Sheet-like structure and method for using same
Patent Information
- Application Number
- JP2022188860
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2022-11-28
- Publication Date
- 2025-11-05
AI Technical Summary
Existing test devices face issues with insufficient reaction time, complex assembly processes, and contamination risks due to high liquid flow rates, leading to inaccurate quantitative analysis.
A sheet-like structure with a porous structure layer and a support layer, featuring a separation section that blocks fluid flow between channels, allowing for sufficient reaction time and improved accuracy by separating and reuniting flow paths to control fluid flow.
The structure ensures adequate reaction time and enhances the accuracy of quantitative analysis by preventing fluid circulation and contamination, thereby improving the reliability of test results.
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Abstract
Description
[Technical field]
[0001] The present invention relates to a sheet-like structure and a method for using the same. [Background technology]
[0002] Development of testing devices that enable simple and rapid diagnosis in daily life and clinical settings is progressing. A typical example of a testing device is a pregnancy test. When a test liquid containing a target substance such as an antigen is introduced into the testing device, the test liquid flows through a flow path in the testing device. Then, a labeling medium such as an antibody that has been placed in the flow path beforehand reacts with the target substance in the test liquid to develop color (color), and the presence of the target substance can be confirmed.
[0003] Test chips, which are an example of testing devices, are sometimes called "μ-PADs (microfluidic paper-based analytical devices)" and have many advantages, such as (1) being inexpensive, (2) being pump-free, (3) not requiring large-scale equipment, and (4) being easy to dispose of, and research into improving them is being conducted worldwide.
[0004] Various types of test chips (test devices) have already been reported. For example, a test device has been proposed in which a liquid absorbing pad (paper disk) is provided between each layer of a plurality of paper chips constituting the test device in order to provide a device with a stronger coloring reaction intensity and higher accuracy by sufficiently securing the reaction time between the phosphorus-based pesticide as a specimen and acetylcholine esterase (AChE) that reacts with the phosphorus-based pesticide (see Non-Patent Document 1). The test device secures the reaction time between the specimen and AChE by utilizing the flow delay of the liquid caused by the liquid absorbing pad. In addition, a test chip has been proposed in which a three-dimensional flow path is formed in a sheet-like material in order to significantly suppress color unevenness (see Patent Document 1). [Prior art documents] [Patent documents]
[0005] [Patent Document 1] Patent Publication No. 2021-175970 [Non-patent literature]
[0006] [Non-Patent Document 1] Quoc Trung Hua et al.,analytical sciences,April,2019,Vol.35,p393-399 Summary of the Invention [Problem to be solved by the invention]
[0007] However, in the test device including the technology described in the above-mentioned Non-Patent Document 1, the liquid flows without sufficient primary reaction (reaction between the specimen and AChE), and since multiple substrates with flow paths are attached with double-sided tape, it is necessary to fill the gap between the substrates by the thickness of the double-sided tape, and there is a concern that the assembly process is complicated. In addition, in the test chip described in the above-mentioned Patent Document 1, the liquid flows quickly and the reaction time in the primary reaction cannot be sufficiently secured, so the specimen and the test reagent (e.g., antigen and antibody) must be mixed in advance and reacted before being added. At this time, there is room for improvement in the disposal of the container used for mixing and reaction, contamination of the specimen, simplicity, etc.
[0008] The present invention aims to solve the above-mentioned problems in the prior art and to achieve the following object: That is, the present invention aims to provide a sheet-like structure that can ensure a sufficient reaction time and improve the accuracy of quantitative analysis. [Means for solving the problem]
[0009] The means for solving the above problems are as follows. <1> The porous structure layer has at least a part of a flow path having a porous structure through which a fluid can flow, exposed on a surface thereof, and a support layer. The sheet-like structure is characterized in that the flow paths have separation parts capable of separating adjacent flow paths to block the flow of the fluid in the flow paths. <2> the separation portion is a cutting portion that cuts the flow path in a direction intersecting a flow direction of the fluid in the flow path; <1> 2. The sheet-like structure according to claim 1 . <3> At least a part of the flow path exposed to the surface is a fluid receiving portion. <1> 2. The sheet-like structure according to claim 1 . <4> The separation section separates the fluid receiving section from the flow path adjacent to the fluid receiving section, and is capable of blocking the fluid received in the fluid receiving section from flowing through the flow path adjacent to the fluid receiving section. <3> 2. The sheet-like structure according to claim 1 . <5> The support layer is disposed in a region of the porous structure layer where the fluid receiving portion is not located. <3> 2. The sheet-like structure according to claim 1 . <6> The support layer is water impermeable. <1> 2. The sheet-like structure according to claim 1 . <7> The exposed shape of the flow path exposed on one surface of the porous structure layer is different from the exposed shape of the flow path exposed on the other surface of the porous structure layer. <1> 2. The sheet-like structure according to claim 1 . <8> At least a part of the flow path exposed to the surface is a detection unit, and the detection unit is disposed at a position in the flow path different from the fluid receiving unit. <3> 2. The sheet-like structure according to claim 1 . <9> The above <1> From the above <8> A method for using the sheet-like structure according to any one of the preceding claims, a first flow path is provided on one side of the separation section, and the first flow path and the second flow path are separated at the separation section to block the flow of the fluid so that the fluid received in the first flow path does not flow into a second flow path on the other side of the separation section; This is a method of using a sheet-like structure, characterized in that after a certain period of time has elapsed, the first flow path and the second flow path are brought into contact with each other in the separation section, thereby allowing the fluid to circulate between the first flow path and the second flow path. <10> The first flow path is a fluid receiving portion, and a detection portion is disposed in a part of the second flow path. <9> A method for using the sheet-like structure described in the above. Effect of the Invention
[0010] According to the present invention, it is possible to provide a sheet-like structure that can ensure a sufficient reaction time and improve the accuracy of quantitative analysis. [Brief description of the drawings]
[0011] [Figure 1A] FIG. 1A is a schematic perspective view of a sheet-like structure according to a first embodiment. [Figure 1B] FIG. 1B is a schematic cross-sectional view of the sheet-like structure of FIG. 1A taken along line aa'. [Figure 2A] FIG. 2A is an explanatory diagram for explaining the function of the separation unit. [Figure 2B] FIG. 2B is an explanatory diagram for explaining another function of the separation unit. [Figure 3A] FIG. 3A is an explanatory diagram for explaining an example of the distribution of the support layer. [Figure 3B] FIG. 3B is an explanatory diagram for explaining another example of the distribution of the support layer. [Figure 3C] FIG. 3C is an explanatory diagram for explaining still another example of the distribution of the support layer. [Figure 4A] FIG. 4A is a schematic cross-sectional view of a sheet-like structure according to a second embodiment. [Figure 4B]FIG. 4B is a schematic plan view of the porous structure layer of FIG. 4A when viewed from the α direction. [Figure 4C] FIG. 4C is a schematic plan view of the porous structure layer of FIG. 4A when viewed from the β direction. [Figure 5A] FIG. 5A is a schematic cross-sectional view of a sheet-like structure according to a third embodiment. [Figure 5B] FIG. 5B is a schematic plan view of the porous structure layer of FIG. 5A when viewed from the α direction. [Figure 5C] FIG. 5C is a schematic plan view of the porous