy is completely stored in the energy storage element 2102 during the advancement of the plunger head 1742 within the tubular container 2030.

[0412] For example, the spring 2103 may include a compression spring that is in a stationary, fully uncompressed state before the plunger head 1742 is advanced within the tubular container 2030, such as Fig. 12A and Fig.13AThe advancement of the plunger head 1742 within the tubular container 2030 compresses the spring 2103, thereby storing energy in the spring, such as in Fig. 12B and Fig. 13C This advancement also typically pushes a portion of the liquid sample 22 through the filter 60 and into the waste receiving portion 1656. When the advancement of the plunger head 1742 within the tubular container 2030 is completed, the spring 2103 releases some or all of the stored energy that moves the tubular container 2030 proximally relative to the plunger head 1742 (and typically relative to the container housing 2022), such as Fig. 12C and Fig. 13C 1656. This proximal movement pushes another portion of the liquid sample sample 22 through the filter 60 and into the waste receiving portion 1656. As used in this application, including the claims, the plungers described herein are still considered plungers even if the plungers described herein remain stationary when inserted and, such as by proximal movement of the tubular container 2030, push the liquid sample sample 22 through the filter 60 and into the waste receiving portion 1656. This is somewhat similar to how the plunger of a conventional syringe would still be considered a plunger if the plunger remains stationary when the barrel moves proximally toward the handle of the plunger.

[0413] In some applications of the present invention, the spring 2103 is disposed at other locations other than the above-described locations. For example, the spring 2103 may be disposed at the proximal end of the tubular container 2030, in which case the spring 2103 may include a tension spring that stores energy when the tubular container 2030 is propelled distally within the container housing 2022. Alternatively, the spring 2103 may be disposed within or beside the plunger 1740.

[0414] Reference FIG. 14A to FIG. 14E . In this configuration of the sampling device 2120, 2120E, the energy storage element 2102, 2102D is disposed within the tubular container 2030. For some applications, the energy storage element 2102, 2102D includes a flexible container 2128 containing a gas, such as air. The flexible container 2128 may or may not be elastic. Optionally, the flexible container 2128 is coupled to an inner surface of the tubular container 2030, such as the bottom of the tubular container 2030, to prevent the flexible container from floating upward and contacting the filter 60. Optionally, the flexible container 2128 ruptures at the end of the plunger stroke when the flexible container is squeezed between the plunger head 1742 and the bottom of the tubular container 2030.

[0415] Now refer to FIG. 15A to FIG. 15B , FIG. 15A to FIG. 15B220A and 2220A are schematic diagrams of sampling devices 2220 and 2220A and methods of using the sampling devices 2220 and 2220A according to corresponding applications of the present invention.

[0416] Further references FIG. 16A to FIG. 16D , FIG. 16A to FIG. 16D is a schematic cross-sectional view of a sampling device 2220, 2220A and a method of using the sampling device 2220, 2220A according to respective applications of the present invention. The sampling device 2220, 2220A includes a filter assembly 2224, 2224A.

[0417] Still further reference FIG. 17A to FIG. 17D , FIG. 17A to FIG. 17D are schematic cross-sectional views of sampling devices 2220, 2220B, 2220C, 2220D and methods of using the sampling devices 2220, 2220B, 2220C, 2220D according to respective applications of the present invention.

[0418] See also 18A to 18D , 18A to 18D 2220, 2220B and a method of using the sampling device 2220, 2220B according to the corresponding application of the present invention. The sampling device 2220, 2220B includes a filter assembly 2224, 2224B.

[0419] Also refer to 19A to 19D , 19A to 19D is a schematic cross-sectional view of a sampling device 2220, 2220C and a method of using the sampling device 2220, 2220C according to respective applications of the present invention. The sampling device 2220, 2220C includes a filter assembly 2224, 2224C.

[0420] Also refer to FIG. 20A to FIG. 20D , FIG. 20A to FIG. 20D 2220, 2220D and a method of using the sampling device 2220, 2220D according to the corresponding application of the present invention. The sampling device 2220, 2220D includes a filter assembly 2224, 2224D.

[0421] Further references FIG. 21A to FIG. 21C , FIG. 21A to FIG. 21C 2220, 2220E and a method of using the sampling device 2220, 2220E according to the corresponding application of the present invention. The sampling device 2220, 2220E includes a filter assembly 2224, 2224E.

[0422] The sampling device 2220 and the filter assembly 2224 are generally similar to those described above with reference to FIG. 8A to FIG. 14EThe sampling device 2120 and the filter assembly 2124 described herein are similar to those described herein, and like reference numerals refer to like parts. Alternatively or additionally, the features of the sampling device 2220 may be implemented in combination with any of the other sampling devices described herein, including but not limited to those described above with reference to Figures 1A to 4 The sampling device 1620 described and / or referred to above FIG. 5A to FIG. 7E For example, the sampling device 2220 may optionally include a collection bottle 1650, such as FIG. 16A to FIG. 16D , 18A to 18D , 19A to 19D and FIG. 20A to FIG. 20D as shown in (and with FIG. 21A to FIG. 21C 1650, and the sampling device 2220 can be configured so that the filter 60 can be advanced into (e.g., fully into) the collection bottle 1650 through the bottle opening 1652, while the collection bottle 1650 is connected to the filter assembly in a removable manner, such as the above reference Figure 2C and as described in FIG. 3 .

[0423] The sampling device 2220 includes a preloaded energy storage element 2202 that does not rely on the advancement of the plunger head 1742 within the tubular container 2030 to store energy in the energy storage element. For some applications, the preloaded energy storage element 2202 includes a gas source 2204. For example, the gas source 2204 can include one or more substances 2205 that produce a gas 2208 when combined with each other and / or with a liquid, such as a liquid sample 22. For some applications, the one or more substances 2205 can include a solid substance 2205A and a liquid substance 2205B. For example, the solid substance 2205A can include sodium bicarbonate and the liquid substance 2205B can include an acidic solution (e.g., including acetic acid or citric acid), which when combined produces carbon dioxide gas 2208; or the solid substance 2205A can include sodium bicarbonate and anhydrous citric acid and the liquid substance 2205B can include water, which when combined produces carbon dioxide gas 2208. Alternatively, the one or more substances 2205 may include one or more substances provided in combination, such as sodium bicarbonate and anhydrous citric acid, which produce carbon dioxide gas 2208 when combined with the liquid of the liquid test sample 22 (configuration not shown). Further alternatively, the one or more substances 2205 may include two or more liquids. In these configurations, the tubular container 2030 typically forms a movable fluid-tight seal with the inner wall of the container housing 2022, such as using an O-ring 1743. For example, the solid substance 2205A may include 0.5g-2g of sodium bicarbonate, and the liquid substance 2205B may include 1mL-5mL of acetic acid.

[0424] Typically, when the gas 2208 is released or generated, the pressure generated gradually increases during the filtration. This increase in pressure is helpful during the final stage of pushing the liquid sample sample 22 through the filter 60, which generally requires the greatest pressure, because the filter 60 generally becomes more clogged gradually during the filtration. In contrast, during the early stages of filtration, before the filter is particularly clogged, lower pressures are desirable because the use of lower pressures results in better filtration. Therefore, the gas source 2204 appropriately applies a lower pressure at the beginning of the filtration, and gradually increases the pressure through the filtration, which corresponds to and helps to resolve the gradual increase in the clogging of the filter 60 during the filtration.

[0425] The gas source 2204 may include at least one container 2206, such as a bag, in which one of the one or more substances 2205 (e.g., solid substance 2205A or liquid substance 2205B) is typically stored in the at least one container 2206 and isolated from another of the one or more substances 2205 in applications in which two or more substances 2205 are provided and combined with each other.

[0426] The gas source 2204 is configured to provide a gas 2208 into a space 2234 defined between (a) the proximally facing inner surface 2108 of the container housing 2022 and (b) the outer surface 2106, 2106A of the tubular container 2030 defined by the distal end 2107 of the tubular container 2030. The space 2234 is generally gas-tight. Providing the gas 2208 into the space 2234 increases the pressure in the space 2234, thereby causing the tubular container 2030 to move proximally relative to the plunger head 1742 (and generally relative to the container housing 2022), such as Fig. 16B , Fig. 16C and Fig.16D between, Fig. 18C and Fig.18D between, Fig.19C and Fig.19D between, Fig. 20C and Fig.20D Between and Fig. 21B and Fig. 21C 2234. This proximal movement of the tubular container 2030 pushes a portion of the liquid sample 22 through the filter 60 and into the waste receiving portion 1656. This proximal movement of the tubular container 2030 also increases the volume of the space 2234, which thus defines a variable volume.

[0427] For some applications, such as FIG. 15A to FIG. 15B , FIG. 16A to FIG. 16D , FIG. 17A to FIG. 17D , 18A to 18D and 19A to 19D, the filter assembly 2224 is configured such that the movement of the plunger head 1742 within the tubular container 2030 causes the gas source 2204 to provide the gas 2208. Typically, in these configurations, the movement of the plunger head 1742 within the tubular container 2030 is insufficient to push a meaningful portion of the liquid sample 22 through the filter 60.

[0428] For some of these applications, movement of the plunger head 1742 within the tubular container 2030 causes distal movement of the tubular container 2030 within the container housing 2022. Such distal movement of the tubular container 2030 within the container housing 2022 can open the container 2206 of the gas source 2204. For example, such distal movement of the tubular container 2030 can open the container 2206 by damaging (e.g., rupturing, penetrating, and / or tearing) the container 2206, such as by pushing one or more spikes 2242 into the wall of the container 2206. Optionally, the one or more spikes 2242 are defined by the distal end of the shaft 2238, and the proximal end of the shaft 2238 is pushed distally by the distal end 2107 of the tubular container 2030. The opening of the container 2206 causes a reaction that produces gas 2208, such as described above.

[0429] exist FIG. 15A to FIG. 15B and FIG. 16A to FIG. 16D In the configuration shown in , movement of the plunger head 1742 within the tubular container 2030 is generally caused by rotation of the plunger head 1742 relative to the container housing 2022.

[0430] exist FIG. 17A to FIG. 17D , 18A to 18D and 19A to 19D In the configuration shown in , the movement of the plunger head 1742 within the tubular container 2030 is generally caused by the plunger head 1742 being inserted into the tubular container 2030 non-rotatably relative to the container housing 2022. For example, the filter assembly 2224, 2224B, 2224C can also include a plunger support 2258 that is coupled to the proximal portion of the plunger 1740. The plunger support 2258 (e.g., by FIG. 17A to FIG. 17B The hinge 2260 (denoted in FIG. 2 ) can be hingedly attached to the container housing 2022, generally to enable a change in orientation between the central longitudinal axis of the plunger 1740 and the central longitudinal axis of the container housing 2022. This change in orientation transitions the container opening 2036 from an open position to a closed position in which the plunger head 1742 covers the container opening 2036.

[0431] For other applications, such as FIG. 20A to FIG. 20D, the filter assembly 2224 is configured such that movement of the plunger head 1742 within the tubular container 2030 does not necessarily cause the gas source 2204 to provide gas 2208. For example, the tubular container 2030 may have been disposed distally within the container housing 2022. Instead, the plunger support 2258 opens the container 2206 of the gas source 2204, such as by destroying (e.g., rupturing, penetrating and / or tearing) the container 2206, such as via the elongated element 2230, when moving (e.g., articulating) relative to the container housing 2022. For example, the elongated element 2230 can be shaped to define a spike 2231. The movement of the plunger support 2258 relative to the container housing 2022 can also transition the container opening 2036 from an open position to a closed position in which the plunger head 1742 covers the container opening 2036.

