Fluid collection unit and related devices and methods

Abstract

Described herein is a fluid collection unit comprising: a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit.

Description

[0001] FLUID COLLECTION UNIT AND RELATED DEVICES AND METHODS

[0002] Field

[0003] The present invention relates to collection of fluid samples. More specifically, the present invention is, in aspects, concerned with fluid collection units and related methods and devices comprising same.

[0004]

[0005] Lateral flow test devices are known and conventionally require a bodily fluid sample, such as blood or saliva. In the case of saliva, a subject is required to expectorate saliva into a small tube, which is both difficult and uncomfortable. In addition, this typically results in a sample containing many bubbles. Other conventional devices involve a sponge or pad, which is used to collect saliva in the mouth. These require a large volume of saliva and still generally require that the saliva be squeezed from the sponge or pad prior to use.

[0006] U.S. Patent No. 7883899 describes analytical methods, platforms, and devices for the rapid and efficient immunochromatic determination of one or more components in fluid samples. The devices are especially useful for identifying analytes in small volumes of whole blood samples utilizing one membrane principally for separating particles such as red blood cells from plasma and a second membrane as the site for reactions to identify the analytes.

[0007] PCT Publication No. WO 2018 / 163109 describes a fluid collection unit comprising: a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit.

[0008] There is a need for alternative compositions to overcome or mitigate at least some of the deficiencies of the prior art, or to provide a useful alternative.

[0009] In accordance with an aspect, there is provided a lateral flow device comprising a modified window for increasing visibility of a test result.

[0010] In an aspect, the modified window is magnified.

[0011] In an aspect, the modified window is colored.

[0012] In an aspect, the modified window is illuminated.

[0013] In an aspect, the modified window is integral with the device.

[0014] In an aspect, the modified window is removable from the device.

[0015] In an aspect, the modified window is coupled to the top of the device and fits into place over an existing window in the device.In an aspect, the lateral flow device comprises: a fluid collection unit comprising a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit.

[0016] In an aspect, the fluid flow path comprises a vent, optionally in the bottom wall of the fluid flow path.

[0017] In an aspect, the vent is at a proximal end of the fluid flow path.

[0018] In an aspect, the receptacle comprises an indentation.

[0019] In an aspect, the indentation is substantially cylindrical.

[0020] In an aspect, the indentation comprises an open sidewall in fluid communication with the fluid flow path.

[0021] In an aspect, the indentation comprises an absorbent member, such as a membrane, pad, or sponge.

[0022] In an aspect, the receptacle comprises a channel in fluid communication with the fluid flow path.

[0023] In an aspect, the receptacle is formed within a slanted protrusion.

[0024] In an aspect, the receptacle is surrounded by flanges to direct the fluid sample to the receptacle.

[0025] In an aspect, the device further comprises a region of concavity for directing fluid towards the receptacle, wherein the region of concavity is substantially parallel with and above the fluid flow path, wherein the region of concavity comprises an open bottom wall in fluid communication with the fluid flow path.

[0026] In an aspect, the open bottom wall is sized to allow sufficient surface pressure such that, in use, fluid will not enter the fluid flow path through the open bottom wall until a front of fluid reaches the open bottom wall while passing through the fluid flow path.

[0027] In an aspect, the open bottom wall is sized so that large air bubbles or solid materials can be blocked from entering the fluid flow path.

[0028] In an aspect, the fluid flow path comprises a proximal constriction.

[0029] In an aspect, the fluid flow path holds from about 10 pl to about 200 pl of fluid.

[0030] In an aspect, the device does not comprise an absorbent pad or sponge for collecting the fluid.

[0031] In an aspect, the device does not require the addition of a buffer or diluent to effect flow of the fluid through the fluid flow path.In an aspect, the device is for testing a water sample for contamination, the device comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

[0032] In an aspect, the water sample is waste water.

[0033] In an aspect, the waste water comprises urine, fecal matter, vomit, or combinations thereof.

[0034] In an aspect, the waste water is in a toilet bowl.

[0035] In an aspect, the waste water is in a water treatment plant.

[0036] In an aspect, the water sample is from a body of water, such as a lake, pond, river, or ocean.

[0037] In an aspect, the water sample is drinking water.

[0038] In an aspect, the drinking water is in a tap, water fountain, or water cooler.

[0039] In an aspect, the large particles comprise protozoa, algae, plant matter, non-living debris, or combinations thereof.

[0040] In an aspect, the exclusion membrane comprises filter paper.

[0041] In an aspect, the sample comprises serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, crevicular fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, semen, vaginal fluid, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

[0042] In an aspect, the device is for detecting one or more analytes associated with a pathogen, disease, condition, or drug.

[0043] In an aspect, the device is for detecting a bacterial, viral, yeast, fungal, or parasite infection.

[0044] In an aspect, the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial or plant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.

[0045] In an aspect, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

[0046] In an aspect, the hydrolytic enzyme cleaves peptidoglycan.In an aspect, the hydrolytic enzyme comprises a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase.

[0047] In an aspect, the hydrolytic enzyme cleaves viral capsid proteins.

[0048] In an aspect, the hydrolytic enzyme comprises trypsin.

[0049] In an aspect, the hydrolytic enzyme cleaves the analyte to produce more free epitopes for detection, thereby increasing sensitivity of the test.

[0050] In an aspect, the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding.

[0051] In an aspect, the hydrolytic enzyme comprises Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase?, Caspase8, Caspase9, Caspasel 0, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.

[0052] In an aspect, the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the device.

[0053] In an aspect, the device comprises a reagent that indicates when a sufficient amount of sample has been applied to the device.

[0054] In an aspect, the reagent is stationary is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test.

[0055] In an aspect, the reagent is free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test.

[0056] In an aspect, the reagent is a water-reactive indicator.

[0057] In an aspect, the device comprises a fluid collection unit for detecting an analyte in crevicular fluid, the fluid collection unit comprising a head for rubbing on and / or between the teeth and collecting the crevicular fluid and a fluid flow path in fluid communication with the head, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit.

[0058] In an aspect, the head comprises an interdental brush.

[0059] In an aspect, the head comprises a floss pick.

[0060] In an aspect, the head is bristled.

[0061] In an aspect, the bristles are plastic, rubber, or silicone.

[0062] In an aspect, the head comprises an absorbent pad.

[0063] In an aspect, the device is for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

[0064] In an aspect, the device detects CrP and Serum Amyloid A in separate lines or in a single line.In an aspect, the device only detects CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.

[0065] In an aspect, the device comprises one or more flow channels for detecting one or more analytes or for detecting one or more analytes at different sensitivities or for detecting one or more analytes using different detection methods.

[0066] In an aspect, the device comprises multiple flow channels and at least one flow channel starts at a different point on a membrane.

[0067] In an aspect, the flow channel width is adjusted depending on the surface tension of the fluid sample.

[0068] In accordance with an aspect, there is provided a lateral flow device for testing a water sample for contamination, the device comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

[0069] In an aspect, the water sample is waste water.

[0070] In an aspect, the waste water comprises urine, fecal matter, vomit, or combinations thereof.

[0071] In an aspect, the waste water is in a toilet bowl.

[0072] In an aspect, the waste water is in a water treatment plant.

[0073] In an aspect, the water sample is from a body of water, such as a lake, pond, river, or ocean.

[0074] In an aspect, the water sample is drinking water.

[0075] In an aspect, the drinking water is in a tap, water fountain, or water cooler.

[0076] In an aspect, the large particles comprise protozoa, algae, plant matter, non-living debris, or combinations thereof.

[0077] In an aspect, the exclusion membrane comprises filter paper.

[0078] In an aspect, the device detects one or more analytes associated with a pathogen, disease, condition, ordrug.

[0079] In an aspect, the device is for detecting a bacterial, viral, yeast, fungal, or parasite infection.

[0080] In an aspect, the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial orplant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.

[0081] In an aspect, the device comprises: a fluid collection unit comprising a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit, wherein the fluid flow path is in communication with the exclusion membrane and the analytical membrane.

[0082] In an aspect, the fluid flow path comprises a vent, optionally in the bottom wall of the fluid flow path.

[0083] In an aspect, the vent is at a proximal end of the fluid flow path.

[0084] In an aspect, the receptacle comprises an indentation.

[0085] In an aspect, the indentation is substantially cylindrical.

[0086] In an aspect, the indentation comprises an open sidewall in fluid communication with the fluid flow path.

[0087] In an aspect, the indentation comprises an absorbent member, such as a membrane, pad, or sponge.

[0088] In an aspect, the receptacle comprises a channel in fluid communication with the fluid flow path.

[0089] In an aspect, the receptacle is formed within a slanted protrusion.

[0090] In an aspect, the receptacle is surrounded by flanges to direct the fluid sample to the receptacle.

[0091] In an aspect, the device further comprises a region of concavity for directing fluid towards the receptacle, wherein the region of concavity is substantially parallel with and above the fluid flow path, wherein the region of concavity comprises an open bottom wall in fluid communication with the fluid flow path.

[0092] In an aspect, the open bottom wall is sized to allow sufficient surface pressure such that, in use, fluid will not enter the fluid flow path through the open bottom wall until a front of fluid reaches the open bottom wall while passing through the fluid flow path.

[0093] In an aspect, the open bottom wall is sized so that large air bubbles or solid materials can be blocked from entering the fluid flow path.

[0094] In an aspect, the fluid flow path comprises a proximal constriction.

[0095] In an aspect, the fluid flow path holds from about 10 pl to about 200 pl of fluid.

[0096] In an aspect, the device does not comprise an absorbent pad or sponge for collecting the fluid.In an aspect, the device does not require the addition of a buffer or diluent to effect flow of the fluid through the fluid flow path.

[0097] In an aspect, the device comprises a window for viewing a test result.

[0098] In an aspect, the window is modified for increasing visibility of the test result.

[0099] In an aspect, the modified window is magnified.

[0100] In an aspect, the modified window is colored.

[0101] In an aspect, the modified window is illuminated.

[0102] In an aspect, the modified window is integral with the device.

[0103] In an aspect, the modified window is removable from the device.

[0104] In an aspect, the modified window is coupled to the top of the device and fits into place over an existing window in the device.

[0105] In an aspect, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

[0106] In an aspect, the hydrolytic enzyme cleaves peptidoglycan.

[0107] In an aspect, the hydrolytic enzyme comprises a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase.

[0108] In an aspect, the hydrolytic enzyme cleaves viral capsid proteins.

