Sampling device and method and test kit and method

Abstract

A kit comprising: a protein-containing substance for dispersion in a liquid; a sample collection device for collecting a sample from the liquid, the sample containing a substance derived from a fecal material; and a test device configured to detect one or more analytes in the sample. A sample collection apparatus and method for collecting a sample derived from a fecal material, and a method for testing a sample derived from a fecal material are also disclosed.

Description

Technical Field

[0001] The present disclosure relates to a sampling method and device. Specifically, the present disclosure relates to a sampling device and method, which can be used to obtain a sample derived from fecal material. Further disclosed is a kit and method for testing relevant biomarkers in a sample derived from fecal material. Background Art

[0002] Early detection of colorectal cancer may significantly reduce patient mortality. Detection of blood in stool (also referred to herein as fecal material or stool) has been recognized as an effective means of screening for early indications of colorectal cancer and its precursors polyps, adenomas or other bowel abnormalities.

[0003] Fecal occult blood test (FOBT) is widely used to screen for blood that may be present in stool. Two types of FOBT include immunochemical FOBT (iFOBT), also known as fecal immunochemical test (FIT) and guaiac FOBT. iFOBT or FIT involves collecting stool samples using devices such as spoons, and the stool is stored in a container. The collection container is then usually returned to a laboratory or doctor for testing of the sample. Guaiac FOBT requires individuals to collect stool samples from two to three bowel movements in a container. Then, a smear is usually applied to a card using devices such as an applicator stick. Once dry, the card may be sent to a doctor or laboratory for testing. If a positive result for blood is detected in a stool sample, further testing (such as colonoscopy) may be required to locate the source of bleeding and / or diagnose the disease.

[0004] An immunochemical FOBT (iFOBT), also known as a fecal immunochemical test (FIT), is a FOBT that involves collecting a sample of stool, which is then typically returned to a laboratory or physician for testing for the presence of blood, and in particular, hemoglobin in the sample. Specifically, a quantitative FIT (qFIT) is a FIT for determining the amount of hemoglobin in a stool sample. The latest developments in FIT and iFOBT technology involve collecting a sample of fecal material in toilet water containing stool. If it is a positive result for blood, and in particular if hemoglobin is detected in the sample and / or the hemoglobin concentration exceeds a threshold, further testing, such as a colonoscopy, may be required to locate the source of bleeding and / or diagnose the disease.

[0005] Although these techniques are often successful in detecting hemoglobin in stool (which may indicate colorectal cancer and / or its precursor polyps), a persistent barrier to effective screening is the reluctance of most risk groups to collect and submit identified stool samples for analysis. For example, the Australian government offers free FIT to individuals aged 50-74 through its National Bowel Cancer Screening program, but only about 40% of subjects participate. These tests are designed to be performed at home and require subjects to collect samples of fecal material themselves. It has been observed that screening participation rates across eligible screening groups are very low. One obstacle to high participation rates and therefore more effective screening may be the reluctance of eligible screening groups to collect and submit stool samples for analysis because the process of handling fecal material to obtain samples is unpleasant and the waiting time to receive test results is long.

[0006] There may be additional limitations associated with conventional sampling and testing techniques. First, the collected sample may contain only trace amounts of blood, which may quickly become undetectable when diluted in water, possibly due to changes or losses in the hemoglobin (Hb) analyte at high dilutions. Second, only a very small portion of the entire stool (usually less than 1%) is sampled, so the resulting sample may not be representative of the entire stool. If blood is present in the stool, but not necessarily in the small sample collected, this may result in a false negative test result.

[0007] More recent developments involve detecting blood from stool in toilet water, in one case by using a brush to collect a sample of the water around the stool and applying it to a testing device. However, the use of such brush devices still requires close contact with fecal matter and may not be effective in obtaining a sample that is representative of a complete stool.

[0008] Any discussion of documents, acts, materials, devices, articles or the like contained in this specification should not be taken as an admission that any or all of these matters formed part of the prior art base or were common general knowledge in the field relevant to the present disclosure as they existed before the priority date of each appended claim. Summary of the invention

[0009] The present disclosure provides examples of methods, devices, and kits that can enable the collection and / or testing of samples derived from fecal matter (e.g., for colorectal cancer screening). Specifically, one or more of the disclosed examples may be suitable for obtaining a sample while reducing contact between a user collecting the sample and the fecal matter from which the sample is derived. One or more of the disclosed examples may determine the presence of hemoglobin with greater sensitivity than conventional FIT.

[0010] According to one aspect of the present disclosure, there is provided a method for collecting a sample derived from fecal material, the method comprising:

[0011] placing a liquid permeable membrane across the liquid containing fecal material to conceal the fecal material;

[0012] advancing a sample collection device toward the liquid permeable membrane;

[0013] manipulating the sample collection device to stir or agitate the liquid to disperse material derived from fecal material in the liquid; and

[0014] collecting a sample from the liquid that has passed through the liquid permeable membrane using the sample collection device,

[0015] wherein the liquid permeable membrane has sufficient strength to substantially maintain its shape during the step of stirring or agitating the liquid.

[0016] In some embodiments, the liquid may comprise water. In some instances, the liquid may comprise toilet water. In other instances, the liquid may be provided in an alternative container. In some embodiments, the substance derived from the fecal material may comprise occult blood.

[0017] In some embodiments, advancing the sample collection device toward the liquid permeable membrane may include placing a portion of the sample collection device (e.g., a distal tip of the sample collection device) on the liquid permeable membrane. The sample collection device may contact the upper surface of the liquid permeable membrane (in use). The sample collection device may be manipulated to stir or agitate liquid while remaining on or in contact with the upper surface of the liquid permeable membrane.

[0018] In some embodiments, the method may further include pressing a region of the liquid-permeable membrane into the liquid using the distal tip of the sample collection device. The region of the liquid-permeable membrane may be pressed before manipulating the sample collection device to stir or agitate the liquid. For example, the liquid-permeable membrane may be pressed by contacting and applying pressure to the region of the liquid-permeable membrane. Pressing the region of the liquid-permeable membrane may partially or completely submerge the region of the liquid-permeable membrane. When pressed, the liquid-permeable membrane (or a portion thereof) may be folded and / or wrapped around the distal portion of the sample collection device.

[0019] Agitation of the liquid may disperse substances from the fecal material into the liquid, such as toilet water. A portion of the liquid containing the dispersed substances from the fecal material may then pass through the liquid permeable membrane prior to collecting the sample of the liquid using the collection device.

[0020] In some embodiments, the method may further comprise testing the sample. Testing the sample may comprise transferring the sample to an assay device or a testing device. The terms "assay device" and "testing device" are used interchangeably herein. In some embodiments, the assay device may comprise a test strip, such as a lateral flow test strip.

[0021] Testing the sample may include testing the sample for the presence of one or more analytes. At least one of the analytes may indicate a pathological condition in the fecal material from which the sample is derived. In some embodiments, at least one analyte may indicate occult blood, for example, the at least one analyte may include hemoglobin. Additionally or alternatively, one or more analytes may indicate other pathological conditions. For example, one or more analytes may indicate one or more tumor-derived antigens.

[0022] In some embodiments, the sample collection device may include a pipette. The pipette may include a hollow flexible ball and a hollow tube, wherein the proximal end of the hollow tube is in fluid communication with the hollow ball, and the distal end of the tube defines an opening. The opening may be located at or near the distal tip of the sample collection device. In other embodiments, the sample collection device may include a brush or brush-like device. The brush may include flexible or semi-flexible bristles.

[0023] According to an embodiment of the present disclosure, a sample collection device or a kit may be used to perform the method described in any of the preceding paragraphs.

[0024] According to one aspect of the present disclosure, there is provided a sample collection device for collecting a sample derived from fecal material, the sample collection device comprising:

[0025] a liquid permeable membrane configured for placement across a liquid containing fecal material to conceal the fecal material; and

[0026] a collecting device configured to collect a sample from said liquid that has passed through said liquid permeable membrane, said sample containing material derived from fecal material,

[0027] wherein the collection device is configured to be manipulated by a user to stir or agitate the liquid prior to collecting the sample so as to disperse substances derived from fecal material in the liquid, and

[0028] wherein the liquid permeable membrane has sufficient strength to substantially maintain its shape during stirring or agitation of the liquid.

[0029] In some embodiments, the liquid may comprise water. For example, the liquid may comprise toilet water. The substance derived from fecal material may comprise occult blood.

[0030] In some embodiments, the collecting device may comprise a pipette having any of the previously disclosed features. However, similarly, in another embodiment, the collecting device may be a brush or a brush-like device having flexible or semi-flexible bristles. The collecting device may be configured to collect a volume of liquid substantially corresponding to the volume required to test the sample.

[0031] The liquid permeable membrane can be configured to conceal the fecal material so that substantially all of the fecal material is hidden from view of a user collecting the sample. For example, in some embodiments, the liquid permeable membrane can be sized and / or shaped to extend substantially across the entire surface area of ​​the liquid in the toilet bowl. In some embodiments, the liquid permeable membrane can be sized and / or shaped to cover the surface area of ​​the liquid and to contact the inner wall of the toilet bowl. In other embodiments, the liquid permeable membrane can be sized to partially extend across the surface area of ​​the liquid in the toilet bowl and / or partially conceal the fecal material.