structure layer of FIG. 5A when viewed from the β direction. [Figure 6A] FIG. 6A is a schematic cross-sectional view of a sheet-like structure according to a fourth embodiment. [Figure 6B] FIG. 6B is a schematic plan view of the porous structure layer of FIG. 6A when viewed from the α direction. [Figure 6C] FIG. 6C is a schematic plan view of the porous structure layer of FIG. 6A when viewed from the β direction. [Figure 7A] FIG. 7A is a schematic plan view of a porous structure layer in a sheet-like structure of the fifth embodiment, as viewed from the α direction. [Figure 7B] FIG. 7B is a schematic plan view of the porous structure layer in the sheet-like structure of the fifth embodiment when viewed from the β direction. [Figure 8A] FIG. 8A is a schematic plan view of a porous structure layer in a sheet-like structure of the sixth embodiment when viewed from the α direction. [Figure 8B] FIG. 8B is a schematic plan view of the porous structure layer in the sheet-like structure of the sixth embodiment when viewed from the β direction. [Figure 9A] FIG. 9A is a schematic plan view of a porous structure layer in a sheet-like structure of the seventh embodiment as viewed from the α direction. [Figure 9B] FIG. 9B is a schematic plan view of the porous structure layer in the sheet-like structure of the seventh embodiment when viewed from the β direction. [Figure 10A] FIG. 10A is a schematic plan view of a porous structure layer in a sheet-like structure of the eighth embodiment, as viewed from the α direction. [Figure 10B]FIG. 10B is a schematic plan view of the porous structure layer in the sheet-like structure of the eighth embodiment when viewed from the β direction. [Figure 11A] FIG. 11A is a schematic plan view of a porous structure layer in a sheet-like structure of the ninth embodiment, as viewed from the α direction. [Figure 11B] FIG. 11B is a schematic plan view of the porous structure layer in the sheet-like structure of the ninth embodiment when viewed from the β direction. [Figure 12A] FIG. 12A is a schematic plan view of a porous structure layer in a sheet-like structure of the tenth embodiment, as viewed from the α direction. [Figure 12B] FIG. 12B is a schematic plan view of the porous structure layer in the sheet-like structure of the tenth embodiment when viewed from the β direction. [Figure 13A] FIG. 13A is an explanatory diagram for explaining a specific flow channel shape in an embodiment. [Figure 13B] FIG. 13B is an explanatory diagram for explaining a specific flow channel shape in the embodiment. [Figure 13C] FIG. 13C is an explanatory diagram for explaining a missing flow channel shape in the embodiment. [Figure 13D] FIG. 13D is an explanatory diagram for explaining a missing flow channel shape in an embodiment. [Figure 14A] FIG. 14A is an explanatory diagram for explaining a single-sided or double-sided printing flow path in the embodiment. [Figure 14B] FIG. 14B is a cross-sectional photograph of the single-sided printing flow path taken along line ff' in FIG. 14A. [Figure 14C] FIG. 14C is a cross-sectional photograph of the double-sided printing flow path taken along line ff' in FIG. 14A. [Figure 15] FIG. 15 is a schematic cross-sectional view for explaining a porous structure layer in an example. [Figure 16] FIG. 16 is a schematic cross-sectional view for explaining a sheet-like structure in an embodiment. [Figure 17] FIG. 17 is a schematic cross-sectional view for explaining a sheet-like structure in an embodiment. [Figure 18A]FIG. 18A is a graph showing the measurement results of the quantitative analysis in the example. [Figure 18B] FIG. 18B is a graph showing the measurement results of the quantitative analysis in the example. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0012] (Sheet-like structure) The sheet-like structure of the present invention has a porous structure layer in which at least a part of a flow path of a porous structure through which a fluid can flow is exposed on the surface, and a support layer, The flow paths have a separation portion capable of separating adjacent flow paths to block the flow of the fluid in the flow paths.
[0013] The present invention will be described in detail below based on several embodiments, but the present invention is not limited to the following description in any way.
[0014] <First aspect> Fig. 1A is a schematic perspective view of a sheet-like structure according to a first embodiment, and Fig. 1B is a schematic cross-sectional view of the sheet-like structure of Fig. 1A taken along line aa'. The sheet-like structure 11 has a porous structure layer 101, a support layer 301, and a separation section X. Although details will be described later, the sheet-like structure 11 has such a configuration, and thus can block the flow of fluid in the flow path of the porous structure layer 101, and can ensure, for example, a sufficient reaction time between a specimen and a reaction reagent.
[0015] -Porous structure layer- The porous structure layer 101 in the sheet-like structure 11 is provided with flow paths A, B, and C, each made of a porous structure through which a fluid can flow by capillary action or the like, as well as a non-flow path Y in an area other than the flow paths A to C. The flow path C is connected to both the flow paths A and B, and the fluid can flow in the order of flow path A, flow path C, and flow path B, or in the order of flow path B, flow path C, and flow path A. For example, as shown in FIG. 1B, when a fluid is received in the flow path A, the fluid flows in the order of flow path A, flow path C, and flow path B.
[0016] The flow path of the porous structure may be formed so that at least a part of it is exposed on the surface of the porous structure layer, and may be formed so that it is exposed on the entire surface of the porous structure layer. In addition, the porous structure layer may have the porous structure (flow path) formed only on a part of the porous structure layer, or may be formed on the entire surface. In the porous structure layer, it is preferable that at least a part of the flow path exposed on the surface is a fluid receiving part. For example, in the porous structure layer shown in FIG. 1B, flow path A into which a fluid is introduced can be the fluid receiving part. In addition, it is preferable that at least a part of the flow path exposed on the surface is a detection part, and the detection part is disposed at a position in the flow path different from the fluid receiving part. For example, in the porous structure layer shown in FIG. 1B, flow path B can be the detection part.
[0017] Here, the "fluid" is not particularly limited and can be appropriately selected depending on the purpose as long as it can flow through the flow path of the porous structure by capillary action, etc. When the sheet-like structure of the present invention is applied to a testing device, examples of the fluid include a solution containing a specimen or a reaction reagent that reacts with the specimen. The viscosity of the fluid is not particularly limited as long as the fluid can flow through the flow paths of the porous structure, and can be appropriately adjusted depending on the purpose.
[0018] Here, the term "porous structure" refers to a structure having a plurality of interconnected pores, and is generally also referred to as a bicontinuous structure or a monolith structure. The porous structure has continuously interconnected pores that extend three-dimensionally, allowing fluid to permeate (i.e., capillary action). The cross-sectional shape of the pores in the porous structure can be appropriately set in consideration of the physical properties such as the viscosity of the fluid, and examples thereof include a substantially circular shape, a substantially elliptical shape, and a substantially polygonal shape. The size of the pores in the porous structure is not particularly limited and can be appropriately selected according to the purpose. The cross-sectional shape and size of the pores can be obtained, for example, from a cross-sectional photograph taken with a scanning electron microscope (SEM) or the like. The porosity of the porous structure can be appropriately set in consideration of the physical properties of the liquid, such as the viscosity, etc. The method for measuring the porosity is not particularly limited, but for example, a method can be used in which the porous structure is filled with unsaturated fatty acid (commercially available butter), and then osmium staining is performed, after which the internal cross-sectional structure is cut out with an FIB, and the porosity is measured using a scanning electron microscope (SEM) or the like. The distribution of pores in the porous structure can be appropriately set in consideration of the physical properties of the fluid, such as the viscosity, so long as the fluid can flow through it, but it is preferable that the pores are distributed uniformly within the flow path region.
