Sample collection device and method, and inspection kit and method

Abstract

A kit comprising a proteinaceous substance for dispersion in a liquid, a sample collection device for collecting a sample containing a substance derived from fecal material from the liquid, and an inspection device configured to detect one or more analytes in the sample. A sample collection apparatus and method for collecting a sample derived from fecal material, and a method for inspecting a sample derived from fecal material are also disclosed.

Description

Detailed Description of the Invention

[0001] [Technical Field] The present disclosure relates to a sample collection method and apparatus. Specifically, the present disclosure relates to a sample collection apparatus and method that can be used to obtain a sample from fecal material. Kits and methods for testing a sample from fecal material for relevant biomarkers are further disclosed.

[0002] [Background Art] Early detection of colorectal cancer can significantly reduce the mortality rate of patients. Detection of blood in feces (also referred to herein as fecal material or stool) is well established as an effective means of screening for early signs of colorectal cancer and its precursor polyps, adenomas, or other bowel abnormalities.

[0003] Fecal occult blood testing (FOBT) is widely used for screening for blood that may be present in feces. Two types of FOBT include immunochemical FOBT (iFOBT), also known as fecal immunochemical testing (FIT), and guaiac FOBT. iFOBT or FIT involves collection of a fecal sample using a device such as a spoon and storage of the feces in a container. The collection container is typically returned to a laboratory or physician for testing of the sample. Guaiac FOBT requires an individual to collect a fecal sample in a container from each of two to three bowel movements. In that case, typically a device such as an applicator stick is used to apply a smear specimen to a card. When dried, the card can be sent to a physician or laboratory for testing. If a positive result for blood is detected in the fecal sample, further testing such as a colonoscopy may be required to identify the source of the bleeding and / or diagnose the disease.

[0004] Immunochemical fecal occult blood testing (iFOBT), also known as fecal immunochemical testing (FIT), is a type of FOBT that involves the collection of a fecal sample, which is typically returned to a laboratory or physician for testing for the presence of blood, specifically hemoglobin, in the sample. Specifically, quantitative FIT (qFIT) is a type of FIT that is used to determine the amount of hemoglobin in a fecal sample. Recent developments in FIT and iFOBT techniques involve the collection of a sample of fecal material that is in toilet water containing feces. Further testing, such as a colonoscopy, may be required to identify the source of bleeding and / or diagnose a disease if a positive result for blood, particularly if hemoglobin is detected in the sample, and / or if the concentration of hemoglobin exceeds a threshold.

[0005] These techniques typically detect hemoglobin in feces that may indicate colorectal cancer and / or precancerous polyps of the colorectum without problems, but a consistent obstacle to effective screening is that most of the at-risk population is reluctant to collect and submit a specified fecal sample for analysis. For example, the Australian government provides free FIT to individuals aged 50 to 74 through a national bowel cancer screening program, but only approximately 40% of the target population participates. These tests are intended to be performed at home and require the subject to collect a sample of fecal matter themselves. It is recognized that the participation rate in screening is very low across the entire eligible screening population. One obstacle to a high participation rate, and thus more effective screening, may be that the eligible screening population dislikes collecting and submitting a fecal sample for analysis due to the unpleasantness of handling fecal matter to obtain the sample and the long waiting time to receive the test results.

[0006] There may also be additional limitations associated with conventional sampling and testing techniques. First, the collected sample may contain only trace amounts of blood that can suddenly become undetectable when diluted in water, possibly due to changes or losses of hemoglobin (Hb) analyte at high dilutions. Second, only a very small portion of the entire feces (typically less than 1%) is sampled, thus resulting in a sample that may not be representative of the entire feces. This can lead to false-negative test results when blood is present in the feces but not necessarily in the small sample obtained.

[0007] More recent developments have involved detecting blood from feces in toilet water, in one case by using a brush to collect a water sample from around the feces and applying this sample to a test device. However, the use of such a brush device still requires facing the fecal matter closely and may not be effective in obtaining a sample representative of the entire feces.

[0008] The discussion of the documents, acts, materials, devices, articles, etc. included herein is not to be regarded as an admission that any or all of these matters form part of the basis of the prior art or were common general knowledge in the relevant fields of the present disclosure as they existed prior to the priority date of each of the appended claims.

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

[0010] According to one aspect of the present disclosure, a method for collecting a sample from a fecal material is provided, the method comprising Spread a liquid-permeable membrane over a liquid containing fecal material to cover the fecal material, and Advance a sample collection device toward the liquid-permeable membrane, and Operate the sample collection device to stir or agitate the liquid so as to disperse substances derived from the fecal material into the liquid, and Collect a sample from the liquid that has passed through the liquid-permeable membrane using the sample collection device, and The liquid-permeable membrane has sufficient strength to substantially maintain the form of the liquid-permeable membrane during the step of stirring or agitating the liquid.

[0011] In some embodiments, the liquid may include water. In some examples, the liquid may include toilet water. In other examples, the liquid may be provided in an alternative container. In some embodiments, the substances derived from the fecal material may include occult blood.

[0012] 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., the distal tip of the sample collection device) on the liquid-permeable membrane. The sample collection device may contact (during use) the upper surface of the liquid-permeable membrane. The sample collection device may be operated to stir or agitate the liquid while remaining on the upper surface of the liquid-permeable membrane or while in contact with the upper surface of the liquid-permeable membrane.

[0013] In some embodiments, the method may further include using the distal tip of the sample collection device to push down a region of the liquid-permeable membrane into the liquid. Pushing down the region of the liquid-permeable membrane may be performed before operating the sample collection device to stir or agitate the liquid. For example, the liquid-permeable membrane may be pushed down by contacting and applying pressure to a region of the liquid-permeable membrane. When the region of the liquid-permeable membrane is pushed down, the region of the liquid-permeable membrane may be partially or fully immersed. When pushed down, the liquid-permeable membrane (or a portion of the liquid-permeable membrane) may fold around and / or wrap around the distal portion of the sample collection device.

[0014] The sloshing of the liquid can disperse substances derived from fecal material into the liquid such as the water in the toilet bowl. Subsequently, a portion of the liquid containing the dispersed substances derived from fecal material can pass through the liquid-permeable membrane before collecting a sample of the liquid using a collection device.

[0015] In some embodiments, the method can further include examining the sample. Examining the sample can include transferring the sample to an assay device or a test device. The terms "assay device" and "test device" are used interchangeably herein. In some embodiments, the assay device can include a test strip such as a lateral flow test strip.

[0016] Examining the sample can include detecting the presence of one or more analytes in the sample. At least one of the analytes can indicate a pathological condition in the fecal material from which the sample is derived. In some embodiments, at least one analyte can indicate occult blood; for example, at least one analyte can include hemoglobin. Additionally or alternatively, one or more analytes can indicate other pathological conditions. For example, one or more analytes can indicate one or more tumor-derived antigens.

[0017] In some embodiments, the sample collection device can include a pipette. The pipette can include a hollow flexible valve and a hollow tube, the proximal end of the hollow tube being in fluid communication with the hollow valve and the distal end of the tube defining an opening. The opening can be at or adjacent to the distal tip of the sample collection device. In other embodiments, the sample collection device can include a brush or a brush-like device. The brush can include flexible or semi-flexible bristles.

[0018] The method described in any of the preceding paragraphs can be carried out using a sample collection device or kit according to an embodiment of the present disclosure.

[0019] 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 A liquid-permeable membrane configured to be spread and disposed in a liquid containing fecal material to conceal the fecal material, a collection device configured to collect a sample containing a substance derived from fecal material from the liquid that has passed through the liquid-permeable membrane, The collection device is configured to be operated by a user to stir or agitate the liquid so as to disperse the substance derived from fecal material in the liquid before collection of the sample. The liquid-permeable membrane has sufficient strength to substantially maintain the form of the liquid-permeable membrane during stirring or agitation of the liquid.

[0020] In some embodiments, the liquid may include water. For example, the liquid may include the water in a toilet bowl. The substance derived from fecal material may include occult blood.

[0021] In some embodiments, the collection device may include a pipette having any of the previously disclosed features. However, similarly, in another embodiment, the collection device may be a brush or brush-like device having flexible or semi-flexible hairs. The collection device may be configured to collect a volume of liquid substantially corresponding to the volume required to examine the sample.

