Method for manufacturing an immunochromatographic test kit

Abstract

To provide an immunochromatographic test kit manufacturing method which allows for more stably manufacturing immunochromatographic test kits compared with conventional manufacturing method.SOLUTION: A method of manufacturing an immunochromatographic test kit is provided, the method comprising preparing a carrier 6 consisting of porous member, and forming a plurality of detection sections by applying a capture antibody to the carrier 6 using an application needle 21 holding the capture antibody having a property to bind to a detection target at a tip thereof.SELECTED DRAWING: Figure 10

Description

Technical Field

[0001] The present invention relates to a method for manufacturing an immunochromatographic test kit.

Background Art

[0002] Immunochromatography is currently being implemented in society as an aid for diagnosing various diseases, mainly influenza viruses. Its principle utilizes the antigen-antibody reaction, and due to its simplicity and effectiveness, it is widely used in the medical field.

[0003] In conventional immunochromatography, the presence or absence of color development in the detection part of an immunochromatographic test kit (also called a development support or chromatographic medium) is visually observed. Specifically, when the detection target bound to the labeled antibody is captured by the capture antibody fixed in the detection part and sufficiently accumulated on the detection part, the color development derived from the labeled antibody is visually confirmed.

[0004] International Publication No. 2010 / 061772 (Patent Document 1) discloses an immunochromatographic test kit in which the detection part is formed to have a size of several millimeters or more that can be visually determined.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] As methods for forming the detection part of the immunochromatographic test kit as described above, a dispenser method and an inkjet method can be mentioned. In these methods, in order to form the detection part in a small size of several millimeters or less, it is necessary to make the opening width of the nozzle tip smaller.

[0007] However, when the liquid containing the capture antibody has a high viscosity, clogging occurs when the opening width at the tip of the nozzle is decreased.

[0008] Therefore, depending on the viscosity of the liquid, it is difficult to reduce the size of the detection part, the amount of the expensive capture antibody used cannot be suppressed, and it has been difficult to reduce the cost.

[0009] A main object of the present invention is to provide a method for manufacturing an immunochromatographic test kit that can suppress the amount of capture antibody used and can manufacture an immunochromatographic test kit at low cost as compared with a conventional method for manufacturing an immunochromatographic test kit.

Means for Solving the Problems

[0010] The method for manufacturing an immunochromatographic test kit according to the present invention is a method for manufacturing an immunochromatographic test kit including a specimen dropping part on a porous member where a specimen is dropped, a conjugate part to which a labeled antibody having a property of binding to a detection target in the specimen is attached, and at least one detection part to which a capture antibody having a property of binding to the detection target is attached. The method for manufacturing the immunochromatographic test kit includes a step of forming at least one detection part by applying a capture antibody using at least one application needle holding the capture antibody at its tip.

[0011] In the method for manufacturing the immunochromatographic test kit, the outer diameter of the tip of at least one application needle may be less than 1 mm.

[0012] In the step of forming and applying at least one detection part in the method for manufacturing the immunochromatographic test kit, the capture antibody may be applied in a dot shape by at least one application needle.

[0013] In the step of forming at least one detection part in the method for manufacturing the immunochromatographic test kit, a recess may be formed in the porous member using at least one application needle, and at the same time, the capture antibody may be applied to the bottom surface of the recess.

[0014] In the method for manufacturing the immunochromatographic test kit, in the step of forming at least one detection part, a capture antibody may be applied at intervals in one dimension or two dimensions using a plurality of application needles to form a plurality of detection parts.

[0015] In the method for manufacturing the immunochromatographic test kit, the plurality of application needles may include a first application needle holding a first capture antibody having a property of binding to a first type of analyte at its tip, and a second application needle holding a second capture antibody having a property of binding to a second type of analyte at its tip. In the step of forming the plurality of detection parts, the first capture antibody may be applied to a first region using the first application needle to form a first detection part, and the second capture antibody may be applied to a second region using the second application needle to form a second detection part.

[0016] In the method for manufacturing the immunochromatographic test kit, the plurality of application needles may include a first application needle holding a first capture antibody having a property of binding to a first type of analyte at its tip, a second application needle holding a second capture antibody having a property of binding to a second type of analyte at its tip, and a third application needle holding a third capture antibody having a property of binding to a third type of analyte at its tip. In the step of forming the plurality of detection parts, the first capture antibody may be applied to a first region using the first application needle to form a first detection part, the second capture antibody may be applied to a second region using the second application needle to form a second detection part, and the third capture antibody may be applied to a third region using the third application needle to form a third detection part.

[0017] In the method for manufacturing the immunochromatographic test kit, the sample dropping part, the conjugate part, and at least one detection part may be formed on a single porous member.

[0018] In the method for manufacturing the immunochromatographic test kit, the sample dropping part, the conjugate part, and at least one detection part may be formed on a plurality of porous members.

Advantages of the Invention

[0019] According to the present invention, there is provided a method for manufacturing an immunochromatographic test kit that can suppress the amount of capture antibody used and manufacture an immunochromatographic test kit at low cost, as compared with the conventional method for manufacturing an immunochromatographic test kit.

Brief Description of the Drawings

[0020]

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Mode for Carrying Out the Invention

[0021] Hereinafter, with reference to the drawings, embodiments as an example of the present invention will be described. In the following drawings, the same or corresponding parts are denoted by the same reference numerals, and the description thereof will not be repeated.

[0022] (Embodiment 1) <Immunochromatographic Test Kit> As shown in FIGS. 1 to 2, the immunochromatographic test kit 100 according to Embodiment 1 mainly includes a specimen dropping part 1, a conjugate part 2, a detection area t including a plurality of detection parts 3, a control area c including a control part 4, and an absorption part 5. As shown in FIGS. 1 and 2, the specimen dropping part 1, the conjugate part 2, the detection area t, the control area c, and the absorption part 5 are arranged in the above-described order along the development direction D.

[0023] The sample dropping part 1 is the part where the sample is dropped. The sample dropping part 1 is formed of a porous member such as a glass fiber pad, a cellulose fiber pad, and a polyester pad, for example.

[0024] The conjugate part 2 is the part where a labeled antibody having the property of binding to the analyte in the sample is immobilized. The labeled antibody is a conjugate of an antibody that specifically recognizes and binds to the first part (first epitope) of the analyte and a labeling substance. The antibody can be arbitrarily selected according to the analyte. The labeling substance can be arbitrarily selected from the labeling substances used in conventional immunochromatography. The labeling substance includes, for example, at least one selected from the group consisting of colored fine particles such as metal nanoparticles (metal fine particles), latex fine particles, organic polymer fine particles, inorganic fine particles, and liposomes containing a coloring agent. The labeling substance includes, for example, at least one selected from the group consisting of noble metal nanoparticles such as gold nanoparticles, platinum nanoparticles, platinum-gold nanoparticles, silver nanoparticles, titanium nanoparticles, iron nanoparticles, nickel nanoparticles, and cadmium nanoparticles as the metal nanoparticles. The above metal nanoparticles may be colloidal metal nanoparticles having a particle size of 1 nm or more and 100 nm or less. The conjugate part 2 is adjusted, for example, by applying a suspension containing the labeled antibody to a porous member such as a glass fiber pad, a cellulose fiber pad, and a polyester pad and then drying it.

