Detection device

Abstract

According to the present invention, an inspection kit (1018) comprises: a flow passage (1002) which is provided on a substrate formed of a resin and transports a liquid sample; a solid-phase part which is provided in the flow passage (1002) and in which an antibody or an antigen is in a solid phase; a detection part (sensing zone (1003y)) which detects a reaction of the liquid sample with respect to the antibody or the antigen; and a fine recesses-protrusions structure which has a plurality of protrusions that are integrally formed on the substrate in which the flow passage (1002) is formed, wherein the flow passage (1002) has a curved path part (here, a vortex-like path) in which a path is bent or curved.

Description

[Technical field]

[0001] The present invention relates to a detection device for detecting a target substance in a liquid sample. [Background technology]

[0002] In recent years, point-of-care test (POCT) reagents that use antigen-antibody reactions to test for infectious diseases and pregnancy, and measure blood glucose levels, have been attracting attention. Tests and measurements using POCT reagents can determine results in a short time. In addition, POCT reagents are easy to use and inexpensive. Because of these characteristics, POCT reagents are often used for examinations when symptoms are mild and for regular checkups. POCT reagents will also be important diagnostic tools in home medical care, which is expected to increase in the future.

[0003] In testing or diagnosis using a test kit, which is a type of POCT reagent, a liquid sample such as blood is introduced into the test kit, and a specific target substance contained in the liquid sample is detected. Immunochromatography is often used as a method for detecting a specific target substance from a liquid sample. In immunochromatography, the liquid sample is dropped onto a membrane carrier provided in the test kit, and the target substance specifically and selectively binds to a substance fixed in the test kit (hereinafter referred to as the detection substance). The resulting changes in color and weight of the test kit are detected. The detection substance may also be called a reagent.

[0004] Nitrocellulose membranes are often used as membrane carriers for moving liquid samples (see Patent Document 1 below). Nitrocellulose membranes have many fine pores with diameters of about several μm, through which liquid samples move by capillary force.

[0005] However, since nitrocellulose membranes are derived from natural products and the pore size and the connection between the pores in the membrane are not uniform, the flow rate of the liquid sample through the membrane varies depending on the membrane. If there is a difference in the flow rate, the time required to detect the target substance also changes. As a result, it may be erroneously determined that the target substance is not detected before it binds to the labeling substance or reagent.

[0006] In order to solve the above problems, a method for artificially creating a microchannel for a liquid sample has been devised (see Patent Documents 2 and 3 below). By using this method, a membrane carrier having a uniform structure can be created. As a result, it is possible to reduce the possibility of making a mistaken decision that the target substance is not detected before it binds to a labeling substance or a reagent. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2014-062820 A [Patent Document 2] Patent No. 4597664 [Patent Document 3] Special Publication No. 2012-524894 Summary of the Invention [Problem to be solved by the invention]

[0008] In the immunochromatography method, a liquid sample is dropped onto a membrane carrier provided in a test kit, and the substance to be detected binds specifically and selectively to a substance fixed in the test kit (hereinafter referred to as the "detection substance"). The resulting changes in color and weight of the test kit are detected. A well-known method for detecting a detection substance is to detect a color change in the detection zone caused by the detection substance bound to a labeling substance such as colored latex particles, fluorescent particles, or metal colloid particles binding to a reagent fixed in the detection zone using an optical measuring device such as an absorbance meter (color change detection method). There is also a method (electrochemical immunochromatography method) in which the concentration of a biomarker is converted into the concentration of an electrochemically active substance and then detected.

[0009] In electrochemical immunochromatography, it is necessary to develop multiple types of solutions, such as reaction solution, washing solution, and secondary reaction solution, which increases the labor required for use and increases the detection time, which has been an obstacle to the widespread use of test kits using electrochemical immunochromatography.In other words, there has been a demand for a POCT reagent (test kit) that can determine results in a short time, is easy to use, and is inexpensive. Considering actual use, there was a demand for POCT reagents (test kits) to be made more compact from the standpoint of ease of handling and securing storage space.

[0010] The present invention has been made in consideration of the above circumstances, and aims to provide a technology that can reduce the effort required during use, shorten the detection time, and make the entire device compact when developing multiple types of solutions such as reaction solutions, washing solutions, and secondary reaction solutions in a test kit using immunochromatography. [Means for solving the problem]

[0011] The test device (test kit) of the present invention includes a flow path provided on a substrate made of resin and for transporting a liquid sample; a solid phase portion provided in the flow channel, on which an antibody or an antigen is immobilized; a detection unit for detecting a reaction of the liquid sample with the antibody or the antigen; a fine concave-convex structure having a plurality of convex portions formed integrally with the substrate in a region where the flow path is provided; having The flow path has a bent or curved path portion. Effect of the Invention

[0012] According to the present invention, when multiple types of solutions such as reaction solutions, washing solutions, and secondary reaction solutions are deployed in a test kit using immunochromatography, it is possible to provide a technology that eliminates the hassle of use, shortens the detection time, and makes the entire device more compact. [Brief description of the drawings]

[0013] [Figure 1] FIG. 2 is a top view of the test kit according to the first embodiment. [Diagram 2] FIG. 2 is a top view of the membrane carrier of the first embodiment. [Diagram 3] FIG. 2 is a diagram showing a microstructure and protrusions of the first embodiment. [Figure 4] FIG. 2 is a perspective view of a protrusion according to the first embodiment. [Diagram 5] FIG. 2 is an enlarged view showing boundaries of regions in the microstructure of the first embodiment. [Figure 6] FIG. 2 is a chart showing an example of a testing method using the test kit of the first embodiment. [Figure 7] FIG. 4 is a top view of a membrane carrier according to a second embodiment. [Figure 8] FIG. 11 is an enlarged view showing the boundaries of the regions of the microstructure of the second embodiment. [Figure 9] 13A to 13C are diagrams showing examples of a backflow prevention structure for a solution in a microstructure according to a third embodiment. [Figure 10] FIG. 13 is a plan view illustrating a flow path of the test kit according to the fourth embodiment. [Figure 11]FIG. 13 is a plan view illustrating a flow path of the test kit according to the fifth embodiment. [Figure 12] FIG. 13 is a plan view illustrating a flow path of the test kit according to the sixth embodiment. [Figure 13] FIG. 13 is a plan view illustrating a flow path of the test kit according to the seventh embodiment. [Figure 14] FIG. 23 is a plan view illustrating a flow path of the test kit according to the eighth embodiment. [Figure 15] FIG. 13 is a plan view illustrating a flow path of the test kit according to the ninth embodiment. [Figure 16] FIG. 23 is a plan view illustrating a flow path of the test kit according to the tenth embodiment. [Figure 17] FIG. 23 is a plan view illustrating the flow path of the test kit of the eleventh embodiment. [Figure 18] FIG. 23 is a plan view illustrating the flow path of the test kit of the twelfth embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] In the following, embodiments of the present invention will be described. First, in the first embodiment, the basic configuration of a test kit using an immunochromatography method will be described. Next, in the second embodiment, an example of a test kit in which a buffer region is provided in a flow path will be described, and further, in the third embodiment, an example of a structure for preventing backflow of a solution in a flow path will be described. Furthermore, in the fourth to tenth embodiments, an example of a test kit in which a curved path (such as a curve or bend) other than a straight line is provided in the flow path to make it compact will be described, and in the eleventh and twelfth embodiments, an example of a technique for adjusting the transport speed of a solution will be described.