[0019] The shape of the channels A to C in a plan view is not particularly limited as long as it allows fluid to flow therethrough and can be appropriately selected depending on the purpose. Examples of the shape include a circle, an ellipse, a square, and a rectangle. The diameters of the channels A and B are not particularly limited and can be appropriately selected depending on the purpose, and can be, for example, φ3 mm or more and φ10 mm or less. The width of the channel C is not particularly limited and can be appropriately selected depending on the purpose, and can be, for example, 1 mm or more and 5 mm or less.
[0020] The material M of the flow paths A to C is not particularly limited as long as it has a porous structure through which a fluid can flow and can be appropriately selected depending on the purpose, and examples thereof include paper such as filter paper, nonwoven fabric, nitrocellulose, polypropylene, etc. Among these, filter paper is more preferable from the viewpoint of simplicity and low cost.
[0021] The non-flow path Y is an area other than the flow paths A to C in the porous structure layer, that is, an area where no fluid flow occurs. The material M' of the non-channel Y is not particularly limited and can be appropriately selected depending on the purpose as long as it does not allow fluid flow, and can be obtained, for example, by impregnating the material M with a hydrophobic material. From the viewpoint of ease of production of the porous structure layer, the hydrophobic material is preferably one having a melting point of 90°C or less, and examples thereof include wax or a composition containing the same. The hydrophobic material can be appropriately blended with a viscosity adjusting component such as a resin, a dispersing agent, a filler, etc.
[0022] When the material M of the flow path is impregnated with a hydrophobic material, the hydrophobic material is preferably heated and melted. The heating temperature can be appropriately set in consideration of the melting points of the hydrophobic material and the viscosity adjusting component. The viscosity of the hydrophobic material when melted can be appropriately set so that the porous structure layer can be impregnated as desired, taking into consideration the average thickness and basis weight (density) of the porous structure layer.
[0023] When the material M of the flow path is impregnated with a hydrophobic material, it is preferable that the impregnation rate of the hydrophobic material with respect to the material M is within a range of 14% or more and 32% or less. By manufacturing the porous structure layer so that the impregnation rate is 14% or more, the flow path wall surface (the interface between material M and material M') becomes sufficiently uniform, and for example, the flow of fluid from flow path to flow path can be made smoother. Furthermore, by manufacturing the porous structure layer so that the impregnation rate is 32% or less, problems such as blockages that occur when impregnating material M with a hydrophobic material can be sufficiently avoided, and a porous structure layer having a desired flow path structure can be more reliably obtained. Here, the "impregnation rate" refers to the impregnation rate of the material M' in the region of the porous structure layer that is made of the material M' over the entire thickness direction. The impregnation rate can be considered to be 100% for the material M' obtained by immersing the material M in a hydrophobic material that has been heated to a sufficiently low viscosity (e.g., heated to 120°C) and leaving it for a sufficient time (e.g., 3 minutes) while maintaining the temperature. The impregnation rate can be adjusted, for example, by adjusting the amount of hydrophobic material to be impregnated (e.g., the thickness of the hydrophobic film).
[0024] The method for measuring the impregnation rate of the hydrophobic material into the material M is not particularly limited and can be appropriately selected depending on the purpose. For example, the following method can be mentioned. [Method of measuring impregnation rate] The filter paper is cut to an appropriate size and dried at 120°C for 3 minutes, after which the dry mass M0 (g) is measured. The filter paper is then immersed in a hydrophobic material and left at 120°C for 3 minutes. After immersion, the filter paper is sandwiched between the same type of filter paper and a slide glass, and left at 120°C for 1 minute under a load of 100 gf to remove excess hydrophobic material. The mass M1 (g) of the filter paper is then measured, and the maximum amount of impregnation per unit area Pmax (g / m2) is calculated using the following formula: 2 ) is calculated. Formula...Pmax(g / m 2 )=(M1-M0)×1000
[0025] The viscosity of the hydrophobic material is not particularly limited and can be appropriately selected depending on the purpose. For example, from the viewpoint of sufficiently avoiding problems such as clogging when impregnating the material M, the viscosity of the hydrophobic material is preferably set at 140° C. and a shear rate of 3000 s -1 is preferably 100 mPa s or less, more preferably 50 mPa s or less, and even more preferably 30 mPa s or less. The method for measuring the viscosity is not particularly limited, and can be, for example, measured using a rheometer (for example, AR-G2 rheometer, product name, manufactured by TA Instruments).
[0026] The material M' is preferably colored to allow easy visual confirmation of the flow of liquid, but may be white or transparent, or may be uncolored. The coloring of the material M' can be achieved, for example, by impregnating the material M with a colorant in addition to the hydrophobic material. Such colorants include pigments such as carbon black (black pigment), and are preferably hydrophobic. In addition, it is preferable to select a colorant that does not adversely affect the reagents used in the test, etc.
[0027] The shape of the porous structure layer 101 in a plan view is not particularly limited and can be appropriately selected depending on the purpose. Examples of the shape include a rectangle, a substantially circular shape, a substantially elliptical shape, and a substantially rectangular shape.
[0028] -Separation part- The porous structure layer 101 in the sheet-like structure 11 is provided with a separation section capable of separating adjacent flow paths in the flow paths in the porous structure layer 101 to block the flow of fluid in the flow paths. In addition, it is preferable that the separation section separates the fluid receiving section from the flow path adjacent to the fluid receiving section to block the flow of the fluid received in the fluid receiving section to the flow path adjacent to the fluid receiving section. More specifically, for example, when the flow path A in Figures 1A and 1B is the fluid receiving section, it is preferable that the separation section separates the flow path A from the flow path C adjacent to the flow path A to block the flow of the fluid received in the flow path A to the flow path C. Here, "separating adjacent flow paths to block the flow of fluid in the flow paths" means separating the porous structure forming the flow paths based on the separation section, thereby preventing the flow of fluid.
[0029] There are no particular restrictions on the location of the separation section as long as it can separate adjacent flow paths, but it is preferable that it is between the fluid receiving section and the detection section, and in an area excluding the fluid receiving section and the detection section. The number of the separation sections is not particularly limited and can be appropriately set depending on the purpose. By increasing the number of the separation sections, multiple reactions (multi-stage reactions) can be carried out in one sheet-like structure.
[0030] The separation section is not particularly limited as long as it can separate adjacent flow paths, and can be appropriately selected depending on the purpose, but is preferably a cutting section. The cutting section is a region that cuts the flow path in a direction intersecting the flow direction of the fluid in the flow path, as shown in Figures 1A and 1B. Here, the "direction intersecting the flow direction of the fluid" is not particularly limited, and may be, for example, a direction perpendicular to the flow direction of the fluid, or a direction approximately perpendicular to the flow direction of the fluid, as shown in Figure 1A. In addition, in an embodiment where the separation portion is not a cut portion, for example, the porous structure can be pulled in the vertical or horizontal direction (horizontal direction in FIG. 1A) to form a region in the porous structure layer where the porous structures are separated from each other as the separation portion. In this case, the support described later is preferably made of a material (e.g., an elastic member) that can be pulled in the vertical or horizontal direction.