[0025] The detection region t is arranged on the side opposite to the sample dropping part 1 with respect to the conjugate part 2 in the developing direction D. The detection region t is formed on a carrier 6 made of a porous member. The detection region t includes a plurality of detection parts 3. Each detection part 3 is connected to the sample dropping part 1 via the conjugate part 2. Each detection part 3 is arranged on the side opposite to the sample dropping part 1 with respect to the conjugate part 2 in the developing direction D. Each detection part 3 is a part where a capture antibody having a property of binding to a detection target is fixed. The capture antibody is an antibody that specifically recognizes and binds to a second part (second epitope) different from the first part among the detection targets. From a different perspective, the capture antibody has a property of binding to a test object bound to a labeling substance. The capture antibody can be arbitrarily selected according to the detection target.

[0026] As shown in FIG. 2, the out-of-plane shape of each detection part 3 is dot-shaped. The dot width of each detection part 3 is the minimum size observable by visual inspection, or a size that is not observable by visual inspection but is observable by a microscope. The dot width of each detection part 3 is, for example, less than 1 mm. Preferably, the dot width of each detection part 3 is equivalent to the field of view of an electron microscope or the like capable of directly observing a labeling substance having a size of 1 μm or less that binds to the labeled antibody. The dot width of each detection part 3 is, for example, 100 μm or less.

[0027] Incidentally, the width of the detection unit 3 is measured as follows. First, a specimen containing a sufficient amount of the detection target is dropped onto the specimen dropping portion 1 to cause an antigen-antibody reaction to occur on the immunochromatographic test kit 100. Next, an electron microscope image of the detection unit 3 is acquired according to the inspection method described later. When the detection unit 3 includes the bottom surface 7A of the recess 7 as in the immunochromatographic test kit 100 according to the first embodiment, the electron microscope image acquired with the bottom surface 7A in focus is used. Next, the outer shape of the region where the labeled antibody is observed in the image is specified as the outer shape of the detection unit 3. Next, the width of the outer shape of the detection unit 3 is measured. As shown in FIG. 3, when the outer contour line of the region where the labeled antibody is observed undulates inward and outward, the diameter D1 of the circumscribed circle CC of the outer contour line and the diameter D2 of the inscribed circle IC of the outer contour line are calculated by image processing, and the intermediate value between the diameter D1 and the diameter D2 is defined as the width of the outer shape of the detection unit 3.

[0028] As shown in FIG. 2, the detection units 3 are arranged at intervals in a direction intersecting (for example, perpendicular to) the development direction D. Each detection unit 3 is arranged one-dimensionally in a direction intersecting (for example, perpendicular to) the development direction D. The distance between two adjacent detection units 3 is, for example, less than 1 mm.

[0029] The out-of-plane shape of each detection unit 3 is not particularly limited as long as it is dot-shaped, but is, for example, circular. Note that the out-of-plane shape of each detection unit 3 may be elliptical, square, rectangular, or the like.

[0030] As shown in Fig. 4, a plurality of recesses 7 are formed in the detection region t of the carrier 6. Each recess 7 is recessed with respect to the upper surface of the carrier 6. Each recess 7 has a bottom surface 7A and a wall surface 7B that connects the bottom surface 7A and the upper surface of the carrier 6, and the opening of the upper surface 6A and the bottom surface 7A are dot-shaped. In the cross-section shown in Fig. 4, the bottom surface 7A and the wall surface 7B form an obtuse angle. In other words, the cross-sectional shape of each recess 7 shown in Fig. 4 has a tapered shape such that the interval between the opposing wall surfaces 7B becomes narrower as it approaches the bottom surface 7A, but the opening diameter of the upper surface 6A and the diameter of the bottom surface 7A may be the same. The width of the bottom surface 7A of each recess 7 is the minimum size that can be confirmed by visual observation, for example, less than 1 mm. Preferably, the width of the bottom surface 7A of each recess 7 is desirably equivalent to the field of view of an electron microscope or the like that can directly observe a labeling substance having a size of 1 μm or less that binds to the labeled antibody. For example, the dot width of each bottom surface 7A is 100 μm or less. The depth of each bottom surface 7A is deeper than the depth of focus of the electron microscope. The depth of each bottom surface 7A is, for example, 10 μm or more.

[0031] The out-of-plane shape of each bottom surface 7A is, for example, circular. Note that the out-of-plane shape of each bottom surface 7A may be an elliptical shape, a square shape, a rectangular shape, or the like.

[0032] Each detection unit 3 includes the bottom surface 7A of each recess 7. Each detection unit 3 is formed in each recess 7 of the carrier 6. Each detection unit 3 and each recess 7 are, for example, formed on the carrier 6 simultaneously. The method of simultaneously forming the detection unit 3 and the recess 7 on the carrier 6 will be described in detail in the method for manufacturing an immunochromatographic test kit described later.

[0033] The control region c is arranged on the side opposite to the conjugate portion 2 with respect to the detection region t in the development direction D. The control region C includes a control unit 4. The control unit 4 is a portion where a control antibody that binds to the labeled antibody is fixed. The out-of-plane shape of the control unit 4 may be any shape, for example, a linear shape.

[0034] The control unit 4 is formed on the carrier 6. The control unit 4 is arranged on the side opposite to the conjugate unit 2 with respect to the detection unit 3 in the deployment direction D.

[0035] In addition, in FIGS. 1 and 2, for convenience of explanation, the ranges of the detection region t and the control region c are shown by broken lines. In an actual immunochromatographic test kit, for example, the above broken lines are not shown.

[0036] The absorption unit 5 is a part that absorbs excess specimens and the like after development. The absorption unit 5 is formed of a porous member such as a glass fiber pad, a cellulose fiber pad, and a polyester pad, for example. The absorption unit 5 is arranged on the side opposite to the detection region t with respect to the control region c in the deployment direction D.

[0037] The out-of-plane shape of the carrier 6 is rectangular. The carrier 6 has a longitudinal direction along the deployment direction D and a short-side direction orthogonal to the deployment direction D. The material constituting the carrier 6 may be any porous material, but includes at least one of, for example, nitrocellulose and polyvinylidene fluoride (PVDF). That is, in the immunochromatographic test kit 100 according to Embodiment 1, the plurality of detection units 3 and the control unit 4 are formed on a porous member separate from the porous members constituting the specimen dropping part 1, the conjugate unit 2, and the absorption unit 5. The porous member constituting the specimen dropping part 1 is adhered to the porous member constituting the conjugate unit 2, for example. Each porous member constituting the conjugate unit 2 and the absorption unit 5 is adhered to each porous member constituting the carrier 6, for example.

