JP7606536B2 - Detection Equipment - Google Patents

Description

The present invention relates to a detection device for detecting a substance to be detected in a liquid sample.

In recent years, point of care test (POCT) reagents, which use antigen-antibody reactions to test for infectious diseases and pregnancy, and measure blood sugar levels, have been attracting attention. Tests and measurements using POCT reagents allow results to be determined 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.

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 detectable substance contained in the liquid sample is detected. Immunochromatography is often used as a method for detecting a specific detectable substance from a liquid sample. In immunochromatography, the liquid sample is dropped onto a membrane carrier provided in the test kit, and the detectable 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.

Nitrocellulose membranes are often used as membrane carriers for moving liquid samples (see Patent Document 1 below). Nitrocellulose membranes have many minute pores with diameters of about a few μm, through which the liquid sample moves by capillary force.

However, because nitrocellulose membranes are derived from natural products, the pore size and connections between the pores in the membrane are not uniform, so the flow rate of the liquid sample through the membrane varies depending on the membrane. Differences in flow rate also change the time it takes to detect the target substance. As a result, it may be erroneously determined that the target substance is not detected before it binds to the labeling substance or reagent.

To solve the above problems, a method has been devised for artificially creating a microchannel for a liquid sample (see Patent Documents 2 and 3 below). Using this method, a membrane carrier with a uniform structure can be created. As a result, it is possible to reduce the possibility of making the erroneous determination that the target substance is not detected before it binds to a labeling substance or a reagent.

JP 2014-062820 A Patent No. 4597664 Special Publication No. 2012-524894

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 the substance to be detected 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 for detection.

In the electrochemical immunochromatography method, it is necessary to develop multiple types of solutions such as a reaction solution, a washing solution, and a 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 for a test kit using electrochemical immunochromatography.
When considering actual operations, 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.

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 more compact when multiple types of solutions, such as reaction solutions, washing solutions, and secondary reaction solutions, are deployed in a test kit using immunochromatography.

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.

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.

FIG. 2 is a top view of the test kit according to the first embodiment. FIG. 2 is a top view of the membrane carrier of the first embodiment. FIG. 2 is a diagram showing a microstructure and protrusions of the first embodiment. FIG. 2 is a perspective view of a protrusion according to the first embodiment. FIG. 2 is an enlarged view showing the boundaries of each region of the microstructure of the first embodiment. FIG. 2 is a chart showing an example of a testing method using the test kit of the first embodiment. FIG. 4 is a top view of the membrane carrier of the second embodiment. FIG. 13 is an enlarged view showing the boundaries of each region of the microstructure of the second embodiment. 13A to 13C are diagrams showing examples of a backflow prevention structure for a solution in a microstructure according to a third embodiment. FIG. 13 is a plan view illustrating a flow path of the test kit according to the fourth embodiment. FIG. 13 is a plan view illustrating a flow path of the test kit according to the fifth embodiment. FIG. 13 is a plan view illustrating a flow path of the test kit of the sixth embodiment. FIG. 13 is a plan view illustrating a flow path of the test kit of the seventh embodiment. FIG. 23 is a plan view illustrating a flow path of the test kit of the eighth embodiment. FIG. 13 is a plan view illustrating a flow path of the test kit of the ninth embodiment. FIG. 23 is a plan view illustrating the flow path of the test kit of the tenth embodiment. FIG. 23 is a plan view illustrating the flow path of the test kit of the eleventh embodiment. FIG. 23 is a plan view illustrating the flow path of the test kit of the twelfth embodiment.

The following describes embodiments of the present invention. First, in the first embodiment, the basic configuration of a test kit using immunochromatography is described. Next, in the second embodiment, an example of a test kit in which a buffer region is provided in the flow path is described, and in the third embodiment, an example of a structure to prevent backflow of the solution in the flow path is described. Furthermore, in the fourth to tenth embodiments, an example of a test kit that is made compact by providing a curved path (such as a curve or bend) other than a straight line in the flow path is described, and in the eleventh and twelfth embodiments, an example of a technology for adjusting the transport speed of the solution is described.