[0109] In an aspect, the hydrolytic enzyme comprises trypsin.

[0110] In an aspect, the hydrolytic enzyme cleaves the analyte to produce more free epitopes for detection, thereby increasing sensitivity of the device.

[0111] In an aspect, the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding.

[0112] In an aspect, the hydrolytic enzyme comprises Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase7, Caspase8, Caspase9, Caspasel 0, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.

[0113] In an aspect, the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the device.

[0114] In an aspect, the device comprises a reagent that indicates when a sufficient amount of sample has been applied to the device.

[0115] In an aspect, the reagent is stationary is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test.

[0116] In an aspect, the reagent is free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test.

[0117] In an aspect, the reagent is a water-reactive indicator.In an aspect, the device is for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

[0118] In an aspect, the device detects CrP and Serum Amyloid A in separate lines or in a single line.

[0119] In an aspect, the device only detects CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.

[0120] In an aspect, the device comprises one or more flow channels for detecting one or more analytes or for detecting one or more analytes at different sensitivities or for detecting one or more analytes using different detection methods.

[0121] In an aspect, the device comprises multiple flow channels and at least one flow channel starts at a different point on a membrane.

[0122] In an aspect, the flow channel width is adjusted depending on the surface tension of the fluid sample.

[0123] In accordance with an aspect, there is provided a lateral flow device for detecting an analyte in a fluid sample, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

[0124] In an aspect, the hydrolytic enzyme cleaves peptidoglycan.

[0125] In an aspect, the hydrolytic enzyme comprises a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase.

[0126] In an aspect, the hydrolytic enzyme cleaves viral capsid proteins.

[0127] In an aspect, the hydrolytic enzyme comprises trypsin.

[0128] In an aspect, the hydrolytic enzyme cleaves the analyte to produce more free epitopes for detection, thereby increasing sensitivity of the device.

[0129] In an aspect, the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding.

[0130] In an aspect, the hydrolytic enzyme comprises Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase?, Caspase8, Caspase9, Caspasel 0, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.

[0131] In an aspect, the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the device.

[0132] In an aspect, the device further comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

[0133] In an aspect, the fluid sample is waste water.

[0134] In an aspect, the waste water comprises urine, fecal matter, vomit, or combinations thereof.In an aspect, the waste water is in a toilet bowl.

[0135] In an aspect, the waste water is in a water treatment plant.

[0136] In an aspect, the fluid sample is from a body of water, such as a lake, pond, river, or ocean.

[0137] In an aspect, the fluid sample is drinking water.

[0138] In an aspect, the drinking water is in a tap, water fountain, or water cooler.

[0139] In an aspect, the large particles comprise protozoa, algae, plant matter, non-living debris, or combinations thereof.

[0140] In an aspect, the exclusion membrane comprises filter paper.

[0141] In an aspect, the sample comprises serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, crevicular fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, semen, vaginal fluid, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

[0142] In an aspect, the device detects one or more analytes associated with a pathogen, disease, condition, ordrug.

[0143] In an aspect, the device is for detecting a bacterial, viral, yeast, fungal, or parasite infection.

[0144] In an aspect, the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial or plant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.

[0145] In an aspect, the device comprises: a fluid collection unit comprising a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit.

[0146] In an aspect, the fluid flow path comprises a vent, optionally in the bottom wall of the fluid flow path.

[0147] In an aspect, the vent is at a proximal end of the fluid flow path.

[0148] In an aspect, the receptacle comprises an indentation.

[0149] In an aspect, the indentation is substantially cylindrical.In an aspect, the indentation comprises an open sidewall in fluid communication with the fluid flow path.

[0150] In an aspect, the indentation comprises an absorbent member, such as a membrane, pad, or sponge.

[0151] In an aspect, the receptacle comprises a channel in fluid communication with the fluid flow path.

[0152] In an aspect, the receptacle is formed within a slanted protrusion.

[0153] In an aspect, the receptacle is surrounded by flanges to direct the fluid sample to the receptacle.

[0154] In an aspect, the device further comprises a region of concavity for directing fluid towards the receptacle, wherein the region of concavity is substantially parallel with and above the fluid flow path, wherein the region of concavity comprises an open bottom wall in fluid communication with the fluid flow path.

[0155] In an aspect, the open bottom wall is sized to allow sufficient surface pressure such that, in use, fluid will not enter the fluid flow path through the open bottom wall until a front of fluid reaches the open bottom wall while passing through the fluid flow path.

[0156] In an aspect, the open bottom wall is sized so that large air bubbles or solid materials can be blocked from entering the fluid flow path.

[0157] In an aspect, the fluid flow path comprises a proximal constriction.

[0158] In an aspect, the fluid flow path holds from about 10 pl to about 200 pl of fluid.

[0159] In an aspect, the device does not comprise an absorbent pad or sponge for collecting the fluid.

[0160] In an aspect, the device does not require the addition of a buffer or diluent to effect flow of the fluid through the fluid flow path.

[0161] In an aspect, the device comprises a window for viewing a test result.

[0162] In an aspect, the window is modified for increasing visibility of a test result.

[0163] In an aspect, the modified window is magnified.

[0164] In an aspect, the modified window is colored.

[0165] In an aspect, the modified window is illuminated.

[0166] In an aspect, the modified window is integral with the device.

[0167] In an aspect, the modified window is removable from the device.

[0168] In an aspect, the modified window is coupled to the top of the device and fits into place over an existing window in the device.

[0169] In an aspect, the device comprises a reagent that indicates when a sufficient amount of sample has been applied to the device.In an aspect, the reagent is stationary is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test.

[0170] In an aspect, the reagent is free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test.

[0171] In an aspect, the reagent is a water-reactive indicator.

[0172] In an aspect, the device comprises a fluid collection unit for detecting an analyte in crevicular fluid, the fluid collection unit comprising a head for rubbing on and / or between the teeth and collecting the crevicular fluid and a fluid flow path in fluid communication with the head, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit.

[0173] In an aspect, the head comprises an interdental brush.

[0174] In an aspect, the head comprises a floss pick.

[0175] In an aspect, the head is bristled.

[0176] In an aspect, the bristles are plastic, rubber, or silicone.

[0177] In an aspect, the head comprises an absorbent pad.

[0178] In an aspect, the device is for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

[0179] In an aspect, the device detects CrP and Serum Amyloid A in separate lines or in a single line.

[0180] In an aspect, the device only detects CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.

[0181] In an aspect, the device comprises one or more flow channels for detecting one or more analytes or for detecting one or more analytes at different sensitivities or for detecting one or more analytes using different detection methods.

[0182] In an aspect, the device comprises multiple flow channels and at least one flow channel starts at a different point on a membrane.

[0183] In an aspect, the flow channel width is adjusted depending on the surface tension of the fluid sample.

[0184] In accordance with an aspect, there is provided a lateral flow device comprising a reagent that indicates when a sufficient amount of sample has been applied to the device.

[0185] In an aspect, the reagent is stationary is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test.In an aspect, the reagent is free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test.

[0186] In an aspect, the reagent is a water-reactive indicator.

[0187] In an aspect, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

[0188] In an aspect, the hydrolytic enzyme cleaves peptidoglycan.

[0189] In an aspect, the hydrolytic enzyme comprises a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase.

[0190] In an aspect, the hydrolytic enzyme cleaves viral capsid proteins.

[0191] In an aspect, the hydrolytic enzyme comprises trypsin.

[0192] In an aspect, the hydrolytic enzyme cleaves the analyte to produce more free epitopes for detection, thereby increasing sensitivity of the device.

[0193] In an aspect, the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding.

[0194] In an aspect, the hydrolytic enzyme comprises Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase?, Caspase8, Caspase9, Caspasel 0, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.

[0195] In an aspect, the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the device.

[0196] In an aspect, the device further comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

[0197] In an aspect, the fluid sample is waste water.

[0198] In an aspect, the waste water comprises urine, fecal matter, vomit, or combinations thereof.

[0199] In an aspect, the waste water is in a toilet bowl.

[0200] In an aspect, the waste water is in a water treatment plant.

[0201] In an aspect, the fluid sample is from a body of water, such as a lake, pond, river, or ocean.

[0202] In an aspect, the fluid sample is drinking water.

[0203] In an aspect, the drinking water is in a tap, water fountain, or water cooler.

[0204] In an aspect, the large particles comprise protozoa, algae, plant matter, non-living debris, or combinations thereof.

[0205] In an aspect, the exclusion membrane comprises filter paper.In an aspect, the sample comprises serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, crevicular fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, semen, vaginal fluid, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

[0206] In an aspect, the device detects one or more analytes associated with a pathogen, disease, condition, ordrug.

[0207] In an aspect, the device is for detecting a bacterial, viral, yeast, fungal, or parasite infection.

[0208] In an aspect, the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial or plant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.

[0209] In an aspect, the device comprises: a fluid collection unit comprising a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit.

[0210] In an aspect, the fluid flow path comprises a vent, optionally in the bottom wall of the fluid flow path.

[0211] In an aspect, the vent is at a proximal end of the fluid flow path.

[0212] In an aspect, the receptacle comprises an indentation.

[0213] In an aspect, the indentation is substantially cylindrical.

[0214] In an aspect, the indentation comprises an open sidewall in fluid communication with the fluid flow path.

[0215] In an aspect, the indentation comprises an absorbent member, such as a membrane, pad, or sponge.

[0216] In an aspect, the receptacle comprises a channel in fluid communication with the fluid flow path.

[0217] In an aspect, the receptacle is formed within a slanted protrusion.

[0218] In an aspect, the receptacle is surrounded by flanges to direct the fluid sample to the receptacle.In an aspect, the device further comprises a region of concavity for directing fluid towards the receptacle, wherein the region of concavity is substantially parallel with and above the fluid flow path, wherein the region of concavity comprises an open bottom wall in fluid communication with the fluid flow path.

[0219] In an aspect, the open bottom wall is sized to allow sufficient surface pressure such that, in use, fluid will not enter the fluid flow path through the open bottom wall until a front of fluid reaches the open bottom wall while passing through the fluid flow path.

[0220] In an aspect, the open bottom wall is sized so that large air bubbles or solid materials can be blocked from entering the fluid flow path.

[0221] In an aspect, the fluid flow path comprises a proximal constriction.

[0222] In an aspect, the fluid flow path holds from about 10 pl to about 200 pl of fluid.