[0031] When the separation portion is a cut portion, it is preferable that the cut portion is present only in the porous structure layer of the sheet-like structure, and not in the support layer described below. In other words, it is preferable to provide the cut portion so that when the sheet-like structure is separated based on the cut portion, the porous structure layer is separated, but the support layer is not separated. By keeping the support layer connected without separation, the support layer functions as a hinge, and it is possible to bring the separated flow paths into contact again and continue the flow of fluid.
[0032] Here, the function of the separation unit will be specifically described with reference to FIGS. 2A and 2B. Fig. 2A is an explanatory diagram for explaining an example of the function of the separation section. Specifically, it is a diagram showing a state in which the sheet-like structure 11 shown in Fig. 1A is folded at about 45° with the separation section X as a reference. Fig. 2B is an explanatory diagram for explaining another example of the function of the separation section. Specifically, it is a diagram showing a state in which the sheet-like structure 11 shown in Fig. 1A is folded at about 180° with the separation section X as a reference. As described above, in both the states of Fig. 2A and Fig. 2B, the support layer 301 remains connected without being separated. 2A and 2B, the porous structure in the porous structure layer 101 is separated, i.e., adjacent flow paths are separated, and the flow of fluid in the flow paths is blocked. More specifically, for example, when flow path A is used as a fluid receiving section, the separation section separates flow path A from flow path C adjacent to flow path A, and the fluid received in flow path A is blocked from flowing to flow path C.
[0033] The sheet-like structure 11 has such a configuration, so that the fluid does not flow through the flow paths and the fluid can be sufficiently retained in the fluid receiving portion. As described above, the support layer 301 is not separated by a separation portion and functions as a hinge, so that after the fluid is retained for a predetermined time, the separated flow paths can be brought into contact again to continue the flow of the fluid, as shown in FIG. 1B. For example, when the sheet-like structure 11 is used as a testing device, a sufficient reaction time between the sample and the reagent (e.g., an antigen and an antibody) can be ensured by introducing a sample and a reagent that reacts with the sample into the fluid receiving portion of the sheet-like structure in the state of Fig. 2A or Fig. 2B. After the reaction is completed (or after a predetermined time has elapsed), the separated flow paths can be brought into contact again as shown in Fig. 1B to continue the flow of the sample and the reagent.
[0034] Furthermore, since the sheet-like structure 11 has such a configuration, it is possible to straighten the fluid received in the fluid receiving section. Specifically, by separating the flow path once using the separation section, it is possible to prevent the fluid from being unevenly distributed in the flow path and the fluid receiving section due to the momentum at the time of receiving the fluid.
[0035] The angle at which the sheet-like structure is folded with respect to the separation portion X is not particularly limited, and can be appropriately set depending on the purpose, so long as the flow path is separated and the flow of fluid is blocked.
[0036] -Support layer- The sheet-like structure 11 has a support layer 301 . As described above, the support layer 301 functions as a hinge for the sheet-like structure 11, and allows the separated flow paths to come into contact again to continue the flow of fluid. The support layer also has a function of reinforcing the physical strength of the sheet-like structure itself.
[0037] Here, the distribution of the support layer will be specifically described with reference to Figures 3A to 3C. Figure 3A is an explanatory diagram for explaining one example of the distribution of the support layer, Figure 3B is an explanatory diagram for explaining another example of the distribution of the support layer, and Figure 3C is an explanatory diagram for explaining yet another example of the distribution of the support layer. The support layer in the sheet-like structure can be disposed in an area where the fluid receiving portion in the porous structure layer is not located. For example, as shown in Figures 1A and 1B, it may be disposed only on the side where the fluid is not introduced into the fluid receiving portion, or it may be disposed on both surfaces of the porous structure layer as shown in Figure 3A. Furthermore, the support layer may be disposed so as to cover only the exposed flow path as shown in Figures 3B and 3C. Note that, when the support layer is disposed on both surfaces of the porous structure layer, particularly on the side where the fluid is introduced into the fluid receiving portion, it is preferable to dispose it so as not to overlap with the separation portion.
[0038] The sheet-like structure having such a configuration can prevent contamination of the fluid flowing through the flow path. For example, when the fluid is a specimen and a reagent (e.g., an antigen and an antibody, etc.), it is preferable to prevent reaction inhibition caused by contamination.
[0039] The support layer is preferably water-impermeable. The material of the water-impermeable support layer is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include polypropylene. The size, structure and shape of the support layer are not particularly limited as long as they can cover the flow path in the porous structure layer, and can be appropriately set depending on the purpose.
[0040] The support layer may be a commercially available product, such as 660-PF (manufactured by Nichiban Co., Ltd.).
[0041] The average thickness of the sheet-like structure 11 of the first embodiment is not particularly limited and can be appropriately selected depending on the purpose, and can be, for example, 100 μm to 300 μm. The average thickness can be measured using a thickness meter such as ID-C112BS (manufactured by Mitutoyo) under the trade name. The size of the sheet-like structure 11 of the first embodiment is not particularly limited and can be appropriately selected depending on the purpose.
[0042] <Second aspect> The porous structure layer may have a shape of the flow path exposed on one surface different from a shape of the flow path exposed on the other surface of the porous structure layer, in other words, the porous structure layer may have two or more layers having different flow path shapes.
[0043] Here, the sheet-like structure 12 of the second embodiment will be specifically described with reference to Figs. 4A to 4C. Fig. 4A is a schematic cross-sectional view of the sheet-like structure of the second embodiment, Fig. 4B is a schematic plan view of the porous structure layer of Fig. 4A when viewed from the α direction, and Fig. 4C is a schematic plan view of the porous structure layer of Fig. 4A when viewed from the β direction. Fig. 4A is also a schematic cross-sectional view taken along the line bb' shown in Figs. 4B and 4C. Furthermore, the separation section X is omitted in Figs. 4B and 4C. The first porous structure layer 102 in the sheet-like structure 12 of the second embodiment is provided with a channel A, a channel B, and a non-channel Y in an area other than the channel A and the channel B. The channel A and the channel B are separated from each other in the first porous structure layer 102. The second porous structure layer 202 in the sheet-like structure 12 of the second embodiment is provided with channels C, D, and E, as well as non-channels Y in areas other than the channels C, D, and E. The channel E is connected to both the channels C and D, and fluid can flow in the order of channel C, E, and D, or channel D, E, and C. In the sheet-like structure 12 of the second embodiment, a support layer 301 is provided on the surface on the side of the second porous structure layer 202 . The first porous structure layer 102 and the second porous structure layer 202 are adjacent to each other with nothing interposed therebetween.