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 membrane carrier 3. Fig. 3 shows the fine structure (also called the "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.

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.

As described above, in the electrochemical immunochromatography method, 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.

<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.

The surface of the membrane carrier 3 has, from the left in the figure, a washing solution zone 3x where washing solution is dropped, a liquid droplet zone 3z where 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).

The cleaning solution zone 3x is exposed at the first opening 18b of the housing 18a. The droplet zone 3z is exposed at the second opening 18d of the housing 18a. The detection zone 3z is exposed at the 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.

Two electrodes 20 (electrode parts) 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 specific application is installed on a mobile terminal such as a smartphone.

<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.

Figure 3(a) is a top view (plan view) of the microstructure 7, and Figure 3(b) is a perspective view of the convex portions 8 that make up the microstructure. The microstructure 7 is the sum of the convex portions 8. More specifically, the membrane carrier 3 comprises a flat portion 9 that corresponds to the bottom surface of the flow path 2 for the liquid sample, and a plurality of convex portions 8 protruding from the flat portion 9.

Due to capillary action, 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 .
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.

The protrusions 8 are, for example, pyramidal, and here, as shown in FIG. 3(b) and FIG. 4, the protrusions 8 are conical. Alternatively, they 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 capillary action and transports the liquid sample.

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

In this embodiment, as shown in Figure 2, 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.

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 protrusions 8 shown in Figure 3).

Figure 5 shows a photograph of a portion of the microstructure 7, enlarged from above. Figure 5(a) shows the region at the boundary (first boundary 41) between the first microstructure region 31 and the second microstructure region 32. Figure 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.

In FIG. 5, the convex portion 8 is a cone, 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 convex portions 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 convex portions 8 in the first microstructure region 31 is the widest, and the distance 5 between the convex portions 8 in the third microstructure region 33 is the narrowest. In the example shown in the figure, the distance 5 between the convex portions 8 in the first microstructure region 31 is 25 μm, the distance 5 between the convex portions 8 in the second microstructure region 32 is 15 μm, and the distance between the convex portions 8 in the third microstructure region 33 is 2 μm.

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 using a color change detection method, the substance to be detected is detected by the color change of the detection zone 3y. If the substance to be detected is electrochemically active, it can be detected by the current value measurement method 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. The specific test method will be described later in "Test method using test kit 18".

<Material of 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 membrane-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).

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 may be 1.0 to 1.0×10 ⁷ Pa. The storage modulus of the thermoplastic at a temperature 20° C. higher than the melting point Tm may be 1.0 to 1.0×10 ⁷ Pa.

If 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 ¹⁰⁷ Pa or less, the thermoplastic is suitable for use as a solid at room temperature and it is easy to prepare a membrane carrier 3 by thermal imprinting.

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, and a decrease in productivity of the membrane carrier 3 can be prevented. 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.

When 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 ¹⁰⁷ Pa or less, the molding pressure required to produce a microstructure can be kept small, and production can be performed under relatively mild conditions, improving production efficiency.

The convex portion 8 of the pyramid (here, a circular cone) can be formed by thermal imprinting using a mold. When forming the pyramid using a mold, the volume of metal cut out from the surface of the metal member when making the mold is significantly reduced compared to when using a mold to form a groove-shaped flow path (hereinafter referred to as a "line and space structure" for convenience), and the processing cost of the mold is reduced.

In addition, the top of the cone is thinner than its base. Therefore, when forming a cone using a mold, the volume of metal that is cut out from the surface of the metal part when making the mold is significantly reduced compared to when a cylinder with the same base as the cone is formed using a mold, and the processing costs of the mold are reduced.

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

<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). In order to facilitate the processing of the mold and to reduce processing costs, 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).