[0432] For some applications, such as FIG. 16A to FIG. 16D , 18A to 18D and FIG. 20A to FIG. 20D As shown in the configuration of , the filter components 2224, 2224A, 2224B, 2224D are shaped to define an energy storage element chamber 2232, and the preloaded energy storage element 2202 is disposed in the energy storage element chamber 2232. The energy storage element chamber 2232 is almost completely isolated from the space 2234. The energy storage element chamber 2232 is fluidically connected to the space 2234 only through one or more narrow openings 2236 having a total (combined) area of ​​75 square microns to 8000 square microns, for example, where a single circular narrow opening 2236 is provided, its diameter may be 10 microns to 100 microns. One or more narrow openings 2236 may help provide a controlled flow rate of the gas 2208 entering the space 2234. Optionally, the one or more narrow openings 2236 are defined by an axis 2238, which also defines one or more spikes 2242 (at FIG. 16A to FIG. 16B In the configuration shown in the figure, the energy storage element chamber 2232 is in fluid communication with the space 2234 via exactly one narrow opening 2236.

[0433] For other applications, such as 19A to 19D As shown in FIG. 2 , the filter assembly is not shaped to define an energy storage element chamber, but rather the preloaded energy storage element 2202 is disposed in the space 2234. For example, the one or more substances 2205 may include a solid substance 2205A disposed at the bottom of the space 2234, and the solid substance 2205A may include a solid, such as a tablet (as shown) or a powder (not shown). Optionally, mutatis mutandis, in this manner (without the energy storage element chamber 2232) FIG. 20A to FIG. 20D configuration.

[0434] For other applications, the preload energy storage element 2202 includes another energy source, such as a preload spring (configuration not shown).

[0435] Reference FIG. 21A to FIG. 21C In this configuration, the preloaded energy storage element 2202 includes a compressed gas container 2240 that stores a gas 2208. When the container 2240 is opened, the gas 2208 is released into the space 2234. For example, FIG. 21A to FIG. 21C As shown in , the plunger support 2258 opens the compressed gas container 2240, such as via the elongated member 2250, when it moves (e.g., articulated) relative to the container housing 2022. Alternatively, the movement of the plunger head 1742 within the tubular container 2030 opens the compressed gas container 2240 (configuration not shown).

[0436] In some applications of the present invention, the preload energy storage element 2202 includes a spring, such as a compression spring (configuration not shown).

[0437] Now refer to FIG. 11B to FIG. 11D In some applications of the present invention, the outer wall of the container shell 2022 is shaped to define an optical window 2270. The filter assembly 2124 also includes a visual indicator 2272. The filter assembly 2124 is configured such that the visual indicator 2272:

[0438] Not visible through the optical window 2270 when the tubular container 2030 is located at a plurality of first distal axial positions 2274A within the filter assembly 2124, where the visual indicator 2272 is not axially aligned with the optical window 2270 (and is therefore typically obscured by the wall of the container housing 2022), such as Fig. 11B As shown in

[0439] · When the tubular container 2030 is located at the second proximal axial position 2274B within the filter assembly 2124, it is visible through the optical window 2270, at which position the visual indicator 2272 is axially aligned with the optical window 2270, as shown in FIG. Fig. 11C and Fig.11D as shown in .

[0440] When the tubular container 2030 is located at multiple first distal axial positions 2274A within the filter assembly 2124, the tubular container 2030 has not yet completed its proximal movement relative to the plunger head 1742, and therefore has not yet completed pushing more of the liquid sample sample 22 through the filter 60 and into the waste liquid receiving portion 1656.

[0441] Optionally, refer to FIG. 10A to FIG. 10E and FIG. 11A to FIG. 11D The radially outward facing surface of the depicted support 2105 includes a visual indicator 2272 .

[0442] When the tubular container 2030 is at the second proximal axial position 2274B within the filter assembly 2124, the tubular container 2030 has completed its proximal movement relative to the plunger head 1742 and has therefore completed pushing more of the liquid sample 22 through the filter 60 and into the waste receiving portion 1656. The visual indicator 2272 provides an indication to the user that filtering of the liquid sample 22 is complete through the visibility of the optical window 2270, and therefore, the filter 60 can be removed from the filter assembly 2124, for example, as described above with reference to Figure 2C to Figure 2D and FIG. 3C to FIG. 3D , FIG. 6C to FIG. 6D and FIG. 7C to FIG. 7D ,or FIG. 9C to FIG. 9D and FIG. 10C to FIG. 10D Described.

[0443] The optical window 2270 is optionally airtight, for example comprising a transparent or translucent covering; alternatively, the optical window 2270 is not airtight, for example being defined by an opening through the outer wall of the container shell 2022.

[0444] In some applications, an outer surface of the plunger support 2058 includes a first rotation indicator 2280A, and an outer surface of the container housing 2022 includes a second rotation indicator 2280B. The rotation indicators are arranged so that the rotation indicators indicate rotational alignment with each other.

[0445] Refer to above FIG. 11B to FIG. 11D Any of the configurations described may be combined with the above reference mutatis mutandis. FIG. 10A to FIG. 10E The sampling devices 2120, 2102A described above with reference to FIG. 12A to FIG. 12C The sampling devices 2120, 2120C described above refer to FIG. 13A to FIG. 13D The sampling devices 2120, 2120D described above refer to FIG. 16A to FIG. 16D The sampling devices 2220, 2220A described above with reference to FIG. 17A to FIG. 18D The sampling devices 2220, 2220B described above refer to 19A to 19D The sampling devices 2220, 2220C described above refer to FIG. 20A to FIG. 20D The sampling devices 2220, 2220D described above and the FIG. 21A to FIG. 21C The features of the described sampling devices 2220, 2220E are implemented.

[0446] Now refer to FIG. 22A to FIG. 22F , FIG. 22A to FIG. 22F is a schematic cross-sectional view of a sampling device 2320 for concentrating a liquid test sample 22 and a method of using the sampling device 2320 according to a corresponding application of the present invention.

[0447] The sampling device 2320 is similar in many respects to the above referenced FIG. 15A to FIG. 21C The sampling device 2220 described herein may be implemented mutatis mutandis in any of the features of the sampling device 2220. Like reference numerals refer to like components. The techniques of the sampling device 2320 may be implemented mutatis mutandis in combination with the techniques of any of the other sampling devices described herein, including but not limited to the sampling devices described above with reference to Figures 1A to 4 , FIG. 16A to FIG. 16D , 18A to 18D , 19A to 19D and FIG. 20A to FIG. 20D The collection bottle 1650 described (and FIG. 21A to FIG. 21C 1650, and the sampling device 2320 can be configured so that the filter 60 can be advanced into (e.g., fully into) the collection bottle 1650 through the bottle opening 1652, while the collection bottle 1650 is connected to the filter assembly in a removable manner, such as the above reference Figure 2C and Figure 3C described.

[0448] The sampling device 2320 includes a filter assembly 2324, which can have any of the properties described above. The filter assembly 2324 includes a tubular container 2330 and a filter 60, which can have any of the properties described above with reference to Figures 1A to 7E Any of the described properties. The filter assembly 2324 also includes a plunger 2340, which includes a plunger head 2342 and a plunger rod 2382.

[0449] Unlike sampling device 2220, in sampling device 2320, plunger head 2342 is not shaped to define a filter support. Instead, distal bottom surface 2398 of tubular container 2330 includes (e.g., is shaped to define) filter support 2362. Filter support 2362 is shaped to define:

[0450] a support surface 2359 which may be perpendicular to the central longitudinal axis of the tubular container 2330 (as shown) or may be angled relative to the central longitudinal axis (configuration not shown),

[0451] a plurality of filtrate passage openings extending through the filter support 2362 into a waste receiving portion 2356 disposed generally distal to the filter support 2362 and the bottom surface 2398 of the tubular container 2330, and

[0452] Optionally, the central opening 2383 (in Fig.22D and Fig.22Emarked in ).

[0453] For some applications, filter assembly 2324 includes a hollow shaft 2376 that extends distally from tubular container 2330 and is shaped to define an internal shaft space 2386 (at Fig.22A and Fig.22E ). The central opening 2383 leads to the internal shaft space 2386.

[0454] For some applications, sampling device 2320 includes an extractor 2392 including a filter extraction shaft 2372 including a distal portion that can be coupled (directly or indirectly) to filter 60 (e.g., as described above mutatis mutandis for other filter extraction shafts described herein). Filter extraction shaft 2372 is disposed (a) through a distal opening 2396 defined by a distal bottom surface 2398 of tubular container 2330, and (b) optionally, through internal shaft space 2386 in a configuration where filter assembly 2324 includes hollow shaft 2376.

[0455] For some applications, extractor 2392 also includes a shaft handle 2305 coupled to a proximal portion of filter extraction shaft 2372. Shaft handle 2305 can have any suitable shape, such as a wing nut shape (as shown) or a circular shape (configuration not shown).

[0456] The filter 60 is disposed (removably) on the support surface 2359, typically on the upstream side of the support surface 2359 (in the configuration of the sampling device 2320, the upstream side is the proximal side of the support surface 2359).

[0457] The filter assembly 2324 is configured such that when the liquid sample 22 is contained in the tubular container 2330 and the filter 60 is disposed in the tubular container 2330, the movement of the plunger head 2342 within the tubular container 2330 (typically advanced distally) pushes at least a portion of the liquid sample sample 22 through the filter 60. The filter 60 is configured to concentrate at least a portion of the liquid sample sample 22 onto the filter 60 while allowing the filtrate 61 to pass through the filter 60. Typically, the distal advancement of the plunger head 2342 within the tubular container 2330 applies pressure to drive (e.g., push) at least a portion of the liquid sample sample 22 contained in the tubular container 2330 through the filter 60 and the filtrate passage opening and into the waste receiving portion 2356, such as Fig. 22B and Fig. 22C The transition between .

[0458] The sampling device 2320 includes a preloaded energy storage element 2202, as described above with reference to FIG. 15A to FIG. 21C The preloaded energy storage element 2202 may optionally implement the above reference FIG. 15A to FIG. 21C The filter assembly 2324 is configured such that when the liquid sample 22 is contained in the tubular container 2330 and the filter 60 is disposed on the support surface 2359, the energy released from the preloaded energy storage element 2202 pushes at least a portion of the liquid sample 22 through the filter 60 and the filtrate passage opening and into the waste receiving portion 2356, such as Fig. 22B and Fig. 22C The transition between .

[0459] For some applications, filter component 2324 also includes:

[0460] A housing 2360 including a tubular container 2330; and

[0461] A plunger support 2358 which is connectable to the housing 2360 (e.g. by screwing as described above, e.g. 1 to 2 turns, e.g. 1 to 1.5 turns, with necessary modifications), and which includes a plunger tube 2364 in which a plunger rod 2382 is at least partially disposed so as to be axially movable relative to the plunger tube 2364.

[0462] The filter assembly 2324 is configured such that energy released from the preloaded energy storage element 2202 causes the plunger rod 2382 to move distally relative to the plunger tube 2364 (which is axially stationary relative to the housing 2360 and the tubular container 2330), thereby pushing at least a portion of the liquid sample 22 through the filter 60 and the filtrate passage opening and into the waste liquid receiving portion 2356.