[0038] Note that the specimen dropping part 1, the conjugate unit 2, the detection unit 3, the control unit 4, the absorption unit 5, and the carrier 6 may be fixed on a base material (also called a backing sheet) (not shown) using an adhesive or an adhesive sheet. The carrier 6 may be a thin film formed on the base material.

[0039] <Inspection method using an immunochromatographic test kit> In the inspection method using an immunochromatographic test kit, the detection unit 3 after the antigen-antibody reaction on the immunochromatographic test kit is observed using an electron microscope. Hereinafter, the antigen-antibody reaction on the immunochromatographic test kit will be described.

[0040] First, a sample is dropped onto the sample dropping part 1. The dropped sample flows along the developing direction D due to capillary action. The analyte in the sample binds to the labeled antibody in the conjugate part 2. The conjugate of the analyte and the labeled antibody moves along the developing direction D together with the labeled antibody not bound to the analyte due to capillary action. The analyte bound to the labeled antibody binds to the capture antibody in the detection unit 3. As a result, the labeled antibody bound to the analyte accumulates in the detection unit 3. The labeling substance bound to the labeled antibody in the detection unit 3 is directly observed using an electron microscope. Furthermore, the labeled antibody not bound to the analyte binds to the control antibody in the control part 4. As a result, the labeled antibody not bound to the analyte is captured in the control part 4. The labeling substance bound to the labeled antibody in the control part 4 is directly observed using an electron microscope. The excess sample that has flowed downstream of the control part 4 in the developing direction D is absorbed by the absorption part 5.

[0041] The inspection method using an immunochromatographic test kit is performed, for example, according to the following procedure. First, after dropping a sample onto the sample dropping part 1, after a specified time has elapsed, a supplementary liquid is dropped.

[0042] The supplementary liquid has conductivity to prevent the generation of charge and heat that contribute to the clarity of the image, and / or the property of polymerizing to form a film, under the measurement conditions using an electron microscope. The supplementary liquid contains, as essential components, glycerin and glycerin substitutes; at least one compound selected from polysorbates such as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 85, and polysorbate substitutes, and contains, as optional components, at least one compound selected from monosaccharides, disaccharides, salts, and buffer solutions.

[0043] Next, the detection unit 3 is observed using an electron microscope. Specifically, first, the carrier 6 is set in the chamber of the electron microscope. Next, while observing the upper surface of the carrier 6, the detection unit 3 is searched for. In the immunochromatographic test kit 100, in the microscopic image (bright field image) of the electron microscope, a focus shift caused by the distance between the upper surface of the carrier 6 and the bottom surface 7A is observed. Therefore, since the recess 7 can be searched for in the microscopic image by confirming the presence or absence of the focus shift, the detection unit 3 can be easily searched for in the image. After that, by adjusting the focus of the image to the bottom surface 7A, the focus of the image can be adjusted to the detection unit 3. Next, an electron microscope image is taken, and the number of labeling substances in the image is measured. In the electron microscope image, since the contour of the labeling substance can be clearly identified, the number of labeling substances in the image can be measured. If the measured number of labeling substances exceeds a predetermined determination criterion, it is determined that the detection target is present in the specimen (that is, "positive").

[0044] The above observation and measurement are performed in the same manner for, for example, a plurality of detection units 3. In this case, for example, the average value, maximum value, minimum value, etc. of the number of labeling substances in the same visual field of each detection unit 3 are calculated, and any one of these calculated values is used as an evaluation value. If the evaluation value exceeds a predetermined determination criterion, it is determined as "positive".

[0045] <Method for manufacturing an immunochromatographic test kit> Next, an example of a method for manufacturing the immunochromatographic test kit 100 will be described. As shown in FIG. 5, the method for manufacturing the immunochromatographic test kit 100 includes a step of preparing a carrier 6 (S1) and a step of forming a plurality of detection units 3 on the prepared carrier 6 (S2).

[0046] In the step of preparing the carrier 6, a carrier 6 having a control unit 4 formed on the upper surface or a carrier 6 having no control unit 4 formed on the upper surface is prepared.

[0047] In the step of forming the plurality of detection units 3, using the application needle 21 (see Fig. 10) holding the capture antibody at its tip, the capture antibody is dot-applied onto the upper surface of the carrier 6. The diameter of the tip of the application needle 21 (hereinafter referred to as the tip diameter) is less than 1 mm. In this step, while the recess 7 is formed in the carrier 6 using the application needle 21, the capture antibody is applied onto the bottom surface 7A of the recess 7. That is, the application needle 21 holding the capture antibody at its tip is further pushed into the carrier 6 after contacting the upper surface of the carrier 6. In this step, the application device shown in Figs. 6 to 10 is used. The configuration of the application device will be described later.

[0048] In this way, the carrier 6 including the plurality of detection units 3 is formed. When the control unit 4 is formed on this carrier 6, the conjugate unit 2 and the absorption unit 5 are connected to the carrier 6, and further, the specimen dropping part 1 is connected to the conjugate unit 2, whereby the immunochromatographic test kit 100 is manufactured. When the control unit 4 is not formed on the carrier 6, the control unit 4 is formed on the carrier. Thereafter, the conjugate unit 2 and the absorption unit 5 are connected to the carrier, and further, the specimen dropping part 1 is connected to the conjugate unit 2, whereby the immunochromatographic test kit 100 is manufactured. In the manufacturing method of the immunochromatographic test kit 100, each of the specimen dropping part 1, the conjugate unit 2, the control unit 4, and the absorption unit 5 can be formed in the same manner as those in the conventional immunochromatographic test kit.

[0049] <Configuration of the Application Device> Next, an example of the application device used for forming the plurality of detection units 3 in the manufacturing method of the immunochromatographic test kit 100 will be described.

[0050] As shown in FIG. 6, the coating apparatus according to Embodiment 1 mainly includes an X-axis table 11, a Y-axis table 12, a Z-axis table 13, a coating mechanism 14, an observation optical system 15, a CCD camera 16, and a control unit. The X-axis table 11, the Y-axis table 12, the Z-axis table 13, the coating mechanism 14, the observation optical system 15, and the CCD camera 16 are arranged, for example, inside the processing chamber. The control unit includes an operation panel 17, a monitor 18, and a control computer 19. The operation panel 17, the monitor 18, and the control computer 19 are arranged, for example, outside the processing chamber.