The diameter 4 of the bottom surface 10 of the convex portion 8 is, for example, 10 to 1000 μm. If the diameter 4 of the bottom surface 10 of the convex portion 8 is smaller than 10 μm, the cost of microfabrication of the mold becomes high, and it is difficult to uniformly fabricate countless microstructures 7 on the surface of the membrane carrier 3 with a large area. Therefore, a microstructure 7 that is too small is not suitable for practical use. Also, 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 metal cut out from the metal member when making the mold becomes large, and the cost of making the mold and membrane carrier 3 becomes high. Also, 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 convex portion 8 (microstructure 7) is a cone, the diameter 4 of the base surface 10 of the convex portion 8 may be the diameter 4 of the base surface 10 (circle) of the cone.

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 into the recesses of the mold (the depressions corresponding to the shape of the protrusions 8 of the microstructure 7) during thermal imprinting.

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 convex portion 8) may be, for example, 0.1 to 10 mm.

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 can 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 the membrane carrier 3 compact and, as a result, making the test kit 18 compact. Such examples will be described in the fourth embodiment and onwards.

The aspect ratio Lv/Lh of the convex portion 8 may be 1/10 to 2/1. If the aspect ratio Lv/Lh is smaller than 1/10, the contact area between the liquid sample and the flow path 2 is small, and the capillary force is reduced, making it difficult to move the liquid sample. If the aspect ratio Lv/Lh is greater than 2/1, the productivity of the membrane carrier 3 by thermal imprinting decreases. In the case where the convex portion 8 is a pyramid (more specifically, a cone) as in this embodiment, the horizontal length Lh of the convex portion 8 may be the diameter 4 of the bottom surface 10 of the convex portion 8. In addition, the vertical length Lv of the convex portion 8 may be the height 6 of the convex portion 8 from the flat portion 9 of the membrane carrier 3.

The ratio D2/D1 of the diameter 4 (D1) of the bottom surface of the convex portion 8 to the closest center-to-center distance (D2) between the convex portions 8 may be greater than 1 and less than 5. The closest center-to-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 path 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-to-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.

In addition, when comparing the pitch (distance between apexes) between the convex portions 8 of the fine uneven structure between adjacent zones, the pitch P1 of the zone with a relatively coarsely configured fine uneven structure and the pitch P2 of the zone with a relatively densely configured fine uneven structure have a ratio (P1/P2) of 1.01 to 10. Here, if 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 to be moved. Note that, when the lower limit of the ratio (P1/P2) is small, there is no speed difference between the zones, and the significance of providing a difference in the degree of coarseness and density of the fine uneven structure is 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.

<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. Note that these surface roughnesses can be calculated by analyzing SEM images such as those shown in FIG.

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

<Method of manufacturing test kit 18>
The manufacturing method of the test kit 18 is as follows.
Step 1...Thermal imprinting step This step involves bringing the surface of a die (mold) on which multiple recesses are formed into contact with a film-like substrate made of a thermoplastic plastic, and heating the substrate, thereby producing 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 manufacturing 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 on which the microstructure 7 is formed, 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.

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

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 substrate made of thermoplastic plastic between upper and lower stages that face each other in parallel, and these are sandwiched between the stages. The mold and substrate are then heated and pressurized via the stages. This type of flat plate press method is superior in terms of molding accuracy. The roll method is a method in which a heated roll mold is used to mold by the sandwiching pressure between the rolls. The roll method is superior in productivity.

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 20 to 50°C higher than the glass transition point Tg, or 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 substrate are held under pressure) may be 3 to 10 minutes. Thermal imprinting under the above conditions makes it easier to accurately transfer the microstructure of the mold to the surface of the substrate.

Depending on the type of thermoplastic that constitutes 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 portion 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 (i.e., the solid phase portion 50) of the membrane carrier 3.

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.

The reagent (detection substance) immobilized in the detection zone 3y may be, for example, an antibody. For example, in FIG. 1, an antibody is immobilized in the solid phase portion 50 of the third microstructure region 33. The solid phase portion 50 is provided upstream of the second electrode 20 in the transport direction d of the solution.