[0463] As mentioned above FIG. 15A to FIG. 21C As described, for some applications, the preload energy storage element 2202 includes a gas source 2204. In some of these applications, the gas source 2204 is configured to provide gas 2208 into a space 2334 by releasing or generating gas 2208. The space 2334 is defined between (a) a proximal surface 2366 of the plunger rod 2382 and (b) a distally facing inner surface 2368 of the plunger support 2358. The filter assembly 2324 is configured such that providing gas 2208 into the space 2334 increases the pressure in the space 2334, thereby causing the plunger rod 2382 to move distally relative to the plunger tube 2364. In these applications, the plunger rod 2382 typically forms a movable fluid-tight seal with the inner wall of the plunger tube 2364, such as shown, using an O-ring.

[0464] For some applications, in some applications, the preload energy storage element 2202 includes a gas source 2204, and the coupling of the plunger support 2358 to the housing 2360 causes the plunger rod 2382 to move proximally within the plunger support 2358. This proximal movement of the plunger rod 2382 within the plunger support 2358 can open the container 2206 of the gas source 2204. For example, this proximal movement of the plunger rod 2382 can open the container 2206 by damaging (e.g., rupturing, penetrating and / or tearing) the container 2206, such as by pushing one or more spikes 2242 into the wall of the container 2206. Optionally, the one or more spikes 2242 are defined by the proximal end of the shaft 2338, and the distal end of the shaft 2338 is pushed proximally by the proximal surface 2366 of the plunger rod 2382. The opening of the container 2206 causes a reaction that produces gas 2208, such as described above.

[0465] For some applications, the filter assembly 2324 is shaped to define an energy storage element chamber 2332, in which the preloaded energy storage element 2202 is disposed. The energy storage element chamber 2332 is almost completely isolated from the space 2334. The energy storage element chamber 2332 is in fluid communication with the space 2334 only through one or more narrow openings 2236 having a total (combined) area of, for example, 75 square microns to 8000 square microns, for example, where a single circular narrow opening 2236 is provided, its diameter may be 10 microns to 100 microns. One or more narrow openings 2236 may help provide a controlled flow rate of the gas 2208 entering the space 2334. Optionally, one or more narrow openings 2236 are defined by an axis 2338, which also defines one or more spikes 2242 for piercing the container 2206. In the configuration shown in the figure, the energy storage element chamber 2332 is in fluid communication with the space 2334 via exactly one narrow opening 2236. For other applications, the filter assembly 2324 is not shaped to define an energy storage element chamber, similar to the above reference 19A to 19D The configuration of filter assemblies 2224, 2224C is described.

[0466] For other applications, the preload energy storage element 2202 includes another energy source, such as a preload spring (configuration not shown).

[0467] For some applications, sampling device 2320 is configured such that filter extraction shaft 2372 is withdrawn distally from filter assembly 2324, typically while plunger head 2342 remains within tubular container 2330, and filter 60 is pulled out of filter assembly 2324 via distal opening 2396 defined by distal bottom surface 2398 of tubular container 2330 (and optionally, in a configuration in which filter assembly 2324 includes hollow shaft 2376, via central opening 2383 and / or via internal shaft space 2386), thereby removing filter extraction shaft 2372 and filter 60 from filter assembly 2324. At least a portion of filter 60 is typically gathered from the initial flat shape of the filter when disposed on filter support 2362 into, for example, a flower-like arrangement.

[0468] Note that the filter extraction shaft 2372 of the sampling device 2320 is not an element of the filter assembly 2324, but is capable of being removed from the filter assembly 2324.

[0469] For some applications, the filter assembly 2324 (e.g., distal opening 2396) and the extractor 2392 (shaft handle 2305 or its filter extraction shaft 2372) are shaped to define corresponding threads. The sampling device 2320 is configured so that rotation of the extractor 2392 and the distal opening 2396 relative to each other causes the filter extraction shaft 2372 to extract at least an initial portion distally from the filter assembly 2324. For some applications, once the threads are fully separated (as shown), the remainder of the proximal extraction is performed by simply axially extracting the extractor 2392, while for other applications, the threads are longer and the remainder of the proximal extraction is performed by continuing to rotate the extractor 2392 (configuration not shown).

[0470] For some applications, filter assembly 2324 is configured, with necessary modifications (configuration not shown), so that extractor 2392 can be removed from the filter assembly via plunger rod 2382, such as described above with reference to Figures 1A to 21C Described.

[0471] Now refer to FIG. 23A to FIG. 23E , FIG. 23A to FIG. 23E is a schematic diagram of a sampling device 2420 and a method of using the sampling device 2420 according to corresponding applications of the present invention.

[0472] Also refer to FIG. 24A to FIG. 24E , FIG. 24A to FIG. 24E is a schematic cross-sectional view of a sampling device 2420 and a method of using the sampling device 2420 according to corresponding applications of the present invention.

[0473] The sampling device 2420 is generally similar to the one described above with reference to Figures 1A to 4The sampling device 1620 described herein may be combined with any of the features of the sampling device 1620, mutatis mutandis. Like reference numerals refer to like parts. The features of the sampling device 2420 may be combined with the features of any of the other sampling devices described herein, mutatis mutandis.

[0474] The sampling device 2420 includes an extractor 2492, which includes a filter extraction shaft 2472. The extractor 2492 and the filter extraction shaft 2472 can be implemented as described above with reference to Figures 1A to 4 Any of the features of the extractor 1692 and filter extraction shaft 1672 of the described sampling device 1620.

[0475] Unlike the extractor 1692 of the sampling device 1620, the extractor 2492 of the sampling device 2420 does not include a shaft handle 1605 coupled to the proximal portion of the filter extraction shaft 1672. Instead, the sampling device 2420 includes a knob 2422 that threadedly engages a proximal threaded portion 2424 of the filter extraction shaft 2472 (to this end, the knob 2422 is shaped to define an internal thread 2428). The knob 2422 is axially fixed relative to the plunger support 2458 of the sampling device 2420. Rotation of the knob 2422 causes the filter extraction shaft 2472 to move proximally relative to the knob 2422 (and the plunger support 2458) until the proximal threaded portion 2424 of the filter extraction shaft 2472 is disengaged from the plunger support 2458. The knob 2422 generally remains coupled to the plunger support 2458 even after the filter extraction shaft 2472 is disengaged from the plunger support 2458. Optionally, the knob 2422 is shaped as a wing nut. (The plunger support 2458 is coupled to the proximal portion of the plunger 1640 of the sampling device 2420. The plunger support 2458 may implement any of the features of the plunger support described herein, mutatis mutandis)

[0476] Now refer to Fig.25 , Fig.251 is a schematic diagram of a kit 1000 according to an application of the present invention. The kit 1000 includes an extraction tube 1718, a filter 60, and a liquid 1030 for immersing the filter 60 in the extraction tube 1718. The liquid 1030 may, for example, include one or more reagents, or may, for example, be selected from a group including the following: a lysis buffer, an extraction buffer, a salt solution (e.g., phosphate buffered saline (PBS)), and a transport medium (e.g., a universal transport medium or a virus transport medium). For example, one or more reagents, also referred to as extraction reagents, may include saline, sodium nitrite, an acid (e.g., acetic acid or citric acid), a detergent, and / or a preservative, which may, for example, release a target analyte (e.g., an antigen) from a particle, such as a cell, a bacterium, or a virus.

[0477] For some applications, the kit 1000 includes a container 1022 that contains a liquid 1030; alternatively, the extraction tube 1718 contains the liquid 1030. For some applications, the volume of the liquid 1030 is at least 150 microliters (e.g., at least 200 microliters), no more than 500 microliters (e.g., no more than 300 microliters), and / or 150 microliters to 500 microliters (e.g., 150 microliters to 300 microliters, such as 200 microliters to 300 microliters). The gathered shape of the filter 60 described herein can help immerse the filter 60 in a small amount of liquid 1030. A smaller volume of liquid 1030 generally results in less dilution of the target analyte released into the liquid 1030 from the biological particles captured by the filter 60.

[0478] The kit 1000 also includes a filter shaft 1072 including a distal portion 1008 that is coupled or capable of being coupled to the central portion 1010 of the filter 60 and is configured to insert the filter 60 into the extraction tube 1718 for immersing the filter 60 in the liquid 1030 . (It will be understood that if the distal portion 1008 of the filter shaft 1072 is coupled to a non-central portion of the filter 60, such as a peripheral portion of the filter, the distal portion 1008 of the filter shaft 1072 would not be considered to be coupled to the central portion 1010 of the filter 60.) For some applications, the distal portion 1008 of the filter shaft 1072 is coupled to the central portion 1010 of the filter 60 prior to use of the filter 60 (typically during manufacture), while for other applications, the distal portion 1008 of the filter shaft 1072 can be coupled to the central portion 1010 of the filter 60 during use of the filter 60, such as, by way of example and not limitation, in the above-mentioned International Application PCT / IL2023 / 050014, referenced thereto. Fig.25 A to Fig.25 E and Fig.26 A to Fig.26 E described.

[0479] Optionally, the filter shaft 1072 includes any of the filter extraction shafts described herein and / or in the patent applications or patent application publications incorporated herein by reference; likewise, any of the filter extraction shafts described herein can implement any of the features of the filter shaft 1072. For example, the filter shaft 1072 can include: Figures 1A to 4 The filter extraction shaft 1672 described above (and optionally a collection bottle 1650 may also be provided); or FIG. 5A to FIG. 7E and FIG. 8A to FIG. 21C Filter extraction shaft 1772 is depicted.

[0480] Optionally, the kit 1000 further includes a shaft handle 1105 coupled to the proximal portion of the filter shaft 1072. For example, the shaft handle 1105 can have the shape of the shaft handle 1605 or the shape of the shaft handle 1805 described above.

[0481] For some applications, filter shaft 1072 has a length of at least 2 cm, such as at least 3 cm.

[0482] For some applications, filter 60 is circular when flat. Alternatively, filter 60 has another shape.

[0483] For some applications, filter 60 includes a filter reinforcement 2500 as described in the above-mentioned International Application PCT / IL2023 / 050014 with reference to Figures 39, 40, 41 and / or 42A-42B thereof.

[0484] For some applications, extraction tube 1718 comprises a flexible material.

[0485] For some applications, a sterile package is provided in which the kit 1000 (and / or the kit 1000 described below) is removably disposed. Fig.26 One or more elements of the test kit 1100).

[0486] For some applications, kit 1000 also includes a diagnostic test 1040 for testing a portion of liquid 1030 for the presence of a target analyte released into liquid 1030 from biological particles captured by filter 60 .

[0487] For some applications, diagnostic test 1040 includes a lateral flow test strip 1799 (in which case liquid 1030 typically includes one or more reagents), such as a lateral flow immunoassay test strip. Lateral flow test strip 1799 is configured to detect the presence of particles (e.g., by detecting a target analyte, such as a protein antigen, e.g., from bacteria or from a virus). For some applications in which the lateral flow test strip includes a lateral flow immunoassay test strip, lateral flow immunoassay test strip 1799 is an element of a chromatographic digital immunoassay, such as the BD Veritor Immunoassay described below. TM System), the lateral flow immunoassay test strip 1799 is configured to detect (such as by detecting a target analyte, such as a protein antigen, for example, from bacteria or from a virus) particles and optionally the presence of one or more reagents. (Lateral flow immunoassay test strips (optionally as elements of chromatographic digital immunoassays) are well known in the art. For example, they typically contain antibodies specific for the antigen, and the test sample fluid migrates up the test strip and reacts with the antibodies, thereby producing a line on the test strip; the presence of the line indicates a positive test result. For example, the BD Veritor for rapid detection of SARS-CoV-2 TM The system (Becton, Dickinson and Company, Maryland, USA, Ref: 256082) is a chromatographic digital immunoassay intended for direct and qualitative detection of SARS-CoV-2 nucleocapsid antigens in nasal swabs. ) Alternatively, for some applications, diagnostic test 1040 includes: a rapid molecular test, such as an isothermal nucleic acid amplification (iNAAT) test, such as a rapid molecular test kit using a real-time loop-mediated amplification reaction, such as the Lucira COVID-19 All-in-One Test Kit (Lucira Health, Inc., Emeryville, CA, USA); or a nicking enzyme amplification reaction (NEAR) technology, such as ID NOW TM (Abbott Laboratories, Abbott Park, Illinois, USA) or a molecular test kit manufactured by Visby. Further alternatively, the test 302 may include a CRISPR-based diagnostic test, an ELISA diagnostic test, or a spectroscopy-based diagnostic test.