[0032] The liquid permeable membrane can be configured to be substantially opaque such that the fecal material is not visible through the membrane.

[0033] The liquid permeable membrane may be configured to fold or wrap around the collecting device. For example, when a certain area of ​​the permeable membrane is pressed by the collecting device, the liquid permeable membrane may fold around the collecting device. The liquid permeable membrane may be sized and / or shaped so that when the area of ​​the permeable membrane is pressed by the collecting device, the liquid permeable membrane continues to cover the fecal material.

[0034] In some embodiments, the liquid permeable membrane may include a positively charged material. Alternatively or additionally, the liquid permeable membrane may include a color trapping agent or a dye trapping agent. Examples of positively charged materials, color trapping agents, and dye trapping agents are described in International Application No. PCT / US2021 / 022910, the disclosure of which is hereby incorporated by reference in its entirety.

[0035] In some embodiments, the liquid permeable membrane may be configured to be flushable.

[0036] In another aspect of the present disclosure, there is provided a kit for testing a sample derived from fecal material, the kit comprising;

[0037] A sample collection device according to embodiments described herein; and

[0038] An assay device is adapted to detect one or more analytes in the sample.

[0039] In some embodiments, the assay device can comprise a test strip, eg, a lateral flow test strip.

[0040] In another aspect, a method for collecting a sample derived from fecal material is provided, the method comprising:

[0041] advancing a sample collection device encased in a liquid permeable membrane toward a liquid containing fecal material;

[0042] manipulating the sample collection device to stir or agitate the liquid so as to disperse material derived from the fecal material in the liquid; and

[0043] collecting a sample from the liquid that has passed through the liquid permeable membrane using the sample collection device,

[0044] The liquid permeable membrane has sufficient strength to substantially maintain its shape during the stirring or agitation step of the liquid. The method may further comprise enclosing the sample collection device in the liquid permeable membrane. The sample collection device may be withdrawn from the liquid permeable membrane after collecting the sample.

[0045] In another aspect, there is provided a sample collection device for collecting a sample derived from fecal material, the sample collection device comprising:

[0046] a collection device; and

[0047] a liquid permeable membrane configured to cover the distal end of the collection device,

[0048] wherein the collecting device is configured to collect a sample from liquid that has passed through the liquid permeable membrane, the sample containing material derived from fecal material,

[0049] wherein the collection device is configured to be manipulated by a user to stir or agitate the liquid prior to collecting the sample so as to disperse substances derived from fecal material in the liquid,

[0050] wherein the liquid permeable membrane has sufficient strength to substantially maintain its shape during stirring or agitation of the liquid.

[0051] According to one aspect of the present disclosure, a kit is provided, comprising:

[0052] a protein-containing substance for dispersion in a liquid;

[0053] a sample collection device for collecting a sample from the fluid, the sample containing material derived from fecal material; and

[0054] A test device is configured to detect one or more analytes in the sample.

[0055] In some embodiments, the liquid may include water. For example, the liquid may include toilet water.

[0056] In some embodiments, the sample collection device can be configured to stir or agitate the liquid, for example to disperse the substance derived from the fecal material in the liquid. Additionally or alternatively, the sample collection device can be configured to stir or agitate the liquid to disperse the protein-containing substance in the liquid.

[0057] In one or more embodiments, the protein-containing substance may be derived from milk. In one embodiment, the protein-containing substance may include a powder derived from milk, in particular a dried milk powder. In one example, the protein-containing substance may be a homogenized dried milk powder. In another embodiment, the protein-containing substance may be a substance in the form of a liquid, a paste, a tablet, a mixture or a combination thereof derived from milk. In this embodiment, the protein-containing substance may increase the opacity of the liquid, in particular, making the liquid substantially opaque. In yet another embodiment, the protein-containing substance may be any other suitable protein-containing substance. The protein-containing substance may increase the opacity of the liquid to which it is added. In yet another embodiment, the protein-containing substance may be any other suitable substance, such as bovine serum albumin (BSA), which substantially maintains the transparency of the liquid and does not increase the opacity of the liquid. In another embodiment, the protein-containing substance may be derived from a non-animal protein source, such as a plant-based protein powder.

[0058] In some embodiments of the kit, the sample collection device may be configured to collect a volume of liquid substantially corresponding to the volume required for testing the sample. In some embodiments, the sample collection device may include a pipette. The pipette may include a hollow flexible ball and a hollow tube, wherein the proximal end of the hollow tube is in fluid communication with the hollow ball, and the distal end of the tube defines an opening. The opening may be located at or near the distal tip of the sample collection device. In other embodiments, the sample collection device may include a brush or a brush-like device. The brush may include flexible or semi-flexible bristles, wherein a certain volume of liquid may be collected.

[0059] In some embodiments, at least one of the one or more analytes may indicate a pathological condition. For example, at least one analyte may represent occult blood in the sample, such as hemoglobin. Additionally or alternatively, one or more analytes may indicate other pathological conditions. For example, one or more analytes may indicate one or more tumor-derived antigens.

[0060] In some embodiments, the test device may comprise a fecal immunochemical test device. The test device may comprise a lateral flow test strip. Alternatively, the test device may comprise any other test member suitable for testing the one or more analytes in the sample.

[0061] In some embodiments, the kit may include a liquid permeable membrane. The sample collection device may be configured to collect a sample from a liquid that has passed through the liquid permeable membrane, the sample containing material derived from fecal material. The liquid permeable membrane may have sufficient strength to substantially maintain its shape during stirring or agitation of the liquid.

[0062] In some embodiments, the liquid permeable membrane can be configured to be placed across the liquid, such as placed across the surface of the toilet bowl water to at least partially cover the fecal material. The liquid permeable membrane can be configured to cover the fecal material so that substantially all of the fecal material is hidden outside the field of vision of the user who collects the sample. For example, in some embodiments, the liquid permeable membrane can be sized and / or shaped to extend substantially across the entire surface area of ​​the liquid in the toilet bowl. In some embodiments, the liquid permeable membrane can be sized and / or shaped to cover the surface area of ​​the liquid, and contact the inner wall of the toilet bowl. In other embodiments, the liquid permeable membrane can be sized to partially extend across the surface area of ​​the liquid in the toilet bowl and / or partially cover the fecal material. The liquid permeable membrane can be configured to be substantially opaque so that the fecal material is invisible through the membrane.

[0063] In some embodiments, the liquid permeable membrane may include a positively charged material. Alternatively or additionally, the liquid permeable membrane may include a color trapping agent or a dye trapping agent. Examples of positively charged materials, color trapping agents, and dye trapping agents are described in International Application No. PCT / US2021 / 022910, the disclosure of which is hereby incorporated by reference in its entirety.

[0064] According to one aspect of the present disclosure, there is provided a method for testing a sample derived from fecal material, the method comprising:

[0065] Adding the protein-containing substance to the liquid;

[0066] dispersing the protein-containing substance in the liquid;

[0067] adding fecal material to the liquid;

[0068] collecting a sample from the fluid using a sample collection device, the sample comprising material derived from the fecal material; and

[0069] The sample is tested for one or more analytes using a testing device.

[0070] The method may use a protein-containing material, a sample collection device, and a testing device substantially as described in one or more of the embodiments disclosed herein.

[0071] In some embodiments, the liquid may comprise water. For example, the liquid may comprise toilet water. The substance derived from fecal material may comprise occult blood.

[0072] In some embodiments, the protein-containing material can be added to the liquid before the fecal material is added to the liquid. In other embodiments, the protein-containing material can be added to the liquid after the fecal material is added to the liquid. In some embodiments, the protein-containing material can be added before the sample is collected from the liquid. For example, the protein-containing material can be added to the toilet water before the sample is collected from the toilet water. In such embodiments, the collected sample can include a substance derived from fecal material and a portion of the protein-containing material. However, in other embodiments, the protein-containing material can be added after the sample is collected. For example, a sample including a substance derived from the fecal material can be collected from the liquid, and then the protein-containing material can be added to the liquid of the sample.

[0073] In certain embodiments, the method may include stirring or agitating the liquid. Stirring or agitating the liquid may enhance the dispersion of the material in the liquid that is derived from fecal material and / or the proteinaceous material. In certain embodiments, the sample collection device may be used to stir or agitate the liquid. However, other suitable methods and / or instruments for stirring or agitating the liquid may be used.

[0074] In some embodiments, the method may include actively dispersing a substance derived from fecal material in the liquid prior to collecting the sample. In one embodiment, this may include stirring or agitating the liquid. For example, the method may include manipulating the sample collection device to stir or agitate the liquid so as to disperse the substance derived from the fecal material in the liquid.