[0044] In the sheet-like structure 12 of the second embodiment, the flow path A of the first porous structure layer 102 and the flow path C of the second porous structure layer 202 are adjacent to each other, and the flow path B of the first porous structure layer 102 and the flow path D of the second porous structure layer 202 are adjacent to each other. That is, in the sheet-like structure 12 of the second embodiment, the flow paths are adjacent and connected in the order of flow path A, flow path C, flow path E, flow path D, and flow path B, or in the order of flow path B, flow path D, flow path E, flow path C, and flow path A. In the sheet-like structure 12 of the second embodiment, a separation portion X is formed so as to block the flow path C and the flow path E. 4A, the tip region when the hydrophobic material is impregnated from the first porous structure layer 102 is drawn by a dotted line as a virtual line. Similarly, the tip region when the hydrophobic material is impregnated from the second porous structure layer 202 is drawn by a dotted line as a virtual line. The virtual lines are similarly depicted in the other drawings. The flow path A, the flow path B, the flow path C, the flow path D, the flow path E, and the non-flow path Y are formed of the material M or the material M' described in the above <First embodiment> section.
[0045] 4A, in the sheet-like structure 12 of the second embodiment, the flow paths are adjacent to and connected in the order of flow path A, flow path C, flow path E, flow path D, and flow path B, or in the order of flow path B, flow path D, flow path E, flow path C, and flow path A. In other words, in the sheet-like structure 12 of the second embodiment, when a fluid is dropped into flow path A, the fluid passes through flow path A, flow path C, flow path E, and flow path D in this order by capillary action or the like, and finally flows into flow path B. In this case, the flow path A can be used as a fluid receiving section, and the flow path B can be used as a detection section.
[0046] In the sheet-like structure, the ratio (t2 / t1) of the average thickness of the second porous structure layer (t2) to the average thickness (t1) of the first porous structure layer is preferably 0.56 or more and 2.2 or less. By manufacturing the sheet-like structure so that the average thickness ratio (t2 / t1) is 0.56 or more and 2.2 or less, problems such as blockages when impregnating the material M with a hydrophobic material can be sufficiently avoided, and for example, the flow rate and / or speed stability of the liquid from the flow path to the flow path can be effectively increased. From the same viewpoint, the average thickness ratio (t2 / t1) is more preferably greater than 1.0, that is, the average thickness (t2) of the second porous structure layer is more preferably greater than the average thickness (t1) of the first porous structure layer, more preferably 1.3 or more, and particularly preferably 1.8 or more. The average thickness ratio (t2 / t1) is not particularly limited and can be 3.0 or less.
[0047] The average thickness of the sheet-like structure 12 of the second embodiment is not particularly limited and can be appropriately selected depending on the purpose, and can be, for example, 100 μm to 300 μm. The average thickness can be measured using a thickness meter such as ID-C112BS (manufactured by Mitutoyo) under the trade name. The size of the sheet-like structure 12 in the second embodiment is not particularly limited and can be appropriately selected depending on the purpose.
[0048] <Third aspect> The sheet-like structure 13 of the third embodiment will be specifically described with reference to Figs. 5A to 5C. Fig. 5A is a schematic cross-sectional view of the sheet-like structure of the third embodiment, Fig. 5B is a schematic plan view of the porous structure layer of Fig. 5A when viewed from the α direction, and Fig. 5C is a schematic plan view of the porous structure layer of Fig. 5A when viewed from the β direction. The sheet-like structure 13 shown in Figs. 5A to 5C is the same as the sheet-like structure 12 of the second embodiment except that the flow path structure of the sheet-like structure is different from that of the sheet-like structure of the second embodiment. Fig. 5A is also a schematic cross-sectional view taken along the line cc' shown in Figs. 5B and 5C. Furthermore, the separation section X is omitted in Figs. 5B and 5C. 5B, the sheet-like structure 13 of the third embodiment has a first porous structure layer 103 provided with a channel A, a channel B, a channel F connected to channel A, and a non-channel Y as a portion other than channel F. The channel A and the channel B are separated from each other in the first porous structure layer 103 of the sheet-like structure 13 of the third embodiment. As shown in Figure 5C, the sheet-like structure 13 of the third embodiment has a second porous structure layer 203 provided with flow path D, flow path E, and a non-flow path Y as a portion other than flow path D and flow path E, and flow path E is connected to flow path D. In the sheet-like structure 13 of the third embodiment, a support layer 301 is provided on the surface on the side of the second porous structure layer 203 .
[0049] In the sheet-like structure 13 of the third embodiment, the flow path B of the first porous structure layer 103 and the flow path D of the second porous structure layer 203 are adjacent to each other, and the flow path F of the first porous structure layer 103 and the flow path E of the second porous structure layer 203 are connected to each other. That is, in the sheet-like structure 13 of the third embodiment, the flow paths A, F, E, D, and B are adjacent to each other and connected in this order, or the flow path B, D, E, F, and A are adjacent to each other and connected to each other in this order. In the sheet-like structure 13 of the third embodiment, a separation portion X is formed so as to block the flow path F and the flow path E. The flow paths A, B, D, E, F, and non-flow paths Y are formed of the material M or M' described in the above <First embodiment>.
[0050] 5A, the sheet-like structure 13 of the third embodiment is configured such that, for example, when a fluid is dropped into flow path A, the liquid passes through flow paths A, F, E, and D in this order by capillary action or the like, and finally flows into flow path B. In this case, flow path A can be used as a fluid receiving section, and flow path B can be used as a detection section. Other than the above, explanation of matters common to the <First Aspect> will be omitted.
[0051] <Fourth aspect> The sheet-like structure 14 of the fourth embodiment will be specifically described with reference to Figs. 6A to 6C. Fig. 6A is a schematic cross-sectional view of the sheet-like structure of the fourth embodiment, Fig. 6B is a schematic plan view of the porous structure layer of Fig. 6A when viewed from the α direction, and Fig. 6C is a schematic plan view of the porous structure layer of Fig. 6A when viewed from the β direction. The sheet-like structure 14 shown in Figs. 6A to 6C is the same as the sheet-like structure 12 of the second embodiment, except that the flow path structure of the sheet-like structure is different from that of the sheet-like structure of the second embodiment. Fig. 6A is also a schematic cross-sectional view taken along the line dd' shown in Figs. 6B and 6C. As shown in FIG. 6B, in the sheet-like structure 14 of the fourth embodiment, a channel B and a non-channel Y as a portion other than the channel B are provided in the first porous structure layer 104, and a channel A is not provided. 6C, the sheet-like structure 14 of the fourth embodiment has a second porous structure layer 204 provided with a channel A, a channel D, a channel E, and a non-channel Y as a portion other than the channels A, E, and D. The channel E is connected to both the channel D and the channel A. In the sheet-like structure 14 of the fourth embodiment, a support layer 301 is provided on the surface on the side of the second porous structure layer 204 .
[0052] In the sheet-like structure 14 of the fourth embodiment, the flow path D of the first porous structure layer 104 is adjacent to the flow path B of the second porous structure layer 204. That is, in the sheet-like structure 14 of the fourth embodiment, the flow paths A, E, D, and B are adjacent and connected in this order, or the flow path B, D, E, and A are adjacent and connected in this order. In the sheet-like structure 14 of the fourth embodiment, a separation portion X is formed so as to block the flow path A and the flow path E. The flow paths A, B, D, E, and Y are formed of the material M or M' described in the above <First embodiment>.
[0053] 6A, the sheet-like structure 14 of the fourth embodiment is configured such that, for example, when a fluid is dropped into flow path A, the liquid passes through flow paths A, E, and D in this order by capillary action or the like, and finally flows into flow path B. In this case, flow path A can be used as a fluid receiving section, and flow path B can be used as a detection section. Other than the above, explanation of matters common to the <First Aspect> will be omitted.