[0488] Kit 1000 can be used, for example, to collect a liquid test sample 22 from a subject and test at least a portion of the test sample using a diagnostic test 1040, or to send at least a portion of the test sample in liquid 1030 in an extraction tube 1718 to a remote laboratory, such as for performing a polymerase chain reaction (PCR) test on particles in the liquid test sample 22.

[0489] The particles can be, for example, viruses (e.g., influenza viruses or coronaviruses, such as SARS-CoV-2), bacteria (e.g., Streptococcus bacteria, such as Streptococcus pyogenes (Strep A)), microorganisms, antigens, human cells, cellular biomarkers, hormones, chemical mediators from cells (e.g., inflammatory mediators), pollen, mucus, saliva, sputum, respiratory particles, droplets from the upper and lower respiratory tracts, nucleic acids including DNA and RNA, and chemicals from external vapors. When the particles are microorganisms, the microorganisms can be pathogenic microorganisms or non-pathogenic microorganisms or both pathogenic microorganisms and non-pathogenic microorganisms, such as viruses, bacteria, protozoa, and fungi. When the particles are human cells, the human cells can be epithelial cells, such as columnar epithelial cells mainly derived from the nasal cavity and squamous epithelial cells mainly derived from the oral cavity. Human cells can also be cellular responders of the immune system, such as neutrophils, eosinophils, lymphocytes, monocytes, macrophages, mast cells, and tissue cells.

[0490] For some applications, the kit 1000 also includes a distal plate 1671 that is fixed to the distal end of the distal portion 1008 of the filter shaft 1072 so that the central portion 1010 of the filter 60 is located between the distal end and the distal plate to directly couple the filter 60 to the filter shaft 1072, such as described above with reference to Figure 3A Described.

[0491] Now refer to Fig.26 , Fig.26 1 is a schematic diagram of a test kit 1100 according to an application of the present invention. The test kit 1100 generally includes the above-mentioned Fig.25 The test kit 1100 also includes a sampling device 1020, such as any sampling device described herein and / or in any of the patent applications or patent application publications incorporated herein by reference. The filter 60 is typically disposed within a portion of the sampling device.

[0492] The test kit 1100 can be used, for example, to collect a liquid test sample 22 from a subject and test at least a portion of the test sample using a diagnostic test 1040, or to send at least a portion of the test sample in liquid 1030 in an extraction tube 1718 to a remote laboratory, such as for performing a polymerase chain reaction (PCR) test on particles in the liquid test sample 22.

[0493] For some applications, the test kit 1100 also includes a container 1150 containing an oral rinse fluid 1152. The subject can optionally rinse the mouth with the oral rinse fluid and filter the rinsed oral rinse fluid using the sampling device 1020. Typically, the oral rinse fluid includes a non-irritating solution; for example, the non-irritating solution can include water or consist of water. In some applications, the non-irritating solution includes a saline solution that can be hypertonic, isotonic, or hypotonic, such as a phosphate buffered saline solution. For example, the container 1150 can contain 5 ml-15 ml, such as 5 ml-10 ml of oral rinse fluid 1152.

[0494] The sampling device 1020 may include any of the sampling devices described herein and / or may implement any of the features of any of the sampling devices described herein. Any of the filter extraction shafts described herein may be replaced with the filter shaft 1072 .

[0495] For some applications, sampling device 1020 is configured such that extraction of filter shaft 1072 from the filter assembly of sampling device 1020 removes filter shaft 1072 and filter 60 from the filter assembly and bunches up at least a portion of filter 60, thereby facilitating insertion of the bunched filter into extraction tube 1718. The bunched filter 60 can be used somewhat similar to a conventional swab, and due to the reduction in diameter caused by the bunching up, the bunched filter 60 can be easily inserted into the extraction tube 1718, such as described above and in Fig. 6E and Fig. 7E , Fig.9E and Fig. 10E as well as Fig.14E As shown in .

[0496] For some of these applications, the sampling device 1020 is configured so that the filter shaft 1072 is withdrawn from the filter assembly to remove the filter shaft 1072 and the filter 60 from the filter assembly and to gather at least a portion of the filter 60 into a flower-like arrangement, such as shown in many of the accompanying drawings. Alternatively or additionally, at least a portion of the filter 60 is gathered into a plurality of folds, which are optionally soft folds (i.e., without creases). In this sense, the gathered filter can be considered to be roughly shaped as a soft pleated skirt without an opening at the waist. Typically, the flower-like gathered shape of the filter 60 can produce open soft folds, rather than wrinkled folds and / or closed folds that would create an enclosed space that the liquid 1030 cannot reach.

[0497] For some applications, sampling device 1020 is configured such that extraction of filter shaft 1072 from the filter assembly removes filter shaft 1072 and filter 60 from the filter assembly and brings together at least a portion of filter 60 such that:

[0498] The entire periphery 1085 of the filter 60 extends distally away from the distal portion 1008 of the filter shaft 1072 (such as by way of example and not limitation). Figure 3E ),

[0499] The entire periphery 1085 of the filter 60 is directed distally (such as by way of example and not limitation) Figure 3E ), and / or

[0500] The converged portion of the filter 60 defines an interior space 1087 that is open to the distal end (such as by way of example and not limitation). Figure 3E ) shown and labeled in .

[0501] Typically, the filter 60 is removably disposed in a flat shape on a support surface of a filter support portion of a filter assembly of the sampling device 1020 , as shown in many of the drawings illustrating the sampling device.

[0502] For some applications, the filter assembly of sampling device 1020 is configured such that when liquid sample 22 is contained in the tubular container and filter 60 is disposed on the support surface of the filter support, movement of the plunger head within the tubular container of the filter assembly pushes at least a portion of the liquid sample 22 through filter 60 in an upstream to downstream direction, thereby capturing a portion of the biological particles present in the liquid sample 22 on the upstream surface of filter 60. Such as shown in many of the drawings that illustrate sampling devices.

[0503] For some of these applications, sampling device 1020 is configured such that filter shaft 1072 is withdrawn from the filter assembly to remove filter shaft 1072 and filter 60 from the filter assembly and to bring together at least a portion of filter 60 such that the upstream surface of the filter is located within the gathered filter assembly, such as FIG. 3C to FIG. 3D , FIG. 7C to FIG. 7D and FIG. 10C to FIG. 10D . Thus, any biological particles present in the liquid test sample 22 and captured by the filter 60 are positioned within the gathered filter 60. This location of the biological particles within the gathered filter 60 can help bring the biological particles into and maintain good contact with the liquid 1030 when the gathered filter 60 is inserted into the extraction tube 1718 by creating a containment area for the liquid 1030 to interact with the biological particles.

[0504] For other of these applications, the sampling device 1020 is configured such that the filter shaft 1072 is withdrawn from the filter assembly to remove the filter shaft 1072 and the filter 60 from the filter assembly and to gather at least a portion of the filter 60 such that the downstream surface of the filter is located inside the gathered filter. Thus, any biological particles present in the liquid sample 22 and captured by the filter 60 are located on the outer folded surface of the gathered filter 60. This position of the biological particles can help increase the contact of the biological particles with the liquid 1030 outside the gathered filter 60 when the gathered filter 60 is inserted into the extraction tube 1718.

[0505] Reference Fig.25 and FIG. 5A to FIG. 7E For some applications, kit 1000 also includes a filter receiver 1714 coupled to a distal portion of filter shaft 1072 and shaped to define a distal receiver opening 1716, such as described above with reference to FIG. 5A to FIG. 7E In these applications, the sampling device 1020 is configured such that withdrawal of the filter shaft 1072 from the filter assembly draws the central portion 1010 of the filter 60 into the filter receiver 1714 via the distal receiver opening 1716, thereby causing the remainder of the filter 60 to become gathered and at least partially disposed outside the filter receiver 1714. Optionally, the filter receiver 1714 is slidably coupled to the distal portion of the filter shaft 1072.

[0506] Reference Fig.25 and Fig.26 In the application of the present invention, a method is provided, the method comprising:

[0507] · Using (a) the techniques described with reference to many of the figures in this document, (b) the techniques described in the patent applications or patent application publications incorporated by reference below, such as, by way of example and not limitation, with reference to PCT Publication WO 2021 / 224925 to Levitz et al. FIG. 14A to FIG. 14B , or (c) conventional filtering techniques and devices known in the art, passing at least a portion of the liquid sample sample 22 through the filter 60; for some applications, at least a portion of the liquid sample sample 22 passes through the filter 60 when the filter 60 is in a flat shape, such as shown in many of the figures of the accompanying drawings;

[0508] Gathering at least a portion of the filter 60 when the central portion 1010 of the filter 60 is coupled to the distal portion 1008 of the filter shaft 1072, such as described with reference to many of the figures herein; such gathering of the filter 60 can help facilitate insertion of the filter 60 into the extraction tube 1718; the filter 60 can be coupled to the distal portion 1008 of the filter shaft 1072 before or after the liquid sample 22 passes through the filter 60, such as described herein;

[0509] Placing the liquid 1030 in the extraction tube 1718; alternatively, providing the extraction tube 1718 already containing the liquid 1030;

[0510] Inserting the converged portion of the filter 60 into the extraction tube 1718 (via the proximal end opening 1721 of the extraction tube 1718) before or after the liquid 1030 is placed in the extraction tube 1718, such as described with reference to many of the figures herein;

[0511] · immersing the filter 60 in the liquid 1030 in the extraction tube 1718; and

[0512] Thereafter, a portion of the liquid 1030 is tested for the presence of a target analyte released into the liquid 1030 from the biological particles captured by the filter 60 (e.g., the liquid 1030 can be expelled (e.g., dripped or squeezed) onto a diagnostic test, such as onto a sample pad 1797 of a lateral flow test strip 1799).

[0513] The method may or may not include separating portions of the filter extraction shaft 1772 from each other.

[0514] Reference Fig.26 . For some applications, the filter assembly of the sampling device 1020 is used to pass at least a portion of the liquid sample 22 through the filter 60, while the filter 60 is disposed in a removable manner and the filter shaft 1072 is partially disposed in the filter assembly in a removable manner. The filter assembly of the sampling device 1020 can implement any of the following: (a) the technology of the filter assembly described herein, (b) the technology described in the patent application or patent application publication incorporated by reference below, such as, by way of example and not limitation, reference to PCT publication WO 2021 / 224925 FIG. 14A to FIG. 14B , or (c) conventional filtration techniques and devices known in the art.

[0515] For some applications, use the reference above FIG. 3E to FIG. 3F The described technique inserts the gathered portion of the filter 60 into the extraction tube 1718 .