[0022] The liquid-permeable membrane may be configured to conceal the fecal material such that substantially all of the fecal material is hidden from view of the user collecting the sample. For example, in some embodiments, the liquid-permeable membrane may 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 may 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 may be sized to extend partially across the surface area of the liquid in the toilet bowl and / or to partially conceal the fecal material.

[0023] The liquid-permeable membrane may be configured to be substantially opaque so that the fecal material cannot be seen through the membrane.

[0024] The liquid-permeable membrane can be configured to fold around or enclose the collection device. For example, the liquid-permeable membrane can fold around the collection device when an area of the permeable membrane is pushed down by the collection device. The liquid-permeable membrane can be sized and / or shaped such that when an area of the permeable membrane is pushed down by the collection device, the liquid-permeable membrane continues to cover the fecal material.

[0025] In some embodiments, the liquid-permeable membrane can include a positively charged material. Alternatively or additionally, the liquid-permeable membrane can include a color catcher or a dye capturer. Examples of positively charged materials, color catchers, and dye capturers are described in International Application No. PCT / US2021 / 022910, the disclosure of which is hereby incorporated by reference in its entirety.

[0026] In some embodiments, the liquid-permeable membrane can be configured to be flushable.

[0027] In another aspect of the disclosure, a kit for testing a sample derived from fecal matter is provided, the kit comprising a sample collection device according to the embodiments described herein, and an assay device adapted for detection of one or more analytes in the sample.

[0028] In some embodiments, the assay device can include a test strip, such as a lateral flow test strip.

[0029] In another aspect, a method for collecting a sample from fecal material is provided, the method comprising advancing a sample collection device coated with a liquid-permeable membrane towards a liquid containing fecal material, operating the sample collection device to stir or agitate the liquid to disperse substances from the fecal material into the liquid, and collecting a sample from the liquid that has passed through the liquid-permeable membrane using the sample collection device. The liquid-permeable membrane has sufficient strength to substantially maintain the form of the liquid-permeable membrane during the step of stirring or agitating the liquid. This method may further include coating a sample collection device on the liquid-permeable membrane. The sample collection device can be withdrawn from the liquid-permeable membrane after collecting the sample.

[0030] In another aspect, a sample collection device for collecting a sample from fecal material is provided, and the sample collection device a collection device, and a liquid-permeable membrane configured to cover the distal end of the collection device, and is provided with the collection device is configured to collect a sample containing substances from fecal material from the liquid that has passed through the liquid-permeable membrane, the collection device is configured to be operated by a user to stir or agitate the liquid so as to disperse substances from fecal material in the liquid before collecting the sample, the liquid-permeable membrane has sufficient strength to substantially maintain the form of the liquid-permeable membrane during stirring or agitating of the liquid.

[0031] According to one aspect of the present disclosure, there is provided a kit comprising a protein-containing substance for dispersion in a liquid, and a sample collection device for collecting a sample containing substances from fecal material from the liquid, and a test device configured to detect one or more analytes in the sample, and a kit is provided.

[0032] In some embodiments, the liquid may include water. For example, the liquid may include toilet water.

[0033] In some embodiments, the sample collection device may be configured to stir or agitate the liquid, for example, to disperse substances from fecal material in the liquid. Additionally or alternatively, the sample collection device may be configured to stir or agitate the liquid to disperse the protein-containing substance in the liquid.

[0034] In one or more embodiments, the proteinaceous substance can be milk-derived. In one embodiment, the proteinaceous substance can include a milk-derived powder, specifically, dried milk powder. In one example, the proteinaceous substance can be homogenized dried milk powder. In another embodiment, the proteinaceous substance can be a substance in the form of a milk-derived liquid, paste, tablet, mixture, or combination thereof. In this embodiment, the proteinaceous substance can increase the opacity of the liquid, specifically, render the liquid substantially opaque. In yet another embodiment, the proteinaceous substance can be any other suitable substance containing protein. The proteinaceous substance can increase the opacity of the liquid to which the proteinaceous substance is added. In yet another embodiment, the proteinaceous substance can be any other suitable substance, such as bovine serum albumin (BSA), that substantially maintains the transparency of the liquid and does not increase the opacity of the liquid. In another embodiment, the proteinaceous substance can be derived from a non-animal protein source, such as a plant-based protein powder.

[0035] In some embodiments of the kit, the sample collection device can be configured to collect a volume of liquid that substantially corresponds to the volume required to test the sample. In some embodiments, the sample collection device can include a pipette. The pipette can include a hollow flexible valve and a hollow tube, wherein the proximal end of the hollow tube is in fluid communication with the hollow valve and the distal end of the tube defines an opening. The opening can be at or adjacent to the distal tip of the sample collection device. In other embodiments, the sample collection device can include a brush or brush-like device. The brush can include flexible or semi-flexible bristles, and a volume of liquid can be collected on the bristles.

[0036] In some embodiments, at least one of the one or more analytes can indicate a pathological condition. For example, at least one analyte can represent occult blood in the sample, such as hemoglobin. Additionally or alternatively, the one or more analytes can indicate other pathological conditions. For example, the one or more analytes can indicate one or more tumor-derived antigens.

[0037] In some embodiments, the testing device may include a fecal immunochemical testing device. The testing device may include a lateral flow test strip. Alternatively, the testing device may include any other testing means suitable for testing one or more analytes in the sample.

[0038] In some embodiments, the kit may include a liquid-permeable membrane. The sample collection device may be configured to collect a sample containing substances derived from fecal material from the liquid that has passed through the liquid-permeable membrane. The liquid-permeable membrane may have sufficient strength to substantially maintain its form during agitation or sloshing of the liquid.

[0039] In some embodiments, the liquid-permeable membrane may be configured to be spread over a liquid, for example, over the surface of the water in a toilet bowl, so as to at least partially cover the fecal material. The liquid-permeable membrane may be configured to cover the fecal material such that substantially all of the fecal material is hidden from view of the user collecting the sample. For example, in some embodiments, the liquid-permeable membrane may 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 may 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 may be sized to extend partially over the surface area of the liquid in the toilet bowl and / or to at least partially cover the fecal material. The liquid-permeable membrane may be configured to be substantially opaque so that the fecal material is not visible through the membrane.

[0040] In some embodiments, the liquid-permeable membrane may include a positively charged material. Alternatively or additionally, the liquid-permeable membrane may include a color catcher or a dye scavenger. Examples of positively charged materials, color catchers, and dye scavengers are described in International Application No. PCT / US2021 / 022910, the disclosure of which is incorporated herein by reference in its entirety.

[0041] According to one aspect of the present disclosure, a method for examining a sample derived from fecal material is provided, the method comprising: adding a protein-containing substance to a liquid; dispersing the protein-containing substance in the liquid; adding fecal material to the liquid; using a sample collection device to collect a sample containing a substance derived from fecal material from the liquid; using an inspection device to inspect the sample for one or more analytes in the sample.

[0042] The method may use a protein-containing substance, a sample collection device, and an inspection device substantially as described in connection with one or more of the embodiments disclosed herein.

[0043] In some embodiments, the liquid may include water. For example, the liquid may include toilet water. The substance derived from fecal material may include occult blood.

[0044] In some embodiments, the protein-containing substance may be added to the liquid before adding the fecal material to the liquid. In other embodiments, the protein-containing substance may be added to the liquid after adding the fecal material to the liquid. In some embodiments, the protein-containing substance may be added before collecting the sample from the liquid. For example, the protein-containing substance may be added to the toilet water before collecting the sample from the toilet water. In such embodiments, the collected sample may include a substance derived from fecal material and a portion of the protein-containing substance. However, in other embodiments, the protein-containing substance may be added after collection of the sample. For example, a sample containing a substance derived from fecal material may be collected from the liquid, and then the protein-containing substance may be added to the liquid of the sample.

[0045] In some embodiments, the method can include agitating or rocking the liquid. Agitating or rocking the liquid can enhance the dispersion of substances and / or protein-containing substances derived from fecal material within the liquid. In some embodiments, a sample collection device can be used to agitate or rock the liquid. However, other suitable methods and / or apparatuses for agitating or rocking the liquid can be used.

[0046] In some embodiments, the method can include actively dispersing substances derived from fecal material in the liquid before collecting the sample. In one embodiment, this can include agitating or rocking the liquid. For example, the method can include operating a sample collection device to agitate or rock the liquid so as to disperse substances derived from fecal material in the liquid.

[0047] In some embodiments, dispersing the protein-containing substance in the liquid can include actively dispersing the protein-containing substance in the liquid. In some embodiments, this can include agitating or rocking the liquid. For example, the method can include operating a sample collection device to agitate or rock the liquid so as to disperse the protein-containing substance in the liquid.