[0075] In some embodiments, dispersing the protein-containing material in the liquid may include actively dispersing the protein-containing material in the liquid. In some embodiments, this may include stirring or agitating the liquid. For example, the method may include manipulating the sample collection device to stir or agitate the liquid so as to disperse the protein-containing material in the liquid.

[0076] In some embodiments, the method may include actively dispersing the protein-containing material in the liquid before collecting the sample. For example, the method may include actively dispersing the protein-containing material in the liquid before adding the fecal material and before dispersing the substance derived from the fecal material. Alternatively, the method may include adding the fecal material to the liquid and dispersing the substance derived from the fecal material in the liquid before dispersing the protein-containing material in the liquid. Alternatively, the method may include dispersing the substance derived from the fecal material and the protein-containing material in the liquid at the same time under the same action. In another example, the method may include actively dispersing the protein-containing material in the liquid of the sample after collecting the sample. For example, the protein-containing material may be located in the sample collection device and arranged to contact the sample during or after the collection of the sample. For example, the protein-containing material may be provided in a pipette, such as in a hollow ball of a pipette.

[0077] In some embodiments, the test device may comprise a fecal immunochemical test device. The test device may comprise a lateral flow test strip. Alternatively, the test device may comprise any other test member suitable for testing the one or more analytes in the sample.

[0078] In some embodiments, the method may include providing a liquid permeable membrane. The sample may be collected from a liquid that has passed through the liquid permeable membrane. In one example, providing the liquid permeable membrane may include placing the liquid permeable membrane across the liquid to at least partially cover the fecal material. In another example, providing the liquid permeable membrane may include at least covering the distal end of the sample collection device. In some embodiments, the sample collection device may be covered with the permeable membrane before stirring or agitating the liquid. The liquid permeable membrane may have sufficient strength to substantially maintain its shape during stirring or agitating the liquid. The method may include withdrawing the sample collection device from the liquid permeable membrane before testing the sample.

[0079] Throughout this specification, the word "comprise" or variations such as "comprises" or "comprising" will be understood to imply the inclusion of stated elements, integers or steps or groups of elements, integers or steps, but not the exclusion of any other elements, integers or steps or groups of elements, integers or steps. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] Embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0081] Figure 1A and 1B is a flow chart illustrating steps in a method for collecting a sample derived from fecal material according to an embodiment of the present disclosure;

[0082] Figure 2 is a front view of a sample collection device according to one embodiment of the present disclosure;

[0083] Figure 3 shows a front view of a sample collection device encased in a liquid permeable membrane according to one embodiment of the present disclosure;

[0084] Figure 4 A sample collection device according to an embodiment of the present disclosure is shown, comprising: Figure 2 pipettes and liquid permeable membranes;

[0085] Figure 5 Components of a kit for collecting and testing a sample derived from fecal material according to one embodiment of the present disclosure are shown, the kit comprising Figure 4 Sample collection equipment;

[0086] Figure 6A kit for collecting and testing a sample derived from fecal material according to one embodiment of the present disclosure is shown, the kit comprising a protein-based substance, a sample collection device, and a testing device;

[0087] Fig. 7A An embodiment according to the present disclosure is shown. Figure 6 A front view of a package containing a protein substance in a closed state;

[0088] Figure 7B Shows Fig. 7A A front view of the package in an opened state;

[0089] Fig. 8A and 8B Shows Figure 6 A perspective view of a test device of the test kit before and after testing a sample;

[0090] Fig. 9 A shows a kit for collecting and testing a sample derived from fecal material according to one embodiment of the present disclosure, the kit comprising a protein-based substance, a sample collection device, a testing device, and a liquid permeable membrane;

[0091] Fig. 10A is a flow chart illustrating steps in a method for testing a sample derived from fecal material according to one embodiment of the present disclosure; and

[0092] Fig. 10B is a flow chart illustrating steps in a method for testing a sample derived from fecal material according to another embodiment of the present disclosure. DETAILED DESCRIPTION

[0093] According to the present disclosure, a method for collecting a sample derived from fecal material is as follows Figure 1A The method 1000A comprises placing a liquid permeable membrane across a liquid containing fecal material to conceal the fecal material 1100, advancing a sample collection device toward the liquid permeable membrane 1200, manipulating the sample collection device to stir or agitate the liquid 1300 so as to disperse substances derived from the fecal material in the liquid; and collecting a sample from a portion of the liquid that has passed through the liquid permeable membrane 1400 using the sample collection device.

[0094] Some embodiments include one or more additional steps 1250, 1600, and 1700 of flowchart 1000B, such as Figure 1B The relative positions of the method steps as depicted in flowcharts 1000A and 1000B should not be construed as limiting the steps to be performed in any particular order.

[0095] Applies to Figures 1A to 1C Examples of sample collection devices 200 and liquid permeable membranes 410, 420 for the method of Figure 2-5 The sample collection device 200 and the liquid permeable membranes 410 and 420 and alternative embodiments are disclosed in more detail below.

[0096] In one embodiment, the liquid across which the liquid permeable membrane is placed is water, particularly toilet water. In this embodiment, the liquid permeable membrane is placed across the liquid to include placing the liquid permeable membrane in a toilet containing toilet water and fecal material. Therefore, the liquid permeable membrane is placed to cover the fecal material after defecation. However, in other embodiments, the liquid can be the water in any other container suitable for receiving fecal material. Positioning the liquid permeable membrane in this way creates a barrier between the user and the fecal material so that only liquid can pass through, preventing the fecal material from being sampled. In addition, this will reduce the need to contact or see the stool itself when retrieving the sample, thereby improving the compliance of the individuality of colorectal cancer screening.

[0097] The stirring and agitation of the liquid promotes the mixing or dispersion of the material derived from the fecal material in the liquid in which the fecal material is immersed. In one embodiment, the material derived from the fecal material is occult blood, and therefore contains hemoglobin. The stirring and agitation of the material derived from the fecal material in the surrounding liquid can disperse the hemoglobin of the occult blood, and can promote the more uniform distribution of hemoglobin in the liquid. This may improve the probability of collecting a sample containing occult blood and hemoglobin, even if the sample collected is very small, it can represent the entire fecal material.

[0098] To this end, method 1000B may further include step 1250 of pressing a certain area of ​​the permeable membrane into the liquid using the distal tip of the collection device. The pressure applied to the certain area of ​​the contact and pressing liquid permeable membrane may cause the liquid permeable membrane to fold around the distal portion (adjacent distal end D) of the collection device. Folding the liquid permeable membrane around the collection device can serve as an additional barrier between the collection device and the fecal material below the liquid permeable membrane. This can optimize the user's chance of avoiding direct contact with the fecal material itself. Before stirring or agitating the liquid, a certain area of ​​the permeable membrane can be pressed. Due to the increase in mass provided to the distal end of the collection device, during stirring and agitation, the folding of the liquid permeable membrane around the collection device also helps the dispersion of hemoglobin of occult blood in the liquid.

[0099] The method shown in flowchart 1000B may further comprise step 1600 of testing the sample to detect the presence of one or more analytes in the sample. In one embodiment, testing the sample involves transferring the collected fluid sample to a testing device, such as an assay device.

[0100] As further shown in flow chart 1000B, the test of sample can further include one or more analytes 1700 of detecting pathological conditions in the fecal material from which the indication sample is derived. In one embodiment, screening involves testing at least one analyte representing occult blood, for example, testing for the presence of hemoglobin. Hemoglobin in the sample of liquid can indicate colorectal cancer or its precursor polyps. However, in another embodiment, one or more analytes can represent other pathological conditions, such as one or more tumor-derived antigens. As mentioned above, stirring and agitating the liquid helps the material derived from fecal material to be evenly dispersed in the liquid from which the sample is collected, so that the sample represents a complete stool. This is in contrast to the direct sampling method, which may collect samples of fecal materials without the analyte of interest, even if the analyte may be present in other parts of the stool. Therefore, if there are one or more analytes (e.g., hemoglobin) indicating pathological conditions in the stool, the currently disclosed method and apparatus increase the probability of detecting these analytes. This ultimately improves the sensitivity of the test.

[0101] The liquid permeable membranes 410 , 420 in embodiments of the kits, sampling devices, or methods disclosed herein may include one or more of the features described below.

[0102] Examples of liquid permeable membrane 410 are Figure 4 , 5 9.Liquid permeable membrane 410 can be configured to cover fecal material so that substantially all fecal material is hidden outside the user's field of vision of collecting sample.Although the liquid permeable membrane 410 in the figure has a rectangular shape, other shapes can also be considered.In one embodiment, the liquid permeable membrane 410 can be sized or shaped to cover the surface area of ​​the liquid in the toilet.In another embodiment, the liquid permeable membrane 410 can be sized or shaped to cover the surface area of ​​the liquid, and the inwall of the toilet.In another embodiment, the liquid permeable membrane 410 can be sized or shaped to partially extend across the surface area of ​​the liquid in the toilet and / or partially cover the fecal material.Partially or completely covering the fecal material can minimize the demand for close contact with the fecal material, and can reduce the reluctance of the user when sampling.