[0015] <<First embodiment>> <Overview of the test kit> Fig. 1 is a plan view of a test kit 18 according to this embodiment. Fig. 2 is a plan view showing a schematic diagram of a membrane carrier 3. Fig. 3 shows the fine structure (also called a "fine uneven structure") of the membrane carrier 3 and the convex portions 8 constituting it. Fig. 4 is a perspective view (photograph) of the convex portions 8.

[0016] The test kit 18 has a function of detecting a target substance in the reaction liquid. Although details will be described later, the test kit 18 is a type of POCT reagent. A liquid sample such as blood is introduced into the test kit 18, and a specific target substance contained in the reaction liquid is detected. Immunochromatography is used as a method for detecting the specific target substance from the reaction liquid. In this embodiment, a test kit 18 using an electrochemical immunochromatography method for converting the concentration of a biomarker into the concentration of an electrochemically active substance for detection will be described.

[0017] As described above, in electrochemical immunochromatography, it is necessary to develop multiple types of solutions (liquid samples) such as a reaction solution, a washing solution, and a secondary reaction solution, which generally increases the labor required for use and lengthens the detection time. In this embodiment, the flow path 2 of the membrane carrier 3 is divided into multiple areas (here, three areas: the first to third microstructure regions 31 to 33), and the flow rate of the solution is controlled to be different for each area. As a structure for making the flow rate different, a microstructure formed on the membrane carrier 3, i.e., a structure that causes a capillary action that determines the speed at which the solution is transported, is set for each area. This will be explained in detail below.

[0018] <Details of Test Kit 18> 1, the test kit 18 includes a membrane carrier 3 and a housing 18a that houses the membrane carrier 3. In this figure, the direction from the upstream on the left side to the downstream on the right side of the figure will be described as the traveling direction d of the solution.

[0019] The surface of the membrane carrier 3 has, from the left in the figure, a washing solution zone 3x into which a washing solution is dropped, a liquid droplet zone 3z into which a liquid sample is dropped, and a detection zone 3y for detecting a substance to be detected in a reaction solution. Although not shown here, an absorbent pad for absorbing excess solution is provided downstream of the membrane carrier 3 (to the right in the figure).

[0020] The cleaning solution zone 3x is exposed at a first opening 18b of the housing 18a. The droplet zone 3z is exposed at a second opening 18d of the housing 18a. The detection zone 3z is exposed at a third opening 18c of the housing 18a. The cleaning solution may be dropped at the droplet zone 3z, in which case the first opening 18b may be omitted. That is, when there are multiple types of solutions, inlets (openings) are provided according to the solutions, and inlets are provided according to what solution is to be moved, at what timing, and at what speed. Multiple solutions may be dropped into one inlet, and the timing may be the same or different.

[0021] Two electrodes 20 (electrode units) are provided in the detection zone 3y for detection by an electrochemical detection method. A measuring device 21 is connected to the two electrodes 20. The measuring device 21 may be a general measuring device, or may be configured as a device in which a predetermined application is installed in a mobile terminal such as a smartphone.

[0022] <Details of Membrane Carrier 3> As shown in Fig. 2, the membrane carrier 3 is provided with at least one flow path 2 for transporting a liquid sample. As shown in Fig. 3, a microstructure 7 is provided on the bottom surface of the flow path 2. In this embodiment, the microstructure 7 is provided over the entire surface of the membrane carrier 3, and the entire surface of the membrane carrier 3 functions as the flow path 2 for the liquid sample.

[0023] Fig. 3(a) is a top view (plan view) of the microstructure 7, and Fig. 3(b) is a perspective view of the protrusions 8 that constitute the microstructure. The microstructure 7 is the sum of the protrusions 8. More specifically, the membrane carrier 3 has a flat portion 9 that corresponds to the bottom surface of the flow channel 2 for the liquid sample, and a plurality of protrusions 8 protruding from the flat portion 9.

[0024] The spaces between the multiple protrusions 8 function as flow paths 2 that transport the liquid sample along the surface of the membrane carrier 3 by capillary action. In other words, by capillary action, the voids in the microstructure 7 act as channels 2 that transport the liquid sample along the surface of the membrane carrier 3 . The plurality of protrusions 8 are formed on the surface of the membrane carrier 3 in a regular array, such as in a lattice arrangement, or in a translationally symmetrical manner.

[0025] The protrusions 8 are, for example, pyramidal, and here, as shown in Fig. 3(b) and Fig. 4, the protrusions 8 are conical. Alternatively, the protrusions 8 may be pyramidal, or may have a shape with the top of the pyramid cut off (truncated pyramid). In any case, it is sufficient that the microstructure 7 formed by the protrusions 8 generates a capillary action and transports the liquid sample.

[0026] The liquid sample is transported through the microstructure 7 from the droplet zone 3z on the left hand side of the figure towards the detection zone 3y (along the transport direction d in FIG. 2) by capillary action of the microstructure 7 described above.

[0027] 2, in this embodiment, the membrane carrier 3 is divided into three areas from the left: a first microstructure region 31 (first uneven portion), a second microstructure region 32 (second uneven portion), and a third microstructure region 33 (third uneven portion). The first microstructure region 31, the second microstructure region 32, and the third microstructure region 33 have different microstructures 7, and as a result, the speed at which the solution is transported differs for each area.

[0028] The speed at which a solution is transported can be understood from the Poiseuille equation, which explains the flow between parallel plates. For example, in a microstructure 7 that generates capillary action, such as a structure in which multiple protrusions 8 are arranged, the narrower the distance 5 between the protrusions 8, the faster the solution is transported. In other words, the speed for each area can be controlled by appropriately setting the density of the microstructure (the arrangement of the protrusions 8 shown in Figure 3).

[0029] Fig. 5 shows an enlarged photograph of a portion of the microstructure 7 viewed from above. Fig. 5(a) shows the region at the boundary (first boundary 41) between the first microstructure region 31 and the second microstructure region 32. Fig. 5(b) shows the region at the boundary (second boundary 42) between the second microstructure region 32 and the third microstructure region 33. In all regions, the protrusions 8 are provided to have the same shape and size.

[0030] In Fig. 5, the protrusions 8 are cones with a base diameter of 30 µm and a height of 30 µm. As shown in the figure, the arrangement (degree of density) of the protrusions 8 is the coarsest in the first microstructure region 31 on the left side of the figure and the densest in the third microstructure region 33 on the right side. In other words, the distance 5 between the protrusions 8 in the first microstructure region 31 is the widest and the distance 5 between the protrusions 8 in the third microstructure region 33 is the narrowest. In the example shown in the figure, the distance 5 between the protrusions 8 in the first microstructure region 31 is 25 µm, the distance 5 between the protrusions 8 in the second microstructure region 32 is 15 µm, and the distance between the protrusions 8 in the third microstructure region 33 is 2 µm.