[0048] In some embodiments, the method may include actively dispersing the protein-containing substance in a liquid prior to sample collection. For example, the method may include actively dispersing the protein-containing substance in a liquid before adding the fecal material and before dispersing the substances derived from the fecal material. Alternatively, the method may include adding the fecal material to the liquid and dispersing the substances derived from the fecal material in the liquid before dispersing the protein-containing substance in the liquid. Alternatively, the method may include simultaneously dispersing the substances derived from the fecal material and the protein-containing substance in the liquid in the same operation. In another example, the method may include actively dispersing the protein-containing substance in the liquid of the sample after sample collection. For example, the protein-containing substance may be located within the sample collection device and arranged to contact the sample during or after sample collection. For example, the protein-containing substance may be provided within a pipette such as a hollow valve of the pipette.

[0049] In some embodiments, the test device may include a fecal immunochemical test device. The test device may include a lateral flow test strip. Alternatively, the test device may include any other test means suitable for testing one or more analytes in the sample.

[0050] In some embodiments, the method may include providing a liquid-permeable membrane. The sample may be collected from the liquid that has passed through the liquid-permeable membrane. In one example, providing the liquid-permeable membrane may include spreading and disposing the liquid-permeable membrane on the liquid to at least partially cover the fecal material. In another example, providing the liquid-permeable membrane may include covering at least the distal end of the sample collection device. In some embodiments, the sample collection device may be coated with the permeable membrane prior to agitation or rocking of the liquid. The liquid-permeable membrane may have sufficient strength to substantially maintain its form during agitation or rocking of the liquid. The method may include withdrawing the sample collection device from the liquid-permeable membrane before testing the sample.

[0051] Throughout this specification, the word "comprise", or variations such as "comprises" or "comprising", are to be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0052] [Brief Description of the Drawings] Here, by way of example only, embodiments will be described with reference to the accompanying drawings.

[0053] [Figures 1A and 1B] A flowchart showing the steps in a method for collecting a sample from fecal material according to an embodiment of the present disclosure. [Figure 2] A front view of a sample collection device according to an embodiment of the present disclosure. [Figure 3] A front view showing a sample collection device coated with a liquid-permeable membrane according to an embodiment of the present disclosure. [Figure 4] A sample collection device according to an embodiment of the present disclosure, including the pipette and liquid-permeable membrane of Figure 2. [Figure 5] Components of a kit for collecting and testing a sample from fecal material, comprising the sample collection device of Figure 4, according to an embodiment of the present disclosure. [Figure 6] A kit for collecting and testing a sample from fecal material, including a protein-based substance, a sample collection device, and a testing device, according to an embodiment of the present disclosure. [Figure 7A] A front view of the packaging for the protein-containing substance of Figure 6 in a closed state, according to an embodiment of the present disclosure. [Figure 7B] A front view of the open packaging of Figure 7A. [Figures 8A and 8B] Perspective views of the testing device of the kit of Figure 6 before and after testing a sample. [Figure 9A] A kit for collecting and testing a sample from fecal material, including a protein-based substance, a sample collection device, a testing device, and a liquid-permeable membrane, according to an embodiment of the present disclosure. [FIG. 10A] A flowchart showing steps in a method for examining a sample derived from fecal material according to an embodiment of the present disclosure. [FIG. 10B] A flowchart showing steps in a method for examining a sample derived from fecal material according to another embodiment of the present disclosure.

[0054] [MODE FOR CARRYING OUT THE INVENTION] A method for collecting a sample derived from fecal material according to the present disclosure is shown as flowchart 1000A in FIG. 1A. Method 1000A includes spreading and placing a liquid-permeable membrane on a liquid containing fecal material to cover the fecal material 1100, advancing a sample collection device toward the liquid-permeable membrane 1200, operating 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.

[0055] Some embodiments include one or more additional steps 1250, 1600, and 1700 of flowchart 1000B, illustrated in FIG. 1B. The relative positions of the method steps depicted in flowcharts 1000A and 1000B should not be construed as limiting the implementation of those steps to any particular order.

[0056] Examples of the sample collection device 200 and the liquid-permeable membranes 410, 420 suitable for use in the methods of FIGS. 1A - 1C are shown in FIGS. 2 - 5. The sample collection device 200, and the liquid-permeable membranes 410 and 420, and alternative embodiments are disclosed in more detail below.

[0057] In one embodiment, the liquid in which the liquid permeable membrane is to be spread is water, specifically, the water in a toilet. In this embodiment, therefore, spreading the liquid permeable membrane in the liquid includes placing the liquid permeable membrane in the toilet that contains the toilet water and fecal material. Therefore, the liquid permeable membrane is placed so as to cover the fecal material after defecation. However, in other embodiments, the liquid can be 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 that prevents the fecal material from being sampled so that only the liquid can pass through. In addition, this reduces the need for contact with the feces itself or visual recognition of the feces itself when collecting the sample, thereby improving the compliance of an individual in undergoing a colon cancer screening.

[0058] Agitation and oscillation of the liquid facilitate the mixing or dispersion of substances derived from fecal material in the liquid in which the fecal material is immersed. In one embodiment, the substance derived from fecal material is occult blood and thus contains hemoglobin. Agitation and oscillation of substances derived from fecal material in the surrounding liquid can allow the hemoglobin of occult blood to disperse and can facilitate a more uniform distribution of hemoglobin in the liquid. Thereby, even when the collected sample is small, the probability of collecting a sample containing occult blood and hemoglobin, which represents the whole fecal material, can increase.

[0059] For this purpose, method 1000B may further include step 1250 of using the distal tip of the collection device to push the area of the permeable membrane into the liquid. The pressure applied to contact the area of the liquid-permeable membrane and push down this area may cause the liquid-permeable membrane to break around the distal portion adjacent to the distal end D of the collection device. The breakage of the liquid-permeable membrane around the collection device may act as an additional barrier between the collection device and the fecal material under the liquid-permeable membrane. Thereby, the possibility that the user directly faces the fecal material itself can be optimized to be avoided. Pushing down the area of the permeable membrane may be performed before agitating or rocking the liquid. The breakage of the liquid-permeable membrane around the collection device may also assist in the dispersion of hemoglobin of occult blood in the liquid during agitation and rocking due to the increased mass provided at the distal end of the collection device.

[0060] The method shown in flowchart 1000B may further include step 1600 of examining the sample to detect the presence of one or more analytes in the sample. In one embodiment, examining the sample involves transferring the collected liquid sample to an examination device such as an assay device.

[0061] As further shown in flowchart 1000B, the examination of the sample may further include detecting one or more analytes that indicate a pathological condition in the stool material from which the sample is derived 1700. In one embodiment, the screening involves an examination for at least one analyte indicative of occult blood, for example, an examination for the presence of hemoglobin. Hemoglobin in a liquid sample may indicate colorectal cancer or a precursor polyp of colorectal cancer. However, in another embodiment, the one or more analytes may represent other pathological conditions, for example, one or more tumor-derived antigens. As mentioned above, agitating and rocking the liquid facilitates a uniform dispersion of stool-derived substances in the liquid in which the sample is collected such that the sample represents the entire stool. This is in contrast to a direct sampling method in which a sample of stool material that does not contain the analyte of interest can be collected even though the analyte may be present in other portions of the stool. Thus, the methods and apparatus of the present disclosure increase the probability of detecting one or more analytes that indicate a pathological condition (e.g., hemoglobin) when those analytes are present in the stool. This ultimately increases the sensitivity of the examination.

[0062] 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 as described below.

[0063] Examples of the liquid permeable membrane 410 are shown in FIGS. 4, 5, and 9. The liquid permeable membrane 410 can be configured to conceal fecal material such that substantially all of the fecal material is hidden from view of the user collecting the sample. The liquid permeable membrane 410 in the figures has a rectangular shape, although other shapes are also contemplated. In one embodiment, the liquid permeable membrane 410 can be sized or shaped to cover the surface area of the liquid in the toilet bowl. In another embodiment, the liquid permeable membrane 410 can be sized and / or shaped to cover the surface area of the liquid and contact the inner wall of the toilet bowl. In another embodiment, the liquid permeable membrane 410 can be sized or shaped to extend partially over the surface area of the liquid in the toilet bowl and / or to partially conceal the fecal material. Partial or complete concealment of the fecal material can minimize the need for close contact with the fecal material and can help reduce the user's aversion when performing sample collection.