[0103] When a certain area of ​​the permeable membrane is pressed with the distal end D of the sample collection device 200, the liquid permeable membrane 410 can be configured to be folded or wrapped around the distal end of the sample collection device 200. This can provide a method of filtering liquid to allow liquid to pass through, while inhibiting the passage and collection of solid fecal material or other particulate contaminants during the collection of the sample. This can reduce the risk of user contact with fecal material and can optimize the performance of the test for detecting one or more analytes (such as hemoglobin). Alternatively, the liquid permeable membrane 420 can be provided in the form of a bag or sheath, as described in further detail below.

[0104] Liquid permeable membranes 410, 420 may have sufficient strength to substantially maintain their shape during agitation or stirring of the liquid. For example, liquid permeable membranes 410, 420 may have sufficient strength to withstand any rupture, tearing or other damage that may occur during agitation and / or stirring.

[0105] The liquid permeable membranes 410, 420 can be configured to allow only liquid and substances derived from fecal material that has been dissolved in the liquid to pass through, which in this embodiment can be occult blood containing hemoglobin. Therefore, the liquid permeable membranes 410, 420 can prevent or substantially inhibit solid fecal material (or other specific contaminants) from passing through them, thereby inhibiting the collection of any solid fecal material in the sample. This can optimize the performance of a test for detecting one or more analytes (such as hemoglobin).

[0106] In some embodiments, the liquid permeable membranes 410, 420 are configured to be flushable. Throughout this disclosure, the term "flushable" or variations such as "flushability" means that the product or material, particularly the liquid permeable membranes 410, 420, are configured to be disposable by flushing from a toilet bowl into an outflow and sewer or drain pipe without causing any blockage or damage to the sewer or drain pipe through which it passes.

[0107] In certain embodiments, liquid permeable membrane 410,420 can comprise positively charged material.Liquid permeable membrane can comprise color trapping agent or dye trapping agent additionally or alternatively.Color trapping agent or dye trapping agent can remove any color or capture any entity from the liquid containing fecal material, prevent it from passing through the liquid permeable membrane that may produce negative interference to the test result.In the present disclosure, term "color trapping agent" or "dye trapping agent" means a kind of material, material characteristic or product, and its treatment mode can stop the transfer of any pigment that may penetrate into the liquid.In one embodiment, this means that when liquid passes through, any pigment, color, dye or fecal material related element that may penetrate into the liquid through liquid permeable membrane will be retained in the material of liquid permeable membrane.

[0108] The liquid permeable membranes 410, 420 can be configured to be substantially opaque (e.g., even if saturated with liquid) so that fecal material is not visible through the membrane. This may reduce the need to touch and / or see the stool itself, which may improve user compliance with testing using the kit. In some embodiments, the liquid permeable membranes 410, 420 may contain a color pigment to further hide the fecal material in the liquid. In one embodiment, the collection device may include a pipette. Figure 2 In the embodiment shown, the pipette 200 includes a hollow flexible ball 210 and a hollow tube 220. The hollow tube is fluidically connected to the ball at its proximal end P, and defines an opening 230 at its distal end D. In the embodiment shown, the opening 230 is located at the distal end of the hollow tube, which is the distal tip of the collecting device. The pipette can include a scale indicating the volume of the liquid that can be accommodated. In an alternative embodiment, the pipette can include a rotating part and a plunger, wherein the rotating part allows the plunger volume to be adjusted to the desired volume of the collected sample when rotating. The pipette and any of its components can be constructed by a combination of glass, plastic, rubber or such materials. Collecting samples using a pipette can enable the collection of quantitative or semi-quantitative samples. That is, using a pipette enables the collection of controlled, consistent volumes of liquid suitable for test samples.

[0109] However, in another embodiment, the collection device can be an alternative device suitable for collecting a sample of liquid, such as a brush or a brush-like device having flexible or semi-flexible bristles at or near the distal end. In this case, the volume of liquid in the sample is collected in a semi-quantitative manner because the amount of liquid within the interstitial spaces of the bristles of the sampling device will be a reasonably constant amount for any particular size and configuration of the sampling device.

[0110] In some embodiments, the sample collection device 200 can be configured to stir or agitate the liquid, for example by having sufficient strength to allow stirring or agitation while the liquid is held by the proximal end P. Stirring or agitating the liquid can disperse substances derived from fecal material in the liquid. Similarly, stirring or agitating the liquid or the liquid in the sample can enhance the dispersion and / or dissolution of the protein-containing material 100 in the liquid before collecting the sample or in the liquid of the sample after collecting the sample.

[0111] In certain embodiments, the assay device can be any assay device that can detect one or more analytes of the pathological condition in the fecal material from which the indicator sample is derived. The assay device can include a test strip, such as a lateral flow test strip, also referred to as an immunochromatographic test strip or a rapid test, which allows testing in a relatively short period of time when the sample is introduced into the test kit, thereby providing the accurate determination of the sample when the collection time is provided. The test result can then be read immediately, or read at any time thereafter, without the risk of causing analyte loss during transportation due to degradation as present in other tests. In another embodiment, the test of the sample may involve transporting the sample to a testing facility, such as testing in a laboratory.

[0112] The method may be performed using a sample collection device. Figure 4 A sample collection device 520 is shown for collecting a sample derived from fecal material in accordance with the present disclosure. In the illustrated embodiment, the sample collection device 520 comprises a liquid permeable membrane 410 and a collection device 200, each embodying the features described previously. In this embodiment, the liquid permeable membrane 410 is configured to mask the fecal material such that substantially all of the fecal material is hidden from view of a user collecting the sample, as described previously.

[0113] Figure 3 Another embodiment of a sample collection device 510 is shown in which the sample collection device 200 is encased in a liquid permeable membrane 420. The liquid permeable membrane 420 may include one or more features or characteristics as described herein with respect to the liquid permeable membrane 410. In this embodiment, the liquid permeable membrane 420 is wrapped around the hollow tube and the distal tip of the pipette.

[0114] In this embodiment, the liquid permeable membrane 420 can be in the form of a sleeve or bag into which the sample collection device 200 can be inserted. The liquid permeable membrane 420 can be configured to surround at least the distal end of the sample collection device 200. Figure 3 In some embodiments, the liquid permeable membrane 420 is configured to cover the hollow tube 220 of the sample collection device from its distal end to the proximal region near the ball 210. In other embodiments, the liquid permeable membrane 420 may surround or cover a smaller portion of the sample collection device 200, for example, at least the region adjacent to the distal tip D of the sample collection device 200.

[0115] The pipette 200 and membrane 420 can be used to implement alternative methods of collecting samples, such as Figure 1C The method may include step 1050 of coating the sample collection device 200 in a liquid permeable membrane 420. Alternatively, the sample collection device may be provided pre-coated.

[0116] In this embodiment, as previously described with respect to Figure 1A and 1B As described in steps 1300 and 1400, the coated pipette 200 is advanced into the liquid ( Figure 1C 420) and is used to stir or agitate the liquid and collect a sample of the liquid that passes through the membrane 420. The method may then include further steps 1600 and 1700 of testing the sample and detecting the analyte, as previously described.

[0117] The liquid permeable membrane 420 of the embodiments described above may not be large enough to substantially conceal fecal material. However, the membrane 420 provides a means of filtering the liquid to inhibit fecal material and / or other contaminating particles from passing through the membrane 420 during sample collection. The liquid permeable membrane 420 can be configured to remain in the liquid once wetted and the pipette 200 is withdrawn (e.g., by sliding off the distal end of the pipette 200).

[0118] Figure 5 A kit 5000 for testing a sample derived from fecal material is shown. In the illustrated embodiment, the kit 5000 comprises a sample collection device 520 comprising a liquid permeable membrane 410 and a sample collection device 200 as previously described. Alternatively, the kit 5000 may comprise a sample collection device 520 as previously described. Figure 3 The sample collection device 510 shown. In alternative embodiments, the sample collection device can be any other device suitable for collecting a liquid sample, such as a brush or a brush-like device with flexible or semi-flexible bristles, as previously disclosed. The kit 5000 also includes a testing device, such as an assay device 5100 (or test device 300) suitable for detecting one or more analytes in a sample. The assay device can include any of the features and embody the principles described previously.

[0119] At least one analyte detected in the assay device 5100 is indicative of a pathological condition in the fecal material from which the sample originates. In one embodiment, this analyte may represent occult blood in the sample, such as hemoglobin. However, in another embodiment, this may be any other analyte indicative of a pathological condition, for example, one or more analytes representing one or more tumor-derived antigens.

[0120] Kits and methods according to embodiments of the present disclosure, including protein-containing material 100, are described in more detail below.

[0121] According to one embodiment of the present disclosure, a kit 6000 is provided. Figure 6. The kit 6000 comprises: a protein-containing substance 100 for dispersing in a liquid; a sample collection device 200 for collecting a sample from the liquid, the sample containing a substance derived from fecal material; and a test device 300 configured to detect one or more analytes in the sample. An alternative kit 7000 is also described below, which may include a liquid permeable membrane 410 (or 420). Reference flowcharts 3000A, 3000B are described for methods for testing a sample derived from fecal material.