[0031] When the substance to be detected in the reaction solution reaches the detection zone 3y, it is detected as a current value by the measuring device 21 through the two electrodes 20 provided in the detection zone 3y. That is, a potential difference is applied to the two electrodes 20, and the oxidation current is measured by the measuring device 21. When a color change detection method is used, the substance to be detected is detected by a color change in the detection zone 3y. If the substance to be detected is electrochemically active, it can be detected by the method for measuring the current value using the two electrodes 20 described above, but generally, a separate electrochemically active substance generated according to the concentration of the substance to be detected is detected. A specific test method for this will be described later in the section "Test method using test kit 18".

[0032] <Materials for Membrane Carrier 3> The membrane carrier 3 including the microstructure 7 (multiple convex portions 8) is made of, for example, a thermoplastic. That is, the membrane carrier 3 having the microstructure 7 can be produced by processing a film-shaped substrate made of a thermoplastic by thermal imprinting. The thermoplastic constituting the membrane carrier 3 may be, for example, at least one selected from the group consisting of polyester-based resins, polyolefin-based resins, polystyrene-based resins, polycarbonate-based resins, fluorine-based resins, and acrylic-based resins. A specific thermoplastic may be, for example, at least one of polyethylene terephthalate (PET), cycloolefin polymer (COP), polypropylene (PP), polystyrene (PS), polycarbonate (PC), polyvinylidene fluoride (PVDF), and polymethyl methacrylate (PMMA).

[0033] The glass transition point Tg or melting point Tm of the thermoplastic may be 80 to 180° C. The storage modulus of the thermoplastic at a temperature 20° C. higher than the glass transition point Tg is 1.0 to 1.0×10 7 The storage modulus of a thermoplastic plastic at a temperature 20° C. higher than the melting point Tm may be 1.0 to 1.0×10 7 It may be Pa.

[0034] The glass transition or melting of a thermoplastic occurs at a temperature of 80°C or higher, and the storage modulus of the thermoplastic at a temperature 20°C higher than the glass transition point or melting point is 1.0 x 10 7 If the thermal conductivity is less than 1 Pa, the thermoplastic is suitable for use as a solid at room temperature, and it is easy to fabricate the membrane carrier 3 by thermal imprinting.

[0035] When the glass transition or melting of the thermoplastic occurs at 180° C. or less, the molding temperature during thermal imprinting can be maintained within an appropriate range, preventing a decrease in productivity of the membrane carrier 3. In other words, by setting the temperature required to soften the thermoplastic during thermal imprinting to 180° C. or less, the productivity of the membrane carrier 3 can be maintained at a good level.

[0036] The storage modulus of a thermoplastic plastic at a temperature 20°C higher than the glass transition point or melting point is 1.0 x 10 7 When the pressure is equal to or less than 1 Pa, the molding pressure required for producing the microstructure can be kept small, and the microstructure can be produced under relatively mild conditions, improving production efficiency.

[0037] The cone-shaped (here, circular cone-shaped) protrusions 8 can be formed by thermal imprinting using a mold. When forming the cone using a mold, the volume of metal cut out from the surface of the metal member during mold production is significantly reduced compared to when a mold is used to form groove-shaped flow paths (hereinafter, for convenience, referred to as a "line and space structure"), and the processing costs of the mold are reduced.

[0038] In addition, the top of the pyramid is thinner than the base of the pyramid, so when forming the pyramid using a mold, the volume of metal that is cut out from the surface of the metal member during mold creation is significantly reduced compared to when a cylinder having the same base as the pyramid is formed using a mold, and the processing costs of the mold are reduced.

[0039] Furthermore, the porosity of a microstructure in which the pyramids are regularly aligned is greater than that of a line-and-space structure. Also, the porosity of a microstructure in which the pyramids are regularly aligned is greater than that of a structure in which multiple pillars having the same base as the pyramids are regularly aligned. Therefore, the microstructure in which the pyramids are regularly aligned can increase the flow rate of a liquid sample, which is advantageous for detecting a target substance.

[0040] <Shape and dimensions of membrane carrier 3> As described above, the shape of the bottom surface 10 of the cone (protrusion 8), i.e., the overall shape of the cone (protrusion 8), can be freely selected, and may be, for example, a cone as shown in Figure 3(b) or Figure 4, or a pyramid (such as a square pyramid or a hexagonal pyramid). For ease of processing the mold and to keep processing costs down, it is desirable for the bottom surface 10 of the cone (protrusion 8) to be circular or polygonal (such as a square, rhombus, rectangle, triangle, or hexagon).

[0041] The diameter 4 of the bottom surface 10 of the protrusion 8 is, for example, 10 to 1000 μm. If the diameter 4 of the bottom surface 10 of the protrusion 8 is smaller than 10 μm, the cost of microfabrication of the mold becomes high, and it is difficult to uniformly fabricate numerous microstructures 7 on the surface of the membrane carrier 3 having a large area. Therefore, a microstructure 7 that is too small is not suitable for practical use. If the diameter 4 of the bottom surface 10 of the microstructure 7 is smaller than 10 μm, the capillary force required to move the liquid sample tends to be weak. If the diameter 4 of the bottom surface 10 of the microstructure 7 is larger than 1000 μm, the volume of the metal cut out from the metal member when fabricating the mold becomes large, and the fabrication cost of the mold and membrane carrier 3 becomes high. If the diameter 4 of the bottom surface 10 of the microstructure 7 is larger than 1000 μm, the area of ​​the flow path 2 in the membrane carrier 3 must also be increased, and the test kit 18 becomes large, which is disadvantageous for transporting the test kit 18 itself. When the protrusion 8 (microstructure 7) is a cone, the diameter 4 of the base 10 of the protrusion 8 may be the diameter 4 of the base 10 (circle) of the cone.

[0042] The height 6 of the protrusions 8 is, for example, 10 to 500 μm. If the height 6 of the protrusions 8 is less than 10 μm, the capillary force required to move the liquid sample tends to be weak. If the height 6 of the protrusions 8 is greater than 500 μm, it is difficult to completely fill the thermoplastic plastic into the recesses (recesses corresponding to the shape of the protrusions 8 of the microstructure 7) of the mold during thermal imprinting.

[0043] The overall shape of the membrane carrier 3 is not particularly limited, and may be, for example, a polygon such as a rectangle, a circle, or an ellipse. When the membrane carrier 3 is a rectangle, the vertical width L1 of the membrane carrier 3 may be, for example, 2 to 100 mm, and the horizontal width L2 of the membrane carrier 3 may be, for example, 3 to 100 mm. Furthermore, the horizontal widths L21 to L23 of the first to third microstructure regions 31 may each be, for example, 1 to 50 mm. The thickness of the membrane carrier 3 excluding the height 6 of the microstructure 7 (i.e., the protrusions 8) may be, for example, 0.1 to 10 mm.