[0064] The liquid permeable membrane 410 can be configured to fold or wrap around the distal end of the sample collection device 200 when the area of the permeable membrane is pushed down at the distal end D of the sample collection device 200. Thereby, means can be provided for filtering the liquid to allow the passage of the liquid while preventing the passage and collection of solid fecal material or other particulate contaminants during sample collection. Thereby, the risk of the user contacting the fecal material can be reduced, and the performance of the test in detecting one or more analytes such as hemoglobin can be optimized. Alternatively, the liquid permeable membrane 420 can be provided in the form of a pouch or coating, as will be described in more detail below.

[0065] The liquid permeable membranes 410, 420 can have sufficient strength to substantially maintain their form as liquid permeable membranes during agitation or sloshing of the liquid. For example, the liquid permeable membranes 410, 420 can have sufficient strength to withstand any tearing, breaking, or other damage that may occur during agitation and / or sloshing.

[0066] The liquid-permeable membranes 410 and 420 may be configured in the present embodiment to allow only the passage of a liquid, which may be occult blood containing hemoglobin, and substances derived from fecal material dissolved in the liquid. Thus, the liquid-permeable membranes 410 and 420 prevent or substantially block the passage of solid fecal matter (or other specific contaminants) through the liquid-permeable membranes 410 and 420, and thus may prevent the collection of any solid fecal matter in the sample. Thereby, the implementation of the test in the detection of one or more analytes such as hemoglobin can be optimized.

[0067] In some embodiments, the liquid-permeable membranes 410 and 420 are configured to be flushable. Throughout the present disclosure, the use of the term "flushable" or variations such as "flushability" implies that the product or material, specifically the liquid-permeable membranes 410 and 420, is configured to be disposable by flushing from the toilet into the outflow pipe and into the sewer or drain pipe without causing blockage or damage to the passing sewer or drain pipe.

[0068] In some embodiments, the liquid-permeable membranes 410 and 420 may include a positively charged material. The liquid-permeable membrane may additionally or alternatively include a color catcher or dye trap. The color catcher or dye trap may remove any color that may adversely affect the test results without passing through the liquid-permeable membrane from the liquid containing fecal material, or may capture any entity. In the present disclosure, the term "color catcher" or "dye trap" implies a material, material property, or product treated in such a way as to impede the movement of any pigment that may penetrate the liquid. In one embodiment, this implies that any pigment, color, dye, or associated element of fecal material that may penetrate into the liquid passing through the liquid-permeable membrane is retained in the material of the liquid-permeable membrane as the liquid passes through.

[0069] The liquid-permeable membranes 410, 420 can be configured to be substantially opaque (e.g., even when liquid soaks in) so that fecal material cannot be seen through the membranes. This can reduce the need for contact with and / or visual recognition of fecal matter itself, thereby improving user compliance when performing tests using the kit. In some embodiments, the liquid-permeable membranes 410, 420 may contain color pigments to further conceal fecal material in the liquid. In one embodiment, the collection device may include a pipette. In the embodiment illustrated in FIG. 2, the pipette 200 includes a hollow flexible valve 210 and a hollow tube 220. The hollow tube is fluidly connected to the valve at the proximal end P of the hollow tube and defines an opening 230 at the distal end D of the hollow tube. In the illustrated embodiment, the opening 230 is at the distal end of the hollow tube, which is the distal tip of the collection device. The pipette may include graduations indicating the volume of liquid that can be held. In an alternative embodiment, the pipette may include a rotating portion and a plunger, and when the rotating portion rotates, the volume of the plunger can be adjusted to a desired volume for sample collection. The pipette and any of its components can be made of glass, plastic, rubber, or a combination of such materials. The collection of a sample using a pipette can enable the collection of a quantitative or semi-quantitative sample. That is, the use of a pipette can enable the collection of a controlled and consistent volume of liquid that is suitable for testing the sample.

[0070] However, in another embodiment, the collection device can be an alternative device suitable for collecting a liquid sample, such as a brush or brush-like device having flexible or semi-flexible hairs at or adjacent to the distal end. In this case, the volume of liquid in the sample is collected semi-quantitatively in that the amount of liquid retained within the interstitial space of the hairs of the sampling device is moderately constant for any particular size and configuration of the sampling device.

[0071] In some embodiments, the sample collection device 200 can be configured to agitate or rock the liquid, for example, by having sufficient strength to allow agitation or rocking of the liquid when held by the proximal end P. Agitating or rocking the liquid can disperse substances from the fecal material into the liquid. Similarly, agitating or rocking the liquid or the liquid in the sample can enhance the dispersion and / or dissolution of the proteinaceous material 100 into the liquid before sample collection or into the sample liquid after sample collection.

[0072] In some embodiments, the assay device can be any assay device capable of detecting one or more analytes indicative of a pathological condition in the fecal material from which the sample is derived. The assay device can include an assay strip, such as a lateral flow assay strip, also known as an immunochromatography test strip or a rapid test strip, which allows the test to proceed in a relatively short period of time when the sample is introduced into a cartridge that provides an accurate assay of the sample upon collection. The test results can then be read immediately or at any time thereafter, without the risk of analyte loss due to degradation during transport, as seen in other tests. In another embodiment, testing of the sample can involve transporting the sample to a testing facility, such as a laboratory, for testing.

[0073] The method can be implemented using a sample collection device. FIG. 4 shows a sample collection device 520 according to the present disclosure for collecting a sample from fecal material. In the illustrated embodiment, the sample collection device 520 includes a liquid-permeable membrane 410 and a collection device 200, each embodying the features described above. In this embodiment, the liquid-permeable membrane 410 is configured to cover the fecal material such that substantially all of the fecal material is hidden from view of the user collecting the sample, as described above.

[0074] Figure 3 shows another embodiment of the sample collection device 510 in which the sample collection device 200 is coated with the 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 wraps around the hollow tube and distal tip of the pipette.

[0075] In this embodiment, the liquid permeable membrane 420 may be in the form of a sleeve or pouch into which the sample collection device 200 can be inserted. The liquid permeable membrane 420 may be configured to enclose at least the distal end of the sample collection device 200. In the embodiment of Figure 3, the liquid permeable membrane 420 is configured to coat the hollow tube 220 of the sample collection device from the distal end to the proximal region, adjacent to the valve 210. In other embodiments, the liquid permeable membrane 420 may enclose or coat 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.

[0076] An alternative method of collecting a sample can be implemented using the pipette 200 and the membrane 420, as illustrated in method 1000C of Figure 1C. This method may include a step 1050 of coating the sample collection device 200 with the liquid permeable membrane 420. Alternatively, the sample collection device may be pre-coated and supplied.

[0077] In this embodiment, the coated pipette 200 is advanced into the liquid (step 1210 in Figure 1C) as previously described in connection with steps 1300 and 1400 of Figures 1A and 1B, and this is used to stir or agitate the liquid to collect a sample of the liquid that has passed through the membrane 420. The method may then include further steps 1600 and 1700 of inspecting the sample and detecting the analyte, as previously described.

[0078] The liquid permeable membrane 420 of the embodiment described above may not be large enough to substantially cover the stool material. However, the membrane 420 provides a means for filtering the liquid to prevent the passage of stool material and / or other contaminating particles through the membrane 420 during sample collection. The liquid permeable membrane 420 may be configured to remain in the liquid when the liquid permeable membrane 420 is wet and, for example, the pipette 200 is withdrawn by sliding and removing the distal end of the pipette 200.

[0079] FIG. 5 shows a kit 5000 for examining a sample derived from a stool material. In the illustrated embodiment, the kit 5000 includes a sample collection device 520 that includes a liquid permeable membrane 410 and a sample collection device 200 as described above. Alternatively, the kit 5000 may include a sample collection device 510 as shown in FIG. 3. In an alternative embodiment, the sample collection device may be any other device suitable for collecting a liquid sample, such as a brush or brush-like device having flexible or semi-flexible hairs, as disclosed above. The kit 5000 also includes an assay device, such as an assay device 5100 (or inspection device 300) adapted for detecting one or more analytes in the sample. The assay device may include any of the features and may embody the principles described above.

[0080] At least one analyte detected in the assay device 5100 indicates a pathological condition in the stool material from which the sample is derived. In one embodiment, this analyte may represent occult blood, e.g., hemoglobin, in the sample. However, in another embodiment, this may be any other analyte indicating a pathological condition, e.g., one or more analytes representing tumor-derived antigens.