[0122] Examples of protein-containing material 100 and test devices 300 suitable for inclusion in kits 6000, 7000 and for use in the methods shown in flow charts 3000A, 3000B disclosed herein are provided in Figures 6 to 9 A and described in more detail below. The sample collection device 200 and liquid permeable membrane 410, 420 used in the method 3000A, 3000B or the kit 6000, 7000 may include the above reference Figures 2 to 5 One or more of the described features.

[0123] In one embodiment, the liquid from which the sample is collected is water. For example, the liquid can be toilet bowl water. The protein-containing material 100 can be dispersed in the water. For example, the protein-containing material 100 can be added to the water in the toilet bowl before or after stool is added to the water.

[0124] The protein-containing material 100 may be a material that is dispersible in water. In one embodiment, the protein-containing material 100 may be dissolvable in toilet water. Alternatively, the protein-containing material 100 may be a liquid (such as water) that is dispersible and / or dissolvable in an alternative container suitable for receiving fecal material.

[0125] exist Figure 6 In the illustrated embodiment, the protein-containing material 100 is in powder form. In another embodiment, the protein-containing material 100 can be provided in any other form that can be dispersed and / or dissolved in a liquid. For example, the protein-containing material 100 can include a liquid, a paste, a tablet, a pill, a mixture or a combination thereof. In one embodiment, the protein-containing material 100 is a dried milk powder, such as commercial whole milk powder or skim milk powder. In this embodiment, the dried milk powder can be formed using a variety of powder processing techniques, including fat standardization, pasteurization, evaporation, homogenization and spray drying. The dried milk powder can be a homogenized dried milk powder.

[0126] In another embodiment, the protein-containing substance 100 can be a liquid, for example, the protein-containing substance 100 can include a commercial dairy product, such as whole milk, low-fat milk, or a combination thereof, including a preservative diluted in a liquid such as water. In some embodiments, the user can provide the protein-containing substance 100 to be added to a liquid.

[0127] In another embodiment, protein-containing material 100 may include solid matter, such as tablets or pills derived from milk. In this embodiment, tablets or pills may include powder derived from milk, such as previously described dry milk powder and soluble adhesive components compressed into tablet or pill form. Additionally or alternatively, protein-containing material may include one or more dispersants. One or more dispersants may include one or more active ingredients, such as sodium bicarbonate and / or citric acid, or other suitable dispersants. Dispersants may, for example, help dissolving and / or dispersing of protein-containing material in liquid by providing an effervescent effect. When tablets or pills are added to liquid, soluble adhesive components and / or dispersants may play the role of decomposing the components of tablets when in continuous contact with liquid, so that protein-containing material 100 is dispersed and / or dissolved in liquid. In another embodiment, protein-containing material 100 may include one or more of the following: powder, paste, liquid, tablet or mixture.

[0128] The protein-containing material 100 can be a substantially opaque material. Adding the protein-containing material 100 to a liquid may increase the opacity of the liquid in which it is dispersed and / or dissolved. In some embodiments, the protein-containing material 100 causes the liquid to become substantially opaque. In embodiments where the protein-containing material 100 is added to and dispersed in water, particularly toilet water, the liquid may change from being substantially transparent to being substantially opaque. The increase in the opacity of the liquid may at least partially obscure the contents of the liquid, which may at least partially obscure fecal material in the toilet water.

[0129] The protein-containing material 100 can additionally or alternatively change the consistency and / or color of the liquid, providing a means of substantially covering the fecal material added to the liquid after defecation from the user's field of vision. In some embodiments, the color and opacity of the protein-containing material 100 can be white and / or turbid, which is a typical feature of milk or milk-like products. Therefore, when the protein-containing material 100 is added to the liquid and dispersed in the liquid, the opacity of the liquid is improved from a substantially transparent liquid to a turbid milky white liquid, substantially covering any fecal material from the user's field of vision. The protein-containing material 100 can include a colorant or dye, which can change the color and opacity of the liquid to which the protein-containing material is added, so that the liquid is converted from substantially transparent to substantially opaque and colored liquid.

[0130] Partial or complete masking of fecal material (eg, by increasing opacity and / or changing the color of the fluid) may reduce the visibility of the stool to the user and may reduce the user's reluctance in performing a sample.

[0131] In alternative embodiments, the protein-containing substance 100 can be an alternative powder, paste, liquid, tablet, mixture or combination thereof containing a suitable protein. In some embodiments, the protein-containing substance 100 can include bovine serum albumin (BSA). In some embodiments, adding the protein-containing substance 100 to the liquid may not change the opacity of the liquid, and the liquid may remain substantially transparent. This may be desirable in cases where a transparent sample is required. For example, this may occur when using some quantitative FITs (such as "OC sensors").

[0132] like Fig. 7A As shown in the depicted embodiment, the protein-containing material 100 can be packaged in a capsule 110, which can be provided in a kit 6000. In this embodiment, the capsule 110 includes at least one seal 120 configured to appropriately seal the capsule (e.g., by an airtight seal at one end or around the capsule) to inhibit exposure of the protein-containing material 100 to moisture and / or outside air prior to use. The sealed capsule can inhibit or reduce degradation or contamination of the protein-containing material 100 prior to use.

[0133] like Figure 7B As shown, capsule 110 can be torn, for example near the seal (e.g., according to instructions provided on the package) to form opening 130. Then, capsule 110 can be rotated to a suitable angle to allow the user to dispense the contents of capsule 110, for example, to add protein-containing material 100 to a liquid.

[0134] In another embodiment, the protein-containing material 100 may be provided in a container comprising an airtight seal covering an opening of the container. For example, the container may be included in the packaging of the kit 6000, 7000 or may be integral therewith.

[0135] In alternative embodiments, the protein-containing material 100 can be contained within a portion of the sample collection device 200 and can be released into the liquid of the sample during or after sample collection. For example, the protein-containing material 100 can be contained within the ball or shaft of a pipette. In other embodiments, based on the form of the material previously disclosed, the protein-containing material 100 can be contained and / or packaged in any other member suitable for holding and preserving the protein-containing material 100 prior to use, including, for example, a container, capsule, bag, package or bag.

[0136] The test device 300 is configured to detect at least one analyte of a pathological condition in the fecal material from which the indication sample originates. In one embodiment, the test device 300 is configured to detect at least one analyte representing occult blood, for example, hemoglobin in the sample. Dispersing and / or dissolving the protein-containing material 100 in a liquid can improve the sensitivity of the test. For example, without wishing to be bound by theory, it is assumed that the protein-containing material 100 can play a role in stabilizing the hemoglobin analyte (the analyte is the protein globin part of the hemoglobin molecule) in the sample, for example, by maintaining its conformational stability. Additionally or alternatively, the protein-containing material can also enhance the test sensitivity by displacing the hemoglobin that tends to bind to the fecal material from the fecal material into the liquid. This can improve the availability of the hemoglobin in the liquid from which the sample is extracted, and therefore can improve the consistency of the test results under the detection and high dilution levels of the hemoglobin. The test performed according to the present disclosure has been shown to have a limit of detection (LoD) of blood detection in water less than about 0.05 μL / L (or <7.5ng / ml).

[0137] Fig. 8A and 8B An embodiment of a test device 300 included in a kit 6000 is shown. In this embodiment, the test device 300 is a fecal immunochemical test device, which includes a test strip 310 enclosed in a housing 320 having a front surface 330. The test strip 310 can be a lateral flow test strip, also known as an immunochromatographic test strip or an immunochemical test strip, which is referred to as a "rapid test." The front surface 330 of the housing 320 may include a first opening defining a sample receiving portion 332. The sample receiving portion 332 may allow access to a portion of the test strip 310 configured to receive a sample. The front surface 330 of the housing 320 may include a second opening defining a display portion 334. The display portion 334 may be configured to display a result indicating portion of the test strip 310. The result indicating portion may include a control line 336 and one or more test lines 338. The front surface 330 of the housing 320 may include markings indicating various portions of the test strip. For example, as can be seen from Fig. 8A and 8B As seen in FIG. 1 , in this embodiment, the front surface 330 of the housing 320 includes the letters “C,” “T,” and “S,” indicating a control line 336, a test line 338, and a sample receiving portion 332, respectively.

[0138] In the illustrated embodiment, the control line 336 and the test line 338 comprise colored lines visible in the display portion 334, such as Figure 8B336 and test line 338 may indicate a positive test result (i.e., detection of at least one analyte), while formation and display of only the control line may indicate a negative test result (i.e., no detection of the analyte). The test line is formed when the conjugated markers and antibodies present in the layers of the test strip 310 (e.g., nitrocellulose membrane) bind to one or more target analytes present in the sample. In embodiments where the test device 300 is configured to detect hemoglobin, a positive test result (i.e., a negative test result) may be indicated. Figure 8B The formation and display of both the control line and the test line as shown) indicates the presence of hemoglobin in the sample.