[0044] In order to make the overall shape of the membrane carrier 3 compact, the flow path 2 is not limited to being configured simply with straight lines, but may be configured with a combination of various shapes such as straight lines and curves (the flow path 2 has a bent or curved curved path portion), thereby making it possible to make the membrane carrier 3 compact, and as a result, make it possible to make the test kit 18 compact. Such examples will be described in the fourth embodiment and onwards.

[0045] The aspect ratio Lv / Lh of the protrusion 8 may be 1 / 10 to 2 / 1. When the aspect ratio Lv / Lh is smaller than 1 / 10, the contact area between the liquid sample and the flow channel 2 is small, and the capillary force is reduced, so that the liquid sample tends to be difficult to move. When the aspect ratio Lv / Lh is larger than 2 / 1, the productivity of the membrane carrier 3 by thermal imprinting decreases. When the protrusion 8 is a pyramid (more specifically, a cone) as in this embodiment, the length Lh of the protrusion 8 in the horizontal direction may be the diameter 4 of the bottom surface 10 of the protrusion 8. In addition, the length Lv of the protrusion 8 in the vertical direction may be the height 6 of the protrusion 8 from the flat portion 9 of the membrane carrier 3.

[0046] The ratio D2 / D1 of the diameter 4 (D1) of the bottom surface of the convex portion 8 to the closest center distance (D2) between the convex portions 8 may be greater than 1 and less than or equal to 5. The closest center distance here is the distance between the centers of the bottom surfaces of the convex portions 8 of the convex portions 8 that are closest to each other among the adjacent convex portions 8. The ratio D2 / D1 cannot be less than 1. If the ratio D2 / D1 is greater than 5, the contact area between the liquid sample and the flow channel 2 decreases, the capillary force decreases, and the liquid sample tends to be difficult to move. When the convex portion 8 is a cone as in this embodiment, the diameter 4 (D1) of the bottom surface 10 of the convex portion 8 may be the diameter of the bottom surface of the cone, and the closest center distance D2 may be the distance between the apexes of a pair of adjacent convex portions 8 (cones). The diameter 4 (D1) of the bottom surface 10 of the convex portion 8 may be the horizontal length Lh of the convex portion 8 described above. Therefore, the aspect ratio Lv / Lh may be expressed as Lv / D1.

[0047] In addition, when comparing the pitch (distance between apexes) between the convex portions 8 of the fine concave-convex structure between adjacent zones, the pitch P1 of the zone with the fine concave-convex structure that is relatively sparse and the pitch P2 of the zone with the fine concave-convex structure that is relatively dense have a ratio (P1 / P2) of 1.01 to 10. Here, when the pitch between the convex portions 8 of the first fine structure region 31 is P11, the pitch between the convex portions 8 of the second fine structure region 32 is P21, and the pitch between the convex portions 8 of the third fine structure region 33 is P23, the ratio (P11 / P21) is 1.01 to 10, and the ratio (P21 / P23) is 1.01 to 10. The ratio (P1 / P2) is set depending on the speed at which the solution is desired to move. Regarding the lower limit of the ratio (P1 / P2), if it is small, there will be no speed difference between the zones, and the significance of providing a difference in the degree of coarseness and density of the fine concave-convex structure will be reduced. From this viewpoint, the ratio (P1 / P2) is preferably 1.05 or more, more preferably 1.1 or more. If the upper limit is too large, the difference in the solution movement speed between the zones becomes too large, making it difficult to adjust the speed throughout the test kit 18. From this viewpoint, the ratio is preferably 7 or less, more preferably 5 or less.

[0048] <Structure of electrode part (two electrodes)> The two electrodes 20 which are the electrode portion may be formed on the protrusions 8 of the microstructure 7 . In this case, the maximum peak height Rp of the roughness curve of the electrode portion is 0.005 to 10 μm, and the average length RSm of the roughness curve element is 0.01 to 15 μm. By setting the surface roughness in this manner, a good capillary force can be generated. The surface roughness can be calculated by analyzing the SEM image shown in FIG. 4.

[0049] The two electrodes 20 may be provided separately from the membrane carrier 3 and may be attached to the membrane carrier 3 when the test kit 18 is used. For example, the two electrodes 20 may be provided as terminals of a part of the measuring device 21.

[0050] <Manufacturing method of test kit 18> The manufacturing method of the test kit 18 is obtained by the following steps. Process 1: Thermal imprint process The method includes a step of applying the surface of a metal mold, on which multiple recesses are formed, to a film-shaped substrate made of a thermoplastic plastic and heating the substrate to produce a film carrier 3 having a microstructure (multiple protrusions 8) corresponding to the shape of the recesses and a flat portion 9. The method for producing the test kit 18 further includes a step of fixing a reagent or labeling substance to the detection zone 3y on the surface of the membrane carrier 3 having the microstructure 7, more specifically, to the solid phase portion 50 of the third microstructure region 33. The microfabrication method of the mold used in the thermal imprinting process may be, for example, etching, etching using a photolithography technique, mechanical cutting, laser processing, etc. A microfabrication method suitable for the processing size and processing range can be selected.

[0051] It is desirable to perform a mold release treatment before performing thermal imprinting. In the mold release treatment, for example, a monolayer may be formed on the mold surface to reduce the surface energy. As a result, the membrane carrier 3 made of a thermoplastic plastic can be easily peeled off from the surface of the mold 1 after thermal imprinting.

[0052] The thermal imprinting method may be either a flat plate press method or a roll method. In the flat plate press method, a mold is placed on a base material made of a thermoplastic plastic between upper and lower stages facing each other in parallel, and these are sandwiched between the stages. Then, the mold and the base material are heated and pressed through the stage. Such a flat plate press method is excellent in terms of molding accuracy. The roll method is a method in which a heated roll type mold is used to mold by the sandwiching pressure between the rolls. The roll method is excellent in productivity.

[0053] The conditions for thermal imprinting, such as molding temperature, molding pressure, and transfer time, may be selected according to the size of the microfabrication, the shape of the microstructure (protrusions 8), the size of the processing area, and the like. For example, in the case of a flat plate press type, the molding temperature may be a temperature 20 to 50°C higher than the glass transition point Tg, or a temperature 20 to 50°C higher than the melting point Tm. The molding pressure may be 1 to 10 MPa. The transfer time (the time during which the mold and the substrate are held under pressure) may be 3 to 10 minutes. Thermal imprinting under the above conditions facilitates accurate transfer of the microstructure of the mold to the surface of the substrate.

[0054] Depending on the type of thermoplastic constituting the membrane carrier 3 and the type of reagent (detection substance), it may be difficult to fix the reagent (detection substance) to the solid phase part 50 of the membrane carrier 3. In this case, by performing an appropriate surface treatment in advance only on the detection zone 3y, it becomes easier to fix the reagent (detection substance) to the detection zone 3y of the membrane carrier 3 (i.e., the solid phase part 50).

[0055] The surface treatment method for the detection zone 3y is not limited in any way, and may be various methods such as various plasma treatments, UV treatments, UV / ozone treatments, or surface modification with 3-Aminopropyltriethoxysilane or Glutaraldehyde.