[0516] Refer again Fig.25 and Fig.26 . For some applications, at least a portion of filter 60 is gathered by passing filter 60 through a tube, such as a cylindrical tube. The tube is typically separate from the filter assembly. Alternatively, for some applications, at least a portion of filter 60 is gathered by passing filter 60 into and / or through extraction tube 1718. When a filter assembly that does not gather the filter is used, such as a conventional filter assembly, or by way of example and not limitation, reference is made to PCT Publication WO2021 / 224925. FIG. 14A to FIG. 14B For the filtering components described, these two techniques may be particularly useful.

[0517] Alternatively, the filter shaft 1072 includes a filter extraction shaft 1672, and a collection bottle 1650 is additionally provided, such as described above with reference to Figures 1A to 4 For some of these applications, at least a portion of the filter 60 is gathered by at least partially penetrating the filter 60 into the collection bottle 1650 by sliding the proximal portion 1687 of the filter extraction shaft 1672 through the shaft passage hole 1609 of the collection bottle 1650. This technique can even be used in configurations in which the filter assembly is used without the filter being gathered, in which case the collection bottle 1650 is optionally not initially disposed within the filter assembly, as described above with reference to Figure 1A , FIG. 2A to FIG. 2C and FIG. 3A to FIG. 3C Alternatively or additionally, the technique may be used more than once during a testing procedure, such as for the first time in a filter assembly, as described above with reference to FIG. 2B to FIG. 2D and FIG. 3B to FIG. 3D described, and is used a second time after removing the filter 60 from the extraction tube 1718.

[0518] Still refer to Fig.25 and Fig.26 For some applications, liquid 1030 is selected from the group consisting of: a lysis buffer, an extraction buffer, a saline solution, and a transport medium. For some applications, liquid 1030 includes one or more reagents, and a portion of liquid 1030 is tested for the presence of a target analyte released from biological particles captured by filter 60 into the one or more reagents by testing a portion of the one or more reagents. For some applications, a portion of the one or more reagents is tested by applying a portion of the one or more reagents to a lateral flow test strip 1799.

[0519] For some applications, the gathered portion of filter 60 is not rotated before, during, and / or after extrusion.

[0520] For some applications, the gathered portion of the filter 60 is rotated before, during, and / or after extrusion. For some of these applications, the inner surface of the sidewall of the extraction tube 1718 is shaped to define one or more protrusions that can help change the direction in which the folds of the gathered filter 60 point when the filter is rotated clockwise and counterclockwise (from clockwise to counterclockwise and back). For example, with necessary modifications, the extraction tube 1718 can implement the PCT publication WO 2022 / 044002 of Levitz et al. Fig.13A 13E for the configuration of the receiving portion 1124 thereof.

[0521] Typically, the filter 60 is not agitated in the extraction tube 1718, although it may optionally be agitated.

[0522] For some applications, extraction tube 1718 includes a flexible material, and the gathered portion of filter 60 is squeezed by squeezing the longitudinal portion of extraction tube 1718, along which the gathered portion of filter 60 is disposed, such as Fig. 3I as shown in .

[0523] For some applications, after filter 60 is immersed in liquid 1030 in extraction tube 1718 and before the converged portion of filter 60 is squeezed, excess liquid 1030 is removed (e.g., drained) from extraction tube 1718. Removal of excess liquid can help reduce dilution of liquid absorbed in filter 60 and drained from filter 60.

[0524] For some applications, the gathered portion of filter 60 is removed from extraction tube 1718 before the gathered portion of filter 60 is squeezed (while outside of extraction tube 1718). During this removal, excess liquid 1030 remains in extraction tube 1718, which can help reduce dilution of the liquid absorbed in and discharged from filter 60.

[0525] Refer again Fig.25 and Fig.26 Typically, the filter extraction axis 1772 is away from the first side portion of the filter 60 ( Fig.25 and Fig.26 The top side shown in FIG. 1 extends from the filter 60 and is not far from the second side ( FIG. 14 ) opposite to the first side. Fig.25 and Fig.261030 ) extends from the bottom side of the filter 60 (as shown), or extends less than 10 mm, such as less than 2 mm, away from the second side of the filter 60. Therefore, when a portion of the filter 60 is gathered, the filter extraction shaft 1772 does not extend or extends less than 10 mm (such as less than 2 mm) into the interior space defined by the gathered portion of the filter 60. The absence of the filter extraction shaft 1772 in the gathered portion of the filter 60 leaves the interior space free for the liquid 1030 to fill and make good contact with most of the surface area of ​​the inner surface of the gathered portion of the filter 60. In addition, the absence of the filter extraction shaft 1772 in the gathered portion of the filter 60 can make it easier to squeeze the filter 60 thoroughly compared to the situation where a relatively rigid shaft is in the gathered portion of the filter 60.

[0526] Alternatively, for some applications, the gathered portion of filter 60 is squeezed by inserting an object into extraction tube 1718 and using the object to squeeze the gathered portion of filter 60 (configuration not shown).

[0527] Alternatively or additionally, for some applications, a portion of the liquid 1030 is tested using a diagnostic test, the portion of the liquid 1030 is tested for the presence of a target analyte released from the biological particle into the liquid 1030, and the gathered portion of the filter 60 is squeezed by inserting the portion of the diagnostic test into the extraction tube 1718 and squeezing the gathered portion of the filter 60 using the portion of the diagnostic test (configuration not shown).

[0528] Further alternatively, the gathered portion of the filter 60 is removed from the extraction tube 1718 after being immersed in the liquid 1030, and thereafter the gathered portion of the filter 60 is squeezed to squeeze a portion of the liquid 1030 from the filter 60 (configuration not shown). Alternatively, the gathered portion of the filter 60 is inserted into another tube before squeezing, and is squeezed while in the second tube (configuration not shown).

[0529] Optionally, excess liquid 1030 is drained from extraction tube 1718 before the gathered portion of filter 60 is squeezed (configuration not shown), such as when the gathered portion of filter 60 is located in extraction tube 1718.

[0530] For some applications, at least a portion of filter 60 is gathered into a flower-like arrangement, such as shown in many of the drawings.

[0531] Now refer to FIG. 27A to FIG. 27E , FIG. 27A to FIG. 27E 31 is a schematic cross-sectional view of a container assembly 3100 and a method of using the container assembly 3100 according to the application of the present invention. The container assembly 3100 includes an extraction tube 3118. The extraction tube 3118 can be implemented as described above with reference to Figures 3E to 3K1718, and mutatis mutandis, can be used to perform any of the methods described herein as being performed using extraction tube 1718. Similarly, extraction tube 1718 can implement any of the features of extraction tube 3118, and mutatis mutandis, extraction tube 1718 can be used to perform any of the methods described herein as being performed using extraction tube 3118. Similarly, extraction tube 3118 can be implemented in combination with any of the extraction tubes described in the aforementioned International Application PCT / IL2023 / 050014, including extraction tube 3018 thereof; for example, extraction tube 3118 can be combined with housing 3010 or housing 3410 described in the aforementioned International Application PCT / IL2023 / 050014.

[0532] The extraction tube 3118 is shaped to define:

[0533] an inner wider proximal portion 3120 shaped to define a proximal opening 3122 of the extraction tube 3118, and

[0534] An inner narrower distal portion 3130 shaped to define a closed distal end 3132 of the extraction tube 3118; the closed distal end 3132 may be permanently closed or may be removably closed with a distal tip cap, such as described above with reference to FIG. 3E to FIG. 3I Described with respect to distal tip cap 1749 .

[0535] The container assembly 3100 also includes an elongated sealing insert 3140 that is removably coupled to the extraction tube 3118. The elongated sealing insert 3140 includes:

[0536] a shaft 3142 comprising a distal shaft portion 3144 that is narrower than and removably disposed at least partially within the inner, narrower distal portion 3130 of the extraction tube 3118;

[0537] One or more distal plugs 3150 (e.g., exactly one) positioned along or at a distal end 3152 of the distal shaft portion 3144 and removably disposed within the inner, narrower distal portion 3130 of the extraction tube 3118; and

[0538] One or more proximal plugs 3154 (e.g., exactly one or exactly two) positioned proximal to the one or more distal plugs 3150 along the axis 3142;

[0539] At least a portion of the distal shaft portion 3144 disposed within the inner narrower distal portion 3130 defines a space between the distal shaft portion 3144 and the inner narrower distal portion 3130 .

[0540] The extraction tube 3118 may be cylindrical or other shapes, and the plug may be circular or other shapes.

[0541] The one or more distal plugs 3150 can be integral with the distal shaft portion 3144, e.g., shaped as a protrusion, collar, or projection, and / or include a separate sealing element, e.g., an O-ring, coupled around the distal shaft portion 3144. The one or more distal plugs 3150, when removably disposed within the inner narrower distal portion 3130 of the extraction tube 3118, typically form a movable fluid-tight seal with the inner wall of the inner narrower distal portion 3130 of the extraction tube 3118.

[0542] Similarly, the one or more proximal plugs 3154 can be integral with the shaft 3142, e.g., shaped as a protrusion, collar, or projection, and / or include a separate sealing element, e.g., an O-ring, coupled around the shaft 3142. Alternatively, one of the one or more proximal plugs 3154 (e.g., proximal plug 3154B described below) can be shaped as a cap for the extraction tube 3118.

[0543] The container assembly 3100 still further includes a first substance 3160A and a second substance 3160B that is separate and different from the first substance 3160A.

[0544] like Fig.27A As shown in FIG, the first substance 3160A is contained within the inner narrower distal portion 3130 of the extraction tube 3118 at the distal end of one or more distal plugs 3150, so that the one or more distal plugs 3150 seal the first substance 3160A within the inner narrower distal portion 3130 of the extraction tube 3118.

[0545] Likewise Fig.27A As shown in FIG. 31 , the second substance 3160B is contained within the extraction tube 3118 distal to the one or more proximal plugs 3154 and proximal to the one or more distal plugs 3150 such that:

[0546] One or more proximal plugs 3154 seal the second substance 3160B within the extraction tube 3118, and

[0547] • One or more distal plugs 3150 sealingly isolate the second substance 3160B from the first substance 3160A.

[0548] The container assembly 3100 is configured such that the one or more distal plugs 3150 are withdrawn from the inner narrower distal portion 3130 toward the proximal end of the inner wider proximal portion 3120 by withdrawing the shaft 3142 proximally so that the second substance 3160B is in fluid communication with the first substance 3160A, for example Fig.27A and Fig.27B The transition between .

[0549] For some applications, one or more proximal plugs 3154 include proximal plugs 3154, 3154A positioned along distal shaft portion 3144 and removably disposed within inner narrower distal portion 3130 of extraction tube 3118. Proximal plugs 3154, 3154A generally form a movable fluid-tight seal with an inner wall of inner narrower distal portion 3130 of extraction tube 3118 when removably disposed within inner narrower distal portion 3130 of extraction tube 3118.

[0550] For some applications, one or more proximal plugs 3154 include proximal plugs 3154 , 3154B that removably plug proximal opening 3122 of extraction tube 3118 .

[0551] For some applications, one or more proximal plugs 3154 include:

[0552] a first proximal plug 3154, 3154A located along the distal shaft portion 3144 and removably disposed within the inner narrower distal portion 3130 of the extraction tube 3118, and

[0553] A second proximal plug 3154, 3154B that removably blocks the proximal opening 3122 of the extraction tube 3118.

[0554] Optionally, the proximal plug 3154A is configured to expand when withdrawn proximally from the inner narrower distal portion 3130 so as to form a seal with the inner wall of the inner wider proximal portion 3120, thereby Fig.27B In the state shown in , overflow of the second substance 3160B is suppressed.