[0139] In the case where the control line is not formed and displayed during the test, the test device 300 may be considered to be faulty. The use of the lateral flow test strip 310 allows the test to be run and the result to be indicated in a relatively short period of time after the sample is introduced into the test strip 310, thereby providing an accurate determination of the sample at the time of collection. The test result can be read immediately, or can be read in a specified period of time thereafter, without the risk of causing the loss of analyte due to degradation during transportation as may exist in other tests. The test result may remind the user or the attending physician to seek additional investigation or testing. In another embodiment, an alternative test device or an assay device suitable for detecting one or more analytes may be used for testing samples. Additionally or alternatively, the test of the sample may involve transporting the collected sample to a testing facility, such as a laboratory for testing.

[0140] Another example of a kit 7000 according to the present disclosure is Fig. 9 In this embodiment, the kit 7000 comprises a protein-containing material 100, a sample collection device 200, a test device 300, and a liquid permeable membrane 410. As described above with respect to test methods 1000A and 1000B, the liquid permeable membrane 410 can be configured to be placed across a liquid to conceal fecal material after a bowel movement.

[0141] Additionally or alternatively, the kit 7000 may include a liquid permeable membrane 420 configured to cover the sample collection device 200, such as Figure 3 As shown and described above.

[0142] According to the present disclosure, methods for testing samples derived from fecal material are as follows Fig. 10A Method 3000A includes adding a protein-containing material to a liquid 3100, dispersing the protein-containing material in a liquid 3200, adding fecal material to a liquid 3300, collecting a sample from the liquid 3400 using a sample collection device, and testing the sample 3500 for one or more analytes using a testing device.

[0143] In some embodiments, the method may include one or more additional steps 3255, 3257, 3350, 3355, 3357, and 3450, such as Fig. 10B The relative positions of the method steps as depicted in flowcharts 3000A and 3000B should not be interpreted as limiting the steps to be performed in any particular order.

[0144] The method can be performed using a test kit, such as kit 6000 or 7000, as described above.

[0145] In some embodiments, the liquid can be water, in particular toilet water. In this embodiment, adding the protein-containing substance 3100 to the liquid can include adding the protein-containing substance (e.g., milk powder) to the water contained in the toilet. For example, the contents of the capsule 100 can be sprinkled over the surface of the toilet water.

[0146] Adding fecal material to liquid 3300 can include adding fecal material to toilet water in a toilet, such as by using the toilet to defecate in a normal manner. The presence of urine and / or toilet paper in the toilet does not hinder testing and sampling. However, in another embodiment, the liquid can be water in any other container suitable for receiving fecal material. Adding proteinaceous material to liquid 3100 can include adding proteinaceous material to the water in the container. Similarly, in this embodiment, adding fecal material to liquid 3300 includes adding fecal material to the water in the container suitable for receiving fecal material after defecation. Alternatively, after fecal material and / or proteinaceous material 100 are added to the container, water (or other test liquids) can be added to the container. In some embodiments, before adding fecal material to liquid, proteinaceous material 100 is added to liquid. This may reduce the risk of user contact with fecal material. However, in other embodiments, after adding fecal material to liquid, proteinaceous material 100 is added to liquid. In yet another embodiment, after collecting a sample of the liquid, the protein-containing material 100 is added to the liquid in the sample.

[0147] In some embodiments, the method includes actively dispersing the substance derived from the fecal material in the liquid 3355 by stirring and / or agitating the liquid (e.g., using a sample collection device or another suitable stirring tool) as described herein. Stirring or agitating the liquid can enhance the dispersion of the substance derived from the fecal material to mix or disperse in the liquid in which the fecal material is immersed. Manipulating the sample collection device 200 can include advancing the sample collection device 200 toward the liquid containing the proteinaceous material 100, inserting at least a portion of the distal end of the sample collection device 200 into the liquid, and manipulating the sample collection device 200 from the proximal end P with a stirring motion to actively mix and thereby disperse the substance derived from the fecal material. In an example in which the sample collection device is a pipette 200 as described above, and as Figure 2 , 3 , 6 and 9, the user can hold the pipette at the proximal end P at the top of the hollow ball 210 and advance the pipette in the liquid so that the distal end D of the hollow tube 220 is inserted into the liquid for stirring. In another embodiment, any other sample collection device suitable for stirring and agitating the liquid can be used, such as a brush or spoon-like structure.

[0148] The method may further include dispersing the protein-containing material 100 in the liquid. In some embodiments, this may include allowing the protein-containing material 100 to be passively dispersed in the liquid over time. In another embodiment, allowing the protein-containing material to disperse in the liquid includes active dispersion of the protein-containing material 3255, stirring and / or agitating the liquid (e.g., using a sample collection device as previously described or another suitable stirring tool) to disperse the protein-containing material 100 in the liquid 3257. Although both passive dispersion and active dispersion of the protein-containing material 100 can occur, active mixing and stirring of the protein-containing material can further help disperse and / or dissolve the protein-containing material in the liquid. Dispersion can promote a more uniform distribution of the protein-containing material 100 in the liquid. Dispersion can improve the interaction of the protein-containing material 100 with the fecal material in the liquid. The increased interaction of the protein-containing material with the fecal material increases the probability of a stable hemoglobin analyte, such as by maintaining the conformational stability of the hemoglobin in the collected sample, and thus can improve the detection of hemoglobin at high dilution levels. Additionally, in an embodiment where the protein-containing substance 100 is derived from milk or includes a pigment or dye that can increase the opacity of a liquid, stirring and agitating the liquid containing the protein-containing substance can further help provide a uniform distribution of the protein-containing substance, thereby increasing the opacity of the liquid in a consistent manner, which can enhance the masking of fecal material present in or added to the liquid. In other embodiments, the protein-containing substance 100 may not increase the opacity of the liquid after addition and / or dispersion, thereby maintaining a substantially transparent liquid. For example, in some embodiments, the protein-containing substance can include BSA.

[0149] In one embodiment, before collecting sample, protein-containing material 100 is dispersed in liquid.Before fecal material is added to liquid, protein-containing material dispersion may occur.In one example, before any fecal material is added to liquid, protein-containing material 100 can be added to liquid and dispersed in liquid.In order to help protein-containing material 100 dispersion, the user can stir and / or agitate liquid as described above before fecal material is added to liquid.Then fecal material can be added to liquid.As described above, stirring and / or agitating liquid can be repeated to disperse the material derived from fecal material.For example, stirring and / or agitating can enhance the dispersion of occult blood (and therefore, hemoglobin) in liquid.In one embodiment, protein-containing material 100 and the dispersion of the material derived from fecal material can occur in identical stirring and agitation action.

[0150] In another example, protein-containing material 100 can be added to liquid, and after fecal material is added to liquid, the protein-containing material is dispersed in liquid. In this case, the dispersion of protein-containing material 100 and the material (i.e., occult blood containing hemoglobin) derived from fecal material may occur in one action. For example, the sample collection device 200 can be manipulated to stir and / or agitate the liquid containing protein-containing material 100 and the material derived from fecal material simultaneously. In other embodiments, the dispersion of the material derived from fecal material and protein-containing material 100 can occur in two separate actions, wherein the material derived from fecal material disperses before protein-containing material 100. In another embodiment again, the dispersion of protein-containing material 100 can be carried out after collecting sample, and more specifically, can be carried out after fecal material is added to liquid. In this example, fecal material can be added to liquid, and the material derived from fecal material can be dispersed in liquid before collecting sample, as previously described. After collecting the sample using the sample collection device 200, the proteinaceous material 100 can then be added to and dispersed in the liquid of the sample within a portion of the sample collection device, such as within the hollow ball 210 of the pipette 200, as shown. Figure 2 In this example, the pipette 200 can be manipulated to stir or agitate the liquid of the sample within the hollow ball 210 by shaking or rotating the pipette.

[0151] In one embodiment, the method further comprises providing a liquid permeable membrane 410, 420, wherein the sample is collected from the liquid passing through the liquid permeable membrane, such as Figure 6B shown in step 3350. In one embodiment, providing a liquid permeable membrane (e.g., 410) includes placing the liquid permeable membrane 410 across the liquid to at least partially cover the fecal material. In this embodiment, before collecting the sample, the liquid permeable membrane 410 is placed across the liquid so that it creates a barrier between the liquid and its contents and the user, at least partially covering any fecal material contained in the liquid. In some embodiments, the liquid permeable membrane 410 can be placed across the liquid before the substance derived from the fecal material is actively dispersed in the liquid. In this case, collecting the sample from the liquid involves advancing the sample collection device 200 toward the liquid permeable membrane 410, and using the distal end of the sample collection device 200 (e.g., the distal end D or distal tip of the pipette 200) to press a certain area of ​​the liquid permeable membrane 410 into the liquid. The pressure applied to the contact and pressing of a certain area of ​​the liquid permeable membrane 410 causes the liquid permeable membrane to fold around the distal portion (adjacent to the distal end D) of the collection device. Folding the liquid permeable membrane 410 around the collection device 200 can act as an additional barrier between the sample collection device 200 and the fecal material beneath the liquid permeable membrane 410, thereby preventing any solid fecal material from passing through. This can optimize the user's chances of avoiding direct contact with the fecal material itself.