[0051] The Y-axis table 12 is movable in the Y-axis direction and can mount the carrier 6. For example, a guide rail extending along the Y-axis direction is fixed to the bottom of the processing chamber. A guide portion movable along the guide rail is connected to the lower surface of the Y-axis table 12. The upper surface of the Y-axis table 12 serves as a mounting surface for mounting the carrier 6. A structure straddling the Y-axis table 12 in the X-axis direction is fixed to the bottom of the processing chamber.

[0052] The X-axis table 11 is arranged on a structure installed so as to straddle the Y-axis table 12 in the X-axis direction. A moving body connected to the Z-axis table 13 is installed on the X-axis table 11 so as to be movable in the X-axis direction. The moving body is movable in the X-axis direction using, for example, a ball screw. Note that the X-axis table 11 is fixed to the bottom surface of the processing chamber via the above structure. Therefore, the above-described Y-axis table 12 is movable in the Y-axis direction with respect to the X-axis table 11.

[0053] The above-described Z-axis table 13 is installed on the moving body connected to the X-axis table 11. The observation optical system 15 and the coating mechanism 14 are connected to the Z-axis table 13. The observation optical system 15 is for observing the coating position on the carrier 6. The CCD camera converts the observed image into an electrical signal. The Z-axis table 13 holds the observation optical system 15 and the coating mechanism 14 so as to be movable in the Z-axis direction.

[0054] The operation panel 17, the monitor 18, and the control computer 19 are used to control the Y-axis table 12, the X-axis table 11, the Z-axis table 13, the observation optical system 15, and the coating mechanism 14. The operation panel 17 is used to input commands to the control computer 19. The monitor 18 displays the image data converted by the above-described CCD camera 16 and the output data from the control computer 19.

[0055] <Configuration of the coating mechanism 14> Next, the detailed configuration of the coating mechanism 14 shown in FIG. 6 will be described. As shown in FIGS. 7 and 8, the coating mechanism 14 mainly includes a servo motor 41, a gantry 42, a cam 43, a bearing 44, a cam connecting plate 45, a movable part 46, a coating needle holder 20, a coating needle 21 held by the coating needle holder 20, and a coating material container 22. The servo motor 41 is installed such that the rotation axis extends in the direction along the Z-axis direction shown in FIG. 6. The servo motor 41 is held by the gantry 42. A cam 43 is connected to the rotation axis of the servo motor 41. The cam 43 is rotatable about the rotation axis of the servo motor 41.

[0056] The cam 43 includes a central portion connected to the rotation axis of the servo motor 41 and a flange portion connected to one end portion of the central portion. The upper surface of the flange portion (the surface on the servo motor 41 side) is a cam surface. This cam surface is formed in an annular shape along the outer periphery of the central portion and is formed in a slope shape such that the distance from the bottom surface of the flange portion varies. Specifically, the cam surface includes an upper end flat region where the distance from the bottom surface of the flange portion is the longest, a lower end flat region where the distance from the bottom surface of the flange portion is the shortest, and a slope region connecting the upper end flat region and the lower end flat region. The upper end flat region is arranged at an interval from the lower end flat region in the circumferential direction with respect to the rotation axis.

[0057] The bearing 44 has an outer ring arranged to contact the cam surface of the cam 43 and an inner ring connected to the cam connecting plate 45. As shown in FIG. 7, the bearing 44 is arranged in a specific direction (the right side of the servo motor 41) when viewed from the cam 43. The bearing 44 is biased against the cam surface of the cam 43 by a spring 50 described later. Therefore, when the cam 43 rotates, the bearing 44 is held in a state where the outer peripheral surface of the outer ring contacts the cam surface. The cam connecting plate 45 has one end connected to the inner ring of the bearing 44 and the other end fixed to the movable part 46. A coating needle holder fixing part 47 and a coating needle holder housing part 48 are connected to the movable part 46.

[0058] A fixing pin 51 is installed on the mount 42. A fixing pin 52 is installed on the movable part 46. One end of the spring 50 is connected to the fixing pin 51, and the other end of the spring 50 is connected to the fixing pin 52. Due to the spring 50, the movable part 46 is in a state of receiving a tensile force toward the coating material container 22 side. Further, the tensile force by this spring 50 acts on the bearing 44 via the movable part 46 and the cam connecting plate 45. Due to the tensile force of this spring 50, the bearing 44 maintains a state of being pressed against the cam surface of the cam 43.

[0059] The movable part 46, the coating needle holder fixing part 47, and the coating needle holder housing part 48 are connected to a linear guide 49 installed on the mount 42. The linear guide 49 is arranged to extend in the Z-axis direction. Therefore, the movable part 46, the coating needle holder fixing part 47, and the coating needle holder housing part 48 are movable along the Z-axis direction.

[0060] The coating needle holder 20 is housed in the coating needle holder housing part 48. The coating needle holder 20 includes a coating needle 21. The coating needle 21 is arranged to protrude from the coating needle holder 20 on the lower surface of the coating needle holder 20. The extending direction of the coating needle 21 is along the gravity direction (Z-axis direction in FIG. 6). The shape of the tip of the coating needle 21 is, for example, a frustum of a cone shape. The tip diameter in the radial direction with respect to the central axis of the coating needle 21 is less than 1 mm. Preferably, the tip diameter of the coating needle 21 is 100 μm or less.

[0061] Below the coating needle holder 20, a coating material container 22 is arranged. Inside the coating material container 22, a space for storing the coating material 70 is formed. As shown in FIGS. 9 and 10, a first hole and a second hole connecting the above space to the outside are formed at the bottom and the top of the coating material container 22. The shapes of the first hole and the second hole may be any shape, for example, circular. The first hole and the second hole are provided so as to overlap in the extending direction of the coating needle 21. The coating material 70 contains a capture antibody.

[0062] The coating needle holder 20 and the coating needle 21 move up and down with respect to the coating material container 22 as the coating needle holder housing portion 48 moves in the Z-axis direction. Thereby, a first state in which the tip of the coating needle 21 is immersed in the coating material 70 stored in the coating material container 22 and a second state in which the coating needle 21 protrudes downward from the bottom surface of the coating material container 22 through the hole formed at the bottom of the coating material container 22 are switched.

[0063] <Operation of the coating device> Next, the operation of the coating device in the step of forming a plurality of detection units 3 in the method for manufacturing an immunochromatographic test kit will be described. First, the carrier 6 is mounted on the Y-axis table 12. Next, the tip of the coating needle 21 is set in the first state of being immersed in the coating material 70 stored in the coating material container 22. Next, the X-axis table 11 and the Y-axis table 12 are operated to position the carrier 6 in the X-axis direction and the Y-axis direction so that the region where the detection unit 3 is to be formed is disposed directly below the coating mechanism 14. Next, the Z-axis table 13 is operated to lower the Z-axis table 13 and the coating mechanism 14 by a distance d in the Z-axis direction so that the tip of the coating needle 21 is pushed downward from the upper surface of the carrier 6 when the coating needle is in the second state.