[0223] In an aspect, the device does not comprise an absorbent pad or sponge for collecting the fluid.

[0224] In an aspect, the device does not require the addition of a buffer or diluent to effect flow of the fluid through the fluid flow path.

[0225] In an aspect, the device comprises a window for viewing a test result.

[0226] In an aspect, the window is modified for increasing visibility of the test result.

[0227] In an aspect, the modified window is magnified.

[0228] In an aspect, the modified window is colored.

[0229] In an aspect, the modified window is illuminated.

[0230] In an aspect, the modified window is integral with the device.

[0231] In an aspect, the modified window is removable from the device.

[0232] In an aspect, the modified window is coupled to the top of the device and fits into place over an existing window in the device.

[0233] In an aspect, the device comprises a fluid collection unit for detecting an analyte in crevicular fluid, the fluid collection unit comprising a head for rubbing on and / or between the teeth and collecting the crevicular fluid and a fluid flow path in fluid communication with the head, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit.

[0234] In an aspect, the head comprises an interdental brush.

[0235] In an aspect, the head comprises a floss pick.

[0236] In an aspect, the head is bristled.

[0237] In an aspect, the bristles are plastic, rubber, or silicone.

[0238] In an aspect, the head comprises an absorbent pad.In an aspect, the device is for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

[0239] In an aspect, the device detects CrP and Serum Amyloid A in separate lines or in a single line.

[0240] In an aspect, the device only detects CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.

[0241] In an aspect, the device comprises one or more flow channels for detecting one or more analytes or for detecting one or more analytes at different sensitivities or for detecting one or more analytes using different detection methods.

[0242] In an aspect, the device comprises multiple flow channels and at least one flow channel starts at a different point on a membrane.

[0243] In an aspect, the flow channel width is adjusted depending on the surface tension of the fluid sample.

[0244] In accordance with an aspect, there is provided a fluid collection unit for detecting an analyte in crevicular fluid, the unit comprising a head for rubbing on and / or between the teeth in communication with a receptacle for passively collecting the crevicular fluid; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit.

[0245] In an aspect, the head comprises an interdental brush.

[0246] In an aspect, the head comprises a floss pick.

[0247] In an aspect, the head is bristled.

[0248] In an aspect, the bristles are plastic, rubber, or silicone.

[0249] In an aspect, the head comprises an absorbent pad.

[0250] In an aspect, the fluid flow path comprises a vent, optionally in the bottom wall of the fluid flow path.

[0251] In an aspect, the vent is at a proximal end of the fluid flow path.

[0252] In an aspect, the receptacle comprises an indentation.

[0253] In an aspect, the indentation is substantially cylindrical.

[0254] In an aspect, the indentation comprises an open sidewall in fluid communication with the fluid flow path.

[0255] In an aspect, the indentation comprises an absorbent member, such as a membrane, pad, or sponge.

[0256] In an aspect, the receptacle comprises a channel in fluid communication with the fluid flow path.

[0257] In an aspect, the receptacle is formed within a slanted protrusion.In an aspect, the receptacle is surrounded by flanges to direct the fluid sample to the receptacle.

[0258] In an aspect, the device further comprises a region of concavity for directing fluid towards the receptacle, wherein the region of concavity is substantially parallel with and above the fluid flow path, wherein the region of concavity comprises an open bottom wall in fluid communication with the fluid flow path.

[0259] In an aspect, the open bottom wall is sized to allow sufficient surface pressure such that, in use, fluid will not enter the fluid flow path through the open bottom wall until a front of fluid reaches the open bottom wall while passing through the fluid flow path.

[0260] In an aspect, the open bottom wall is sized so that large air bubbles or solid materials can be blocked from entering the fluid flow path.

[0261] In an aspect, the fluid flow path comprises a proximal constriction.

[0262] In an aspect, the fluid flow path holds from about 10 pl to about 200 pl of fluid.

[0263] In an aspect, the unit does not comprise an absorbent pad or sponge for collecting the fluid.

[0264] In an aspect, the unit does not require the addition of a buffer or diluent to effect flow of the fluid through the fluid flow path.

[0265] In accordance with an aspect, there is provided a lateral flow device comprising the fluid collection unit described herein, wherein the device comprises a window for viewing a test result.

[0266] In an aspect, the window is modified for increasing visibility of the test result.

[0267] In an aspect, the modified window is magnified.

[0268] In an aspect, the modified window is colored.

[0269] In an aspect, the modified window is illuminated.

[0270] In an aspect, the modified window is integral with the device.

[0271] In an aspect, the modified window is removable from the device.

[0272] In an aspect, the modified window is coupled to the top of the device and fits into place over an existing window in the device.

[0273] In an aspect, the device comprises a reagent that indicates when a sufficient amount of sample has been applied to the device.

[0274] In an aspect, the reagent is stationary is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test.

[0275] In an aspect, the reagent is free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test.In an aspect, the reagent is a water-reactive indicator.

[0276] In an aspect, the device comprises a hydrolytic enzyme for improving analyte detection. In an aspect, the hydrolytic enzyme cleaves peptidoglycan.

[0277] In an aspect, the hydrolytic enzyme comprises a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase.

[0278] In an aspect, the hydrolytic enzyme cleaves viral capsid proteins.

[0279] In an aspect, the hydrolytic enzyme comprises trypsin.

[0280] In an aspect, the hydrolytic enzyme cleaves the analyte to produce more free epitopes for detection, thereby increasing sensitivity of the test.

[0281] In an aspect, the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding.

[0282] In an aspect, the hydrolytic enzyme comprises Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase?, Caspase8, Caspase9, Caspasel 0, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.

[0283] In an aspect, the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the test.

[0284] In an aspect, the unit or device detects one or more analytes associated with a pathogen, disease, condition, or drug.

[0285] In an aspect, the device is for detecting a bacterial, viral, yeast, fungal, or parasite infection.

[0286] In an aspect, the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial or plant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.

[0287] In an aspect, the device is for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

[0288] In an aspect, the device is for detecting CrP and Serum Amyloid A in separate lines or in a single line.

[0289] In an aspect, the device is for detecting only CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.In an aspect, the device comprises one or more flow channels for detecting one or more analytes or for detecting one or more analytes at different sensitivities or for detecting one or more analytes using different detection methods.

[0290] In an aspect, the device comprises multiple flow channels and at least one flow channel starts at a different point on a membrane.

[0291] In an aspect, the flow channel width is adjusted depending on the surface tension of the fluid sample.

[0292] In accordance with an aspect, there is provided a lateral flow device for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

[0293] In an aspect, the device detects CrP and Serum Amyloid A in separate lines or in a single line.

[0294] In an aspect, the device only detects CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.

[0295] In an aspect, the device comprises a reagent that indicates when a sufficient amount of sample has been applied to the device.

[0296] In an aspect, the reagent is stationary is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test.

[0297] In an aspect, the reagent is free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test.

[0298] In an aspect, the reagent is a water-reactive indicator.

[0299] In an aspect, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

[0300] In an aspect, the hydrolytic enzyme cleaves peptidoglycan.

[0301] In an aspect, the hydrolytic enzyme comprises a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase.

[0302] In an aspect, the hydrolytic enzyme cleaves viral capsid proteins.

[0303] In an aspect, the hydrolytic enzyme comprises trypsin.

[0304] In an aspect, the hydrolytic enzyme cleaves the analyte to produce more free epitopes for detection, thereby increasing sensitivity of the test.

[0305] In an aspect, the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding.

[0306] In an aspect, the hydrolytic enzyme comprises Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase?, Caspase8, Caspase9, Caspasel 0, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.In an aspect, the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the device.

[0307] In an aspect, the device further comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

[0308] In an aspect, the fluid sample is waste water.

[0309] In an aspect, the waste water comprises urine, fecal matter, vomit, or combinations thereof.

[0310] In an aspect, the waste water is in a toilet bowl.

[0311] In an aspect, the waste water is in a water treatment plant.

[0312] In an aspect, the fluid sample is from a body of water, such as a lake, pond, river, or ocean.

[0313] In an aspect, the fluid sample is drinking water.

[0314] In an aspect, the drinking water is in a tap, water fountain, or water cooler.

[0315] In an aspect, the large particles comprise protozoa, algae, plant matter, non-living debris, or combinations thereof.

[0316] In an aspect, the exclusion membrane comprises filter paper.

[0317] In an aspect, the sample comprises serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, crevicular fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, semen, vaginal fluid, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

[0318] In an aspect, the device detects one or more analytes associated with a pathogen, disease, condition, ordrug.

[0319] In an aspect, the device is for detecting a bacterial, viral, yeast, fungal, or parasite infection.

[0320] In an aspect, the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial or plant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.

[0321] In an aspect, the device comprises: a fluid collection unit comprising a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with thereceptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit.

[0322] In an aspect, the fluid flow path comprises a vent, optionally in the bottom wall of the fluid flow path.

[0323] In an aspect, the vent is at a proximal end of the fluid flow path.

[0324] In an aspect, the receptacle comprises an indentation.

[0325] In an aspect, the indentation is substantially cylindrical.

[0326] In an aspect, the indentation comprises an open sidewall in fluid communication with the fluid flow path.

[0327] In an aspect, the indentation comprises an absorbent member, such as a membrane, pad, or sponge.

[0328] In an aspect, the receptacle comprises a channel in fluid communication with the fluid flow path.

[0329] In an aspect, the receptacle is formed within a slanted protrusion.

[0330] In an aspect, the receptacle is surrounded by flanges to direct the fluid sample to the receptacle.

[0331] In an aspect, the device further comprises a region of concavity for directing fluid towards the receptacle, wherein the region of concavity is substantially parallel with and above the fluid flow path, wherein the region of concavity comprises an open bottom wall in fluid communication with the fluid flow path.

[0332] In an aspect, the open bottom wall is sized to allow sufficient surface pressure such that, in use, fluid will not enter the fluid flow path through the open bottom wall until a front of fluid reaches the open bottom wall while passing through the fluid flow path.

[0333] In an aspect, the open bottom wall is sized so that large air bubbles or solid materials can be blocked from entering the fluid flow path.

[0334] In an aspect, the fluid flow path comprises a proximal constriction.

[0335] In an aspect, the fluid flow path holds from about 10 pl to about 200 pl of fluid.

[0336] In an aspect, the device does not comprise an absorbent pad or sponge for collecting the fluid.

[0337] In an aspect, the device does not require the addition of a buffer or diluent to effect flow of the fluid through the fluid flow path.