[0081] The kits and methods according to embodiments of the present disclosure that include the proteinaceous substance 100 are described in more detail below.

[0082] FIG. 6 shows a kit 6000 according to an embodiment of the present disclosure. The kit 6000 includes a protein-containing substance 100 for dispersion in a liquid, a sample collection device 200 for collecting a sample containing a substance derived from fecal material from the liquid, and an inspection device 300 configured to detect one or more analytes in the sample. An alternative kit 7000 that may include a liquid-permeable membrane 410 (or 420) will also be described below. A method for inspecting a sample derived from fecal material will be described with reference to flowcharts 3000A and 3000B.

[0083] Examples of the protein-containing substance 100 and the inspection device 300 suitable for inclusion in the kits 6000 and 7000 and suitable for use in the methods shown in the flowcharts 3000A and 3000B disclosed herein are shown in FIGS. 6 to 9A and will be described in more detail below. The sample collection device 200 and the liquid-permeable membranes 410 and 420 as used in the methods 3000A and 3000B or the kits 6000 and 7000 may include one or more of the features as described above with reference to FIGS. 2 to 5.

[0084] In one embodiment, the liquid in which the sample is to be collected is water. For example, the liquid can be the water in a toilet bowl. The protein-containing substance 100 can be dispersed in water. For example, the protein-containing substance 100 can be added to the water in a toilet bowl either before or after the addition of feces to the water.

[0085] The protein-containing substance 100 can be a substance capable of being dispersed in water. In one embodiment, the protein-containing substance 100 can be capable of dissolving in the water in a toilet bowl. Alternatively, the protein-containing substance 100 can be capable of being dispersed and / or dissolved in a liquid (such as water) in an alternative container suitable for receiving fecal material.

[0086] In the embodiment shown in FIG. 6, the protein-containing substance 100 is in the form of a powder. In another embodiment, the protein-containing substance 100 can be provided in any other form that can be dispersed and / or dissolved in a liquid. For example, the protein-containing substance 100 can include a liquid, a paste, a tablet, a pill, a mixture, or a combination thereof. In one embodiment, the protein-containing substance 100 is a dry milk powder such as commercially available whole milk powder or skim milk powder. In this embodiment, the dry milk powder can be formed using several powder processing techniques including fat standardization, pasteurization, evaporation, homogenization, and spray drying. The dry milk powder can be homogenized dry milk powder.

[0087] In another embodiment, the protein-containing substance 100 can be a liquid. For example, the protein-containing substance 100 can include commercially available dairy products such as whole milk, low-fat milk, or a combination thereof, containing a preservative diluted in a liquid such as water. In some embodiments, the user can supply the protein-containing substance 100 for addition to a liquid.

[0088] In another embodiment, the protein-containing substance 100 can include a solid substance such as a tablet or pill derived from milk. In this embodiment, the tablet or pill can include a milk-derived powder such as the dry milk powder described above, and a soluble binder component compressed into the form of a tablet or pill. Additionally or alternatively, the protein-containing substance can include one or more dispersants. The one or more dispersants can include one or more active ingredients such as sodium bicarbonate and / or citric acid, or other suitable dispersants. The dispersant can assist in the dissolution and / or dispersion of the protein-containing substance in a liquid, for example, by providing a foaming action. When the tablet or pill is added to a liquid, the soluble binder component and / or the dispersant can function to break down the components of the tablet by continuous contact with the liquid so that the protein-containing substance 100 is dispersed and / or dissolved in the liquid. In another embodiment, the protein-containing substance 100 can include one or more of a powder, a paste, a liquid, a tablet, or a mixture.

[0089] The protein-containing substance 100 can be a substantially opaque substance. When the protein-containing substance 100 is added to a liquid, the opacity of the liquid in which the protein-containing substance 100 is dispersed and / or dissolved can increase. In some embodiments, the protein-containing substance 100 renders the liquid substantially opaque. In embodiments where the protein-containing substance 100 is added to water, specifically toilet water, and is dispersed in the water, the liquid can change from substantially transparent to substantially opaque. The increased opacity of the liquid can at least partially conceal the contents of the liquid, thereby potentially at least partially concealing the fecal material in the toilet water.

[0090] The protein-containing substance 100 can additionally or alternatively provide a means for changing the consistency and / or color of the liquid and substantially concealing fecal material from the user's view, which is added to the liquid after defecation. In some embodiments, the color and opacity of the protein-containing substance 100 are white and / or can be cloudy, as is typical of milk or dairy products. Thus, when the protein-containing substance 100 is added to a liquid and dispersed therein, the liquid increases in opacity from a substantially transparent liquid to a cloudy milky white liquid, substantially concealing any fecal material from the user's view. The protein-containing substance 100 can include a colorant or dye that can change the color and opacity of the liquid to which the protein-containing substance is added such that the liquid transitions from a substantially transparent liquid to a substantially opaque and colored liquid.

[0091] For example, by increasing the opacity and / or changing the color of the liquid, partial or complete concealment of fecal material can serve to reduce the visibility of defecation to the user and can reduce the user's aversion when performing sample collection.

[0092] In an alternative embodiment, the proteinaceous substance 100 can be an alternative powder, paste, liquid, tablet, mixture, or combination thereof containing a suitable protein. In some embodiments, the proteinaceous substance 100 can include bovine serum albumin (BSA). In some embodiments, adding the proteinaceous substance 100 to a liquid may not change the opacity, and the liquid may remain substantially transparent. This can be desirable in situations where a clear sample is required. This can apply, for example, when using some quantitative FITs such as an "OC sensor".

[0093] As shown in the embodiment depicted in FIG. 7A, the proteinaceous substance 100 can be packaged in a sachet 110 that can be provided in the kit 6000. In this embodiment, the sachet 110 is configured to be appropriately sealed, for example, via an airtight seal at one end or around the sachet, to prevent exposure of the proteinaceous substance 100 to moisture and / or outside air before use. Sealing the sachet can prevent or reduce degradation or contamination of the proteinaceous substance 100 before use.

[0094] As shown in FIG. 7B, the sachet 110 can be torn, for example, near the seal (e.g., following the direction provided on the package) to form an opening 130. The sachet 110 can then be rotated at a suitable angle to enable the user to administer the contents of the sachet 110, for example, to add the proteinaceous substance 100 to a liquid.

[0095] In another embodiment, the proteinaceous substance 100 can be provided in a container that includes an airtight seal covering the opening of the container. The container can be provided in, for example, the packages of the kits 6000, 7000, or can be integrated with this package.

[0096] In an alternative embodiment, the proteinaceous substance 100 can be housed within a portion of the sample collection device 200 and released into the liquid of the sample during or after sample collection. For example, the proteinaceous substance 100 can be housed within the valve or stem of a pipette. In other embodiments, the proteinaceous substance 100 can be housed and / or packaged in any other means suitable for holding and preserving the proteinaceous substance 100 prior to use, based on the form of the substance as disclosed above, such as, for example, a container, capsule, pouch, wrap, or bag.

[0097] The assay device 300 is configured to detect at least one analyte indicative of a pathological condition in the fecal material from which the sample is derived. In one embodiment, the assay device 300 is configured to detect at least one analyte in the sample that represents occult blood, e.g., hemoglobin. Dispersing and / or dissolving the proteinaceous substance 100 in the liquid can enhance the sensitivity of the assay. For example, without wishing to be bound by theory, it is hypothesized that the proteinaceous substance 100 can function to stabilize a hemoglobin analyte in the sample (the analyte being the protein globin portion of the hemoglobin molecule), e.g., by maintaining its conformational stability. Additionally or alternatively, the proteinaceous substance can also enhance assay sensitivity by functioning to transfer hemoglobin, which has a tendency to bind to fecal material, from the fecal material into the liquid. This can improve the availability of hemoglobin in the liquid from which the sample is extracted, and thus improve the detection of hemoglobin at high levels of dilution and the consistency of assay results. Assays conducted in accordance with the present disclosure have been shown to have a limit of detection (LoD) for detecting blood in water of less than about 0.05 μL / L (or <7.5 ng / ml).