[0064] Next, operate the servo motor 41 of the coating mechanism 14 to switch from the above first state to the second state. Specifically, by operating the servo motor 41, the rotating shaft of the servo motor 41 is rotated to rotate the cam 43. As a result, since the height of the cam surface of the cam 43 changes in the Z-axis direction, the position of the bearing 44 in contact with the cam surface in the Z-axis direction also varies according to the rotation of the drive shaft of the servo motor 41. In response to the position variation of the bearing 44 in the Z-axis direction, the movable part 46, the coating needle holder fixing part 47, the coating needle holder housing part 48, and the coating needle holder 20 held in the coating needle holder housing part 48 also move in the Z-axis direction. As a result, by operating the servo motor 41, the coating needle 21 moves in the Z-axis direction, and the first state shown in FIG. 9 and the second state shown in FIG. 10 are switched. In the above coating mechanism 14, since the rotational motion of the servo motor 41 can be converted into the motion (vertical motion) of the coating needle 21 in the Z-axis direction, the coating needle 21 can be moved quickly and accurately in the Z-axis direction.

[0065] In the first state shown in FIG. 9, the coating needle 21 is arranged at the uppermost position in its movable range. At this time, the tip of the coating needle 21 is immersed in the coating material 70 held in the coating material container 22. In the first state, the outer ring of the bearing 44 is in contact with the upper end flat region of the cam surface of the cam 43.

[0066] In the second state shown in FIG. 10, the coating needle 21 is arranged at the lowermost position in its movable range. At this time, the coating material containing the capture antibody is held at the tip of the coating needle 21. Specifically, the coating material containing the capture antibody is held on the end face and side face of the tip of the coating needle 21. The tip of the coating needle 21 passes through the hole formed in the bottom of the coating material container 22 and protrudes downward from the bottom surface of the coating material container 22, and is pushed below the upper surface of the carrier 6.

[0067] In this way, by operating the servo motor 41 to switch from the first state to the second state, a recess 7 is formed in the carrier 6, and at the same time, the capture antibody is applied to the bottom surface 7A of the recess 7. Next, the servo motor 41 is operated to switch from the second state to the first state.

[0068] Furthermore, after operating only the X-axis table 11 and the Y-axis table 12 to place the region where the detection unit 3 is to be formed second directly below the coating mechanism 14, the Z-axis table 13 is lowered by a distance d, and then the servo motor 41 of the coating mechanism 14 is operated to switch from the first state to the second state. Also, after further switching from the second state to the first state, the Z-axis table 13 is raised by a distance d.

[0069] By continuously repeating the above operations, a plurality of detection units 3 are formed on the upper surface of the carrier 6. <Advantages and effects> The advantages and effects of the manufacturing method of the immunochromatographic test kit 100 according to Embodiment 1 will be described in comparison with a manufacturing method (hereinafter simply referred to as Comparative Example 1) in which each detection unit 3 is formed using a dispenser, and a manufacturing method (hereinafter simply referred to as Comparative Example 2) in which each detection unit 3 is formed by an inkjet method.

[0070] In Comparative Examples 1 and 2, in order to form the detection unit 3 with a minute size, it is necessary to reduce the opening width of the tip of the dispenser or the nozzle. However, when a coating material 70 with high viscosity is used, the coating material 70 cannot be discharged, and there is a possibility of clogging. Also, in Comparative Example 2, in the method of instantaneously increasing the pressure inside the container using a piezo element or the like to discharge the liquid material containing the capture antibody, since the discharge pressure is high, the liquid material is likely to spread when it lands on the carrier 6, and there are problems such as the shape of the detection unit 3 not being stable.

[0071] On the other hand, in the manufacturing method of the immunochromatographic test kit 100, in order to form the minute detection unit 3, it is only necessary to reduce the tip diameter of the coating needle 21. Therefore, regardless of the viscosity, clogging as in Comparative Examples 1 and 2 does not occur. Further, in the above manufacturing method, since the position of the tip of the coating needle 21 in the Z-axis direction with respect to the upper surface of the carrier 6 can be precisely controlled by the Z-axis table 13, variations in the size of the detection unit 3 can be reduced, and the immunochromatographic test kit 100 can be stably manufactured.

[0072] Also, in Comparative Example 1, in order to apply the liquid droplet, it is difficult to stably form the detection unit 3 with a dot width of less than 1 mm, and particularly difficult to stably form the detection unit 3 with a dot width of less than 100 μm.

[0073] On the other hand, in the manufacturing method of the immunochromatographic test kit 100, since the coating needle 21 is used, the immunochromatographic test kit 100 in which the out-of-plane shape of each detection unit 3 is dot-shaped and the width of each detection unit 3 is less than 1 mm can be easily and stably manufactured.

[0074] Furthermore, in the manufacturing method of the immunochromatographic test kit 100, since the recess 7 is formed in the carrier 6 using the coating needle 21 and at the same time the capture antibody is applied to the bottom surface 7A of the recess 7, the formation of the detection unit 3 including the bottom surface 7A of one recess 7 and the application of the capture antibody can be performed in one operation. Therefore, there is no increase in tact time associated with the formation of the detection unit 3, and the manufacturing cost does not increase.

[0075] Next, the effects of the immunochromatographic test kit 100 according to Embodiment 1 will be described in comparison with a conventional immunochromatographic test kit (hereinafter simply referred to as Comparative Example 3). In Comparative Example 1, the detection unit is formed on a flat plane, and the color development at the detection unit derived from the labeled antibody is provided so as to be visually confirmed. Therefore, in Comparative Example 1, a sufficient area of the detection unit (for example, several mm 2 or more) is required so as not to make a misjudgment by visual determination, and it has been difficult to reduce the amount of expensive capture antibody fixed to the detection unit. As a result, in Comparative Example 1, it has been difficult to reduce the manufacturing cost.

[0076] In contrast, in the immunochromatographic test kit 100, the dot width of each detection unit 3 can be made less than 1 mm by reducing the tip diameter of the coating needle 21. That is, in the immunochromatographic test kit 100, since the area of each detection unit 3 can be made smaller than the area of each detection unit in Comparative Example 3, the amount of capture antibody immobilized on each detection unit 3 can be reduced compared to the amount of capture antibody immobilized on each detection unit in Comparative Example 3. As a result, the manufacturing cost of the immunochromatographic test kit 100 can be reduced compared to the manufacturing cost of Comparative Example 3.

[0077] Furthermore, according to the immunochromatographic test kit 100, by confirming the detection unit 3 using an electron microscope and measuring the number of labeled antibodies captured by the detection unit 3 in the electron microscope image, the analyte in the specimen can be quantitatively evaluated.