[0338] In an aspect, the device comprises a window for viewing a test result.

[0339] In an aspect, the window is modified for increasing visibility of the test result.

[0340] In an aspect, the modified window is magnified.

[0341] In an aspect, the modified window is colored.In an aspect, the modified window is illuminated.

[0342] In an aspect, the modified window is integral with the device.

[0343] In an aspect, the modified window is removable from the device.

[0344] In an aspect, the modified window is coupled to the top of the device and fits into place over an existing window in the device.

[0345] In an aspect, the device comprises a fluid collection unit for detecting an analyte in crevicular fluid, the fluid collection unit comprising a head for rubbing on and / or between the teeth and collecting the crevicular fluid and a fluid flow path in fluid communication with the head, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit.

[0346] In an aspect, the head comprises an interdental brush.

[0347] In an aspect, the head comprises a floss pick.

[0348] In an aspect, the head is bristled.

[0349] In an aspect, the bristles are plastic, rubber, or silicone.

[0350] In an aspect, the head comprises an absorbent pad.

[0351] In an aspect, the device comprises one or more flow channels for detecting one or more analytes or for detecting one or more analytes at different sensitivities or for detecting one or more analytes using different detection methods.

[0352] In an aspect, the device comprises multiple flow channels and at least one flow channel starts at a different point on a membrane.

[0353] In an aspect, the flow channel width is adjusted depending on the surface tension of the fluid sample.

[0354] In accordance with an aspect, there is provided a modified window for a lateral flow device, the modified window increasing visibility of a test result.

[0355] In an aspect, the modified window is magnified.

[0356] In an aspect, the modified window is colored.

[0357] In an aspect, the modified window is illuminated.

[0358] In an aspect, the modified window is integral with the device.

[0359] In an aspect, the modified window is removable from the device.

[0360] In an aspect, the modified window is coupled to the top of the device and fits into place over an existing window in the device.

[0361] In an aspect, the modified window is in combination with a lateral flow device.

[0362] In an aspect, the lateral flow device is the device described herein.

[0363] In an aspect, the device is transparent.

[0364] In an aspect, the device comprises a handle.In an aspect, the handle is an indented circle for supporting a thumb or finger.

[0365] In an aspect, the handle is detachable from the device.

[0366] In an aspect, the device comprises a lateral flow membrane.

[0367] In accordance with an aspect, there is provided a one-step method of collecting a sample, the method comprising inserting the lateral flow device or unit described herein in or near a sample and allowing the sample to be drawn into the fluid flow path.

[0368] In an aspect, the obtained sample is substantially bubble-free.

[0369] Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from said detailed description.

[0370] Description of the Figures

[0371] The present invention will be further understood from the following description with reference to the Figures, in which:

[0372] Figure 1 shows a perspective view of a first embodiment of a lateral flow device described herein.

[0373] Figure 2 shows a top plan view of the lateral flow device of Figure 1.

[0374] Figure 3 shows a bottom plan view of the lateral flow device of Figure 1.

[0375] Figure 4 shows a side view of the lateral flow device of Figure 1.

[0376] Figure 5 shows a front view of the lateral flow device of Figure 1.

[0377] Figure 6 shows a back view of the lateral flow device of Figure 1.

[0378] Figure 7 shows a top exploded perspective view of the lateral flow device of Figure 1 with addition of a lateral flow membrane and a device cover.

[0379] Figure 8 shows a bottom exploded perspective view of the lateral flow device of Figure 1 with addition of a lateral flow membrane and a device cover.

[0380] Figure 9 shows a cross-sectional view along line 9 — 9 of the lateral flow device of Figure 1.

[0381] Figure 10 shows a top plan view of a second embodiment of a lateral flow device described herein.

[0382] Figure 11 shows a bottom plan view of the lateral flow device of Figure 10.

[0383] Figure 12 shows a side view of the lateral flow device of Figure 10.

[0384] Figure 13 shows a front view of the lateral flow device of Figure 10.

[0385] Figure 14 shows a back view of the lateral flow device of Figure 10.Figure 15 shows a top and bottom exploded perspective view of the lateral flow device of Figure 10.

[0386] Figure 16 shows a top exploded perspective view of the lateral flow device of Figure 10 in the presence of a lateral flow membrane and a device cover.

[0387] Figure 17 shows a top exploded perspective view of a third embodiment of a lateral flow device described herein.

[0388] Figure 18 shows a cross-sectional view of the fluid collection unit along line 18 — 18 of the lateral flow device of Figure 17.

[0389] Figure 19 shows a top plan view of the lateral flow device of Figure 17 in the absence of a device cover.

[0390] Figure 20 shows a bottom plan view of the lateral flow device of Figure 17 in the absence of a device cover.

[0391] Figure 21 shows a side view of the lateral flow device of Figure 17 in the absence of a device cover.

[0392] Figure 22 shows a front view of the lateral flow device of Figure 17 in the absence of a device cover.

[0393] Figure 23 shows a back view of the lateral flow device of Figure 17.

[0394] Figure 24 shows a perspective view of a reader body portion of the lateral flow device of Figure 17.

[0395] Figure 25 shows a series of views of a modified window for use with a lateral flow device.

[0396] Detailed Description

[0397] Described herein, in aspects, are fluid collection units for obtaining a fluid sample. The fluid collection units may advantageously be included as part of a lateral flow device. While the fluid collection units described herein are particularly advantageous for collecting saliva samples, they may find use in collecting any type of fluid sample. In certain aspects, the fluid collection units passively collect the sample, for example, saliva, so that no expectoration of the saliva is required. The device may simply be placed in the mouth at a location so that the user can comfortably push saliva to the fluid collection opening at the top. In certain aspects, the fluid collection unit may be placed under the tongue or in a cheek pocket. Through a combination of capillary action and gravity forces, a sufficient yet small volume of saliva will be collected in the unit.

[0398] In this way, the collection units described herein may avoid collection of bubbles and / or large particulates in the saliva, which can affect accurate volume control and fluid flow leading tofailure of a subsequent assay, and may also avoid the multiple steps required when saliva is collected with a sponge or pad, subsequently requiring squeezing out the saliva from the sponge or pad. Due to its higher fluid recovery and associated reduced fluid wasting, the fluid collection units described herein allow for easier fluid collection.

[0399] In aspects, the collection units and lateral flow devices described herein can achieve a one-step operation, wherein the device is placed in the mouth, saliva is collected, and a test result is obtained without requiring extra steps of expelling a sample from a sponge or pad, or applying a buffer solution, waiting for more sample to be collected, or waiting for bubbles to settle out of a fluid sample.

[0400] Also described herein are fluid collection units that have an incorporated head for collecting crevicular fluid from between the teeth, Crevicular fluid can be a reservoir for analytes that can be indicative of certain disease conditions, such as syphilis or HIV, for example. Much like with the saliva collection device described above, these devices collect crevicular fluid and saliva effectively and easily.

[0401] Also described herein are lateral flow devices comprising modified windows, as well as modified windows for use with lateral flow devices. These windows are typically magnified, colored, or illuminated in order to assist a user in reading a test result. These tests are typically small and it is helpful to have an integrated mechanism by which to assist in viewing a test result either by enlarging it, improving contrast, resolution, or by providing lighting.

[0402] Also described herein are lateral flow devices that may comprise an exclusion membrane for filtering out large particles. These are typically used, for example, for dipping in a potentially contaminated water source or a toilet in order to test for analytes of interest. The large molecular weight exclusion membrane or filter paper is important for filtering out larger particles that may interfere with the subsequent test result.

[0403] Also described herein are lateral flow devices comprising a hydrolytic enzyme. This works to clean up a sample by breaking down impurities and / or by cleaving an analyte of interest in order to expose more antigenic sites, thereby increasing the sensitivity of the test. Hydrolytic enzymes digest specific sugars bonds in complex structures such as the peptidoglycan outer wall in gram positive bacterium.

[0404] Also described herein are lateral flow devices comprising an indicator that advises a user that sufficient sample has been applied to the device in order to fully and successfully carry out a test. The indicator may become visible once sufficient sample has been applied, providing a line or spot upon use. The indicator may, in addition or alternatively, move along with the sample front and, once it reaches a predetermined place on the device, it will be clear to the user that sufficient sample has been applied.Also described herein are lateral flow devices that specifically test for a combination of specific antibody to a pathogen, serum CrP and serum amyloid A, above a threshold, optionally in combination with one or more Lyme disease antigens or syphilis antigens (treponemes).

[0405] Definitions

[0406] The term “proximal” as used herein refers to portions of the collection unit or device that are closer to the end comprising the receptacle, whereas the term “distal” as used herein refers to portions of the collection unit or device that are closer to the end comprising the handle. The terms “upstream” and “downstream” refer to flow of a fluid from the proximal end (upstream) to the distal end (downstream).

[0407] The term “analyte” is intended to encompass any chemical or biological substance that is measured quantitatively or qualitatively. In typical aspects, the analyte is one that would be found in a saliva sample. Analytes can include small molecules, sugars, proteins, antibodies, DNA, RNA, nucleic acids, carbohydrates, lipids, organic anabolites or metabolites, virus components or intact viruses, bacteria components or intact bacteria, cellular components or intact cells and complexes and derivatives thereof. The human salivary glands secrete a rich mixture of biological chemicals, electrolytes, proteins, genetic material, polysaccharides, and other molecules. The level of each salivary component varies considerably depending on the health status of the individual and the presence of disease (oral or systemic) or the presence of drugs. By measuring these components in the saliva, it is possible to screen for a variety of things, including, but not limited to, infections, allergies (IgE / A), hormonal disturbances, neoplasms, drug use, and to obtain genetic material for subsequent testing.

[0408] For example, the collection units described herein find particular use in point of care devices to identify overdoses or roadside testing devices to identify drivers under the influence of alcohol or cannabis. Drugs that can be tested using collection units described herein include, but are not limited to, psychedelic agents, psychostimulants, sedatives, depressants, abused inhalants, hypnotics and alcohol. According to a particular embodiment, the one or more analytes to be detected are one or more drugs selected from the group of alcohol, opiates, cocaine, cannabinoids such as tetrahydrocannabinol (THC), amphetamines, methamphetamines, morphine, benzodiazepines, l-(T-phenylcyclohexyl) piperidine (PCP), barbiturates, fentanyl, methadone, and heroin or other opioids with a morphine-like action, such as, but not limited to, codeine, papaverine, noscapine, hydrocodone, or fentanyl. Derivatives or metabolites of these drugs may also be detected.