[0054] <Fifth aspect> The sheet-like structure of the fifth embodiment will be specifically described with reference to Figures 7A to 7B. Figure 7A is a schematic plan view of the porous structure layer in the sheet-like structure of the fifth embodiment when viewed from the α direction, and Figure 7B is a schematic plan view of the porous structure layer in the sheet-like structure of the fifth embodiment when viewed from the β direction. As shown in Figures 7A and 7B, the sheet-like structure of the fifth embodiment is similar to that of Figures 4B and 4C, except that the flow path D provided in the second porous structure layer 205 has a ring-shaped structure, and a non-flow path Y1 is formed inside the ring-shaped structure. The flow channel D, which is an annular structure, can have any contour shape such as a circle, an ellipse, a rectangle, etc., but preferably has a contour shape that substantially matches the contour shape of the flow channel B in a plan view of the sheet-like structure. In addition, the non-flow channel Y formed inside the flow channel D preferably has a shape that is a scaled version of the contour shape of the flow channel D in a plan view of the sheet-like structure.
[0055] <Sixth aspect> The sixth embodiment of the sheet-like structure will be specifically described with reference to Figures 8A and 8B. Figure 8A is a schematic plan view of the porous structure layer in the sixth embodiment of the sheet-like structure when viewed from the α direction, and Figure 8B is a schematic plan view of the porous structure layer in the sixth embodiment of the sheet-like structure when viewed from the β direction. 8A and 8B, the sheet-like structure of the sixth embodiment is similar to that of Fig. 7A and 7B, except that the second porous structure layer 206 has a structure having a plurality of flow paths E (two flow paths E1 and E2 in Fig. 8B). In the above structure, a plurality of flow paths F may be provided in the number of flow paths E, and the plurality of flow paths F in the first porous structure layer and the plurality of flow paths E in the second porous structure layer may be connected to each other.
[0056] <Seventh aspect> The seventh embodiment of the sheet-like structure will be specifically described with reference to Figures 9A and 9B. Figure 9A is a schematic plan view of the porous structure layer in the seventh embodiment of the sheet-like structure when viewed from the α direction, and Figure 9B is a schematic plan view of the porous structure layer in the seventh embodiment of the sheet-like structure when viewed from the β direction. As shown in Figs. 9A and 9B, the sheet-like structure of the seventh embodiment is a combination of the flow channel shapes shown in Figs. 7A, 7B, 8A, and 8B.
[0057] <Eighth aspect> The sheet-like structure of the eighth embodiment will be specifically described with reference to Figures 10A to 10B. Figure 10A is a schematic plan view of the porous structure layer in the sheet-like structure of the eighth embodiment when viewed from the α direction, and Figure 10B is a schematic plan view of the porous structure layer in the sheet-like structure of the eighth embodiment when viewed from the β direction. 10A and 10B, the sheet-like structure of the eighth embodiment is generally similar to that of Fig. 9B, except that the second porous structure layer 208 has three channels E (E1, E2, and E3). In the sheet-like structure shown in Fig. 10B, the three channels E are connected to a channel D so as to face each other.
[0058] <Ninth aspect> The sheet-like structure of the ninth embodiment will be specifically described with reference to Figures 11A to 11B. Figure 11A is a schematic plan view of the porous structure layer in the sheet-like structure of the ninth embodiment when viewed from the α direction, and Figure 11B is a schematic plan view of the porous structure layer in the sheet-like structure of the ninth embodiment when viewed from the β direction. As shown in Figures 11A and 11B, the sheet-like structure of the ninth embodiment is generally similar to that of Figure 10B, except that it has a structure in which flow path E3 branches into two (E31 and E32) and is connected to flow path D.
[0059] <Tenth aspect> The sheet-like structure of the tenth embodiment will be specifically described with reference to Figures 12A to 12B. Figure 12A is a schematic plan view of the porous structure layer in the sheet-like structure of the tenth embodiment when viewed from the α direction, and Figure 12B is a schematic plan view of the porous structure layer in the sheet-like structure of the tenth embodiment when viewed from the β direction. 12A and 12B, the sheet-like structure of the tenth embodiment is generally similar to that of Fig. 11B, except that it has a structure having two channels E (E3 and E4) in addition to channels E1 and E2. In the sheet-like structure shown in Fig. 12B, the four channels E are connected to a channel D so as to face each other.
[0060] 8A to 12B, from the viewpoint of suppressing an increase in the amount of liquid, the number of channels E (and channels F) is preferably 4 or less, more preferably 3 or less, and even more preferably 2. Moreover, the number of connection points of channel E to channel D is preferably 4 or less, more preferably 3 or less, and even more preferably 2. At least two of the multiple flow paths E are preferably connected to the flow path D so as to face each other. In addition, at least two of the multiple flow paths E preferably have substantially the same shape.
[0061] The above-mentioned sheet-like structure can be manufactured, for example, by forming a predetermined portion (such as flow path B) in a sheet-like material to produce a first porous structure layer, forming a predetermined portion (such as flow path D) in another sheet-like material to produce a second porous structure layer, and laminating these. Alternatively, the above-mentioned sheet-like structure can also be manufactured by forming a predetermined portion in a part of one sheet-like material to produce a first porous structure layer, forming a predetermined portion in another part of the single sheet-like material to produce a second porous structure layer, and folding the single sheet-like material while adjusting the positions of the first porous structure layer and the second porous structure layer. The sheet-like structure of the present invention is preferably produced by forming a first porous structure layer on one side of a sheet-like material and a second porous structure layer on the other side. Such a sheet-like structure, in which a first porous structure layer and a second porous structure layer are formed on both sides of a sheet-like material, respectively, has various advantages, such as (1) the labor and cost of stacking (or folding) can be avoided, (2) liquid circulation by capillary action is ensured between the first porous structure layer and the second porous structure layer, and (3) disposal is easy because no tool or the like for maintaining the stacked (folded) sheet-like material is required.
[0062] As a specific method for producing the sheet-like structure, for example, it can be produced by the following method. [An example of a method for manufacturing a sheet-like structure] First, a hydrophobic material, a colorant, and a resin are blended, and melt-mixed at, for example, 100°C to 140°C to prepare a WAX ink. The WAX ink is applied to a substrate such as a polyethylene terephthalate film to prepare an ink ribbon. Next, a specific flow path shape is printed on high-quality paper using a thermal transfer printer (for example, product name: Respri R412v-ex, manufactured by Sato Holdings Corporation), to form a missing flow path pattern in the printed portion of the ink ribbon. The ink ribbon on which the missing flow path pattern is formed is fixed to the front and back of a filter paper, and then passed through a thermal laminator (for example, product name: GL535ML, manufactured by GBG Co., Ltd.) set at a predetermined temperature and line speed, whereby the WAX ink is transferred and penetrated into the filter paper to form a three-dimensional flow path, and a sheet-like structure can be produced. Here, the filter paper is not particularly limited and can be appropriately selected depending on the purpose. For example, the filter paper may have an average thickness of 310 μm and a basis weight of 94 g / m 3 , and CFR (Capillary flow rate) 13.9 sec / 4 cm can be used. Here, the "predetermined temperature and line speed" are not particularly limited as long as the conditions are such that the WAX ink can penetrate and be transferred to the filter paper, but for transfer, a line speed of 10 mm / sec at 85°C can be used, and for penetration, a line speed of 5 mm / sec at 85°C can be used.