[0078] Also, when miniaturizing the detection unit formed on a flat plane as in Comparative Example 1, for example, it is necessary to enlarge the detection unit with a microscope or the like to confirm the labeled antibody, but it is difficult to search for and align the minute detection unit with a microscope. As a countermeasure, a method of providing a mark on the kit and providing the detection unit at a predetermined distance from there can be considered. However, in this case, equipment for providing the mark is required separately from the equipment for forming the detection unit, and the number of processes also increases, so the production tact cannot be reduced and it is difficult to achieve cost reduction.

[0079] In contrast, in the above immunochromatographic test kit 100, a plurality of recesses 7 are formed in the carrier 6, and each detection unit 3 includes the bottom surface 7A of one recess 7. Therefore, when directly confirming the labeling substance on the detection unit 3 using an electron microscope, the focus shift due to the distance between the upper surface of the carrier 6 and the bottom surface 7A can be confirmed in the microscope image of the electron microscope. Therefore, the recess 7 can be searched in the microscope image of the electron microscope using this focus shift. As a result, in the immunochromatographic test kit 100, each detection unit 3 can be miniaturized compared to Comparative Example 1.

[0080] Furthermore, by adjusting the focus of the image to the bottom surface 7A, the focus of the image can be easily aligned with the detection unit 3. That is, in the immunochromatographic test kit 100, compared with the case where each detection unit 3 does not include the bottom surface 7A of one recess 7, the time required to search for the detection unit 3 can be shortened.

[0081] In addition, in the immunochromatographic test kit 100, unlike Comparative Example 1, there is no need to separately provide a mark used when searching for the detection unit 3, and there is no need to prepare equipment for providing the mark separately from the equipment for forming the detection unit. Furthermore, in the immunochromatographic test kit 100, since the recess 7 can be formed simultaneously with the detection unit 3, the manufacturing tact can be reduced compared to the case of providing a mark in Comparative Example 1.

[0082] In the immunochromatographic test kit 100, the width of each detection unit can be made as small as 100 μm or less. In such an immunochromatographic test kit 100, since the amount of the capture antibody fixed to each detection unit 3 is significantly reduced compared to the amount of the capture antibody fixed to each detection unit in Comparative Example 3, the manufacturing cost of the immunochromatographic test kit 100 can be significantly reduced compared to the manufacturing cost of Comparative Example 3.

[0083] The immunochromatographic test kit 100 includes a plurality of detection units 3. In such an immunochromatographic test kit 100, compared with an immunochromatographic test kit having only one detection unit 3, since the labeling substances of the plurality of detection units 3 can be confirmed in the electron microscope image, the reliability of the test result is improved.

[0084] In the immunochromatographic test kit 100, the plurality of detection units 3 are arranged one-dimensionally with respect to the development direction D. In such an immunochromatographic test kit 100, compared with an immunochromatographic test kit in which the plurality of detection units 3 are randomly arranged, since the detection target efficiently flows through all the detection units 3 and binds to the capture antibody, a stable test result can be obtained.

[0085] In the immunochromatographic test kit 100, the shortest distance between two adjacent detection units among the plurality of detection units 3 is less than 1 mm. In such an immunochromatographic test kit 100, compared with an immunochromatographic test kit in which the shortest distance is 1 mm or more, a plurality of detection units 3 can be observed even in a relatively small field of view, so that each detection unit 3 can be easily searched for.

[0086] <Modification Example 1> The immunochromatographic test kit 100 according to Embodiment 1 may adopt the following modification examples.

[0087] The detection region t only needs to include at least one detection unit 3. In the immunochromatographic test kit 100, each detection unit 3 has an equivalent configuration to each other, but it is not limited thereto. In the immunochromatographic test kit 100, the concentration of the capture antibody fixed to each detection unit 3 is constant, but the concentrations of the capture antibodies fixed to each detection unit 3 may be different from each other. For example, in a direction orthogonal to the development direction D, the concentration of the capture antibody may be gradually decreased from one side to the other side. In addition, a set of patterns composed of a plurality of detection units 3 having different capture antibody concentrations may be arranged side by side. Such a plurality of detection units 3 can be easily formed by using a plurality of coating mechanisms 14 in which the concentrations of the capture antibodies in the coating material stored in the coating material container 22 are different from each other.

[0088] In addition, at least any one of the out-of-plane shape of each detection unit 3, the dot width of each detection unit 3, the distance between two adjacent detection units 3, the out-of-plane shape of the bottom surface 7A of each recess 7, the maximum width of each bottom surface 7A, and the depth of each bottom surface 7A may be different. Such a plurality of detection units 3 can be easily formed by using a plurality of types of coating needles 21 or by using a plurality of types of coating conditions.

[0089] In the immunochromatographic test kit 100, a plurality of recesses 7 are formed in the detection region t of the carrier 6, and one detection unit 3 includes the bottom surface 7A of one recess 7, but it is not limited thereto.

[0090] Each detection unit 3 may include the entire bottom surface 7A of each recess 7 and at least a part of the wall surface 7B. Further, each detection unit 3 may include the entire bottom surface 7A and the entire wall surface 7B of each recess 7. Further, each detection unit 3 may include the entire bottom surface 7A and the entire wall surface 7B of each recess 7, and an annular region continuous with the wall surface 7B on the upper surface of the carrier 6.

[0091] The plurality of detection units 3 may include at least one detection unit 3 shown in FIG. 4 and at least one detection unit 3 shown in FIG. 11. The plurality of detection units 3 shown in FIG. 11 include only the upper surface of the carrier 6. Such a detection unit 3 can be easily formed by moving upward without being pushed downward after the tip of the application needle 21 or the applied material 70 attached to the tip contacts the upper surface of the carrier 6 in the above manufacturing method. Further, all of the detection units 3 may be configured as the detection unit 3 shown in FIG. 11. That is, a plurality of recesses 7 may not be formed in the detection region t of the carrier 6.

[0092] As shown in FIG. 12, in the immunochromatographic test kit 100, the plurality of detection units 3 may be arranged at intervals in the developing direction D. The distance between two adjacent detection units 3 in the developing direction D is, for example, equal to the distance between two adjacent detection units 3 in a direction orthogonal to the developing direction D.

[0093] In the manufacturing method of the immunochromatographic test kit 100, one application needle 21 is used to form the plurality of detection units 3, but a plurality of application needles 21 may be used to form the plurality of detection units 3. In other words, the application device may include a plurality of application mechanisms 14.

[0094] In order to further improve the accuracy in the process of applying the coating material 70 by the application needle 21, the moving speed of the application needle 21 in the Z-axis direction may be changed according to the position of the application needle 21. For example, when switching from the first state to the second state, the moving speed of the application needle 21 is decreased before the second state is realized. The decrease in the moving speed of the application needle 21 is realized by decreasing the rotational speed of the servo motor 41.