[0555] For some applications (configurations not shown), container assembly 3100 further includes a third substance contained within extraction tube 3118 proximal to first proximal plug 3154, 3154A and distal to second proximal plug 3154, 3154B such that:

[0556] The second proximal plug 3154, 3154B seals the third substance within the extraction tube 3118, and

[0557] The first proximal plug 3154, 3154A seals the third substance from the second substance 3160B, and

[0558] The container assembly 3100 is constructed as follows:

[0559] The shaft 3142 is withdrawn proximally to withdraw the first proximal plug 3154, 3154A from the inner narrower distal portion 3130 toward the proximal end of the inner wider proximal portion 3120, so that the third substance is in fluid communication with the second substance 3160B, and

[0560] The one or more distal plugs 3150 are withdrawn from the inner narrower distal portion 3130 toward the proximal end of the inner wider proximal portion 3120 by further proximal withdrawal of the shaft 3142, so that the second substance 3160B and the third substance are in fluid communication with the first substance 3160A.

[0561] The first substance 3160A and the second substance 3160B (and the third substance, if provided) can include liquids and / or solids (e.g., powders). The substances, when separated or after combination, can have the properties described above with reference to Figures 1A to 4 , Fig.25 and / or Fig.26 Any of the properties of the liquid 1030 described herein and / or may be used in tests such as those described herein, for example with reference to Figures 1A to 4 , Fig.25 and / or Fig.26 , or using any test device in the test device described herein to test. For example, the substance may include one or more reagents, such as one or more reagents configured to be used with a lateral flow test strip, or may be selected from a group including the following: a lysis buffer, an extraction buffer, a saline solution (e.g., phosphate buffered saline (PBS)) and a transport medium (e.g., a universal transport medium or a virus transport medium). For example, one or more reagents also referred to as extraction reagents may include saline, sodium nitrite, an acid (e.g., acetic acid or citric acid), a detergent and / or a preservative, which may, for example, release a target analyte (e.g., an antigen) from a particle, such as a cell, a bacterium or a virus.

[0562] In some applications, second substance 3160B includes a non-toxic citric acid solution or acetic acid solution at a concentration to prevent small amounts of second substance from being spilled during removal of shaft 3142 from extraction tube 3118. In these applications, first substance 3160A may include, for example, sodium nitrite in solution or solid form.

[0563] For some applications, container assembly 3100 includes a base for maintaining extraction tube 3118 vertically relative to the surface on which it is mounted so as to orient container assembly 3100 such that proximal opening 3122 of extraction tube 3118 of container assembly 3100 is located above closed distal end 3132 of extraction tube 3118 relative to the ground.

[0564] Reference FIG. 27D to FIG. 27E In some applications of the present invention, a kit is provided, the kit comprising a container assembly 3100 and further comprising a filter assembly, the filter assembly comprising:

[0565] Filter 60;

[0566] The collection bottle 1650 described above; and

[0567] ·The filter shaft 1672 described above includes: (a) a proximal portion 1687, which is slidably arranged to pass through an axis passage hole 1609, which passes through the end 1604 of the collection bottle 1650 opposite to the bottle opening 1652; and (b) a distal portion 1608, which is connected to the filter 60.

[0568] The kit is configured such that the collection bottle 1650 can be at least partially inserted into the extraction tube 3118 and can be advanced distally within the extraction tube 3118 until the filter 60 is positioned adjacent the closed distal end 3132 of the extraction tube 3118. The extraction tube 3132 is shaped to prevent the collection bottle 1650 from reaching the closed distal end 3132 of the extraction tube 3118, so that the collection bottle 1650 slides upwardly over a portion of the filter extraction shaft 1672 when the filter 60 is positioned adjacent the closed distal end 3132, thereby dislodging the filter 60 from the bottle opening 1652 and exposing the filter 60 to the first substance 3160A and the second substance 3160B in the inner narrower distal portion 3130 of the extraction tube 3118.

[0569] Alternatively, a method is provided which does not have a reference FIG. 27D to FIG. 27E A container assembly 3100 of additional elements of a kit is described.

[0570] Alternatively, the method of using the container assembly 3100 does not include reference to FIG. 27D to FIG. 27E Describe the steps.

[0571] Refer again FIG. 27A to FIG. 27C In the application of the present invention, a method of using the container assembly 3100 is provided, the method comprising:

[0572] Orienting the container assembly 3100 such that the proximal opening 3122 of the extraction tube 3118 of the container assembly 3100 is located above the closed distal end 3132 of the extraction tube 3118 relative to the ground; and

[0573] • The one or more distal plugs 3150 are proximally withdrawn from within the inner narrower distal portion 3130 to the inner wider proximal portion 3120 by proximally withdrawing the shaft 3142 so that the second substance 3160B is in fluid communication with the first substance 3160A.

[0574] For some applications, container assembly 3100 also includes a third substance, which is contained within extraction tube 3118 proximal to first proximal plug 3154, 3154A and distal to second proximal plug 3154, 3154B, such that (a) second proximal plug 3154, 3154B seals the third substance within extraction tube 3118, and (b) first proximal plug 3154, 3154A seals the third substance from second substance 3160B. The method further includes, before proximally withdrawing the one or more distal plugs 3150 from the inner narrower distal portion 3130 to the inner wider proximal portion 3120, proximally withdrawing the first proximal plugs 3154, 3154A from the inner narrower distal portion 3130 to the inner wider proximal portion 3120 by proximally withdrawing the shaft 3142 so that the third substance is in fluid communication with the second substance 3160B. By further proximally withdrawing the shaft 3142, the one or more distal plugs 3150 are proximally withdrawn from the inner narrower distal portion 3130 to the inner wider proximal portion 3120 so that the second substance 3160B and the third substance are in fluid communication with the first substance 3160A.

[0575] For some applications, the method also includes, after withdrawing one or more distal plugs 3150 proximally from the inner narrower distal portion 3130 to the inner wider proximal portion 3120, at least partially inserting the collection bottle 1650 of the filter assembly into the extraction tube 3118, and pushing the collection bottle 1650 distally in the extraction tube 3118 until the filter 60 of the filter assembly is positioned near the closed distal end 3132 of the extraction tube 3118, wherein the filter assembly also includes a filter shaft 1672, which includes (a) a proximal portion 1687, which is slidably configured to pass through an axis passage hole 1609, which passes through an end 1604 of the collection bottle 1650 opposite to the bottle opening 1652; and (b) a distal portion 1608, which is connected to the filter 60. The extraction tube 3132 is shaped to prevent the collection bottle 1650 from reaching the closed distal end 3132 of the extraction tube 3118, so that the collection bottle 1650 slides upward on a portion of the filter extraction shaft 1672 when the filter 60 is positioned near the closed distal end 3132, thereby expelling the filter 60 from the bottle opening 1652 and exposing the filter 60 to the first substance 3160A and the second substance 3160B in the inner narrower distal portion 3130 of the extraction tube 3118.

[0576] In embodiments, the techniques and apparatus described herein are combined with techniques and apparatus described in one or more of the following patent applications, which are assigned to the assignee of the present application and are incorporated herein by reference:

[0577] Fruchter et al., U.S. Patent Application Publication No. 2019 / 0381498;

[0578] U.S. Provisional Application No. 62 / 727,268 filed on September 5, 2018;

[0579] PCT Publication No. WO 2020 / 049566 by Fruchter et al.

[0580] Fruchter et al., U.S. Patent Application Publication No. 2021 / 0215585;

[0581] U.S. Provisional Application No. 62 / 988,145 filed on March 11, 2020;

[0582] U.S. Provisional Application No. 62 / 988,259 filed on March 11, 2020;

[0583] U.S. Provisional Application Nos. 63 / 020,723, filed May 6, 2020; 63 / 037,707, filed June 11, 2020; 63 / 067,535, filed August 19, 2020; 63 / 117,294, filed November 23, 2020; 63 / 156,843, filed March 4, 2021; 63 / 158,005, filed March 8, 2021; 63 / 166,378, filed March 26, 2021; and 63 / 176,565, filed April 19, 2021;

[0584] U.S. Provisional Application No. 63 / 071,529, filed on August 28, 2020;

[0585] PCT Publication No. WO 2021 / 044417 by Holtz et al.

[0586] U.S. Patent Application Publication No. 2021 / 0102876 by Fruchter et al.

[0587] PCT Publication WO 2021 / 181338 and its U.S. national phase U.S. Patent Application Publication 2023 / 0098151 by Fruchter et al.

[0588] PCT Publication WO 2021 / 181339 and its U.S. national phase U.S. Patent Application Publication 2023 / 0096409 by Feldman et al.

[0589] Levitz et al. PCT Publication WO 2021 / 224925 and national phase U.S. Application 17 / 921,672;

[0590] Levitz et al. PCT publication WO 2022 / 044002 and national phase U.S. application 18 / 023,607;

[0591] U.S. provisional application 63 / 134,282 filed on January 6, 2021;

[0592] PCT Publication WO 2022 / 149135 by Feldman et al.

[0593] U.S. provisional application 63 / 275,130, filed on November 3, 2021;

[0594] U.S. provisional application 63 / 277,238, filed on November 9, 2021;

[0595] U.S. provisional application 63 / 388,851, filed on July 13, 2022;

[0596] U.S. application Ser. No. 17 / 980,200, filed Nov. 3, 2022, published as U.S. Patent Application Publication No. 2023 / 0061094 to Levitz et al.;

[0597] Feldman et al., U.S. Patent Application Publication No. 2023 / 0152192;

[0598] PCT Publication WO 2023 / 095146 by Levitz et al.

[0599] U.S. Provisional Application No. 63 / 432,231, filed on December 13, 2022; and

[0600] International application PCT / IL2023 / 050014 filed on January 5, 2023.

[0601] In embodiments, the techniques and devices described herein are similar to those described in PCT Publication WO 2022 / 149135 by Feldman et al. Figure 1A Combination of techniques and devices described in connection with Figure 35B.

[0602] It will be appreciated by those skilled in the art that the present invention is not limited to what has been specifically shown and described above. Specifically, the scope of the present invention includes both the combination and sub-combination of the various features described above, as well as variations and modifications not in the prior art that those skilled in the art will think of when reading the preceding description.

Claims

1. A sampling device for concentrating a liquid test sample, the sampling device comprising a filter assembly, the filter assembly comprising: a tubular container shaped to define an inner wall and a proximal container opening for receiving the liquid test sample; a plunger (i) comprising a plunger head and a plunger rod, the plunger rod having a distal end portion coupled to the plunger head and (ii) insertable into the tubular container via the proximal container opening such that a lateral surface of the plunger head forms a movable fluid tight seal with the inner wall of the tubular container; A waste liquid receiving part; Filters; a filter support shaped to define (a) a support surface on which the filter is removably disposed, and (b) a plurality of filtrate passage openings through the filter support into the waste receiving portion; as well as Preload the energy storage element, Wherein, the filter assembly is configured such that when the liquid sample is contained in the tubular container and the filter is disposed on the supporting surface, the energy release of the preloaded energy storage element pushes at least a portion of the liquid sample sample through the filter and the filtrate passage opening and into the waste liquid receiving portion.

2. The sampling device according to claim 1, wherein: The pre-loaded energy storage element includes a gas source.

3. The sampling device according to claim 2, wherein: The gas source includes one or more substances that generate a gas.

4. The sampling device according to claim 2, wherein: The gas source includes a compressed gas container.

5. The sampling device according to claim 2, wherein: The filter assembly is configured such that movement of the plunger head within the tubular container causes the gas source to provide gas by releasing or generating gas.