An antibody is a substance that undergoes an antigen-antibody reaction with a 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 undergoing an antigen-antibody reaction with an 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, RS 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, or 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, pesticides, and environmental hormones. In particular, the usefulness of the test kit according to the present 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.

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

S1: Device Preparation Step First, the test kit 18 and 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.

S2: Reaction Liquid Spreading Step When the reaction liquid is dropped from the liquid droplet zone 3z onto the second fine structure region 32, it moves to the third fine structure region 33 due to the capillary action of the fine structure 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.

S3: Washing Liquid Spreading Step Next, a washing liquid 93 is dropped from the washing liquid zone 3x to wash away the target substance 91a and the target substance (labeled substance) 92a that are not fixed to the solid phase portion 50 and remain in the third microstructure region 33. The target substance (labeled substance) 92a has an alkaline phosphatase (ALP) label.

S4: Secondary reaction liquid 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 substance to be detected (labeled substance) 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 substance to be detected (labeled substance) 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.

As described above, according to this embodiment, in the test kit 18 using the immunochromatography method, 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, cleaning 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 required for timing adjustments, etc., which would normally 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.

<<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 the differences will be mainly described, and descriptions of the same configurations and functions will be omitted as appropriate.

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

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 has 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 the protrusions in the microstructure, and as a result, the speed due to capillary action is different.

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). In addition, a solid phase portion 150 is provided in the fourth microstructure region 134.

In addition, a buffer area of a predetermined width L31 is provided at the second boundary 142 between the second microstructure region 132 and the third microstructure region 133. As shown in FIG. 8B, the buffer area does not have a microstructure (i.e., a convex portion). Similarly, as shown in FIG. 8C, a buffer area of a predetermined width L32 is also provided at the third boundary 143 between the third microstructure region 133 and the fourth microstructure region 134. By providing such a buffer area, 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, in the second microstructure region 132 and the third microstructure region 133, the microstructure of the downstream third microstructure region 133 is coarse. Therefore, the movement speed of the solution is higher in the second microstructure region 132. As a result, if there is no buffer area at the second boundary 142, backflow may occur depending on the amount of solution developed. However, as in this embodiment, by providing a buffer area where capillary force is not generated, it is possible to prevent the occurrence of backflow due to the movement speed of the solution or the amount developed.

<<Third embodiment>>
In this embodiment, six examples of the backflow prevention structure for the solution 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 present invention can also be applied to other regions.

In the membrane carrier 203 shown in Figure 9 (a), a step portion 241 is provided at the boundary between the first microstructure region 231 and the second microstructure region 232 so that the second microstructure region 232 side is lower.

In the membrane carrier 303 shown in FIG. 9(b), an inclined 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 inclined portion 341 may be a buffer region without a convex portion, or may be a fine concave-convex structure region having a convex portion.

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.

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

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.

In the membrane carrier 703 shown in FIG. 9(f), the first microstructure region 731, the second microstructure region 732, and the third microstructure region 733 are all inclined so that they become lower toward the downstream side. Here, a configuration in which all have the same inclination angle is shown, but the inclination angle may be different for each region.

The configurations in Figures 9 (a) to (f) above can be appropriately combined to create the desired membrane carrier, thereby realizing the optimal flow path and solution movement speed depending on the type and amount of solution to be developed.

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

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

The flow path 1002 provided on the surface of the membrane carrier 1003 is divided into three areas from the outer end 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 Figures 3 and 4 above), and as a result, the speed at which the solution is transported differs for each area.

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 droplet zone 1003z provided midway between the cleaning solution zone 1003x and the detection zone 1003y.

In this embodiment, as in 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 electrochemical detection techniques.

In this embodiment, the test kit 1018 has a flow path 1002 with a spiral curved path, which prevents the test kit 1018 from becoming elongated when viewed from above, unlike the first embodiment described above, and allows the test kit 1018 to be made compact overall. In addition, a reinforcing structure is required because an elongated shape makes the test kit 1018 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, but may be a shape close to an ellipse.

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

The flow path 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 the first microstructure region 1131, a second path 1122 in the second microstructure region 1132, and a third path 1123 in the 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 for each area.