[0095] By performing such control, when the application needle 21 contacts the carrier 6, the moving speed of the application needle 21 is sufficiently small, so that the contact time between the tip of the application needle 21 or the coating material 70 attached to the tip and the carrier 6 can be lengthened. For this reason, the amount of the capture antibody applied to the carrier 6 can be increased and the concentration can be increased, so that the antigen-antibody reaction with the detection target can be made more stable.

[0096] In the immunochromatographic test kit 100, the specimen dropping part 1 and the conjugate part 2 may be formed on a single porous member that is separate from the carrier 6. In the immunochromatographic test kit 100, the conjugate part 2 is formed on the carrier 6, and the specimen dropping part 1 may be formed on a porous member that is separate from the carrier 6. In the immunochromatographic test kit 100, the absorption part 5 may be formed on the carrier 6.

[0097] (Embodiment 2) The immunochromatographic test kit 101 according to Embodiment 2 has basically the same configuration as the immunochromatographic test kit 100 according to Embodiment 1 and exhibits the same effects, but is different from the immunochromatographic test kit 100 in that a plurality of detection parts 3 include a first detection part 3A and a second detection part 3B as shown in FIG. 13.

[0098] A first capture antibody having the property of binding to a first type of detection target is immobilized on the first detection part 3A. A second capture antibody having the property of binding to a second type of detection target different from the first type of detection target is immobilized on the second detection part 3B.

[0099] As shown in FIG. 13, the plurality of detection units 3 includes, for example, a plurality of first detection units 3A and a plurality of second detection units 3B. The plurality of first detection units 3A are arranged at intervals in a direction orthogonal to the deployment direction D. The plurality of first detection units 3A are arranged, for example, one-dimensionally. The plurality of second detection units 3B are arranged at intervals in a direction orthogonal to the deployment direction D. The plurality of second detection units 3B are arranged, for example, one-dimensionally.

[0100] The plurality of first detection units 3A and the plurality of second detection units 3B are arranged at intervals in a direction orthogonal to the deployment direction D. The shortest distance between the first detection unit 3A and the second detection unit 3B is longer than the shortest distance between two adjacent first detection units 3A and the shortest distance between two adjacent second detection units 3B. The plurality of first detection units 3A and the plurality of second detection units 3B are arranged, for example, one-dimensionally as a whole.

[0101] Each of the first detection unit 3A and the second detection unit 3B has the same configuration as each detection unit 3 in Embodiment 1. The dot width of the first detection unit 3A is equal to, for example, the dot width of the second detection unit 3B. Note that the dot width of the first detection unit 3A may be narrower or wider than the dot width of the second detection unit 3B, for example.

[0102] The detection region t is divided into a first detection region t1 where the plurality of first detection units 3A are arranged and a second detection region t2 where the plurality of second detection units 3B are arranged. The first detection region t1 and the second detection region t2 are arranged side by side in a direction orthogonal to the deployment direction D.

[0103] Each first detection unit 3A includes the bottom surface 7A of each recess 7. Each second detection unit 3B includes the bottom surface 7A of each recess 7.

[0104] According to the immunochromatographic test kit 101 according to Embodiment 2, two types of detection targets can be detected from a single specimen by immunochromatography.

[0105] The immunochromatographic test kit 101 can be manufactured in the same manner as the immunochromatographic test kit according to Embodiment 1. Preferably, the coating device includes a first coating mechanism 14 for forming the first detection unit 3A by coating the carrier 6 with the first capture antibody, and a second coating mechanism 14 for forming the second detection unit 3B by coating the carrier 6 with the second capture antibody. The first coating mechanism 14 includes a first coating needle 21 and a first coating material container 22 in which a coating material containing the first capture antibody is stored. The second coating mechanism 14 includes a second coating needle 21 and a second coating material container 22 in which a coating material containing the second capture antibody is stored.

[0106] In the method for manufacturing the immunochromatographic test kit 101, the first coating needle 21 holds the first capture antibody at its tip. The second coating needle 21 holds the second capture antibody at its tip. In the step of forming the plurality of detection units 3, the first detection unit 3A is formed by applying the first capture antibody to the first region of the carrier 6 using the first coating needle 21. Further, the second detection unit 3B is formed by applying the second capture antibody to the second region of the carrier 6 using the second coating needle 21.

[0107] By manufacturing the immunochromatographic test kit 101 using such a coating device, the manufacturing man-hours can be reduced compared to the case of manufacturing the immunochromatographic test kit 101 using one coating device having only one coating mechanism 14, and the manufacturing cost can be reduced compared to the case of manufacturing the immunochromatographic test kit 101 using a plurality of coating devices each having only one coating mechanism 14.

[0108] <Modification Example 2> The immunochromatographic test kit 101 according to Embodiment 2 can also adopt the same modification examples as the immunochromatographic test kit 100 according to Embodiment 1.

[0109] Furthermore, the immunochromatographic test kit 101 can adopt the following modification examples. Each of the plurality of first detection units 3A and the plurality of second detection units 3B may be arranged alternately side by side.

[0110] As shown in FIGS. 14 to 16, in addition to the first detection unit 3A and the second detection unit 3B, the plurality of detection units 3 may further include a plurality of third detection units 3C. Each third detection unit 3C has a third capture antibody fixed thereto that has a property of binding to a third type of detection target different from the first type of detection target and the second type of detection target.

[0111] As shown in FIG. 14, each of the plurality of first detection units 3A, the plurality of second detection units 3B, and the plurality of third detection units 3C is arranged side by side one by one, for example, in a direction orthogonal to the developing direction D.

[0112] As shown in FIG. 15, each of the plurality of first detection units 3A, the plurality of second detection units 3B, and the plurality of third detection units 3C is arranged side by side in plural numbers, for example, in a direction orthogonal to the developing direction D. In this case, the distance between two adjacent first detection units 3A and the distance between two adjacent second detection units 3B are, for example, shorter than the distance between an adjacent first detection unit 3A and second detection unit 3B. The distance between two adjacent second detection units 3B and the distance between two adjacent third detection units 3C are, for example, shorter than the distance between an adjacent second detection unit 3B and third detection unit 3C.

[0113] As shown in FIG. 16, each of the plurality of first detection units 3A, the plurality of second detection units 3B, and the plurality of third detection units 3C is arranged one-dimensionally, for example, in the developing direction D. Further, each of the plurality of first detection units 3A, the plurality of second detection units 3B, and the plurality of third detection units 3C is arranged side by side one by one in a direction orthogonal to the developing direction D. The distance between an adjacent first detection unit 3A and second detection unit 3B in the direction orthogonal to the developing direction D is, for example, longer than the distance between two adjacent first detection units 3A and the distance between two adjacent second detection units 3B in the developing direction D. The distance between an adjacent second detection unit 3B and third detection unit 3C in the direction orthogonal to the developing direction D is, for example, longer than the distance between two adjacent second detection units 3B and the distance between two adjacent third detection units 3C in the developing direction D.