[0409] The analyte to be tested may be a drug of abuse, some of which are listed above, or it may be a drug that is often mistakenly overdosed on, such as acetaminophen. Further, theanalyte may be a disease marker, such as troponin or C-reactive protein. Numerous examples of such markers exist and would be well known to a skilled person.

[0410] The term “passive” or “passively” in reference to collecting a saliva sample is intended to exclude active efforts by the end user to expectorate or spit into the collection unit. Rather, passive collection means that the collection unit is placed into the mouth, typically under the tongue or in a cheek pocket, and saliva secretions are collected simply by virtue of the collection unit being placed in proximity to the secretions. Some mouth movement would be expected during use, and such movement is encompassed by the term “passive,” provided it is not the act of actively spitting into the collection unit.

[0411] In understanding the scope of the present application, the articles “a”, “an”, “the”, and “said” are intended to mean that there are one or more of the elements. Additionally, the term "comprising" and its derivatives, as used herein, are intended to be open ended terms that specify the presence of the stated features, elements, components, groups, integers, and / or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and / or steps. The foregoing also applies to words having similar meanings such as the terms, "including", "having" and their derivatives.

[0412] It will be understood that any aspects described as “comprising” certain components may also “consist of” or “consist essentially of,” (or vice versa) wherein “consisting of” has a closed-ended or restrictive meaning and “consisting essentially of” means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention.

[0413] It will be understood that any component defined herein as being included may be explicitly excluded from the claimed invention by way of proviso or negative limitation, whether implicitly or explicitly defined herein. For example, in an aspect, the devices herein do not use a sponge or collection pad for absorbing saliva as an initial step in the testing method.

[0414] In addition, all ranges given herein include the end of the ranges and also any intermediate range points, whether explicitly stated or not.

[0415] Finally, terms of degree such as "substantially", "about" and "approximately" as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies.Lateral Flow Device

[0416] Figures 1 to 9 show a first lateral flow device 10. As shown, the device 10 comprises a fluid collection unit 12 and a body 14. The body 14 contains a handle 16 and a window 18, through which results of an assay can be read visually or by a machine. The device 10 is typically transparent, but can be of any desired color and opacity and combinations thereof, provided the test can still be read. It will be understood that in a completely transparent device 10, the window 18 is optional.

[0417] The fluid collection unit 12 typically comprises an elongate body comprising a region of concavity 20 and a receptacle 22. The region of concavity 20 and the receptacle 22 both lead to a fluid flow path 24, which is best seen in Figure 8. The fluid flow path 24 functions to direct a fluid sample from the receptacle 22 to a lateral flow membrane 26 at opposite ends of the collection unit 12.

[0418] In certain aspects, the volume held by the fluid flow path 24 is rationally selected so as to be equal to or greater than the volume required for accurate function of the lateral flow membrane 26. In this way, the test will not initiate until a sufficient amount of sample is present in the collection unit 12, as the fluid front must reach the lateral flow membrane 26 for the test to begin. In aspects, the fluid flow path 24 has a volume of from about 10 pl to about 200 pl, such as from about 10 pl to about 100 pl, such as about 25 pl to about 50 pl, such as about 40 pl.

[0419] The receptacle 22 is typically a cylindrical indentation integrally formed in the collection unit 12. The receptacle 22 has an open sidewall 28 through which fluid in the receptacle 22 can enter the fluid flow path 24. The region of concavity 20 assists in directing additional fluid towards the receptacle 22.

[0420] As shown, the region of concavity 20 is formed in a wall above the fluid flow path 24 and comprises three slanted walls 30 that converge together at an open bottom wall 32 that is contiguous with the fluid flow path 24. As shown, two of the slanted sidewalls 30 cooperate to form in part the receptacle 22.

[0421] The open bottom wall 32 of the region of concavity 20 is sized to allow surface pressure to stop fluid flow such that, in use, fluid will not enter the fluid flow path 24 through the open bottom wall 32 until a front of fluid from the receptacle 22 reaches the open bottom wall 32 while passing through the fluid flow path 24. This assists in both drawing in fluid from the region of concavity 20 while reducing the likelihood of bubbles entering the fluid flow path 24 or otherwise interrupting the fluid in the fluid flow path 24 with air.

[0422] As shown in Figures 8 and 9, the fluid flow path 24 comprises a constriction 34 near the receptacle 22. The constriction 34 is simply a narrowing of the fluid flow path 24, thereby locally reducing its cross-sectional area. In doing so, the constriction 34 increases the capillary force ofthe fluid surface at the leading edge of the fluid sample in the fluid flow path 24 relative to the remaining surface of the fluid sample. If too little fluid is present in the receptacle 22 upstream of the constriction 34, the fluid in the fluid flow path 24 will not flow to ensure test will not start without enough sample present. However, once sufficient fluid has pooled in the receptacle 22, the destruction of the fluid surface at the constriction 34 will allow flow to continue along the fluid flow path 24. The size of constriction 34 is selected to reduce the likelihood of a bubble entering the fluid flow path 24.

[0423] The collection unit 12 may be integral with the device 10 or it may be separable from the rest of the device 10. In certain aspects, the collection unit 12 is frangibly coupled in the device 10 so that the collection unit 12 can be easily snapped off after use for disposal and / or for inserting at least a portion of the device 10 into a reader for measuring the test result, as such readers may not be sized to fit the collection unit 12 when attached to the body 14.

[0424] The collection unit 12 is typically provided with a cover 36 as shown in Figures 7 and 8. The cover 36 is removable so that the collection unit 12 can be used. The cover 36 can then be placed back on the collection unit 12 for sanitary and / or protective reasons. The cover 36 may be completely removable or it may, in aspects, remain partially attached to the device 10 and / or the collection unit 12 to reduce the chances of the cover 36 being misplaced or otherwise contaminated.

[0425] The device 10 typically comprises a handle 16, which, like the collection unit 12 may be frangibly coupled in the device 10 so that the handle 16 can be snapped away from the rest of device 10 and a conventional reader can be used with the rest of device 10. The handle 16 is typically rounded with an indent sized to facilitate handling with a thumb or finger.

[0426] The device 10 is typically formed by mated upper 38 and lower 40 portions, as shown in Figures 7 and 8, for ease of manufacturing and insertion of a desired lateral flow membrane 26. The device 10 could also be formed as a single unit. As shown, there are mated friction-fit components 42 that hold the upper 38 and lower 40 portions together. The upper 38 and lower 40 portions also contain guides 44 that securely hold the lateral flow membrane 26 in position so that it is in fluid communication with the fluid flow path 24.

[0427] As can be seen in Figures 7 and 8, the receptacle 22, region of concavity 20, and fluid flow path 24 are all formed in the upper portion 38 of the device 10. It will be understood that one or more of these features could be formed in part or in whole by the bottom portion 40 of the device 10.

[0428] Figures 10 to 16 show a second lateral flow device 110, which is constructed somewhat differently from the first lateral flow device 10, but operates under similar principles. As shown, the device 110 comprises a fluid collection unit 112 and a body 114. The body 114 contains ahandle 116 and a window 118, through which results of an assay can be read visually or by a machine. The device 110 is typically transparent, but can be of any desired color and opacity and combinations thereof, provided the test can still be read. It will be understood that in a completely transparent device 110, the window 118 is optional.

[0429] The fluid collection unit 112 typically comprises an elongate body comprising a region of concavity 120 and a receptacle 122. In this aspect, the receptacle 122 is much smaller than the receptacle 22 described above in relation to Figures 1-9. Receptacle 122 is simply a small channel or opening leading to a fluid flow path 124. This design effectively reduces dead volume in the fluid collection unit 112. The region of concavity 120 also leads to the fluid flow path 124, as described above. The fluid flow path 124 functions to direct a fluid sample from the receptacle 122 to a lateral flow membrane 126 at opposite ends of the collection unit 112. As shown in Figures 10 and 16, the receptacle 122 is surrounded by flanges 156 that assist in collecting and directing the fluid sample towards the receptacle 122.

[0430] In certain aspects, the volume held by the fluid flow path 124 is rationally selected so as to be equal to or greater than the volume required for accurate function of the lateral flow membrane 126. In this way, the test will not initiate until a sufficient amount of sample is present in the collection unit 112, as the fluid front must reach the lateral flow membrane 126 for the test to begin. In aspects, the fluid flow path 124 has a volume of from about 10 pl to about 200 pl, such as from about 10 pl to about 100 pl, such as from about 25 pl to about 50 pl, such as about 40 pl. In still other aspects the original sample volume may be 150 ul and there may be additional mass of adsorbents place inside the round distal end of the device with some minor plastic changes to allow a washing step of the device after the 150 ul has entered up to 1 ml of volume.

[0431] The receptacle 122 is typically a small vertical channel integrally formed in the collection unit 112. The receptacle 122 has an open sidewall 128 through which fluid in the receptacle 122 can enter the fluid flow path 124. The region of concavity 120 assists in directing additional fluid towards the receptacle 122.

[0432] As shown, the region of concavity 120 is formed in a wall above the fluid flow path 124 and comprises three slanted walls 130 that converge together at an open bottom wall 132 that is contiguous with the fluid flow path 124. As shown, two of the slanted sidewalls 130 cooperate to form in part the receptacle 122, which is also formed in part by a slanted protrusion 108.

[0433] The open bottom wall 132 of the region of concavity 120 is sized to effectively block air bubbles and large particulates from entering the fluid flow path 124. It also allows surface pressure to stop initial fluid flow such that, in use, fluid will not enter the fluid flow path 124 through the open bottom wall 132 until a front of fluid from the receptacle 122 reaches the openbottom wall 132 while passing through the fluid flow path 124. This assists in both drawing in fluid from the region of concavity 120 while reducing the likelihood of bubbles entering the fluid flow path 124 or otherwise interrupting the fluid in the fluid flow path 124 with air.

[0434] As shown in Figures 11, 15, and 16, the fluid flow path 124 comprises a vent 135 near the receptacle 122 located in the bottom wall of the fluid flow path. Typically, the vent 135 opening is significantly wider than the openings of the receptacle 122 and the open bottom wall 132 allowing surface pressure to be reduced. For example, the vent 135 is typically about 1.5 to about 2.5 times wider than the openings of the receptacle 122 and / or the open bottom wall 132, such as about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0, about 2.1 , about 2.2, about 2.3, about 2.4, or about 2.5 times wider. In a particular aspect, the vent 135 is typically about 0.8 to about 1.0 mm wide, whereas the openings of the receptacle 122 and / or the open bottom wall 132 are about 0.3 to about 0.5 mm wide.