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 portions) are provided in the detection zone 1103y for detection by an electrochemical detection method.

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 becoming elongated when viewed from above, as in the fourth embodiment, making the kit compact overall and making it easier to ensure strength.

<<Sixth embodiment>>
The test kit of this embodiment will be described with reference to Fig. 12. Here, the description will focus 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.

Specifically, the flow path 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 path with a straight path extending up and down that bends to the right side at the top and bottom of the figure. The flow path 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. As in the first embodiment, the first microstructure region 1231, the second microstructure region 1232, and the third microstructure region 1233 have different microstructures 7, and as a result, the speed at which the solution is transported differs for each area.

In this embodiment, as in 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 portions) are provided in the detection zone 1203y for detection by an electrochemical detection method.

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

<<Seventh embodiment>>
The test kit of this embodiment will be described with reference to FIG. 13. Here, the description will focus 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). In addition, the vertically extending section of the zigzag path is shorter on the downstream side. Due to the flow path 1302, the overall external shape of the test kit is approximately triangular.

The flow path 1302 is divided into three areas from the upstream side to the downstream side: a first path 1321 in the first microstructure region 1331, a second path 1322 in the second microstructure region 1332, and a third path 1323 in the 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.

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

In this embodiment, the test kit has a flow path 1302 that is 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.

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 Y-shaped branched path, 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.

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.

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

As in this embodiment, the test kit has a flow path 1402 consisting of multiple branched paths, which prevents the shape from becoming elongated when viewed from above, as in the fourth to seventh embodiments, making it possible to make the entire kit compact and making it easier to ensure strength. In addition, the drip area and drip timing of the liquid sample solution and cleaning solution can be flexibly set.

<<Ninth embodiment>>
The test kit of this embodiment will be described with reference to Fig. 15. Here, the description will focus 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 combined into one path (fourth path 1524).

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

The flow path 1502 is divided into four areas: a first microstructure region 1531 provided in the first path 1521, a second microstructure region 1532 provided in the second path 1522, a third microstructure region 1533 provided in the third path 1523, and a fourth microstructure region 1534 provided in the fourth path 1524. As in the above-mentioned 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.

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

As in this embodiment, the test kit has a flow path 1502 consisting of multiple branched paths, which prevents the shape from becoming elongated when viewed from above, as in the fourth to eighth embodiments, making it possible to make the entire kit compact and making 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.

In the eighth and ninth embodiments, a configuration in which a path branching on the upstream side joins a single path on the downstream side has been exemplified. However, the present invention is not limited to this, and a single path on the upstream side may be branched into multiple paths on the downstream side, and paths that have once branched may be rejoined. With such a configuration, for example, a process in which a cleaning solution dropped at one location is branched into multiple paths with different flow rates, and the cleaning solution is supplied from the different paths at a time lag in a specified area on the downstream side, can be performed.

<<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 path 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 path has an upward path and a downward path that move up and down three-dimensionally. This prevents the path from becoming long in a plane, and realizes a compact test kit.

Specifically, as shown in the figure, from the upstream side, there is a planar first path 1621, a second path 1622 having a peak-valley structure (uneven structure) in which peaks and valleys are arranged in a regular sequence, and a planar third path 1623.

The first to third paths 1621 to 1623 have first to third microstructure regions 1631 to 1633, each having a different microstructure 7.

In this way, by providing the flow path 1602 three-dimensionally, the flow path 2 can be made compact. As a result, the test kit can be made compact and strength can be easily ensured. This configuration can be appropriately combined with the configuration of the above embodiment.

<<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).

The flow path 1702A in FIG. 17(a) has a first upstream path 1721A linearly arranged with a width t1, and a second downstream path 1722A linearly arranged with a width t2 narrower than the first path 1721A. Furthermore, the flow path 1702A is a path connecting the first and second paths 1721A and 1722A, and is provided with a narrow path section 1723A (path width change section) in which the path width gradually narrows. The narrow path section 1723A can adjust the speed and amount of the solution flowing through the flow path 1702A. The first and second paths 1721A and 1722A and the narrow path section 1723A may have the same or different microstructures 7.