[0056] The reagent (detection substance) immobilized in the detection zone 3y may be, for example, an antibody. For example, in Fig. 1, the antibody is immobilized on the solid phase part 50 of the third microstructure region 33. The solid phase part 50 is provided upstream of the two electrodes 20 in the transport direction d of the solution.

[0057] The antibody is a substance that causes an antigen-antibody reaction with the substance to be detected. The antibody may be a polyclonal antibody or a monoclonal antibody. The substance to be detected is not limited in any way, and may be any substance capable of causing an antigen-antibody reaction with the antibody, such as various pathogens and various clinical markers. Specific examples of the substance to be detected may be virus antigens such as influenza virus, norovirus, adenovirus, respiratory syncytial virus, HAV, HBs, and HIV. The substance to be detected may be bacterial antigens such as MRSA, group A streptococcus, group B streptococcus, and Legionella, and toxins produced by bacteria. The substance to be detected may be hormones such as mycoplasma, chlamydia trachomatis, and human chorionic gonadotropin. The substance to be detected may be C-reactive protein, myoglobin, cardiac troponin, various tumor markers, agricultural chemicals, and environmental hormones. In particular, the usefulness of the test kit according to this embodiment is particularly great when it is necessary to detect a substance to be detected, such as influenza virus, norovirus, C-reactive protein, myoglobin, and cardiac troponin, and to take urgent measures to treat diseases caused by these substances. The substance to be detected may be an antigen that can induce an immune reaction by itself. The substance to be detected may be a hapten that cannot induce an immune reaction by itself but can bind to an antibody through an antigen-antibody reaction with the antibody.

[0058] <Testing method using Test Kit 18> The testing method using the test kit 18 will be described with reference to the chart shown in Fig. 6 and the above-mentioned Figs. 1 to 5. In Fig. 6, attention is focused on the third microstructure region 33 of the microstructure 7.

[0059] S1: Device preparation process First, the test kit 18 and the solutions to be used (reaction solution, washing solution, secondary reaction solution) are prepared. As described above, the antibody 51 is fixed to the solid phase portion 50 of the third microstructure region 33.

[0060] S2: Reaction solution development process When the reaction liquid is dropped from the liquid droplet zone 3z onto the second microstructure region 32, it moves to the third microstructure region 33 due to the capillary action of the microstructures 7. The target substance 91 and the target substance (labeled substance) 92 in the reaction solution are immobilized by reacting with the antibody 51. Excess reaction solution is absorbed by the water-absorbing pad, but a part of the target substance 91a and the target substance (labeled substance) 92a is not immobilized and remains on the third microstructure region 33.

[0061] S3: Cleaning solution development process Next, a washing solution 93 is dropped from the washing solution zone 3x to wash away the detection target substance 91a and the detection target substance (labeled substance) 92a that are not fixed to the solid phase portion 50 and remain in the third microstructure region 33. The detection target substance (labeled substance) 92a has an alkaline phosphatase (ALP) label.

[0062] S4: Secondary reaction solution development step After washing, the secondary reaction liquid (e.g., p-aminophenyl phosphate 94) dropped onto the second microstructure region 32 moves to the third microstructure region 33 by the capillary action of the microstructure 7. The p-aminophenyl phosphate 94 reacts with the target substance (label) 92 immobilized on the antibody 51 to generate an electrically active substance (here, p-aminophenol 95). This substance is correlated (proportional) to the amount (concentration) of the target substance (label) 92 immobilized on the antibody 51. Therefore, the concentration of the target substance can be measured accurately and stably from the value of the oxidation current measured by the two electrodes 20.

[0063] As described above, according to this embodiment, in the test kit 18 to which the immunochromatography method is applied, the speed at which the solution moves in the flow channel 2 of the microstructure 7 of the membrane carrier 3 (speed due to capillary action) can be set in multiple regions with different speeds. As a result, even when multiple types of solutions such as reaction solutions, washing solutions, and secondary reaction solutions need to be developed, the timing at which these solutions are developed can be adjusted according to the mode of use. Therefore, the effort of timing adjustment, etc., which would otherwise be required, can be eliminated, and stable and appropriate testing can be performed. Specifically, each solution can be dropped simultaneously, that is, each solution can be developed with only one operation.

[0064] <<Second embodiment>> The test kit of this embodiment will be described with reference to Figures 7 and 8. The difference from the first embodiment is in the structure of the membrane carrier 103, and mainly the different points will be described, and the description of the same configurations and functions will be omitted as appropriate.

[0065] Fig. 7 is a plan view showing a schematic view of the membrane carrier 103. Fig. 8 shows enlarged images of the boundaries between adjacent regions. Fig. 8(a) is an image of a region B11 in the vicinity of a first boundary 141 between the first microstructure region 131 and the second microstructure region 132. Fig. 8(b) is an image of a region B12 in the vicinity of a second boundary 142 between the second microstructure region 132 and the third microstructure region 133. Fig. 8(c) is an image of a region B13 in the vicinity of a third boundary 143 between the third microstructure region 133 and the fourth microstructure region 134.

[0066] As shown in the figure, the membrane carrier 103 has a rectangular shape with a predetermined vertical width L10 and horizontal width L20. From the left, the membrane carrier 103 comprises a first microstructure region 131 (horizontal width L201), a second microstructure region 132 (horizontal width L202), a third microstructure region 133 (horizontal width L203), and a fourth microstructure region 134 (horizontal width L204). As in the first embodiment, these regions have different densities of protrusions in the microstructure, and as a result, the speed due to capillary action is different.

[0067] Specifically, the first microstructure region 131 is the coarsest (region A11), the third microstructure region 133 is the second coarsest (region A13), the second microstructure region 132 is the third coarsest (region A12), and the fourth microstructure region 134 is the densest (region A14). Also, a solid phase portion 150 is provided in the fourth microstructure region 134.

[0068] In addition, a buffer region of a predetermined width L31 is provided at the second boundary 142 between the second fine structure region 132 and the third fine structure region 133. As shown in FIG. 8(b), the buffer region does not have a fine structure (i.e., a convex portion). Similarly, as shown in FIG. 8(c), a buffer region of a predetermined width L32 is also provided at the third boundary 143 between the third fine structure region 133 and the fourth fine structure region 134. By providing such a buffer region, it is possible to absorb the difference in the transport amount of the solution for each region and prevent the occurrence of backflow, etc. For example, between the second fine structure region 132 and the third fine structure region 133, the microstructure of the third fine structure region 133 on the downstream side is coarse. Therefore, the movement speed of the solution is higher in the second fine structure region 132. As a result, if there is no buffer region at the second boundary 142, backflow may occur depending on the amount of solution developed. However, by providing a buffer region in which no capillary force is generated as in this embodiment, it is possible to prevent the occurrence of backflow due to the movement speed of the solution or the amount developed.

[0069] <<Third embodiment>> In this embodiment, six examples of the solution backflow prevention structure will be described. Note that, although the cross-sectional views of some regions of the configurations corresponding to the above-mentioned membrane carriers 3 and 103 will be extracted and described here, the same can be applied to other regions.