[0435] If no fluid is present above the fluid flow path 124, once the fluid flow path 124 is totally or partially filled, fluid surfaces formed at the openings of the receptacle 122 and the open bottom wall 132 may stop fluid in the fluid flow path 124 from flowing downstream due to opposite surface pressure generated at the openings of the receptacle 122 and the open bottom wall 132 by surface tension. However, air may break into the fluid flow path 124 through the vent 135, thereby facilitating continued downstream fluid flow in the fluid flow path 124.

[0436] In other words, fluid normally enters the fluid flow path 124 until there is no more fluid above the fluid flow path 124, at either the receptacle 122 or the open bottom wall 132. At this moment the new surface formed at the openings of the receptacle 122 and the open bottom wall 132 will stop fluid flow in the fluid flow path 124 because the fluid flow path 124 is much wider than the openings of the receptacle 122 and the open bottom wall 132. Therefore the capillary force generated towards the downstream direction is less than the opposite capillary force generated by the surfaces at the openings of the receptacle 122 and the open bottom wall 132. The fluid also cannot overcome the capillary force at the vent 135 because the fluid flow path 124 and the vent 135 have a similar size. However, if the fluid has reached a lateral flow membrane 126, which has a stronger capillary force, the fluid will be able to overcome the capillary force at the vent 135 leading to continued fluid flow to the lateral flow membrane 126, even if it may still not be able to overcome the opposite capillary force at the openings of the receptacle 122 and the open bottom wall 132.

[0437] The collection unit 112 may be integral with the device 110 or it may be separable from the rest of the device 110. In certain aspects, the collection unit 112 is frangibly coupled into the device 110 so that the collection unit 112 can be easily snapped off after use for disposal and / orfor inserting the rest of the device 110 into a reader for measuring the test result, as such readers may not be sized to fit the collection unit 112 when attached to the body 114.

[0438] The collection unit 112 is typically provided with a cover 136 as shown in Figure 16. The cover 136 is removable so that the collection unit 112 can be used. The cover 136 can then be placed back on the collection unit 112 for sanitary and / or protective reasons. The cover 136 may be completely removable or it may, in aspects, remain partially attached to the device 110 and / or the collection unit 112 to reduce the chances of the cover 136 being misplaced or otherwise contaminated.

[0439] The device 110 typically comprises a handle 116, which, like the collection unit 112 may be frangibly coupled in the device 110 so that the handle 116 can be snapped away from the rest of device 110 and a conventional reader can be used with the rest of device 110. The handle 116 is typically rounded with an indent sized to facilitate handling with a thumb or finger.

[0440] The device 110 is typically formed by mated upper 138 and lower 140 portions, as shown in Figures 15 and 16, for ease of manufacturing and insertion of a desired lateral flow membrane 126. The device 110 could also be formed as a single unit. As shown, there are mated friction-fit components 142 that hold the upper 138 and lower 140 portions together. The upper 138 and lower 140 portions also contain guides 144 that securely hold the lateral flow membrane 126 in position so that it is in fluid communication with the fluid flow path 124.

[0441] As can be seen in Figures 15 and 16, the region of concavity 120 and fluid flow path 124 are formed in the upper portion 138 of the device 110. The receptacle 122 is formed in the lower portion 140 of the device 110. It will be understood that one or more of these features could be formed in part or in whole by the either portion 138, 140 of the device 110.

[0442] Figures 17-24 show a third lateral flow device 210, which is similar to the second lateral flow device 110, but produced in several pieces so that part of the device 210 is removable to be able to fit into a conventional reader device. As shown, the device 210 comprises a holder 202, a reader body 204 comprised of an upper portion 238 and a lower portion 240, and a cover 236 for the reader body 204. When assembled, the device 210 comprises a fluid collection unit 212 and a body 214, much like the devices 10, 110 described above. The body 214 contains a handle 216 and a cavity to hold the reader body 204, which has a window 218, through which results of an assay can be read visually or by machine. The device 210 is typically transparent, but can be of any desired color and opacity and combinations thereof, provided the test can still be read. It will be understood that in a completely transparent device 210, the window 218 is optional.

[0443] As above, the fluid collection unit 212 typically comprises an elongate body comprising a region of concavity 220 and a receptacle 222. Receptacle 222 is simply a small channel oropening leading to a fluid flow path 224. The region of concavity 220 also leads to the fluid flow path 224, as described above. The fluid flow path 224 functions to direct a fluid sample from the receptacle 222 to a lateral flow membrane 226 at opposite ends of the collection unit 212. As shown in Figures 17-20, the receptacle 222 is surrounded by flanges 256 that assist in collecting and directing the fluid sample towards the receptacle 222.

[0444] As can be seen in Figures 17 and 18, the fluid flow path 224 is formed by mating a fluid collection portion 206 with the proximal end of the holder 202 and by mating a top portion 238 and a bottom portion 240 of the reader body 204. The top portion 238 and bottom portion 240 of the reader body 204 comprise protrusions 246 that overlap with the surface of the fluid flow path 224. This overlapping prevents a gap from forming between the proximal end of the fluid flow path 224, formed by mating the fluid collection portion 206 with the proximal end of the holder 202, and the distal end of the fluid flow path, formed by mating the top portion 238 and bottom portion 240 of the reader body 204.

[0445] In certain aspects, the volume held by the fluid flow path 224 is rationally selected so as to be equal to or greater than the volume required for accurate function of the lateral flow membrane 226. In this way, the test will not initiate until a sufficient amount of sample is present in the collection unit 212, as the fluid front must reach the lateral flow membrane 226 for the test to begin. In aspects, the fluid flow path 224 has a volume of from about 10 pl to about 200 pl, such as from about 10 pl to about 100 pl, such as from about 25 pl to about 50 pl, such as about 40 pl.

[0446] The receptacle 222 is typically a small vertical channel integrally formed in the collection unit 212. The receptacle 222 has an open sidewall 228 through which fluid in the receptacle 222 can enter the fluid flow path 224. The region of concavity 220 assists in directing additional fluid towards the receptacle 222.

[0447] As shown, the region of concavity 220 is formed in a wall above the fluid flow path 224 and comprises three slanted walls 230 that converge together at an open bottom wall 232 that is contiguous with the fluid flow path 224. As shown, two of the slanted sidewalls 230 cooperate to form in part the receptacle 222, which is also formed in part by a slanted protrusion 208.

[0448] The open bottom wall 232 of the region of concavity 220 is sized to allow surface pressure to stop fluid flow such that, in use, fluid will not enter the fluid flow path 224 through the open bottom wall 232 until a front of fluid from the receptacle 222 reaches the open bottom wall 232 while passing through the fluid flow path 224. This assists in both drawing in fluid from the region of concavity 220 while reducing the likelihood of bubbles entering the fluid flow path 224 or otherwise interrupting the fluid in the fluid flow path 224 with air.As shown in Figures 18 and 20, the fluid flow path 224 comprises a vent 235 near the receptacle 222 located in the bottom wall of the fluid flow path. Typically, the vent 235 opening is significantly wider than the openings of the receptacle 222 and the open bottom wall 232 allowing surface pressure to be reduced. If no fluid is present above the fluid flow path 224, once the fluid flow path 224 is totally or partially filled, fluid surfaces formed at the openings of the receptacle 222 and the open bottom wall 232 may stop fluid in the fluid flow path 224 from flowing downstream due to opposite surface pressure generated at the openings of the receptacle 222 and the open bottom wall 232 by surface tension. However, air may break into the fluid flow path 224 through the vent 235, thereby facilitating continued downstream fluid flow in the fluid flow path 224. In other words, fluid normally enters the fluid flow path 224 until there is no more fluid above the fluid flow path 224, at either the receptacle 222 or the open bottom wall 232. At this moment the new surface formed at the openings of the receptacle 222 and the open bottom wall 232 will stop fluid flow in the fluid flow path 224 because the fluid flow path 224 is much wider than the openings of the receptacle 222 and the open bottom wall 232.

[0449] Therefore the capillary force generated towards the downstream direction is less than the opposite capillary force generated by the surfaces at the openings of the receptacle 222 and the open bottom wall 232. The fluid also cannot overcome the capillary force at the vent 235 because the fluid flow path 224 and the vent 235 have a similar size. However, if the fluid has reached a lateral flow membrane 226, which has a stronger capillary force, the fluid will be able to overcome the capillary force at the vent 235 leading to continued fluid flow to the lateral flow membrane 226, even if it may still not be able to overcome the opposite capillary force at the openings of the receptacle 222 and the open bottom wall 232. If the fluid has not reached the lateral flow membrane 226 and no more sample is left above the fluid flow path 224, the flow will stop until more sample is added. In this way, the configuration of the device ensures that the test is only initiated when there is enough sample in the device.

[0450] In this aspect, the reader body 204 is shaped and sized to fit a conventional reader device and is removable from the holder 202 for insertion into the reader device. Once the test is complete, the reader body 204 is removed from the device 210, an optional cover 236 is placed over the reader body 204 to prevent contamination of the reader device, and the reader body 204 is inserted into the reader for measuring the test result. The reader body 204 together with cover 236 is shown separate from the device 210 in Figure 24.

[0451] Thus, it will be understood that the reader body 204 may be disposable, whereas the holder 202 may be reusable and optionally sterilisable. In this way, a single patient requiring repeated testing may reuse the holder multiple times or the holder may be sterilized for use between different patients in a clinic or hospital setting. The holder 202, reader body 204, andcover 236 may be made from the same or different materials and may independently be transparent, translucent, or opaque, or a combination thereof.

[0452] As shown in Figures 17 and 20, the holder 202 comprises an open region 248 that facilitates removal of the reader body 204 from the holder 202. For example, a user can push through the open region 248 in order to expel the reader body 204 from the holder 202. In aspects, the holder 202 also includes a protrusion 250 that assists in properly aligning the reader body 204 in the holder 202 and optionally offers a friction fit mating that assists in keeping the reader body 204 tightly in the holder 202 until it is desired to be removed by force.