The flow path 1702B in FIG. 17(b) has a first upstream path 1721B that is linearly arranged with a width t1, and a second downstream path 1722B that is linearly arranged 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 width t1, a narrow portion 1723B3 with the narrowest width t3, and a second neck portion 1723B2 that gradually widens from width t3 to 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 change portion) may have the same or different microstructures 7.

<<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 part of the flow channel 1802, and Fig. 18(b) is a side view thereof. In this embodiment, the size and arrangement density of the convex portions 1808A and 1808B (microstructures 7) provided in the flow channel 1802 differ depending on the area.

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 convex portions 1808A of the first microstructure region 1831 are relatively sparsely arranged. The multiple convex portions 1808B of the second microstructure region 1832 are relatively densely arranged.

In addition, 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.

By adjusting the size and density of the convex portions 1808A and 1808B that constitute such a microstructure 7, the speed of the solution flowing through the flow path 2 can be adjusted.

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.

2, 1002, 1102, 1202, 1302, 1402, 1502, 1602, 1702A, 1702B, 1802 Flow path 3, 103, 203, 303, 403, 503, 603, 703, 1003 Membrane carrier 3x, 1003x, 1103x, 1203x, 1303x Washing solution zone 3y, 1003y, 1103y, 1203y, 1303y, 1403y, 1503y Detection zone 3z, 1003z, 1103z Droplet zone 8 Convex portion 18 Test kit 18a, 1018a Housing 18b, 1018x, 1118x, 1218x, 1318x, 1418x1, 1518x1 First opening 18c, 1018z, 1118z Second opening 18d, 1018y, 1118y Third opening 20, 1020, 1120, 1220, 1320, 1420, 1520 Two electrodes 21 Measurement device 31, 131, 231, 331, 431, 531, 631, 731, 1031, 1131, 1231, 1331, 1431, 1531, 1631, 1831 First microstructure region 32, 132, 232, 332, 432, 532, 632, 732, 1032, 1132, 1232, 1332, 1432, 1532, 1632, 1832 Second microstructure region 33, 133, 1033, 1133, 1233, 1333, 1433, 1533 Third microstructure region 134, 1534 Fourth microstructure region 41, 141, 241 First boundary 42, 142 Second boundary 143 Third boundary 50, 150 Solid phase portion 51 Antibody 341, 441 Inclined portion 541 Recess 1021, 1121, 1221, 1321, 1421, 1521, 1621, 1721A, 1721B, 1821 First path 1022, 1122, 1222, 1322, 1422, 1522, 1622, 1722A, 1722B, 1822 Second path 1023, 1123, 1223, 1323, 1423, 1523, 1623 Third path 1524 Fourth path 1723A Narrow path section (path width change section)
1723B Path neck section (path width change section)

Claims (12)

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. The detection device according to claim 1, wherein the joint is located at a position different from the curved path portion. The detection device according to claim 1, wherein the joint is located at the same position as the curved path portion. The detection device according to any one of claims 1 to 3, wherein the at least two flow paths have an opening at the end opposite the joint through which the reaction liquid can be introduced. The detection device according to any one of claims 1 to 4, wherein the flow path further includes a path width change section in which the flow path width changes. The detection device according to any one of claims 1 to 5, wherein the flow path has an upward path section that is inclined in the upward direction and a downward path section that is inclined in the downward direction, when the protruding direction of the convex portion is the vertical direction. 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. 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. The detection device according to claim 7 or 8, which has a buffer area at the boundary between the first uneven portion and the second uneven portion where the protrusions are not provided. 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. The detection device according to any one of claims 7 to 10, comprising a recessed area in which a recess is provided at the boundary between the first uneven portion and the second uneven portion. The detection device according to any one of claims 1 to 11, wherein the detection unit has an electrode unit that detects an electrochemical reaction.

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