[0152] In another embodiment, providing a liquid permeable membrane (e.g., liquid permeable membrane 410 or 420) can include covering at least the distal end D of the sample collection device 200. In this embodiment, the sample collection device is covered by the liquid permeable membrane 410, 420 before collecting the sample. The liquid permeable membrane 410, 420 can be configured to partially cover the sample collection device from the distal end D and / or distal tip of the device, or substantially cover the sample collection device from the distal end D and / or distal tip to the proximal end P of the device. In one embodiment, the sample collection device 200 can be covered by the liquid permeable membrane 420 before actively dispersing the substance derived from the fecal material in the liquid. In this embodiment, before collecting the sample, the sample collection device 200 covered in the liquid permeable membrane 420 is advanced toward the liquid for collecting the sample and manipulating the liquid.

[0153] The liquid permeable membranes 410, 420 may be configured to be folded or wrapped around the sample collection device. Additionally or alternatively, the liquid permeable membranes 410, 420 may be in the form of a sleeve or bag. Advancing the sample collection device 200 encased in the liquid permeable membrane 420 may further include pressing a certain area of ​​the liquid permeable membrane 420 when the distal end D and / or the distal tip of the sample collection device 200 is in contact with the liquid. The method may include withdrawing the sample collection device 200 from the liquid permeable membrane 420 before testing the sample, and in particular before transferring the sample to the testing device.

[0154] In one embodiment, collecting the sample includes collecting a volume of liquid substantially corresponding to the volume required for testing the sample. Testing the sample may include transferring the sample from the sample collection device to the testing device 3450, for example, by transferring the sample from the pipette 200 to the sample receiving portion 332 of the testing device 300. In another embodiment, testing of the sample may involve transporting the sample to a testing facility, such as a laboratory for testing.

[0155] Testing a sample using the test device 300 may include testing one or more analytes of pathology or other pathological conditions in the fecal material from which the indication sample originates, such as testing at least one analyte representing occult blood (such as hemoglobin) in the sample. In one embodiment, the test device 300 comprises a fecal immunochemical test device, which embodies the principle described above and comprises a lateral flow test strip 310. If hemoglobin is detected in the sample, the test device may display a positive result, reminding the user that occult blood is present in the stool, which may indicate a pathological condition. This can then prompt the user to seek further medical testing or investigation to further evaluate and diagnose a source of bleeding and / or any associated pathological condition, such as colorectal cancer, precancerous polyps, adenomas or lesions. In another embodiment, an alternative test device or assay device suitable for detecting one or more analytes may be used for testing the sample.

[0156] The method according to the present disclosure can provide a relatively simple, inexpensive sampling method that requires little or no direct stool handling, reduces the likelihood of direct contact with stool, and improves the acceptability of testing in the population. Compared to other known FIT and sampling methods, the kit, device or method according to the present disclosure can provide increased sensitivity, thereby increasing the likelihood of detecting trace amounts of blood.

[0157] Kits and methods according to the present disclosure can increase the likelihood of detecting hemoglobin that is representative of a complete stool sample, rather than a small sample of stool, which is common using conventional FIT and sampling methods.

[0158] Kits, devices and methods according to the present disclosure can be helpful in monitoring subjects with very low fecal hemoglobin levels who may be at risk for developing diseases such as colorectal cancer and precursor polyps. In other examples, test kits, devices and / or methods according to the present disclosure can be applied to forensic testing.

[0159] It should be understood that although some features may be disclosed as being relevant to one or more embodiments, and other features may be disclosed as being relevant to one or more embodiments, it is also within the scope of the present disclosure to combine these features in one or more additional embodiments. Therefore, it is understood that any combination of any disclosed features in the embodiments of the methods, devices, or kits described herein is within the scope of the present disclosure.

[0160] Those skilled in the art will appreciate that, without departing from the broad general scope of the present disclosure, various changes and / or modifications may be made to the embodiments described above. Therefore, the embodiments of the present invention should be considered in all aspects as illustrative and not restrictive.

[0161] Experimental Examples

[0162] Example 1

[0163] In one example, the limit of detection (LoD) of the test kit according to the present disclosure was evaluated. In this example, the sample was tested for the presence of blood using a CTK FOB-HI rapid test device (CTK Biotech Inc, Poway, CA 92064, USA). The sample was collected using a sampling device according to the present disclosure.

[0164] 30 g of whole milk powder was added to a 3-liter container containing 1 liter of tap water. 10 mL of the liquid containing the whole milk powder was collected and stored. The liquid was then sampled and tested (control negative).

[0165] After weighing the container and contents, the stool naturally discharged by healthy subjects is added to the container. The container and its contents are then weighed again to determine the weight of the stool. In this example, the stool weight is 124 grams. Using a sample collection device, a sample is collected from the liquid in the container around the stool and tested (negative control).

[0166] 10 μL of fresh donor blood was collected from the fingertips. The blood was diluted using 10 mL of stock volume of liquid and milk powder. The diluted blood was then added to the container along with the stool so that the cumulative volume of blood was as indicated in Table 1 below. The samples were collected and tested.

[0167] The results were recorded 10 minutes after the sample was added. As shown in Table 1, the LoD was 0.025 μL blood / liter after 10 minutes of testing. After 40 minutes of test development time, the results remained the same. The control negative test results remained stable within 40 minutes of development time. The maximum detection intensity was reached after adding 0.2 μL of blood. The hemoglobin (Hb) concentration of the donor blood was 148 μg / μL. Therefore, in 0.025 μL of blood, the total Hb present in the sample is equal to 148×0.025=3.7 μg. Therefore, in 1 liter of water, the Hb concentration is 3.7 ng / ml. If Hb is contributed by 124 g of stool, the amount of Hb / g of stool will be equal to 3.7 / 124=0.03 μg / g of stool. This experimental indication enables the detection of blood with a concentration of less than 1 μL / liter according to the kit and test method disclosed herein.

[0168] Table 1. Results for samples collected and tested recorded 10 minutes after sample addition.

[0169]

[0170]

[0171] Example 2A

[0172] In another example, further testing was performed to evaluate factors that affect the LoD of the kits and methods. In one example, the LoD of blood in liquid and the effect of adding protein-containing substances were evaluated.

[0173] Blood was added in 2 μL increments until the cumulative volume was 8 μL to 1 liter of water. Samples were collected after each addition of blood using a sample collection device according to the present disclosure. Each sample was tested using a test device according to the present disclosure.

[0174] Even in the largest volume of 8 μL of blood, no blood was detected in any of the samples. This indicates that Hb is unstable in water at higher dilutions.

[0175] To determine whether the denaturation of Hb is reversible, 1 μL of blood (100 μL of blood diluted 1 / 100) was added to 1 liter of water and tested in duplicate. Samples were collected and tested according to the methods discussed previously, resulting in a negative result for the presence of Hb. Then 30 grams of whole milk powder was added to the water, and samples were collected and tested according to the currently disclosed methods, resulting in a negative result for the presence of Hb. Therefore, these results indicate that the addition of protein-containing substances (i.e., whole milk powder) cannot reverse the denaturation of Hb.

[0176] Example 2B

[0177] In another example, the LoD of blood added to a fluid containing proteinaceous material was assessed.

[0178] Blood collected from the fingertips was diluted 1 / 100 with tap water. 30 grams of whole milk powder was added to 1 liter of water, and samples were collected and tested using a sample collection device and a test device according to the present invention. The diluted blood sample was gradually added to 1 liter of water containing 30 grams of whole milk powder in increments of 0.1 μL to 0.5 μL, wherein after each addition, samples were collected and tested using a sample collection device and a test device according to the present disclosure.

[0179] The LoD of blood in a 3% milk solution is 0.3 μL blood / liter. At a blood Hb concentration of 148 μg / μL, the total amount of Hb at the LoD equals 0.3×148=44 μg in 1 liter of water=44 ng / ml. This is close to the claimed analytical sensitivity of Hb in the stabilization buffer of the CTK test device, which is 25 ng / ml, when tested under laboratory conditions.

[0180] Example 2C

[0181] In another example, the LoD of blood in stool added to a fluid was assessed.

[0182] The stool discharged naturally is added to 1 liter of tap water in a 3-liter container. In this example, the weight of the stool is 148 grams. The blood collected from the fingertips is diluted 1 / 100 with tap water. Diluted blood is added to 1 liter of water containing stool samples with a blood increment of 0.1 μL (10 μL of 1 / 100) until LoD is established in duplicate tests. As recorded in Table 2 below, after 10 minutes, LoD is 1 μL of blood / liter of water (1.0 μL), producing a consistent positive result of Hb. In addition, after a 4-hour period, the final blood addition (i.e., with 1.25 μL) was retested, and a positive result of Hb was produced, thus proving that the Hb molecule has been stable for more than 4 hours in the presence of stool samples. The sensitivity of Hb is equal to 1 μL of blood under 148 μg / μL=148 μg / liter or 148 ng / ml. For a stool weight of 148 g, Hb / g stool = 148 / 148 = 1 μg / g. This sensitivity compares favorably with the reported sensitivity of the standard OC sensor of 3.8 μg / g stool.