[0098] Figures 8A and 8B show one embodiment of the test device 300 for inclusion in the kit 6000. In this embodiment, the test device 300 is a lateral flow immunoassay device comprising a test strip 310 housed in a housing 320 having a front face 330. The test strip 310 can be a lateral flow test strip, also known as an immunochromatography test strip, or an immunochemical test strip known as a "rapid test". The front face 330 of the housing 320 can include a first opening that defines a sample receiving portion 332. The sample receiving portion 332 can enable access to a portion of the test strip 310 configured to receive a sample. The front face 330 of the housing 320 can include a second opening that defines a display portion 334. The display portion 334 can be configured to display a result indicator portion of the test strip 310. The result indicator portion can include a control line 336 and one or more test lines 338. The front face 330 of the housing 320 can include markings indicating various portions of the test strip. For example, as can be seen in Figures 8A and 8B, in this embodiment, the front face 330 of the housing 320 includes the letters "C", "T", and "S" indicating the control line 336, the test line 338, and the sample receiving portion 332, respectively.

[0099] In the illustrated embodiment, the control line 336 and the test line 338 include colored lines visible in the display portion 334, as shown in Figure 8B. The formation and appearance of both the control line 336 and the test line 338 can indicate a positive test result (i.e., detection of at least one analyte), and the formation and appearance of the control line only can indicate a negative test result (i.e., no analyte detected). The formation of the test line occurs when conjugated labeled antibodies present in a layer of the test strip 310, such as a nitrocellulose membrane, bind to one or more target analytes present in the sample. In an embodiment where the test device 300 is configured to detect hemoglobin, a positive test result (i.e., the formation and appearance of both the control line and the test line as shown in Figure 8B) indicates the presence of hemoglobin in the sample.

[0100] The test device 300 may be considered defective if the control line is not formed and displayed during the test. The use of the lateral flow test strip 310 enables performing the test and showing the results in a relatively short period after introducing the sample into the test strip 310, providing an accurate assay of the sample at the time of collection. The test results can be read immediately or within a specified subsequent period without the risk of analyte loss due to degradation during transportation, as seen in other tests. The test results can warn the user or the attending physician to seek further investigation or testing. In another embodiment, an alternative test device or assay device suitable for detecting one or more analytes can be used to test the sample. Additionally or alternatively, testing the sample can involve transporting the collected sample to a testing facility, such as a laboratory, for testing.

[0101] Another example of the kit 7000 according to the present disclosure is shown in FIG. 9. In this embodiment, the kit 7000 includes a proteinaceous substance 100, a sample collection device 200, a test device 300, and a liquid-permeable membrane 410. The liquid-permeable membrane 410 can be configured to be spread in a liquid to cover the fecal material after defecation, as described above in connection with the testing methods 1000A and 1000B.

[0102] Additionally or alternatively, the kit 7000 can include a liquid-permeable membrane 420 configured to cover the sample collection device 200, as shown in FIG. 3 and described above.

[0103] A method for testing a sample derived from fecal material according to the present disclosure is shown as flowchart 3000A in FIG. 10A. The method 3000A includes adding a proteinaceous substance into a liquid 3100, dispersing the proteinaceous substance in a liquid 3200, adding fecal material into a liquid 3300, collecting a sample from the liquid 3400 using a sample collection device, and testing the sample for one or more analytes in the sample 3500 using a test device.

[0104] In some embodiments, the method may include one or more additional steps 3255, 3257, 3350, 3355, 3357, and 3450, as shown, for example, in flowchart 3000B of FIG. 10B. The relative positions of the method steps depicted in flowcharts 3000A and 3000B should not be construed as limiting the steps to be performed in any particular order.

[0105] The method may be carried out using an inspection kit such as kit 6000 or 7000, as described above.

[0106] In some embodiments, the liquid may be water, specifically, toilet water. In this embodiment, adding the protein-containing substance 3100 to the liquid may include adding the protein-containing substance (e.g., powdered milk) to the water contained in the toilet. For example, the contents of the sachet 100 may be sprinkled onto the surface of the toilet water.

[0107] Adding fecal material into the liquid 3300 can include, for example, adding fecal material into the water of the toilet bowl by using the toilet for defecation in a normal manner. The presence of urine and / or toilet paper in the toilet bowl does not prevent inspection and sample collection. However, in another embodiment, the liquid can be water in any other container suitable for receiving fecal material. Adding a protein-containing substance into the liquid 3100 can include adding the protein-containing substance into the water in the container. Similarly, in this embodiment, adding fecal material into the liquid 3300 includes adding fecal material into the water in a container suitable for receiving fecal material after defecation. Alternatively, after adding fecal material and / or the protein-containing substance 100 to the container, water (or other test liquid) can be added to the container. In some embodiments, the protein-containing substance 100 is added to the liquid before adding fecal material into the liquid. Thereby, the risk that the user contacts with fecal material can be reduced. However, in other embodiments, the protein-containing substance 100 is added to the liquid after adding fecal material into the liquid. In yet another embodiment, the protein-containing substance 100 is added to the liquid in the sample after collecting the sample of the liquid.

[0108] In some embodiments, the method includes actively dispersing substances from fecal material in the liquid 3355 by agitating and / or rocking the liquid (e.g., using a sample collection device or another suitable agitation device) as described above. Agitating or rocking the liquid can enhance the dispersion of substances from fecal material that mix or disperse in the liquid in which the fecal material is immersed. Operating 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 in a stirring motion from the proximal end P to actively mix and thus disperse substances from fecal material. In one example, where the sample collection device is a pipette 200 as shown in FIGS. 2, 3, 6, and 9 as described above, the user can hold the pipette at the proximal end P at the top of the hollow valve 210 and advance the pipette in the liquid such that the distal end D of the hollow tube 220 is inserted into the liquid for agitation. In another embodiment, any other sample collection device, such as a brush or spoon-like structure, suitable for agitating and rocking the liquid can be used.

[0109] This method may further include dispersing the proteinaceous material 100 in a liquid. In some embodiments, this may include passively dispersing the proteinaceous material 100 in the liquid over time. In another embodiment, dispersing the proteinaceous material in the liquid includes actively dispersing the proteinaceous material 3255 by agitating and / or rocking the liquid (e.g., using the sample collection device or another suitable agitation device described above) to disperse the proteinaceous material 100 in the liquid 3257. Both passive and active dispersal of the proteinaceous material 100 can be performed, but active mixing and agitation of the proteinaceous material can further assist in dispersing and / or dissolving the proteinaceous material in the liquid. Dispersal can facilitate a more uniform distribution of the proteinaceous material 100 in the liquid. Dispersal can improve the interaction between the proteinaceous material 100 and the fecal material in the liquid. An increase in the interaction between the proteinaceous material and the fecal material can increase the probability that the hemoglobin analyte is stabilized, for example, by maintaining the conformational stability of hemoglobin in the collected sample, and thus can improve the detection of hemoglobin at high levels of dilution. Additionally, in one embodiment where the proteinaceous material 100 is derived from milk or contains a pigment or dye that can increase the opacity of the liquid, agitating and rocking the liquid containing the proteinaceous material further aids in providing a uniform distribution of the proteinaceous material and thus can increase the opacity of the liquid in a consistent manner that enhances the masking of the fecal material present in or added to the liquid. In other embodiments, the proteinaceous material 100 does not increase the opacity of the liquid after addition and / or dispersal, and a substantially transparent liquid can be maintained. For example, in some embodiments, the proteinaceous material can include BSA.

[0110] In one embodiment, dispersing the protein-containing substance 100 in the liquid is performed before sample collection. Dispersing the protein-containing substance can be performed before adding the fecal material into the liquid. In one example, the protein-containing substance 100 can be added to the liquid and dispersed in the liquid before adding any fecal material into the liquid. To assist in the dispersion of the protein-containing substance 100, the user can stir and / or agitate the liquid before adding the fecal material into the liquid, as described above. Then, the fecal material can be added to the liquid. As described above, stirring and / or agitating the liquid can be repeated to disperse the substances derived from the fecal material. For example, stirring and / or agitating can enhance the dispersion of occult blood (and thus hemoglobin) in the liquid. In one embodiment, the dispersion of the protein-containing substance 100 and the substances derived from the fecal material can be performed with the same stirring and agitating operations.