6. The sampling device according to claim 5, in, The motion is a non-rotational motion, Wherein, the sampling device also includes a container shell, and Wherein, the filter assembly further includes a plunger support, which is (a) coupled to the proximal portion of the plunger and (b) hingedly attached to the container housing.

7. The sampling device according to claim 1, in, The plunger rod is shaped to define the waste receiving portion within the plunger rod, and Wherein, the plunger head includes the filter support portion.

8. The sampling device according to claim 7, in, The sampling device also includes a container housing, wherein the tubular container is at least partially disposed within the container shell so that the tubular container can move relative to the container shell, and Wherein, the filter assembly is configured so that the release of energy from the preloaded energy storage element causes the tubular container to move proximally relative to the plunger head, thereby pushing at least a portion of the liquid sample through the filter and the filtrate passage opening and into the waste liquid receiving portion.

9. The sampling device according to claim 8, in, The preload energy storage element includes a gas source configured to provide gas by releasing or generating gas into a space defined between (a) a proximal-facing inner surface of the container shell and (b) an outer surface of the tubular container defined by a distal end of the tubular container, and Wherein, the filter assembly is configured such that providing gas into the space increases the pressure in the space, thereby causing the tubular container to move proximally relative to the plunger head.

10. The sampling device according to claim 1, wherein: The distal bottom surface of the tubular container includes the filter support portion.

11. The sampling device according to claim 10, in, The filter assembly also includes: a housing including the tubular container; and a plunger support that is coupleable to the housing and includes a plunger tube in which the plunger rod is at least partially disposed so as to be axially movable relative to the plunger tube, and Wherein, the filter assembly is configured so that the release of energy of the preloaded energy storage element causes the plunger rod to move distally relative to the plunger tube, thereby pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste liquid receiving portion.

12. The sampling device according to claim 11, in, The preload energy storage element includes a gas source configured to provide gas by releasing or generating gas into a space defined between (a) a proximal surface of the plunger rod and (b) a distally facing inner surface of the plunger support, and Wherein, the filter assembly is configured such that providing gas into the space increases the pressure in the space, thereby causing the plunger rod to move distally relative to the plunger tube.

13. The sampling device according to claim 11, in, The preloaded energy storage element includes a gas source, and Wherein, the filter assembly is configured such that coupling of the plunger support to the housing causes the plunger rod to move proximally within the plunger support, which causes the gas source to provide gas by releasing or generating gas.

14. The sampling device according to claim 1, in, The preload energy storage element includes a gas source configured to provide gas to a space defined within the filter assembly by releasing or generating gas, wherein the filter assembly is shaped to define an energy storage element chamber that is in fluid communication with the space only through one or more narrow openings having a total area of ​​75 square microns to 8,000 square microns, and Wherein, the preloaded energy storage element is arranged in the energy storage element chamber.

15. A method for concentrating a liquid test sample, the method comprising: placing the liquid test sample in a tubular container of a filter assembly of a sampling device through a proximal container opening; inserting a plunger head of a plunger of the filter assembly into the tubular container through the proximal container opening of the tubular container so that a lateral surface of the plunger head forms a movable fluid-tight seal with an inner wall of the tubular container, wherein the plunger further comprises a plunger rod having a distal end portion coupled to the plunger head; and A preloaded energy storage element of the filter assembly is caused to release energy, thereby pushing at least a portion of the liquid test sample through a filter removably disposed on a support surface of a filter support portion in the tubular container, wherein the filter support portion is shaped to define a plurality of filtrate passage openings that pass through the filter support portion and into a waste liquid receiving portion of the filter assembly.

16. The method according to claim 15, wherein: The pre-loaded energy storage element includes a gas source.

17. The method according to claim 16, wherein: The gas source includes one or more substances that generate a gas.

18. The method according to claim 16, wherein: The gas source includes a compressed gas container.

19. The method according to claim 16, wherein: Causing the preloaded energy storage element to release energy includes moving the plunger head within the tubular container to cause the gas source to provide gas by releasing or generating gas.

20. The method according to claim 19, in, The sampling device also includes a container housing, wherein the filter assembly further comprises a plunger support (a) coupled to a proximal end portion of the plunger and (b) hingedly attached to the container housing, and Wherein, moving the plunger head within the tubular container includes moving the plunger head non-rotatably within the tubular container.

21. The method according to claim 15, in, The plunger rod is shaped to define the waste receiving portion within the plunger rod, and Wherein, the plunger head includes a filter support portion.

22. The method according to claim 21, in, The sampling device also includes a container housing, wherein the tubular container is at least partially disposed within the container shell so that the tubular container can move relative to the container shell, and The preloaded energy storage element is released to move the tubular container proximally relative to the plunger head, thereby pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste liquid receiving portion.

23. The method according to claim 22, in, The preloaded energy storage element includes a gas source, and Wherein, causing the preloaded energy storage element to release energy includes causing the gas source to provide gas into the space by releasing or generating gas, thereby increasing the pressure in the space, thereby causing the tubular container to move proximally relative to the plunger head, and the space is defined between (a) an inner surface of the container shell facing the proximal end and (b) an outer surface of the tubular container defined by the distal end of the tubular container.

24. The method according to claim 15, wherein: The distal bottom surface of the tubular container includes the filter support portion.

25. The method according to claim 24, in, The filter assembly also includes: a housing including the tubular container; and a plunger support that is coupleable to the housing and includes a plunger tube in which the plunger rod is at least partially disposed so as to be axially movable relative to the plunger tube, and The preloaded energy storage element is released to move the plunger rod distally relative to the plunger tube, thereby pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste liquid receiving portion.

26. The method according to claim 25, in, The preload energy storage element includes a gas source configured to provide gas by releasing or generating gas into a space defined between (a) a proximal surface of the plunger rod and (b) a distally facing inner surface of the plunger support, and Wherein, causing the preloaded energy storage element to release energy includes causing the gas source to provide gas into the space to increase the pressure in the space, thereby causing the plunger rod to move distally relative to the plunger tube.

27. The method according to claim 25, in, The preloaded energy storage element includes a gas source, and Wherein, releasing energy from the preloaded energy storage element comprises coupling the plunger support to the housing so that the plunger rod moves proximally within the plunger support, which causes the gas source to provide gas by releasing or generating gas.

28. The method according to claim 15, in, The preload energy storage element includes a gas source configured to provide gas to a space defined within the filter assembly by releasing or generating gas, wherein the filter assembly is shaped to define an energy storage element chamber that is in fluid communication with the space only through one or more narrow openings having a total area of ​​75 square microns to 8,000 square microns, and Wherein, the preloaded energy storage element is arranged in the energy storage element chamber.

29. The method of claim 15, further comprising detecting the presence of biological particles captured by the filter after the filter has been removed from the tubular container.

30. The method of claim 29, wherein: Detecting the presence of biological particles captured by the filter includes using a lateral flow test strip to detect the presence of biological particles captured by the filter.

31. The method of claim 29, wherein: The biological particles are selected from the group consisting of viruses, bacteria, microorganisms, fungi, spores, mites, biological cells, biological antigens, proteins, protein antigens and carbohydrate antigens.

32. The method according to any one of claims 15 to 31, wherein: The liquid test sample comprises a mouthwash fluid.

33. A sampling device for concentrating a liquid test sample, the sampling device comprising a filter assembly, the filter assembly comprising: a tubular container shaped to define an inner wall and a proximal container opening for receiving the liquid test sample; a plunger (i) comprising a plunger head and a plunger rod, the plunger rod (a) having a distal end portion coupled to the plunger head and (b) shaped to define a waste fluid receiving portion within the plunger rod, and (ii) insertable into the tubular container via the proximal container opening such that a lateral surface of the plunger head forms a movable fluid tight seal with the inner wall; Filters; as well as Mechanical energy storage elements, wherein the plunger head includes a filter support portion shaped to define (a) a support surface on which the filter is removably disposed, and (b) a plurality of filtrate passage openings extending through the filter support portion into the waste liquid receiving portion, and wherein the filter assembly is configured such that when the liquid test sample is contained in the tubular container and the filter is disposed on the support surface, movement of the plunger head within the tubular container: pushing at least a portion of the liquid test sample through the filter and the filtrate passage opening and into the waste receiving portion, and Mechanical energy is stored in the mechanical energy storage element.

34. The sampling device according to claim 33, in, The sampling device also includes a container housing, wherein the tubular container is at least partially disposed within the container shell so that the tubular container can move relative to the container shell, and Wherein, the mechanical energy storage element is arranged inside the container shell and outside the tubular container and is in direct or indirect contact with the outer surface of the tubular container, so that the movement of the plunger head in the tubular container causes the tubular container to move relative to the container shell, thereby storing mechanical energy in the mechanical energy storage element.

35. The sampling device according to claim 33, wherein: The filter assembly is configured to push a greater portion of the liquid test sample through the filter when at least a portion of the mechanical energy stored in the mechanical energy storage element is released.

36. The sampling device according to claim 35, wherein The filter assembly is configured such that release of at least a portion of the mechanical energy causes the tubular container to move proximally relative to the plunger head, thereby pushing a greater portion of the liquid test sample through the filter.

37. The sampling device according to claim 36, in, The outer wall of the container shell is shaped to define an optical window, wherein the filter assembly further comprises a visual indicator, and Wherein, the filter assembly is configured such that the visual indicator: The tubular container is not visible through the optical window when the tubular container is located within the filter assembly at a first plurality of distal axial positions at which the visual indicator is not axially aligned with the optical window, and The tubular container is visible through the optical window when the tubular container is located in a second proximal axial position within the filter assembly, where the visual indicator is axially aligned with the optical window.

38. A sampling device according to any one of claims 33 to 37, wherein The mechanical energy storage element includes a resilient element configured to store mechanical energy.

39. The sampling device according to claim 38, wherein The elastic element includes a spring.

40. The sampling device according to claim 39, wherein The spring is partially preloaded with mechanical energy in a pre-insertion state of the sampling device in which the plunger head is not within the tubular container.

41. The sampling device according to claim 39, in, The sampling device also includes a container housing, wherein the tubular container is at least partially disposed within the container shell so that the tubular container can move relative to the container shell, wherein the mechanical energy storage element is disposed within the container shell, outside the tubular container, and in direct or indirect contact with an outer surface of the tubular container defined by the distal end of the tubular container, so that movement of the plunger head within the tubular container causes the tubular container to move relative to the container shell, thereby storing mechanical energy in the mechanical energy storage element, and Wherein, the spring is arranged between the outer surface of the tubular container and the inner surface of the container shell facing the proximal end.

42. The sampling device according to claim 39, wherein: The spring is arranged to surround at least a longitudinal portion of the tubular container.

43. The sampling device according to claim 39, wherein: The spring is disposed along at least a longitudinal portion of the tubular container.

44. The sampling device according to claim 43, wherein The mechanical energy storage element includes a plurality of springs disposed along at least a longitudinal portion of the tubular container.

45. A sampling device according to any one of claims 33 to 37, wherein The mechanical energy storage element is disposed within the tubular container.

46. ​​The sampling device according to claim 45, wherein The mechanical energy storage element includes a flexible container containing a gas.