[0453] As noted above, the reader body 204 is typically provided with a cover 236 as shown in Figures 17 and 24. The cover 236 is removable so that the reader body 204 can be inserted into the holder 202 and used. The cover 236 can then be placed back on the reader body 204 when it is removed from the holder 202 for sanitary and / or protective reasons and / or for proper fit in a reader device. The cover 236 may be completely removable or it may, in aspects, remain partially attached to the device 210 and / or the reader body 204 to reduce the chances of the cover 236 being misplaced or otherwise contaminated.

[0454] The holder 202 typically comprises a handle 216, which is typically rounded with an indent sized to facilitate handling with a thumb or finger.

[0455] The reader body 204 is typically formed by mated upper 238 and lower 240 portions, as shown in Figures 17 and 24, for ease of manufacturing and insertion of a desired lateral flow membrane 226. The reader body 204 could also be formed as a single unit. As shown, there are mated friction-fit components 242 that hold the upper 238 and lower 240 portions together. The upper 238 and lower 240 portions also contain guides (not shown) that securely hold the lateral flow membrane 226 in position so that it is in fluid communication with the fluid flow path 224.

[0456] The holder 202 is similarly formed from mated upper 252 and lower 254 portions, as shown in Figures 17 and 18. The lower portion 254 contains the handle 216, the body 214, and the bottom half of the proximal end of the fluid flow path 224. The upper portion 252 is much smaller than the top portion 254 and contains the region of concavity 220 and open bottom wall 232. These upper 252 and lower 254 portions mate together with friction to form the proximal end of the fluid flow path 224.

[0457] As can be seen in Figures 17 and 18, the region of concavity 220 and fluid flow path 224 are formed in the upper portion 252 of the holder 202. The receptacle 222 is formed in the lower portion 254 of the holder 202. It will be understood that one or more of these features could be formed in part or in whole by the either portion 252, 254 of the holder 202.

[0458] It will be understood that any lateral flow membrane could be used in the devices described herein and / or in conjunction with the collection units described herein. In a particularaspect, the lateral flow membrane is as described in U.S. Patent Nos. 7,785,865, 8,119,393, or 7,238,538 or in International Patent Application Publication Nos. WO 2009 / 143601 or WO 2013 / 155617.

[0459] While the collection units described herein are particularly suited for use in collecting a saliva sample, it will be understood that they may find use in collecting any fluid, such as, for example, serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

[0460] In particular aspects, the collection units described herein are used for collecting a water sample and can be used to test a water sample for contamination. In aspects, devices used for testing water samples include an exclusion membrane for removing large particles from the sample. Examples of such large particles include protozoa, algae, plant matter, non-living debris, or combinations thereof.

[0461] The water sample may be waste water, such as in a toilet bowl or from a water treatment plant. The waste water may contain urine, fecal matter, vomit, or various combinations thereof. Toilet water can be directly tested by a user to determine if any particular infection or analyte is present. Waste water can be tested on a population level at a water treatment plant in order to determine, for example, levels of infection of certain pathogens or the presence of certain analytes in a population.

[0462] The water sample may be from a body of water, such as a lake, pond, river, or ocean, or it may be drinking water, such as from a tap, water fountain, or water cooler. This can be used to test for analytes present in water that may be useful to know or that may cause illness if left untreated.

[0463] In aspects, the device detects one or more analytes associated with a pathogen, disease, condition, ordrug, such as a bacterial, viral, yeast, fungal, or parasite infection.

[0464] In non-limiting and exemplary aspects, the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial or plant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.Further, the collection units described herein have been described for use in combination with a lateral flow assay in which generally small volumes of sample is needed. However, it will be understood that these collections units may be used to collect a fluid sample for any purpose and may be appropriately sized in order to collect any desired volume of fluid, which may vary depending upon the desired end use. For example, if the saliva is being collected for a DNA sequencing end use, then up to about 5 ml of saliva may be collected, such as from about 0.5 ml to about 5 ml, such as from about 1 ml to about 3 ml, such as about 2 ml.

[0465] As noted above, the constriction 34 is typically formed by reducing the cross-sectional area of the fluid flow path 24, such as by increasing the thickness of the top wall of the fluid flow path 24. It will be understood that the constriction 34 could be formed by increasing the thickness of the top and / or bottom walls of the fluid flow path and the constriction 34 could be of any desired shape, such as a gradual or abrupt narrowing of the flow path in the upstream or downstream direction.

[0466] Figure 25 shows a modified window, in this case a magnified window, for increasing visibility of a test result. The modified window can be integral with the device or it can be removable. In aspects, it is attached, such as glued, to the device and the device is provided with the modified window in place. In other aspects, the modified window is provided separately and can be used with a variety of different flow devices in which a conventional non-modified window is already present.

[0467] The modified window in Figure 25 is shown as being magnified but it will be understood that the window may be modified in many different ways. For example, it may be colored in order to improve contrast or visibility of a colored line that indicates a positive or negative test. Additionally or alternatively, it may be illuminated.

[0468] A positive test for example may result in a very faint colored line, typically a blue or pink line, that may be difficult to see. Increasing magnification, illumination, and / or contrast may assist the user in distinguishing between a positive and negative test result.

[0469] In some aspects, the fluid collection unit is for detecting an analyte in crevicular fluid between the teeth. In this case, the unit comprises a head designed for rubbing on and / or between the teeth in communication with a receptacle for passively collecting the crevicular fluid. A fluid flow path is in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit.

[0470] The head may resemble a typical toothbrush head or it may comprise an interdental brush and / or floss pick. The head may be bristled with, for example, plastic, rubber, or silicone bristles or fingers that assist in collecting crevicular fluid from between the teeth. In aspects, the head comprises an absorbent pad, which assists in collecting the crevicular fluid.In particular aspects, the device may comprise a hydrolytic enzyme for improving analyte detection. Typically, the hydrolytic enzyme cleaves peptidoglycan and / or viral capsid proteins. The hydrolytic enzyme in some aspects cleaves the analyte of interest. This, in aspects, produces more free epitopes for detection, thereby increasing sensitivity of the device. In additional or alternative aspects, the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding in the test.

[0471] Exemplary hydrolytic enzyme include a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase, trypsin, Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase?, Caspase8, Caspase9, Caspasel 0, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.

[0472] In certain aspects, the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the device.

[0473] In additional or alternative aspects, the device comprises a reagent that indicates when a sufficient amount of sample has been applied to the device. For example, the reagent may be stationary and is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test. Alternatively, the reagent may be free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test. In aspects, the reagent is a water- reactive indicator.

[0474] In particular aspects, described herein is a lateral flow device for simultaneously detecting CrP and Serum Amyloid A in a fluid sample. These may be detected in a single line or in separate lines. In some aspects, the device only detects CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.

[0475] Methods of Use

[0476] In use, a fluid collection unit 12, 112, 212 described herein is placed near or in a fluid sample. When the fluid sample is saliva, the fluid collection unit 12, 112, 212 is placed in the mouth such as under the tongue or in the cheek area. The collection unit 12, 112, 212 then passively collects saliva as it is produced in the mouth, without the need for expectorating or otherwise swabbing the mouth.

[0477] As fluid collects in the receptacle 22, 122, 222, it is drawn into the fluid flow path 24, 124, 224 by capillary action. The constriction 34, when present, increases capillary force opposite to the fluid flow direction when sufficient liquid is not available and thereby reduces the likelihood of a bubble entering the fluid flow path 24, 124, 224. As the front of saliva flows along the fluid flow path 24, 124, 224, it will collect fluid that has entered the region of concavity 20, 120, 220due to the destruction of fluid surface tension at the open bottom wall 32, 132, 232, which had theretofore prevented fluid in the region of concavity 20, 120, 220 from entering the fluid flow path 24, 124, 224.

[0478] The size of the open bottom wall 32, 132, 232 at the bottom of the region of concavity 20, 120, 220 is designed so that the surface pressure is sufficient to stop fluid flow into the fluid flow path 24, 124, 224 via the open bottom wall 32, 132, 232 unless the fluid flow path 24, 124, 224 is filled with fluid or until a front of fluid in the fluid flow path 24, 124, 224 contacts fluid at the open bottom wall 32, 132, 232, thereby drawing the fluid into the fluid flow path 24, 124, 224. This not only reduces the risk that the receptacle may be blocked by solid materials existed in fluid sample such as cells and bacteria but also reduces chances for bubbles to enter the fluid flow path 24, 124, 224. Thus, as the front of fluid is drawn along the fluid flow path 24, 124, 224 by capillary action, the liquid surface at the open bottom wall 32, 132, 232 is removed so that fluid held at the open bottom wall 32, 132, 232 by surface pressure can be drawn into fluid flow path. This increases the efficiency of the collection unit 12, 112, 212, as it is able to collect fluid from the region of concavity 20, 120, 220 in addition to fluid present in the receptacle 22, 122, 222.

[0479] When the fluid reaches the end of the fluid flow path 24, 124, 224, it may enter a lateral flow membrane 26, 126, 226, where an assay will be carried out and a test result can be observed. The fluid may alternatively be used in other ways, or it may be collected and stored for future use.

[0480] The above disclosure generally describes the present invention. Changes in form and substitution of equivalents are contemplated as circumstances may suggest or render expedient. Although specific terms have been employed herein, such terms are intended in a descriptive sense and not for purposes of limitation.

[0481] All publications, patents, and patent applications cited above are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety.

[0482] Although preferred embodiments of the invention have been described herein in detail, it will be understood by those skilled in the art that variations may be made thereto without departing from the spirit of the invention or the scope of the appended claims.

Claims

Claims1. A fluid collection unit for detecting an analyte in crevicular fluid, the unit comprising a head for rubbing on and / or between the teeth in communication with a receptacle for passively collecting the crevicular fluid; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit2. The fluid collection unit of claim 1, wherein the head comprises an interdental brush.

3. The fluid collection unit of claim 1 , wherein the head comprises a floss pick.

4. The fluid collection unit of any one of claims 1 to 3, wherein the head is bristled.

5. The fluid collection unit of claim 4, wherein the bristles are plastic, rubber, or silicone.

6. The fluid collection unit of any one of claims 1 to 5 wherein the head comprises an absorbent pad.

7. A lateral flow device comprising the fluid collection unit of any one of claims 1 to 6.

8. A lateral flow device for testing a water sample for contamination, the device comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

9. The lateral flow device of claim 8, wherein the water sample is waste water.

10. The lateral flow device of claim 9, wherein the waste water comprises urine, fecal matter, vomit, or combinations thereof.