[0070] In the membrane carrier 203 shown in FIG. 9(a), a step 241 is provided at the boundary between a first fine structure region 231 and a second fine structure region 232 such that the second fine structure region 232 side is lower.

[0071] 9(b), a sloping portion 341 that becomes lower in the downstream direction is provided at the boundary between the first microstructure region 331 and the second microstructure region 332. The sloping portion 341 may be a buffer region without a convex portion, or may be a fine concave-convex structure region with a convex portion.

[0072] In the membrane carrier 403 shown in Figure 9 (c), a protrusion (step) is formed at the boundary between the first microstructure region 431 and the second microstructure region 432, and the upstream side of this protrusion is an inclined surface 441 and the downstream side is a vertical surface 442.

[0073] In the membrane carrier 503 shown in FIG. 9( d ), a recess 541 is provided at the boundary between the first microstructure region 531 and the second microstructure region 532 .

[0074] In the membrane carrier 603 shown in Figure 9(e), the first microstructure region 631 and the third microstructure region 633 are formed horizontally and so that the third microstructure region 633 is lower than the first microstructure region 631, and the second microstructure region 632 located between them is inclined so that it becomes lower toward the downstream side.

[0075] 9(f), the first microstructure region 731, the second microstructure region 732, and the third microstructure region 733 are all inclined so as to become lower toward the downstream side. Here, a configuration in which all the regions have the same inclination angle is shown, but the inclination angle may be different for each region.

[0076] The configurations of Figs. 9(a) to (f) can be appropriately combined to form a desired membrane carrier, and an optimal flow path and solution movement speed can be realized according to the type and amount of solution to be developed.

[0077] <<Fourth embodiment>> The test kit 18 of this embodiment will be described with reference to FIG. FIG. 10(a) is a plan view of a test kit 1018, and FIG. 10(b) is a plan view focusing on a flow channel 1002 (membrane carrier 1003).

[0078] In the test kit 1018 of this embodiment, the flow path 2 provided in the membrane carrier 1003 has a curved path in the shape of a clockwise spiral. The housing 1018a itself has a substantially square shape when viewed from above. In the flow path 1002, the direction from the outer end of the spiral to the center of the spiral is the traveling direction d of the solution. The configuration and function of the flow path 1002 other than the shape are the same as those of the first to third embodiments described above, and therefore a description thereof will be omitted as appropriate.

[0079] A flow path 1002 provided on the surface of a membrane carrier 1003 is divided into three areas from the outer end side of the spiral toward the center of the spiral: a first microstructure region 1031, a second microstructure region 1032, and a third microstructure region 1033. As in the first embodiment, the first microstructure region 1031, the second microstructure region 1032, and the third microstructure region 1033 have different microstructures 7 (see the above-mentioned Figures 3 and 4, etc.), and as a result, the speed at which the solution is transported differs for each area.

[0080] It also has a cleaning solution zone 1003x provided at the outer end of the spiral, a detection zone 1003y provided in the center of the spiral, and a liquid droplet zone 1003z provided midway between the cleaning solution zone 1003x and the detection zone 1003y.

[0081] In this embodiment, similar to the first embodiment, the cleaning solution zone 1003x is exposed at a first opening 1018x of the housing 1018a. The droplet zone 1003z is exposed at a second opening 1018z of the housing 1018a. The detection zone 1003y is exposed at a third opening 1018y of the housing 1018a. Two electrodes 1020 are provided in the detection zone 1003y for detection by an electrochemical detection method.

[0082] As in the present embodiment, the test kit 1018 has a flow path 1002 with a spiral curved path, and unlike the above-mentioned first embodiment and the like, it is possible to prevent the shape from becoming elongated when viewed from above, and to make the entire kit compact. In addition, a reinforcing structure is required because an elongated shape is prone to breaking, but this embodiment makes it easy to ensure the strength of the entire test kit 1018. As a result, the test kit 1018 is also easy to handle. Note that the shape of the flow path 1002 when viewed from above is not limited to a shape with an outer shape close to a perfect circle as shown in FIG. 10, and may be a shape close to an ellipse.

[0083] <<Fifth embodiment>> The test kit of this embodiment will be described with reference to Fig. 11. Here, the description focuses on the flow channel 1102 provided in the membrane carrier. The flow channel 1102 of this embodiment has a polygonal spiral shape, more specifically, a substantially square shape, and the straight path is bent at multiple points.

[0084] The flow channel 1102 is divided into three areas from the outer end of the spiral (upper left in the figure) toward the center of the spiral: a first path 1121 in a first microstructure region 1131, a second path 1122 in a second microstructure region 1132, and a third path 1123 in a third microstructure region 1133. As in the first embodiment, the first microstructure region 1131, the second microstructure region 1132, and the third microstructure region 1133 have different microstructures 7, and as a result, the speed at which the solution is transported differs from area to area.

[0085] In this embodiment, as in the first embodiment, the cleaning solution zone 1103x is exposed at a first opening 1118x of the housing. The droplet zone 1103z is exposed at a second opening 1118z of the housing. The detection zone 1103y is exposed at a third opening 1118y of the housing. Two electrodes 20 (electrode units) are provided in the detection zone 1103y for detection by an electrochemical detection method.

[0086] As in this embodiment, the test kit has a flow path 1102 that is a polygonal (such as a square) spiral path, which prevents the shape from being elongated when viewed from above, as in the fourth embodiment, making the kit compact overall and making it easier to ensure strength.

[0087] <<Sixth embodiment>> The test kit of this embodiment will be described with reference to Fig. 12. Here, the description focuses on the flow channel 1202 provided in the membrane carrier. The flow channel 1202 of this embodiment is bent in a zigzag shape and has an approximately square outer shape.

[0088] Specifically, the flow channel 1202 extends from the lower left end of the figure as the upstream side toward the downstream side at the upper right end of the figure, while taking a zigzag shape in which a straight path extending vertically bends to the right at the top and bottom of the figure. The flow channel 1202 is divided into three areas: a first path 1221 in the first microstructure region 1231, a second path 1222 in the second microstructure region 1232, and a third path 1223 in the third microstructure region 1233. The first microstructure region 1231, the second microstructure region 1232, and the third microstructure region 1233 have different microstructures 7, as in the first embodiment, and as a result, the speed at which the solution is transported varies from area to area.

[0089] In this embodiment, similarly to the first embodiment, the cleaning solution zone 1203x is exposed at a first opening 1218x of the housing. The droplet zone 1203z is exposed at a second opening 1218z of the housing. The detection zone 1203y is exposed at a third opening 1218y of the housing. Two electrodes 1220 (electrode units) are provided in the detection zone 1203y for detection by an electrochemical detection method.

[0090] As in this embodiment, the test kit has a flow path 1202 that is a curved path that bends in a zigzag shape, which prevents the shape from becoming elongated when viewed from above, as in the fourth and fifth embodiments, making the kit compact overall and making it easier to ensure strength.