[0063] (How to use the sheet-like structure) A method of using the sheet-like structure of the present invention is characterized in that a fluid is received into a first flow path located on one side of the separation section, the first flow path and the second flow path are separated in the separation section to block the flow of the fluid so that the fluid received into the first flow path does not flow into a second flow path located on the other side of the separation section, and after a certain period of time, the first flow path and the second flow path are brought into contact with each other in the separation section to allow the fluid to flow between the first flow path and the second flow path. In the method for using the sheet-like structure, it is preferable that the first flow path is the fluid receiving portion, and the detection portion is disposed in a part of the second flow path.
[0064] A specific description will be given below with reference to FIG. 1B and FIG. 2A to FIG. 2B. The "first flow path" is preferably, in other words, a flow path on the side where a fluid receiving portion that receives a fluid is present when the flow paths are separated based on the separation portion. That is, in Fig. 1B, it is preferably a flow path including flow path A that is present on the left side of separation portion X in the figure. In other words, the "second flow path" is preferably a flow path on the side other than the first flow path, i.e., a flow path on the side where the detection unit is present, when the flow paths are separated based on the separation unit. That is, in Fig. 1B, it is preferably a flow path including flow path B and flow path C that is present on the right side of separation unit X in the figure. Here, "separating the first flow path and the second flow path in the separation section to block the flow of the fluid" means, for example, separating each flow path (porous structure) based on the separation section, as shown in Figures 2A and 2B. The "certain period of time" can be appropriately set depending on the viscosity of the fluid being passed and the reaction time of components (eg, antigens and antibodies) contained in the fluid. Here, "contacting the first flow path with the second flow path in the separation section to allow the fluid to circulate between the first flow path and the second flow path" refers to, for example, returning a sheet-like structure in the state of FIG. 2A or FIG. 2B to the state of FIG. 1B.
[0065] A blocking agent may be applied to the fluid receiving section and the detection section in advance in order to prevent fluids (such as specimens such as antigens and reagents such as antibodies) from flowing through and being adsorbed. Examples of the blocking agent include an albumin aqueous solution, and it is preferable to select an appropriate blocking agent depending on the type of fluid and its physical properties such as viscosity.
[0066] The sheet-like structure of the present invention can be suitably used as a test device, such as a pregnancy test drug or a test device that utilizes a measurement method that combines the principles of sandwich ELISA and chromatography, which is called immunochromatography. EXAMPLES
[0067] Next, the present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to the following examples.
[0068] <Preparation of ink ribbon> The following materials were mixed and melt mixed at 100°C to prepare a wax ink. Paraffin wax as a hydrophobic material (product name: ParaffinWax-135, manufactured by Nippon Seiro Co., Ltd.) 72.0 parts by weight 18.0 parts by weight of synthetic wax as a hydrophobic material (product name: Diacalna (registered trademark) 30, manufactured by Mitsubishi Chemical Corporation) Carbon black as a colorant (product name: MA-100, manufactured by Mitsubishi Chemical Corporation) 1.8 parts by weight Resin (product name: Ultrathene (registered trademark) 722, manufactured by Tosoh Corporation) 11.25 parts by weight The viscosity of the resulting WAX ink was measured at 140°C and a shear rate of 3000 s -1 The viscosity was measured using a rheometer AR-G2 (manufactured by TA Instruments).
[0069] The obtained WAX ink was applied onto a polyethylene terephthalate film (product name: Lumirror (registered trademark) #6C F531, manufactured by Toray Industries, Inc.) having an average thickness of 6 μm to an average thickness of 5 μm to 12 μm to produce an ink ribbon. A thermal transfer printer (product name: Respri R412v-ex, manufactured by Sato Holdings Corporation) was used to print the flow path shape shown in Figures 13A and 13B on high-quality paper, thereby forming a flow path pattern that was missing in the printed area of the ink ribbon (see Figures 13C and 13D).
[0070] <Confirmation of flow path formation> First, it was confirmed whether a flow path was properly formed. Using a printer (product name: Xerox ColorQube8570, manufactured by Xerox), WAX ink was printed on one side of filter paper (product name: Whatman #41) so as to form the flow path pattern shown in FIG. 14A. The paper was then heated in an oven at 120°C for 2 minutes, causing the WAX ink to penetrate the paper and form a single-sided printed flow path. The single-sided printed flow path was then immersed in an aqueous solution of fluorescent ink (fluorescent felt-tip pen, manufactured by Askul Corporation), and cut at the position corresponding to the ff' line in FIG. 14A. A photograph of the cross section of the flow path was taken using a microscope (manufactured by Keyence). The result is shown in FIG. 14B. Similarly, the flow path pattern shown in Figure 14A was printed on both sides of a filter paper (product name: Whatman #41), and penetration was performed under the same conditions to form a double-sided printed flow path in the filter paper. The double-sided printed flow path was immersed in an aqueous solution of fluorescent ink (fluorescent felt-tip pen, manufactured by Askul Corporation), and then cut at the position corresponding to the ff' line in Figure 14A, and a cross-sectional photograph of the flow path was taken using a microscope (manufactured by Keyence). The result is shown in Figure 14C. Fluorescent ink was confirmed only in the dotted-line enclosed areas in Figures 14B to 14C, and no leakage of the fluorescent ink was observed in other areas. This confirmed that the flow path was properly formed. Figure 14B shows single-sided printing, i.e., the WAX ink was permeated from one side of the filter paper, so the flow path formed is tapered, widening from the side where the WAX ink was permeated to the opposite side. Figure 14C shows double-sided printing, i.e., the WAX ink was permeated from both sides of the filter paper, so the flow path formed is symmetrical and diamond-shaped.
[0071] <Quantitative analysis of paraoxon ethyl> Paraoxon ethyl (or paraoxon) is a type of phosphorus-based pesticide. When paraoxon adheres to crops and the like, it is a neurotoxin that inhibits the function of acetylcholinesterase (AChE), which is involved in neurotransmission, and causes convulsions, miosis, and the like when it enters the body. In this example, the concentration of paraoxon ethyl in a sample is quantitatively analyzed using a sheet-like structure.
[0072] -Creating a porous structure layer- Each of the ink ribbons in which the missing flow path patterns shown in FIG. 13C and FIG. 13D were formed was placed on a filter paper (average thickness 310 μm, basis weight 94 g / m 3 After fixing the filter paper to the front and back of a filter paper (capillary flow rate (CFR) 13.9 sec / 4 cm), the filter paper was passed through a thermal laminator (product name: GL535ML, manufactured by GBG) set to a specified temperature, whereby the wax ink was transferred to and penetrated into the filter paper, forming three-dimensional flow paths in the filter paper and producing a porous structure layer. Here, the "specified temperature" refers to 85°C at a line speed of 10 mm / sec for transfer and 85°C at a line speed of 5 mm / sec for penetration. The obtained porous structure layer had the structure shown in Fig. 15. Fig. 15 is a schematic cross-sectional view taken along the line ee' shown in Figs. 13A to 13D. For convenience, the obtained porous structure layer was labeled with flow paths A to H as shown in Fig. 15. A layer having flow path A as a fluid receiving portion and flow path B as a detection portion is shown as a first porous structure layer 111, and a layer other than the first porous structure layer 111 is shown as a second porous structure layer 211.