11. The lateral flow device of claim 8 or 9, wherein the waste water is in a toilet bowl or a water treatment plant.

12. The lateral flow device of claim 8, wherein the water sample is from a body of water, such as a lake, pond, river, or ocean.

13. The lateral flow device of claim 8, wherein the water sample is drinking water.

14. The lateral flow device of any one of claims 8 to 13, wherein the large particles comprise protozoa, algae, plant matter, non-living debris, or combinations thereof.

15. The lateral flow device of any one of claims 8 to 14, wherein the exclusion membrane comprises filter paper.

16. The lateral flow device of any one of claim 8 to 15, wherein the device detects one or more analytes associated with a pathogen, disease, condition, or drug.

17. The lateral flow device of claim 16, wherein the device is for detecting a bacterial, viral, yeast, fungal, or parasite infection.

18. The lateral flow device of claim 16 or 17, wherein the device is for detecting HIV-1, HIV-2 other retroviruses, Hepatitis, Treponema pallidum (Syphilis), Chlamydia trachomatis, Neisseria gonorrhea, hCG, trichomonas, cancers such as prostate cancer, and Streptococcus A, Norovirus, Norwalk virus, LPS, MOMP, VP1, Opa, porins, antibiotic resistance proteins, pilin, protein specific antigen, myoglobin, troponins, and creatinine kinase, Helicobacter pylori, Salmonella, enteric toxins (eg. Shiga), gram positive bacteria such as Bacillus anthracis, S. pyrogenes, S. pneumoniae, M tuberculosis, and E. faecalis (proteins, teichoic acids etc), CRP, Serum Amyloid A, Bacterial or plant exotoxins, such as ricin or abrin, viral proteins, PSA, CA125, Lancefield A epitope, Pb, Hg, Ar, glyphosphate, THC, CBD, Lyme antigens, and combinations thereof.

19. The lateral flow device of any one of claims 8 to 18, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

20. The lateral flow device of any one of claims 8 to 19 comprising a reagent that indicates when a sufficient amount of sample has been applied to the device.

21. The lateral flow device of any one of claims 8 to 20 for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

22. A lateral flow device for detecting an analyte in a fluid sample, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

23. The lateral flow device of claim 22, wherein the hydrolytic enzyme cleaves peptidoglycan.

24. The lateral flow device of claim 22 or 23, wherein the hydrolytic enzyme comprises a peptidoglycan hydrolase and / or an autolysin, such as lysozyme or amylase.

25. The lateral flow device of any one of claims 22 to 24, wherein the hydrolytic enzyme cleaves viral capsid proteins.

26. The lateral flow device of any one of claims 22 to 25, wherein the hydrolytic enzyme comprises trypsin.

27. The lateral flow device of any one of claims 22 to 26, wherein the hydrolytic enzyme cleaves the analyte to produce more free epitopes for detection, thereby increasing sensitivity of the device.

28. The lateral flow device of any one of claims 22 to 27, wherein the hydrolytic enzyme cleaves impurities in the sample, thereby reducing non-specific binding.

29. The lateral flow device of any one of claims 22 to 28, wherein the hydrolytic enzyme comprises Caspasel, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase7, Caspase8, Caspase9, CaspaselO, Enterokinase, Factor Xa, GranzymeB, Thrombin, Tobacco etch virus protease, or combinations thereof.

30. The lateral flow device of any one of claims 22 to 29, wherein the hydrolytic enzyme spares detection reagents, such as rabbit IgG, in the device.

31. The lateral flow device of any one of claims 22 to 30, the device further comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

32. The lateral flow device of any one of claims 22 to 31 , wherein the fluid sample is waste water, wherein the fluid sample is from a body of water, such as a lake, pond, river, or ocean, wherein the fluid sample is drinking water, or wherein the sample comprises serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, crevicular fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, semen, vaginal fluid, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

33. The lateral flow device of any one of claim 22 to 32, wherein the device detects one or more analytes associated with a pathogen, disease, condition, or drug.

34. The lateral flow device of any one of claims 22 to 33 for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

35. A lateral flow device comprising a reagent that indicates when a sufficient amount of sample has been applied to the device.

36. The lateral flow device of claim 35, wherein the reagent is stationary is displayed when the sample front reaches the reagent, indicating that sufficient sample has been applied to carry out the test.

37. The lateral flow device of claim 36, wherein the reagent is free and moves along with sample front and when the reagent reaches a predetermined point on the device it indicates that sufficient samples has been applied to carry out the test.

38. The lateral flow device of any one of claims 35 to 37, wherein the reagent is a water-reactive indicator.

39. The lateral flow device of any one of claims 35 to 38, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

40. The lateral flow device of any one of claims 35 to 39, the device further comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

41. The lateral flow device of any one of claims 35 to 40, wherein the fluid sample is waste water, wherein the fluid sample is from a body of water, such as a lake, pond, river, or ocean, wherein the fluid sample is drinking water, or wherein the sample comprises serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, crevicular fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, semen, vaginal fluid, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

42. The lateral flow device of any one of claims 35 to 41 , wherein the device detects one or more analytes associated with a pathogen, disease, condition, or drug.

43. The lateral flow device of any one of claims 35 to 42 for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

44. A lateral flow device for simultaneously detecting CrP and Serum Amyloid A in a fluid sample.

45. The lateral flow device of claim 44, wherein the device detects CrP and Serum Amyloid A in separate lines or in a single line.

46. The lateral flow device of claim 44 or 45, wherein the device only detects CrP and Serum Amyloid A and, optionally, a Lyme disease antigen or a syphilis antigen.

47. The lateral flow device of any one of claims 44 to 46 comprising a reagent that indicates when a sufficient amount of sample has been applied to the device.

48. The lateral flow device of any one of claims 44 to 47, the lateral flow device comprising a hydrolytic enzyme for improving analyte detection.

49. The lateral flow device of any one of claims 44 to 48, the device further comprising an exclusion membrane for removing large particles from the sample and an analytical membrane for identifying an analyte.

50. The lateral flow device of any one of claims 44 to 49, wherein the fluid sample is waste water, wherein the fluid sample is from a body of water, such as a lake, pond, river, or ocean,wherein the fluid sample is drinking water, or wherein the sample comprises serum, blood, plasma, a cell suspension, cell culture supernatant, saliva, oral fluid, crevicular fluid, cerebrospinal fluid, amniotic fluid, milk, colostrum, mammary gland secretion, lymph, urine, sweat, semen, vaginal fluid, lacrimal fluid, gastric fluid, synovial fluid, mucus, or combinations thereof.

51. The lateral flow device of any one of claims 7 to 50, comprising:a fluid collection unit comprising a receptacle for passively collecting a fluid sample; and a fluid flow path in fluid communication with the receptacle, the fluid flow path passing through the unit for directing the fluid sample from the receptacle to an opposing end of the unit.

52. The lateral flow device of claim 51 , wherein the fluid flow path comprises a vent, optionally in the bottom wall of the fluid flow path and at a proximal end of the fluid flow path.

53. The lateral flow device of claim 51 or 52, wherein the receptacle comprises a substantially cylindrical indentation, wherein the indentation comprises an open sidewall in fluid communication with the fluid flow path.

54. The lateral flow device of claim 53, wherein the indentation comprises an absorbent member, such as a membrane, pad, or sponge.

55. The lateral flow device of any one of claims 7 to 54, wherein the device does not comprise an absorbent pad or sponge for collecting the fluid.

56. The lateral flow device of any one of claims 51 to 55, wherein the receptacle comprises a channel in fluid communication with the fluid flow path, wherein the receptacle is formed within a slanted protrusion, and / or wherein the receptacle is surrounded by flanges to direct the fluid sample to the receptacle.

57. The lateral flow device of any one of claims 51 to 56, further comprising a region of concavity for directing fluid towards the receptacle,wherein the region of concavity is substantially parallel with and above the fluid flow path,wherein the region of concavity comprises an open bottom wall in fluid communication with the fluid flow path,wherein the open bottom wall is sized to allow sufficient surface pressure such that, in use, fluid will not enter the fluid flow path through the open bottom wall until a front of fluid reaches the open bottom wall while passing through the fluid flow path, and wherein the open bottom wall is sized so that large air bubbles or solid materials can be blocked from entering the fluid flow path.

58. The lateral flow device of any one of claims 51 to 57, wherein the fluid flow path comprises a proximal constriction.

59. The lateral flow device of any one of claims 51 to 58 wherein the fluid flow path holds from about 10 pl to about 200 pl of fluid.

60. The lateral flow device of any one of claims 7 to 59, wherein the device does not require the addition of a buffer or diluent to effect flow of the fluid through the fluid flow path.

61. The lateral flow device of any one of claim 7 to 60, wherein the device comprises a window for viewing a test result.

62. The lateral flow device of claim 61 , wherein the window is modified for increasing visibility of the test result.

63. The lateral flow device of claim 62, wherein the modified window is magnified, colored, and / or illuminated and / or wherein the modified window is integral with the device or removable from the device, or wherein the modified window is coupled to the top of the device and fits into place over an existing window in the device.

64. The lateral flow device of any one of claims 8 to 63, comprising a fluid collection unit for detecting an analyte in crevicular fluid, the fluid collection unit comprising a head for rubbing on and / or between the teeth and collecting the crevicular fluid and a fluid flow path in fluid communication with the head, the fluid flow path passing through the unit for directing the crevicular fluid from the head to an opposing end of the unit.

65. The lateral flow device of claim 64, wherein the head comprises an interdental brush or a floss pick.

66. The lateral flow device of claim 64 or 65, wherein the head is bristled.

67. The lateral flow device of any one of claims 64 to 66, wherein the head comprises an absorbent pad.

68. The lateral flow device of any one of claims 7 to 67, comprising one or more flow channels for detecting one or more analytes or for detecting one or more analytes at different sensitivities or for detecting one or more analytes using different detection methods.

69. The lateral flow device of claim 68, wherein the device comprises multiple flow channels and at least one flow channel starts at a different point on a membrane.

70. The lateral flow device of claim 68 or 69, wherein the flow channel width is adjusted depending on the surface tension of the fluid sample.

71. The lateral flow device of any one of claims 7 to 70, comprising a lateral flow membrane.

72. A one-step method of collecting a sample, the method comprising inserting the lateral flow device or unit of any one of claims 1 to 71 in or near a sample and allowing the sample to be drawn into the fluid flow path.

73. The method of claim 72, wherein the obtained sample is substantially bubble-free.

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