[0091] <<Seventh embodiment>> The test kit of this embodiment will be described with reference to FIG. 13. Here, the description focuses on the flow path 1302 provided in the membrane carrier. In this embodiment, the flow path 1302 is bent in a zigzag shape on the upstream side (first path 1321 and second path 1322) and is provided in a straight line on the downstream side (third path 1323). Also, the vertically extending section of the zigzag path becomes shorter toward the downstream side. Due to the flow path 1302, the overall external shape of the test kit is approximately triangular.

[0092] The flow channel 1302 is divided into three areas from the upstream side to the downstream side: a first path 1321 in a first microstructure region 1331, a second path 1322 in a second microstructure region 1332, and a third path 1323 in a third microstructure region 1333. As in the first embodiment, the first microstructure region 1331, the second microstructure region 1332, and the third microstructure region 1333 have different microstructures 7, and as a result, the speed at which the solution is transported differs for each area.

[0093] In this embodiment, as in the first embodiment, the cleaning solution zone 1303x is exposed at a first opening 1318x. The droplet zone 1303z is exposed at a second opening 1318z of the housing. The detection zone 1303y is exposed at a third opening 1318y of the housing. Two electrodes 1320 (electrode section) are provided in the detection zone 1303y for detection by an electrochemical detection method.

[0094] In this embodiment, the test kit has a flow path 1302 composed of a curved path that bends in a zigzag shape and a straight path that connects to the curved path. This prevents the test kit from becoming elongated when viewed from above, as in the fourth to sixth embodiments, and allows the kit to be made compact overall, while also making it easier to ensure strength.

[0095] <<Eighth embodiment>> The test kit of this embodiment will be described with reference to Fig. 14. Here, the description will focus on the flow path 1402 provided in the membrane carrier. The flow path 1402 of this embodiment has a path branched into a Y shape, and two paths (first path 1421 and second path 1422) branching on the upstream side are joined to one path (third path 1423) on the downstream side. Due to this flow path 2, the overall external shape of the test kit is approximately triangular.

[0096] The flow path 1402 is divided into three areas: a first microstructure region 1431 provided in the first path 1421, a second microstructure region 1432 provided in the second path 1422, and a third microstructure region 1433 provided in the third path 1423. As in the first embodiment, the first microstructure region 1431, the second microstructure region 1432, and the third microstructure region 1433 have different microstructures 7, and as a result, the speed at which the solution is transported differs for each area.

[0097] In this embodiment, a first droplet zone 1403x1 is exposed at a first opening 1418x1 on the upstream side of a first path 1421. A second droplet zone 1403x2 is exposed at a second opening 1418x2 on the upstream side of a second path 1422. A detection zone 1403y is exposed at a third opening 1418z on the downstream side of a third path 1423. In this configuration, for example, a cleaning solution is dropped into the first droplet zone 1403x1, and a liquid sample solution is dropped into the second droplet zone 1403x2. Two electrodes 20 (electrode units) are provided in the detection zone 1403y for detection by an electrochemical detection method.

[0098] As in the present embodiment, the test kit has a flow path 1402 consisting of multiple branched paths, so that the shape viewed from above is prevented from becoming elongated, as in the fourth to seventh embodiments, and the overall shape can be made compact and strength can be easily ensured. In addition, the dropping area and dropping timing of the liquid sample solution and cleaning solution can be flexibly set.

[0099] <<Ninth embodiment>> The test kit of this embodiment will be described with reference to Fig. 15. Here, the description focuses on the flow path 1502 provided in the membrane carrier. The flow path 1502 of this embodiment has a path that branches into a roughly F-shape, and three paths (first to third paths 1521 to 1523) are joined to one path (fourth path 1524).

[0100] Specifically, first to third paths 1521-1523 are successively coupled from the upstream side to fourth path 1524. Here, the path lengths of first to third paths 1521-1523 are different, with first path 1521 being the longest and third path 1523 being the shortest. Due to such flow channels 1502, the overall external shape of the test kit is approximately triangular.

[0101] The flow path 1502 is divided into four areas: a first microstructure region 1531 provided in a first path 1521, a second microstructure region 1532 provided in a second path 1522, a third microstructure region 1533 provided in a third path 1523, and a fourth microstructure region 1534 provided in a fourth path 1524. As in the above-described embodiment, the first microstructure region 1531, the second microstructure region 1532, the third microstructure region 1533, and the fourth microstructure region 1534 have different microstructures 7, and as a result, the speed at which the solution is transported differs for each area.

[0102] In this embodiment, a first droplet zone 1503x1 is exposed at a first opening 1518x1 on the upstream side of a first path 1521. A second droplet zone 1503x2 is exposed at a second opening 1518x2 on the upstream side of a second path 1522. A third droplet zone 1503x3 is exposed at a third opening 1518x3 on the upstream side of a third path 1523. A detection zone 1503y is exposed at a fourth opening 1518z on the downstream side of a fourth path 1524. Two electrodes 1520 (electrode portions) are provided in the detection zone 1503y for detection by an electrochemical detection method.

[0103] As in this embodiment, the test kit has a flow path 1502 composed of multiple branched paths, which prevents the shape from becoming elongated when viewed from above, as in the fourth to eighth embodiments, and allows the kit to be made compact as a whole and makes it easier to ensure strength. In addition, since the flow path 2 branches into multiple independent paths, the drip area and drip timing of the liquid sample solution and cleaning solution can be flexibly set.

[0104] In the eighth and ninth embodiments, a configuration in which a path branched on the upstream side is combined into one path on the downstream side is exemplified. However, the present invention is not limited to this, and a configuration in which a single path on the upstream side is branched into multiple paths on the downstream side, and further, a configuration in which paths that have once branched are combined again, may be used. With such a configuration, for example, a process in which a cleaning liquid dropped at one location is branched into multiple paths with different flow rates, and the cleaning liquid is supplied from the different paths at a time difference in a predetermined area on the downstream side, may be possible.

[0105] <<Tenth embodiment>> The test kit of this embodiment will be described with reference to Fig. 16. Here, the description will focus on the cross-sectional structure of the flow channel 1602 provided in the membrane carrier. In the above-mentioned second embodiment, a backflow prevention structure for the solution was exemplified, but in this embodiment, this structure is expanded, and the route has an upward route and a downward route that move up and down three-dimensionally. This prevents the route from becoming long in a plane, and realizes a compact test kit.

[0106] Specifically, as shown in the figure, from the upstream side, there is a flat first path 1621, a second path 1622 which has a peak-valley structure (uneven structure) with regular succession of peaks and valleys, and a flat third path 1623.

[0107] In the first to third paths 1621 to 1623, first to third fine structure regions 1631 to 1633 having different fine structures 7 are formed, respectively.

[0108] In this way, by providing the flow channel 1602 three-dimensionally, the flow channel 2 can be made compact. As a result, the test kit can be made compact and strength can be easily ensured. Note that such a configuration can be appropriately combined with the configuration of the above embodiment.

[0109] <<Eleventh embodiment>> The test kit of this embodiment will be described with reference to Fig. 17. In this embodiment, an example of two paths having a path width changing portion in which the path width changes will be described in Fig. 17(a) and Fig. 17(b).