[0111] In another example, the protein-containing substance 100 can be added to the liquid and dispersed in the liquid after adding any fecal material into the liquid. In this case, the dispersion of the protein-containing substance 100 and the substances derived from the fecal material, namely occult blood containing hemoglobin, can be performed in one operation. For example, the sample collection device 200 can be operated to stir and / or agitate the liquid containing both the protein-containing substance 100 and the substances derived from the fecal material simultaneously. In other embodiments, the dispersion of the substances derived from the fecal material and the protein-containing substance 100 can be performed in two separate operations, with the substances derived from the fecal material being dispersed before the protein-containing substance 100. In yet another embodiment, dispersing the protein-containing substance 100 can be performed after sample collection, more specifically, after adding the fecal material into the liquid. In this example, as described above, the fecal material can be added to the liquid, and the substances derived from the fecal material can be dispersed in the liquid before sample collection. After collecting the sample using the sample collection device 200, the protein-containing substance 100 can then be added to the liquid of the sample in, for example, the hollow valve 210 of the pipette 200 as shown in FIG. 2, within a part of the sample collection device, and dispersed in the liquid. In this example, the pipette 200 can be operated to stir or agitate the liquid of the sample in the hollow valve 210 by vibrating or swirling the pipette.

[0112] In one embodiment, the method further includes providing liquid-permeable membranes 410, 420, and the sample is collected from the liquid that has passed through the liquid-permeable membrane as shown in step 3350 of FIG. 6B. In one embodiment, providing a liquid-permeable membrane, e.g., 410, includes spreading the liquid-permeable membrane 410 over the liquid to at least partially cover the fecal material. In this embodiment, the liquid-permeable membrane 410 is spread over the liquid prior to sample collection such that the liquid-permeable membrane 410 creates a barrier between the liquid and its contents and the user and at least partially covers any fecal material contained in the liquid. In some embodiments, the liquid-permeable membrane 410 can be spread over the liquid prior to actively dispersing substances from the fecal material into the liquid. In this case, collecting the sample from the liquid involves advancing the sample collection device 200 towards the liquid-permeable membrane 410 and using the distal end of the sample collection device 200, e.g., the distal end D or the distal tip of the pipette 200, to push the area of the liquid-permeable membrane 410 into the liquid. The pressure applied to contact and push down on the 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. The folding of the liquid-permeable membrane 410 around the collection device 200 acts as an additional barrier between the sample collection device 200 and the fecal material under the liquid-permeable membrane 410 and can prevent the passage of any solid fecal material. This can optimize the likelihood of avoiding the user having to directly confront the fecal material itself.

[0113] In another embodiment, providing a liquid-permeable membrane, such as liquid-permeable membrane 410 or 420, may 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 membranes 410, 420 prior to sample collection. The liquid-permeable membranes 410, 420 may 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 of the device to the proximal end P. In one embodiment, the sample collection device 200 may be covered by the liquid-permeable membrane 420 prior to actively dispersing substances from fecal material into a liquid. In this embodiment, the sample collection device 200 covered by the liquid-permeable membrane 420 is advanced towards the liquid prior to sample collection, for sample collection, and for manipulation of the liquid.

[0114] The liquid-permeable membranes 410, 420 may be configured to fold around or wrap around the collection device. Additionally or alternatively, the liquid-permeable membranes 410, 420 may be in the form of a sleeve or a pouch. Advancing the sample collection device 200 covered by the liquid-permeable membrane 420 may further include depressing the area of the liquid-permeable membrane 420 when the distal end D and / or distal tip of the sample collection device 200 contacts the liquid. This method may include withdrawing the sample collection device 200 from the liquid-permeable membrane 420 prior to examining the sample, specifically, prior to transferring the sample to an examination device.

[0115] In one embodiment, collecting the sample includes collecting a volume of liquid that substantially corresponds to the volume required to examine the sample. Examining the sample may include transferring the sample from the sample collection device to an examination device 3450, such as by transferring the sample from the pipette 200 to the sample receiving portion 332 of the examination device 300. In another embodiment, examining the sample may involve transporting the sample to an examination facility, such as a laboratory, for examination.

[0116] Examining a sample using the test device 300 can include examining for one or more analytes indicative of a pathological or other condition in the stool material from which the sample is derived, e.g., examining for at least one analyte representative of occult blood (such as hemoglobin) in the sample. In one embodiment, the test device 300 includes a fecal immunochemical test device that embodies the principles described above and includes a lateral flow test strip 310. If hemoglobin is detected in the sample, the test device can display a positive result and alert the user to the presence of occult blood in the stool, which may indicate a pathological condition. This can then prompt the user to seek further medical tests or investigations to further evaluate and diagnose the cause of the bleeding and / or the source of any associated pathological condition, such as colorectal cancer, pre-cancerous polyps, adenomas, or lesions. In another embodiment, an alternative test device or assay device suitable for detecting one or more analytes can be used to examine the sample.

[0117] The method according to the present disclosure provides a relatively simple and inexpensive sampling method with little or no direct fecal handling, reducing the potential for direct contact with feces and improving the acceptability of performing tests within a population. The kit, device, or method according to the present disclosure can provide increased sensitivity that increases the likelihood of detecting trace amounts of blood compared to other known FIT and sampling methods.

[0118] The kit and method according to the present disclosure can increase the likelihood of detecting hemoglobin representative of the entire stool sample, as opposed to a small sample of stool, as is common with conventional FIT and sampling methods.

[0119] The kit, device, and method according to the present disclosure can facilitate the monitoring of subjects with very low fecal hemoglobin levels who may be at risk of developing conditions such as colorectal cancer and precursor polyps. In other examples, the test kit, device, and / or method according to the present disclosure can have applications in forensic examinations.

[0120] Some features are disclosed in relation to one or more embodiments, and other features may be disclosed in relation to one or more other embodiments, but it will be understood that combining these features with each other in one or more further embodiments is within the scope of the present disclosure. As a result, it will be understood that any combination of any disclosed features in one embodiment of the methods, apparatuses, or kits described herein is within the scope of the present disclosure.

[0121] Those skilled in the art will understand that numerous variations and / or modifications can be made to the embodiments described above without departing from the broad general scope of the present disclosure. Accordingly, the present embodiments should be considered in all respects to be illustrative and not restrictive.

[0122] Experimental Examples Example 1 In one example, the limit of detection (LoD) of the test kit according to the present disclosure was evaluated. In this example, a CTK FOB-HI rapid test device (CTK Biotech Inc, Poway, CA 92064, USA) was used to test the sample for the presence of blood. The sample was collected using the sample collection device according to the present disclosure.

[0123] 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 whole milk powder was collected and stored. Then, the liquid was sampled and tested (control negative).

[0124] After weighing the container and its contents, feces naturally excreted from a healthy subject were added to the container. Then, the container and its contents were weighed again to determine the weight of the feces. In this example, the weight of the feces was 124 grams. A sample was collected from the liquid in the container surrounding the feces using the sample collection device and tested (control negative).

[0125] 10 μL of fresh donor blood was collected from a finger prick. A 10 mL storage volume of liquid was used with powdered milk to dilute the blood. The diluted blood was then added to the container with feces up to the cumulative volume of blood shown in Table 1 below. Samples were collected and tested.

[0126] Results were recorded 10 minutes after sample addition. As shown in Table 1, after a 10-minute test, the LoD was 0.025 μL blood / liter. After a 40-minute test development time, the results remained the same. The control negative test results remained stable over the 40-minute development time. After the addition of 0.2 μL of blood, the maximum detection intensity was reached. The concentration of hemoglobin (Hb) in the donor blood was 148 μg / μL. Thus, in 0.025 μL of blood, the total Hb present in the sample is equal to 148 × 0.025 = 3.7 μg. Thus, in 1 liter of water, the Hb concentration is 3.7 ng / ml. If 124 g of feces contributed to the Hb, the amount of Hb / g of feces would be equal to 3.7 / 124 = 0.03 μg / g of feces. This experiment showed that the kit and test method according to the present disclosure enable the detection of blood at a concentration of less than 1 μL / liter.

Table 1

[0127] Example 2A In another example, further tests were performed to evaluate a factor that influenced the LoD of the kit and method. In one example, the LoD of blood in liquid and the effect of adding protein-containing substances were evaluated.

[0128] Blood was added in 2 μL increments up to a cumulative volume of 8 μL to 1 liter of water. Using the sample collection device according to the present disclosure, samples were collected after each addition of blood. Using the test device according to the present disclosure, each sample was tested.

[0129] Even with a maximum volume of 8 μL of blood, blood was not detected in any of the samples. This indicates the instability of Hb in water at higher dilutions.