47. A method for concentrating a liquid test sample, the method comprising: placing the liquid test sample in a tubular container of a filter assembly of a sampling device; inserting a plunger head of a plunger of the filter assembly into the tubular container through the proximal container opening of the tubular container such that a lateral surface of the plunger head forms a movable fluid tight seal with an inner wall of the tubular container, wherein the plunger further comprises a plunger rod (a) having a distal end portion coupled to the plunger head and (b) shaped to define a waste receiving portion within the plunger rod; and The plunger tip is advanced distally within the tubular container to: driving at least a portion of the liquid test sample through a filter removably disposed on a support surface of a filter support in the tubular container, wherein the filter support is shaped to define a plurality of filtrate passage openings through the filter support into the waste receiving portion, and Mechanical energy is stored in a mechanical energy storage element of the filter assembly.

48. The method according to claim 47, in, The sampling device also includes a container housing, wherein the tubular container is at least partially disposed within the container shell so that the tubular container can move relative to the container shell, wherein the energy storage element is disposed inside the container shell, outside the tubular container and in direct or indirect contact with the outer surface of the tubular container, and Wherein, pushing the plunger head distally in the tubular container includes pushing the plunger head distally in the tubular container to move the tubular container relative to the container shell, thereby storing energy in the energy storage element.

49. The method of claim 47, wherein: The filter assembly is configured to push a greater portion of the liquid test sample through the filter when at least a portion of the mechanical energy stored in the mechanical energy storage element is released.

50. The method of claim 49, wherein: The filter assembly is configured such that release of at least a portion of the mechanical energy causes the tubular container to move proximally relative to the plunger head, thereby pushing a greater portion of the liquid test sample through the filter.

51. The method according to claim 50, in, The outer wall of the container shell is shaped to define an optical window, wherein the filter assembly further comprises a visual indicator, and Wherein, the filter assembly is configured such that the visual indicator: The tubular container is not visible through the optical window when the tubular container is in a first plurality of distal axial positions within the filter assembly at which the visual indicator is not axially aligned with the optical window, and The tubular container is visible through the optical window when the tubular container is in a second proximal axial position within the filter assembly, where the visual indicator is axially aligned with the optical window.

52. The method of any one of claims 47 to 51, wherein: The mechanical energy storage element includes a resilient element configured to store mechanical energy.

53. The method of claim 52, wherein: The elastic element includes a spring.

54. The method of claim 53, wherein: The spring is partially preloaded with energy in a pre-insertion state of the sampling device in which the plunger head is not within the tubular container.

55. The method according to claim 53, in, The tubular container is at least partially disposed within the container housing such that the tubular container is movable relative to the container housing, wherein the mechanical energy storage element is disposed within the container shell, outside the tubular container, and in direct or indirect contact with an outer surface of the tubular container defined by the distal end of the tubular container, so that movement of the plunger head within the tubular container causes the tubular container to move relative to the container shell, thereby storing mechanical energy in the mechanical energy storage element, and Wherein, the spring is arranged between the outer surface of the tubular container and the inner surface of the container shell facing the proximal end.

56. The method of claim 53, wherein: The spring is arranged to surround at least a longitudinal portion of the tubular container.

57. The method of claim 53, wherein: The spring is disposed along at least a longitudinal portion of the tubular container.

58. The method of claim 57, wherein: The mechanical energy storage element includes a plurality of springs disposed along at least the longitudinal portion of the tubular container.

59. The method according to any one of claims 47 to 51, wherein: The energy storage element is disposed within the tubular container.

60. The method of claim 59, wherein: The energy storage element includes a flexible container containing a gas.

61. The method of any one of claims 47 to 51 further comprising, after the filter is removed from the tubular container, detecting the presence of biological particles captured by the filter.

62. The method of claim 61, wherein: Detecting the presence of biological particles captured by the filter includes using a lateral flow test strip to detect the presence of biological particles captured by the filter.

63. The method of claim 61, wherein: The biological particles are selected from the group consisting of viruses, bacteria, microorganisms, fungi, spores, mites, biological cells, biological antigens, proteins, protein antigens and carbohydrate antigens.

64. The method of any one of claims 47 to 51, wherein: The liquid test sample comprises a mouthwash fluid.

65. A container assembly comprising: (a) an extraction tube shaped to define: an inner wider proximal portion shaped to define a proximal opening of the extraction tube, and an inner narrower distal portion shaped to define a closed distal end of the extraction tube; (b) an elongated sealing insert removably coupled to the extraction tube and comprising: a shaft including a distal shaft portion that is narrower than the inner narrower distal portion of the extraction tube and that is removably disposed at least partially within the inner narrower distal portion of the extraction tube; one or more distal plugs positioned along or at a distal end of the distal shaft portion and removably disposed within the inner narrower distal portion of the extraction tube; and one or more proximal plugs positioned along the shaft proximal to the one or more distal plugs; (c) a first substance contained within the inner narrower distal portion of the extraction tube at a distal end of the one or more distal plugs such that the one or more distal plugs seal the first substance within the inner narrower distal portion of the extraction tube; and (d) a second substance, isolated from and different from the first substance, the second substance being contained within the extraction tube distal to the one or more proximal plugs and proximal to the one or more distal plugs, such that: The one or more proximal plugs seal the second substance within the extraction tube, and the one or more distal plugs sealingly isolate the second substance from the first substance, The container assembly is configured such that: the one or more distal plugs are proximally withdrawn from the inner narrower distal portion to the inner wider proximal portion by proximally withdrawing the shaft, so that the second substance is fluidically connected to the first substance.

66. The container assembly of claim 65, wherein: Both the first substance and the second substance include liquids.

67. The container assembly of claim 65, wherein: One of the first substance and the second substance includes a liquid, and the other of the first substance and the second substance includes a solid.

68. The container assembly of claim 65, wherein: The one or more proximal plugs include a proximal plug positioned along the distal shaft portion and removably disposed within the inner narrower distal portion of the extraction tube.

69. The container assembly of claim 65, wherein: The one or more proximal plugs include a proximal plug that removably plugs the proximal opening of the extraction tube.

70. The container assembly of claim 65, wherein: The one or more proximal plugs include: a first proximal plug located along the distal shaft portion and removably disposed within the inner narrower distal portion of the extraction tube, and A second proximal plug removably blocks the proximal opening of the extraction tube.

71. The container assembly according to claim 70, in, The container assembly further includes a third substance contained within the extraction tube proximal to the first proximal plug and distal to the second proximal plug such that: The second proximal plug seals the third substance within the extraction tube, and The first proximal plug sealingly isolates the third substance from the second substance, and Wherein, the container assembly is constructed as follows: The first proximal plug is proximally withdrawn from the inner narrower distal portion to the inner wider proximal portion by proximal withdrawal of the shaft, placing the third substance in fluid communication with the second substance, and The one or more distal plugs are proximally withdrawn from within the inner narrower distal portion to the inner wider proximal portion upon further proximal withdrawal of the shaft, placing the second substance and the third substance in fluid communication with the first substance.

72. A kit comprising a container assembly according to any one of claims 65 to 71, the kit further comprising a filter assembly, the filter assembly comprising: Filters; bottle; as well as A filter shaft, the filter shaft comprising: a proximal portion slidably disposed through a shaft passage hole extending through an end of the vial opposite the vial opening; and a distal portion coupled to the filter, wherein the kit is configured such that the bottle can be at least partially inserted into the extraction tube and can be advanced distally within the extraction tube until the filter is positioned adjacent the closed distal end of the extraction tube, and wherein the extraction tube is shaped to prevent the bottle from reaching the closed distal end of the extraction tube, so that the bottle slides upward along a portion of the filter extraction axis when the filter is positioned near the closed distal end, thereby pushing the filter out of the bottle opening and exposing the filter to the first substance and the second substance in the inner narrower distal portion of the extraction tube.

73. A method comprising: orienting the container assembly so that the proximal opening of the extraction tube of the container assembly is located above the closed distal end of the extraction tube relative to the ground, Wherein, the extraction tube is shaped as defined by: an inner wider proximal portion shaped to define a proximal opening of the extraction tube, and an inner narrower distal portion shaped to define a closed distal end of the extraction tube; Wherein, the container assembly further comprises an elongated sealing insert, the elongated sealing insert being removably coupled to the extraction tube, and the elongated sealing insert comprising: a shaft including a distal shaft portion that is narrower than the inner narrower distal portion of the extraction tube and that is removably disposed at least partially within the inner narrower distal portion of the extraction tube; one or more distal plugs located along or at a distal end of the distal shaft portion, and removably disposed within the inner narrower distal portion of the extraction tube; and one or more proximal plugs, the one or more proximal plugs being positioned along the shaft proximal to the one or more distal plugs; wherein the container assembly further comprises: a first substance contained within the inner narrower distal portion of the extraction tube at a distal end of the one or more distal plugs such that the one or more distal plugs seal the first substance within the inner narrower distal portion of the extraction tube; and a second substance, isolated from and distinct from the first substance, contained within the extraction tube distal to the one or more proximal plugs and proximal to the one or more distal plugs, such that (a) the one or more proximal plugs seal the second substance within the extraction tube, and (b) the one or more distal plugs sealingly isolate the second substance from the first substance; and The one or more distal plugs are proximally withdrawn from within the inner narrower distal portion to the inner wider proximal portion by withdrawing the axial proximal end, thereby placing the second substance in fluid communication with the first substance.

74. The method of claim 73, wherein: Both the first substance and the second substance include liquids.

75. The method of claim 73, wherein: One of the first substance and the second substance includes a liquid, and the other of the first substance and the second substance includes a solid.

76. The method of claim 73, wherein: The one or more proximal plugs include a proximal plug positioned along the distal shaft portion and removably disposed within the inner narrower distal portion of the extraction tube.

77. The method of claim 73, wherein: The one or more proximal plugs include a proximal plug that removably plugs the proximal opening of the extraction tube.

78. The method of claim 73, wherein: The one or more proximal plugs include: a first proximal plug located along the distal shaft portion and removably disposed within the inner narrower distal portion of the extraction tube, and A second proximal plug removably blocks the proximal opening of the extraction tube.

79. The method according to claim 78, in, The container assembly further includes a third substance contained within the extraction tube proximal to the first proximal plug and distal to the second proximal plug such that: The second proximal plug seals the third substance within the extraction tube, and The first proximal plug sealingly isolates the third substance from the second substance, and The method further comprises, before withdrawing the one or more distal plugs proximally from the inner narrower distal portion to the inner wider proximal portion: withdrawing the first proximal plug proximally from within the inner narrower distal portion to the inner wider proximal portion by withdrawing the axial proximal end, thereby placing the third substance in fluid communication with the second substance, and wherein proximally withdrawing the one or more distal plugs comprises proximally withdrawing the one or more distal plugs from the inner narrower distal portion to the inner wider proximal portion by further proximally withdrawing the shaft, thereby placing the second substance and the third substance in fluid communication with the first substance.

80. The method of any one of claims 73 to 79, further comprising, after proximally withdrawing the one or more distal plugs from within the inner narrower distal portion to the inner wider proximal portion: inserting a bottle of a filter assembly at least partially into the extraction tube and advancing the bottle distally within the extraction tube until the filter of the filter assembly is positioned adjacent the closed distal end of the extraction tube, wherein The filter assembly also includes a filter shaft including (a) a proximal portion slidably disposed through a shaft passage hole extending through an end of the bottle opposite the bottle opening; and (b) a distal portion coupled to the filter, wherein the extraction tube is shaped to prevent the bottle from reaching the closed distal end of the extraction tube, so that the bottle slides upward along a portion of the filter extraction axis when the filter is positioned near the closed distal end, thereby pushing the filter out of the bottle opening and exposing the filter to the first substance and the second substance in the inner narrower distal portion of the extraction tube.

Images