[0110] The flow channel 1702A in FIG. 17(a) has a first path 1721A on the upstream side that is linearly provided with a width t1, and a second path 1722A on the downstream side that is linearly provided with a width t2 narrower than the first path 1721A. Furthermore, the flow channel 1702A is a path that connects the first and second paths 1721A and 1722A, and is provided with a narrow path section 1723A (path width changing section) where the path width gradually narrows. The narrow path section 1723A can adjust the speed and amount of the solution flowing through the flow channel 1702A. The first and second paths 1721A and 1722A and the narrow path section 1723A may have the same or different microstructures 7.

[0111] The flow path 1702B in FIG. 17(b) has a first path 1721B on the upstream side that is linearly provided with a width t1, and a second path 1722B on the downstream side that is linearly provided with a width t2 narrower than the first path 1721B. Furthermore, the flow path 1702B is a path that connects the first and second paths 1721B and 1722B, and is provided with a path neck portion 1723B (path width change portion) in which the path width gradually narrows at one end and then gradually widens. Specifically, the flow path 2 has, from the upstream side, a first neck portion 1723B1 that gradually narrows from a width t1, a narrow portion 1723B3 with a narrowest width t3, and a second neck portion 1723B2 that gradually widens from the width t3 to a width t2. The speed and amount of the solution flowing through the flow path 1702B can be adjusted by the path neck portion 1723B (path width change portion). The first and second paths 1721B, 1722B and the path neck portion 1723B (path width changing portion) may have the same or different microstructures 7.

[0112] <<Twelfth embodiment>> The test kit of this embodiment will be described with reference to Fig. 18. Fig. 18(a) is an enlarged plan view of a portion of the flow channel 1802, and Fig. 18(b) is a side view thereof. In this embodiment, the size of the convex portions 1808A, 1808B (microstructures 7) provided in the flow channel 1802 and the density at which they are arranged vary depending on the area.

[0113] Specifically, the flow path 1802 has, from the upstream side, a first path 1821 which is a first microstructure region 1831, and a second path 1822 which is a second microstructure region 1832. The multiple protrusions 1808A of the first microstructure region 1831 are relatively sparsely arranged. The multiple protrusions 1808B of the second microstructure region 1832 are relatively densely arranged.

[0114] Moreover, the size of the convex portion 1808A of the first microstructure region 1831 is set to be larger than the size of the convex portion 1808B of the second microstructure region 1832. Here, the base area and height of the convex portion 1808A are larger than the base area and height of the convex portion 1808B, but either one may be larger.

[0115] By adjusting the size and arrangement density of the convex portions 1808A and 1808B constituting the fine structure 7, the speed of the solution flowing through the flow channel 2 can be adjusted.

[0116] This application claims priority based on Japanese Patent Application No. 2020-199456, filed on December 1, 2020, the disclosure of which is incorporated herein in its entirety. [Explanation of symbols]

[0117] 2, 1002, 1102, 1202, 1302, 1402, 1502, 1602, 1702A, 1702B, 1802 flow path 3, 103, 203, 303, 403, 503, 603, 703, 1003 Membrane carriers 3x, 1003x, 1103x, 1203x, 1303x Cleaning Solution Zone 3y, 1003y, 1103y, 1203y, 1303y, 1403y, 1503y Detection Zone 3z, 1003z, 1103z Droplet Zone 8 Convex 18 Test Kits 18a, 1018a housing 18b, 1018x, 1118x, 1218x, 1318x, 1418x1, 1518x1 First opening 18c, 1018z, 1118z 2nd opening 18d, 1018y, 1118y, third opening 20, 1020, 1120, 1220, 1320, 1420, 1520 two electrodes 21 Measuring Equipment 31, 131, 231, 331, 431, 531, 631, 731, 1031, 1131, 1231, 1331, 1431, 1531, 1631, 1831 1st fine structure region 32, 132, 232, 332, 432, 532, 632, 732, 1032, 1132, 1232, 1332, 1432, 1532, 1632, 1832 Second fine structure region 33, 133, 1033, 1133, 1233, 1333, 1433, 1533 3rd fine structure region 134, 1534 4th fine structure region 41, 141, 241 first boundary 42, 142 second boundary 143 Third boundary 50, 150 solid phase part 51 Antibodies 341, 441 Slope 541 Recess 1021, 1121, 1221, 1321, 1421, 1521, 1621, 1721A, 1721B, 1821 First Route 1022, 1122, 1222, 1322, 1422, 1522, 1622, 1722A, 1722B, 1822 Second Route 1023, 1123, 1223, 1323, 1423, 1523, 1623 3rd Route 1524 4th Route 1723A Narrow path section (path width change section) 1723B Path neck section (path width change section)

Claims

1. A flow channel provided on a substrate made of resin for transporting a reaction solution; a solid phase portion provided in the flow channel, on which an antibody or an antigen is immobilized; a detection unit for detecting a reaction of the reaction solution with the antibody or the antigen; a fine concave-convex structure having a plurality of convex portions formed integrally with the substrate in a region where the flow path is provided; having The flow path has a curved path portion, A plurality of the flow paths are provided, At least two of the flow paths are joined together at a joint, A detection device, wherein among the at least two flow paths, the micro-relief structure of at least one flow path is different from the micro-relief structure of the other flow paths.

2. The detection device according to claim 1 , wherein the coupling portion is located at a position different from the curved path portion.

3. The detection device according to claim 1 , wherein the coupling portion is at the same position as the curved path portion.

4. The detection device according to claim 1 , wherein the at least two flow paths have an opening through which the reaction liquid can be introduced, at an end opposite to the joint portion.

5. The detection device according to claim 1 , wherein the flow path further includes a path width changing section in which a flow path width changes.

6. The detection device according to any one of claims 1 to 5, wherein the flow path has, when the protruding direction of the convex portion is the vertical direction, a continuous upward path portion inclined in an upward direction and a downward path portion inclined in a downward direction.

7. The fine uneven structure is a first concave-convex portion provided with the plurality of convex portions; a second concave-convex portion in which the plurality of convex portions are provided more densely than the first concave-convex portion; having The detection device according to claim 1 , wherein, when the direction in which the reaction liquid is transported to the detection section is from upstream to downstream, the first uneven portion is located upstream of the second uneven portion.

8. The detection device according to claim 7, wherein, when comparing the convex portions of the first uneven portion and the convex portions of the second uneven portion, the area of ​​the bottom surface of the convex portions of the first uneven portion is larger than the area of ​​the bottom surface of the convex portions of the second uneven portion.

9. The detection device according to claim 7 , further comprising a buffer region where no convex portion is provided at a boundary between the first concave-convex portion and the second concave-convex portion.

10. A step or a slope is provided at a boundary between the first uneven portion and the second uneven portion, The detection device according to claim 7 , wherein a region of the step or the slope on the side of the first uneven portion is higher than a region of the step or the slope on the side of the second uneven portion.

11. The detection device according to claim 7 , further comprising a recessed region in which a recess is provided at a boundary between the first concave-convex portion and the second concave-convex portion.

12. The detection device according to claim 1 , wherein the detection unit has an electrode unit for detecting an electrochemical reaction.

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