[0130] 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 examined in two ways. Samples were collected and examined according to the method discussed above, and a negative result for the presence of Hb was obtained. Then, 30 grams of whole milk powder was added to the water, and samples were collected and examined according to the method of the present disclosure, and a negative result for the presence of Hb was obtained. Therefore, these results suggest that the denaturation of Hb cannot be reversed by the addition of a protein-containing substance (i.e., whole milk powder).

[0131] Example 2B In another example, the LoD of blood added to a liquid containing a protein-containing substance was evaluated.

[0132] Blood collected from a finger prick was diluted 1 / 100 with tap water. 30 grams of whole milk powder was added to 1 liter of water, and samples were taken and examined using the sample collection device and the test device according to the present disclosure. Diluted blood samples were gradually added in 0.1 μL increments up to 0.5 μL to 1 liter of water containing 30 grams of whole milk powder, and samples were taken and examined after each addition.

[0133] The LoD for blood in a 3% milk solution was 0.3 μL blood / liter. At a blood Hb concentration of 148 μg / μL, the total amount of Hb at the LoD is equal to 0.3 × 148 = 44 μg = 44 ng / ml in 1 liter of water. This is close to the required analytical sensitivity for Hb in the stabilizing buffer of the CTK test device when tested under laboratory conditions of 25 ng / ml.

[0134] Example 2C In another example, the LoD of blood added to feces in a liquid was evaluated.

[0135] One liter of tap water in a 3-liter container was added with feces defecated naturally. In this example, the weight of the feces was 148 grams. Blood collected from fingerpricks was diluted 1 / 100 with tap water. Diluted blood was added to the 1 liter of water containing the fecal sample in 0.1 μL blood increments (1 / 100 of 10 μL) until the LoD was established in two tests. As recorded in Table 2 below, after 10 minutes, the LoD was 1 μL blood / liter of water (1.0 μL), and consistent positive results for the presence of Hb were obtained. Further, after 4 hours, the final blood addition (i.e., at 1.25 μL) was retested and positive results for the presence of Hb were obtained, thus providing evidence that Hb molecules were stable in the presence of the fecal sample for over 4 hours. The sensitivity of Hb is equal to 1 μL of blood at 148 μg / μL = 148 μg / liter or 148 ng / ml. For feces with a weight of 148 g, Hb / g of feces = 148 / 148 = 1 μg / g. This sensitivity is good compared to the reported sensitivity of the standard OC sensor of 3.8 μg / g of feces.

Table 2

[0136] Example 2D In another example, the effect on the test LoD by adding a protein-containing substance to the liquid containing feces was evaluated. In this example, samples were collected using the coated sample collection device according to the present disclosure and tested using the test device according to the present disclosure.

[0137] To a 3-liter container containing 1 liter of tap water, feces defecated naturally from a healthy subject, having a weight of 232 grams, were added. Samples were collected using the sample collection device and the samples were tested using the test device as described previously.

[0138] To a container containing 1 liter of water (0.05 μL of blood, or equivalent to about 7.4 ng / ml) and a fecal sample, 5 μL of a 1 / 100 blood diluent was added. The sample was collected using a sample collection device and the sample was examined using an inspection device as described previously. Next, whole milk powder was added to the container in 5-gram increments up to a maximum of 30 grams. The sample was collected and examined in two ways each time whole milk powder was added.

[0139] 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. After adding 15 grams of whole milk powder, the peak intensity was reached.

[0140] These results indicate that the addition of whole milk powder decreased the LoD and thus increased the sensitivity of the test from 1 μL to 0. 05 μL of blood / liter of water, corresponding to a 20-fold increase in sensitivity. Feces added to 30 g of milk powder in 1 liter of water decreased 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 feces and milk powder can have a complementary effect on the test sensitivity for blood in water.

[0141] Also, after 1 hour, the test results of Test 0 without added blood or whole milk powder and Test 1 containing the initially added blood but no milk powder did not show any detection of a slight positive indication and remained negative, thus proving to be evidence of the stability of the negative result. A sample containing the final addition of whole milk powder (i.e., a total of 30 grams) was taken 4 hours later and re-examined. Hb was stable over 4 hours in the presence of feces in water containing 3% whole milk powder.

[0142] It is clear that there was a gain in sensitivity from the addition of 5g (0.5%) of whole milk powder. The addition of 0.05 μL of blood at an Hb concentration of 148 μg / μL provides an Hb concentration of 7.4 ng / ml. The required sensitivity of the CTK test device under laboratory conditions is 25 ng / ml. In this test, the added Hb is equal to 0.05 × 148 = 7.4 μg. 232 g of feces = 0.3 μg / g of feces. For the OC sensor, either increase the sensitivity by 126 times or increase the sensitivity to Hb in feces required for the CTK test used in this example of testing the kits and methods disclosed herein by 116 times.

Table 3

[0143] Further tests have shown that alternative sources of proteins such as whole milk or bovine serum albumin (BSA) can be replaced with milk powder having a similar effect.

[0144] The results of the examples from the above experiments conducted using the kits and methods according to the present disclosure show the following: · Hb is unstable at higher dilutions in water or undergoes conformational changes so that it is not detected by the CTK test device. · Protein-containing substances such as whole milk powder stabilize Hb. · The presence of feces in the liquid stabilizes Hb. · There is an unexpected synergistic effect resulting from the addition of both protein-containing substances and feces to water, which increases the sensitivity of the test beyond the level at which either protein or feces alone are present (in this example, to a sensitivity of 0.025 μL / liter). This is well above the reported detection limit for Hb in feces for conventional test methods.

[0145] Compared with conventional test kits and test methods, the kits and methods according to the present disclosure that follow the tests in the above examples illustrate a significantly improved sensitivity to the presence of Hb.

[0146] Some features are disclosed in relation to one or more embodiments, and other features may be disclosed in relation to one or more other embodiments. However, it will be understood that combining these features in one or more further embodiments is within the scope of the present disclosure. As a result, it will be understood that any combination of any of the disclosed features in one embodiment of the methods, apparatuses, or kits described herein is within the scope of the present disclosure.

[0147] Those skilled in the art will understand that numerous variations and / or modifications can be made to the embodiments described above without departing from the broad general scope of the present disclosure. Accordingly, the present embodiments should be considered in all respects as illustrative and not restrictive.

Brief Description of the Drawings

[0148]

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Claims

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

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

3. The kit according to claim 1 or 2, wherein the protein-containing substance contains 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 contains bovine serum albumin (BSA).

6. A method for inspecting a sample derived from fecal material, the method comprising: adding a protein-containing substance to a liquid; dispersing the protein-containing substance in the liquid; adding fecal material to the liquid; collecting a sample containing a substance derived from the fecal material from the liquid using a sample collection device; inspecting the sample for one or more analytes in the sample using an inspection device.

7. A method for collecting a sample derived from fecal material, the method comprising: spreading and disposing a liquid-permeable membrane on a liquid containing fecal material to cover the fecal material; advancing a sample collection device towards the liquid-permeable membrane; operating the sample collection device to stir or agitate the liquid so as to disperse a substance derived from the fecal material therein; 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 the form of the liquid-permeable membrane during the step of stirring or agitating the liquid.

8. The method according to claim 7, further comprising using a distal tip of the sample collection device to push down a region of the liquid-permeable membrane into the liquid before operating 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 coated with a liquid-permeable membrane towards a liquid containing fecal material; Operating the sample collection device to stir or agitate the liquid so as to disperse the substance derived from the fecal material in the liquid; 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 the form of the liquid-permeable membrane during the step of stirring or agitating the liquid.

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

11. The method according to any one of claims 7 to 10, further comprising examining the sample to detect the presence of one or more analytes in the sample, wherein at least one of the one or more analytes indicates a pathological condition in the fecal material that is the source of the sample.

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; a collection device configured to collect a sample containing a substance derived from the fecal material from the liquid that has passed through the liquid-permeable membrane, wherein the collection device is configured to be operated by a user to stir or agitate the liquid so as to disperse the substance derived from the fecal material in the liquid before collection of the sample, wherein the liquid-permeable membrane has sufficient strength to substantially maintain the form of the liquid-permeable membrane during stirring or agitation of the liquid.

13. The sample collection device according to claim 12, wherein the liquid-permeable membrane is configured to be spread over the liquid containing the fecal material so as to at least partially cover the fecal material.

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

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

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

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

18. The sample collection device according to any one of claims 12 to 17, wherein the liquid-permeable membrane contains a color catcher or a dye scavenger.

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

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

21. The method, sample collection device, or kit according to any one of the preceding claims, wherein the collection device includes a pipette.

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