[0183] Table 2: Test device results after cumulative addition of blood volume in 0.1 μL increments to 1 L of water containing stool samples.

[0184] Test No. Cumulative blood volume (μL) result 1 0 Negative 2-7 0.1 to 0.5 Negative 8 0.7 Trace 9 0.8 1 trace, 1 low+ 10 0.9 2x Trace 11 1.0 3x low positive, 1x trace 12 1.25 Positive 4 hours later 12 1.25 Positive

[0185] Example 2D

[0186] In another example, the effect of adding a protein-containing substance to a stool-containing liquid on the test LoD was evaluated. In this example, a sample was collected using a coated sample collection device according to the present disclosure and tested using a test device according to the present disclosure.

[0187] Normal stool (weighing 232 grams) from a healthy subject was added to a 3 liter container containing 1 liter of tap water. The sample was collected using a sample collection device and tested using a test device as previously described.

[0188] 5 μL of 1 / 100 blood dilution was added to a container containing 1 liter of water (corresponding to 0.05 μL of blood, or about 7.4 ng / ml) and stool samples. The samples were collected using a sample collection device and tested using a test device as previously described. Whole milk powder was then added to the container in 5 gram increments, with a maximum of 30 grams added. After each addition of whole milk powder, samples were collected and tested in duplicate.

[0189] As shown in Table 3 below, after adding 5 grams of whole milk powder, a low positive result was returned for the presence of Hb in the sample. The peak intensity was reached after adding 15 grams of whole milk powder.

[0190] These results indicate that adding whole milk powder reduces the LoD and therefore increases the sensitivity of the test from 1 μL of blood / liter of water to 0.05 μL of blood / liter of water, corresponding to a 20-fold increase in sensitivity. Adding stool to 30 g of milk powder in 1 liter of water reduces the LoD from 0.3 μL of blood / liter of water to 0.05 μL of blood / liter of water, i.e., a 6-fold increase in sensitivity. This indicates that stool and milk powder may have complementary effects on the test sensitivity of blood in water.

[0191] It is also noted that after a 1 hour period, the test results for Test 0, where no blood or whole milk powder was added, and Test 1, where blood was first added but no milk powder was added, did not show any signs of detecting a positive reading and remained negative, thus demonstrating the stability of the negative results. A sample containing the last addition of whole milk powder (i.e., 30 grams in total) was taken and retested after a 4 hour period. In the presence of stool in water containing 3% whole milk powder, Hb was stable for 4 hours.

[0192] It is clear that the addition of 5g (0.5%) of whole milk powder has a gain in sensitivity. Adding 0.05μL of blood at a Hb concentration of 148μg / μL provides an Hb concentration of 7.4ng / ml. The claimed sensitivity of the CTK test device under laboratory conditions is 25ng / ml. In the current test, the added Hb is equal to 0.05×148=7.4μg. For a stool weight of 232g=03μg / g of stool:=126 times the sensitivity of the OC sensor, or 116 times the sensitivity of the CTK test claimed for Hb in stool used to test the kits and methods disclosed herein in this example.

[0193] Table 3: Test device results after cumulative addition of whole milk powder in 5 gram increments to 1 liter of water containing stool samples and 0.05 μL of blood.

[0194]

[0195]

[0196] Further testing indicated that alternative protein sources such as whole milk or bovine serum albumin (BSA) could replace milk powder with similar effects.

[0197] The results of the above experimental examples performed using the kits and methods according to the present disclosure indicate:

[0198] Hb is unstable or undergoes conformational changes at higher dilutions in water and therefore cannot be detected by the CTK test device;

[0199] ●Protein-containing substances (such as whole milk powder) can stabilize Hb;

[0200] The presence of stool in the fluid stabilizes Hb; and

[0201] The addition of both protein-containing material and stool to water produces an unexpected synergistic effect that increases the sensitivity of the test beyond the levels where either protein or stool are present by themselves (in this example, a sensitivity of 0.025 μL / liter is achieved). This is well beyond the reported detection limit of conventional testing methods for Hb in stool.

[0202] When compared to conventional test kits and methods, the kits and methods according to the present disclosure exhibit greatly improved sensitivity for the presence of Hb as tested in the above examples.

[0203] It should be understood that although some features may be disclosed as being relevant to one or more embodiments, and other features may be disclosed as being relevant to one or more embodiments, it is also within the scope of the present disclosure to combine these features in one or more additional embodiments. Therefore, it is understood that any combination of any disclosed features in the embodiments of the methods, devices, or kits described herein is within the scope of the present disclosure.

[0204] Those skilled in the art will appreciate that, without departing from the broad general scope of the present disclosure, various changes and / or modifications may be made to the embodiments described above. Therefore, the embodiments of the present invention should be considered in all aspects as illustrative and not restrictive.

Claims

1. A kit comprising: a protein-containing substance for dispersion in a liquid; a sample collection device for collecting a sample from the fluid, the sample containing material derived from fecal material; as well as A test device is configured to detect one or more analytes in the sample.

2. The kit according to claim 1, wherein the protein-containing material is derived from milk.

3. A kit according to claim 1 or claim 2, wherein the protein-containing material comprises a powder.

4. The kit according to any one of claims 1 to 3, wherein the protein-containing substance increases the opacity of the liquid.

5. The kit according to claim 1, wherein the protein-containing substance comprises bovine serum albumin (BSA).

6. A method for testing a sample derived from fecal material, the method comprising: Adding the protein-containing substance to the liquid; dispersing the protein-containing substance in the liquid; adding fecal material to the liquid; collecting a sample from the fluid using a sample collection device, the sample comprising material derived from the fecal material; as well as The sample is tested for one or more analytes using a testing device.

7. A method for collecting a sample derived from fecal material, the method comprising: placing a liquid permeable membrane across the liquid containing fecal material to conceal the fecal material; advancing a sample collection device toward the liquid permeable membrane; manipulating the sample collection device to stir or agitate the liquid so as to disperse material derived from the fecal material therein; as well as collecting a sample from the liquid that has passed through the liquid permeable membrane using the sample collection device, wherein the liquid permeable membrane has sufficient strength to substantially maintain its shape during the step of stirring or agitating the liquid.

8. The method of claim 7, further comprising pressing an area of ​​the liquid permeable membrane into the liquid using a distal tip of the sample collection device prior to manipulating the sample collection device to stir or agitate the liquid.

9. A method for collecting a sample derived from fecal material, the method comprising: advancing a sample collection device encased in a liquid permeable membrane toward a liquid containing fecal material; manipulating the sample collection device to stir or agitate the liquid so as to disperse material derived from the fecal material in the liquid; as well as collecting a sample from the liquid that has passed through the liquid permeable membrane using the sample collection device, wherein the liquid permeable membrane has sufficient strength to substantially maintain its shape during the step of stirring or agitating the liquid.

10. A method according to any one of claims 7 to 9, wherein the liquid comprises toilet water.

11. The method of any one of claims 7 to 10, further comprising testing the sample to detect the presence or absence of one or more analytes in the sample, wherein at least one analyte of the one or more analytes is indicative of a pathological condition in the fecal material from which the sample is derived.

12. A sample collection device for collecting a sample derived from fecal material, the sample collection device comprising: a liquid permeable membrane configured to filter a liquid containing fecal material; and a collecting device configured to collect a sample from the liquid that has passed through the liquid permeable membrane, the sample containing material derived from the fecal material, wherein the collection device is configured to be manipulated by a user to stir or agitate the liquid prior to collecting the sample so as to disperse the substance derived from the fecal material in the liquid, and wherein the liquid permeable membrane has sufficient strength to substantially maintain its shape during stirring or agitation of the liquid.

13. The sample collection device of claim 12, wherein the liquid permeable membrane is configured for placement across the liquid containing the fecal material to at least partially conceal the fecal material.

14. A sample collection device according to claim 12 or claim 13, wherein the liquid permeable membrane is configured to cover the distal end of the collection means.

15. The sample collection device of claim 13 or claim 14, wherein the liquid permeable membrane is configured to mask the fecal material such that substantially all of the fecal material is hidden from view of a user collecting the sample.

16. The sample collection device of any one of claims 12 to 15, wherein the liquid permeable membrane is substantially opaque.

17. The sample collection device of any one of claims 12 to 16, wherein the liquid permeable membrane comprises a positively charged material.

18. The sample collection device of any one of claims 12 to 17, wherein the liquid permeable membrane comprises a color scavenger or dye trapping agent.

19. The sample collection device of any one of claims 12 to 18, wherein the liquid permeable membrane is configured to be flushable.

20. The kit of any one of claims 1 to 5 or the method of claim 6 or claim 11, wherein at least one of the one or more analytes comprises hemoglobin.

21. The method, sample collection device or kit of any preceding claim, wherein the collection means comprises a pipette.

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