[0073] -Blocking and Fixation- To prevent AChE (Sigma-Aldrich) from being adsorbed onto the filter paper, 2 μL of a 0.8% aqueous albumin solution (Fujifilm Wako Pure Chemical Industries, Ltd.) was dropped onto the fluid receiving section (flow path A) as a blocking agent, and the fluid was dried at 30° C. for 15 minutes. Next, 2 μL of PDDA (polydiallyldimethylammonium chloride) aqueous solution 0.25 (w / v%) (Sigma-Aldrich) was dropped into the detection section (flow path B) as an immobilizing agent for indoxyl acetate (IDA), and dried at 30° C. for 15 minutes. IDA is a substrate that reacts with AChE to produce a blue color. Next, IDA (Sigma-Aldrich) was dissolved in methanol (Fujifilm Wako Pure Chemical Industries, Ltd.), and then diluted with pure water to prepare a solution with a weight ratio of methanol to water of 70 / 30 and 40 mM IDA. 3 μL of this solution was dropped into the detection section (flow path B) and dried at 30°C for 15 minutes.
[0074] -Preparation of support layer- Adhesive tape (product name: 660PF, manufactured by Nichiban Co., Ltd.) was superposed as a support layer on both sides of the support layer so as not to cover the flow path A, which is the fluid receiving portion in the obtained porous structure, and laminated using a hand roller under room temperature conditions. Here, for convenience, the support layer on the side of the first porous structure layer 111 is designated as 302, and the support layer on the side of the second porous structure layer 211 is designated as 301, as shown in FIG. Next, a separation section X was formed by cutting between the fluid receiving section (flow path A) and the flow path C adjacent to the fluid receiving section with a cutter, thereby obtaining a sheet-like structure 15. At this time, care was taken not to make any cuts in the support layer 301. The obtained sheet-like structure 15 had the structure shown in FIG. The obtained sheet-like structure 15 was folded 180° with the separated portion X as a reference as shown in FIG. 17, and fixed with a clip.
[0075] -reaction- AChE was prepared at 100 U / mL using Tris-HCl (pH 8.0) (manufactured by Nippon Gene Co., Ltd.), 3 μL of which was dropped onto the fluid receiving part (flow path A) and dried at 30° C. for 15 minutes. Tris-HCl (pH 8.0) with added EtOH (Fujifilm Wako Pure Chemical Industries, Ltd.) to a concentration of 6 vol% was prepared, and solutions with paraoxon ethyl (Sigma-Aldrich) concentrations of 0 μg / L, 200 μg / L, 400 μg / L, and 800 μg / L were made. Each solution was placed in the fluid receiving section (flow path A) and allowed to react at room temperature. After being left to stand for 5 minutes, the clips were removed, and the flow paths of the sheet-like structure 15 were brought into contact again (returned to the state shown in FIG. 16) to continue the flow of the fluid. After being left to stand for 10 minutes, the coloring in the detection section B was measured using a Konica Minolta FD-05 densitometer, * a * b * The results are shown in Table 1 and in Figures 18A and 18B.
[0076] [Table 1]
[0077] Compared to the sample in which the sheet-like structure was not folded at the separation portion, the sample in which the sheet-like structure was folded at the separation portion had a larger L * Increase in value, and b * In other words, by folding the sheet-like structure at the separation section and completely blocking the adjacent flow channels, it was possible to ensure sufficient reaction time between paraoxon ethyl and AChE, thereby improving the accuracy of the quantitative analysis. [Explanation of symbols]
[0078] 11 First sheet-like structure of the first embodiment 12 First sheet-like structure of the second embodiment 13 First sheet-like structure of the third embodiment 14 First sheet-like structure of the fourth embodiment 15 First sheet-like structure of the fifth embodiment 16 First sheet-like structure of the sixth embodiment 17 First sheet-like structure of the seventh embodiment 18 First sheet-like structure of the eighth embodiment 19 First sheet-like structure of the ninth embodiment 101 Porous structure layer 102 First porous structure layer 103 First porous structure layer 104 First porous structure layer 105 First porous structure layer 106 First porous structure layer 107 First porous structure layer 108 First porous structure layer 109 First porous structure layer 110 First porous structure layer 111 First porous structure layer 202 Second porous structure layer 203 Second porous structure layer 204 Second porous structure layer 205 Second porous structure layer 206 Second porous structure layer 207 Second porous structure layer 208 Second porous structure layer 209 Second porous structure layer 210 Second porous structure layer 211 Second porous structure layer 301 Support layer 302 Support layer 303 Support layer 304 Support layer A flow path B flow channel C Flow Path D Flow Path E flow path E1 flow path E2 flow path E3 flow path E31 Flow path E32 Flow Path E4 flow path F flow path G flow path H flow path X1 flow path X2 flow path Y Non-flow path Y1 Non-flow path M Material M´ Material X separation section
Claims
1. The porous structure layer has at least a part of a flow path having a porous structure through which a fluid can flow, exposed on a surface thereof, and a support layer. A sheet-like structure, wherein the flow paths have separation parts capable of separating adjacent flow paths to block the flow of the fluid in the flow paths.
2. The sheet-like structure according to claim 1 , wherein the separation portion is a cutting portion that cuts the flow path in a direction intersecting a flow direction of the fluid in the flow path.
3. The sheet-like structure according to claim 1 , wherein at least a part of the flow path exposed on the surface serves as a fluid receiving portion.
4. The sheet-like structure of claim 3, wherein the separation portion separates the fluid receiving portion from the flow path adjacent to the fluid receiving portion, thereby blocking the fluid received in the fluid receiving portion from flowing through the flow path adjacent to the fluid receiving portion.
5. The sheet-like structure according to claim 3 , wherein the support layer is disposed in an area of the porous structure layer where the fluid receiving portion is not located.
6. 2. The sheet-like structure according to claim 1, wherein the support layer is water-impermeable.
7. The sheet-like structure according to claim 1 , wherein an exposed shape of the flow passage exposed on one surface of the porous structure layer is different from an exposed shape of the flow passage exposed on the other surface of the porous structure layer.
8. The sheet-like structure according to claim 3 , wherein at least a part of the flow path exposed on the surface is a detection portion, and the detection portion is disposed at a position in the flow path different from the fluid receiving portion.
9. A method for using the sheet-like structure according to any one of claims 1 to 8, comprising the steps of: a first flow path is provided on one side of the separation section, and the first flow path and the second flow path are separated at the separation section to block the flow of the fluid so that the fluid received in the first flow path does not flow into a second flow path on the other side of the separation section; A method for using a sheet-like structure, characterized in that after a certain period of time has elapsed, the first flow path and the second flow path are brought into contact with each other in the separation section, thereby allowing the fluid to circulate between the first flow path and the second flow path.
10. The method for using the sheet-like structure according to claim 9 , wherein the first flow path is a fluid receiving portion, and a detection portion is disposed in a part of the second flow path.