[0114] In the modification examples shown in FIGS. 14 to 16, in a set of a first detection unit 3A, a second detection unit 3B, and a third detection unit 3C, at least any one of the out-of-plane shape of each detection unit 3, the dot width of each detection unit 3, the distance between two adjacent detection units 3, the out-of-plane shape of the bottom surface 7A of each concave portion 7, the maximum width of each bottom surface 7A, and the depth of each bottom surface 7A may be different from each other.

[0115] For example, the dot width of the second detection unit 3B may be narrower than the dot width of the first detection unit 3A and wider than the dot width of the third detection unit 3C. The maximum width of the bottom surface 7A included in the second detection unit 3B may be narrower than the maximum width of the bottom surface 7A included in the first detection unit 3A and wider than the maximum width of the bottom surface 7A included in the third detection unit 3C.

[0116] The out-of-plane shape of the second detection unit 3B may be rectangular, and the out-of-plane shape of each detection unit 3 of the first detection unit 3A and the third detection unit 3C may be circular.

[0117] The depth of the bottom surface 7A included in the second detection unit 3B may be shallower than the maximum width of the bottom surface 7A included in the first detection unit 3A and deeper than the maximum width of the bottom surface 7A included in the third detection unit 3C.

[0118] The distance between the first detection unit 3A and the second detection unit 3B may be longer than the distance between the second detection unit 3B and the third detection unit 3C and the distance between the third detection unit 3C and the first detection unit 3A.

[0119] Such first detection unit 3A, second detection unit 3B, and third detection unit 3C can be easily formed by using a plurality of types of coating needles 21 or by using a plurality of types of coating conditions.

[0120] In this way, within one field of view, the first detection unit 3A, the second detection unit 3B, and the third detection unit 3C can be easily identified.

[0121] (Embodiment 3) The immunochromatographic test kit 102 according to Embodiment 3 has basically the same configuration as the immunochromatographic test kit 100 according to Embodiment 1 and exhibits the same effects, but is different from the immunochromatographic test kit 100 in that the sample dropping portion 1 and the conjugate portion 2 are formed on the carrier 6. That is, in the immunochromatographic test kit 102, the sample dropping portion 1, the conjugate portion 2, the plurality of detection portions 3, and the control portion 4 are formed on the upper surface of a single porous member (one carrier 6).

[0122] In the immunochromatographic test kit 102 shown in FIG. 17, the absorption portion 5 is also formed on the carrier 6.

[0123] The sample dropping portion 1 is a region on the carrier 6 where the sample is dropped and is arranged on one side in the developing direction D. The conjugate portion 2 is a region on the upper surface of the carrier 6 where the labeled antibody is applied and is arranged between the sample dropping portion 1 and the detection region t in the developing direction D. The absorption portion 5 is a region on the carrier 6 where the excess sample is absorbed and is arranged on the other side in the developing direction D with respect to the control region C.

[0124] According to the immunochromatographic test kit 102, since the number of parts is reduced as compared with the immunochromatographic test kit 100, the manufacturing cost of the immunochromatographic test kit 102 can be reduced as compared with the manufacturing cost of the immunochromatographic test kit 100.

[0125] <Modification 3> The immunochromatographic test kit 102 according to Embodiment 3 can also adopt the same modifications as the immunochromatographic test kit 100 according to Embodiment 1 and the immunochromatographic test kit 101 according to Embodiment 2.

[0126] (Embodiment 4) The immunochromatographic test kit 103 according to Embodiment 4 has basically the same configuration as the immunochromatographic test kit 100 according to Embodiment 1 and exhibits the same effects, but is different from the immunochromatographic test kit 100 in that, as shown in FIG. 18, it is configured as a connected body in which a plurality of immunochromatographic test kits 100A to 100C are connected in a direction orthogonal to the deployment direction D. The detection targets of each of the immunochromatographic test kits 100A to 100C are different from each other.

[0127] Each of the immunochromatographic test kits 100A to 100C may be fixed to each other by any method, but for example, they are adhered.

[0128] According to the immunochromatographic test kit 103 according to Embodiment 4, three types of detection targets can be detected by immunochromatography using one immunochromatographic test kit 103 configured as a connected body.

[0129] (Example 1) In this example, the results of observation using an electron microscope of the detection unit 3 of the immunochromatographic test kit 100 will be described.

[0130] <Sample> The carrier 6 was a porous member made of nitrocellulose. Each detection unit 3 was formed so as to include the bottom surface 7A of the recess 7 using an application needle 21 having a frustum shape at the tip and a tip diameter of 50 μm.

[0131] <Observation method> FIG. 19 is a microscopic image obtained by observing the detection unit 3 of the above sample using a microscope.

[0132] As shown in FIG. 19, in the microscopic image, due to the defocusing caused by the recess 7, a difference occurs between the background and the detection unit 3, so that the bottom surface 7A of the recess 7 can be easily searched, and the minute detection unit 3 including the bottom surface 7A can be easily searched.

[0133] (Example 2) In this embodiment, the results of immunochromatography performed using the immunochromatography test kit 100 will be described.

[0134] <Sample> The sample dropping part 1 and the conjugate part 2 were made of glass fiber pads. The carrier 6 was made of a porous member of nitrocellulose. Each detection part 3 was formed so as to include the bottom surface 7A of the recess 7 using an application needle 21 having a frustum of a cone shape at the tip and a tip diameter of 50 μm.

[0135] <Inspection method> The inspection method was made equivalent to the inspection method of the above-described immunochromatography test kit.

[0136] FIG. 20 is an electron microscope image obtained by observing the detection part 3 of the above sample using an electron microscope.

[0137] As shown in FIG. 20, since contrast between light and dark due to the recess 7 occurs in the electron microscope image, the bottom surface 7A of the recess 7 could be easily searched, and the minute detection part 3 including the bottom surface 7A could be easily searched.

[0138] Also, FIG. 21 is an electron microscope image observing the detection part 3 before the auxiliary liquid is dropped, and FIG. 22 is an electron microscope image observing the detection part 3 after the auxiliary liquid is dropped.

[0139] In the image shown in FIG. 22, it was confirmed that the edge of the image is clearer compared to the image shown in FIG. 21.

[0140] The disclosed embodiments and examples should be considered illustrative in all respects and not restrictive. The scope of the present invention is shown by the scope of claims rather than the above description, and it is intended that all meanings equivalent to the scope of claims and all modifications within the scope are included.

Explanation of reference numerals

[0141] 1 Specimen dropping part, 2 Conjugate part, 3 Detection part, 3A First detection part, 3B Second detection part, 3C Third detection part, 4 Control part, 5 Absorption part, 6 Carrier, 7 Concave part, 7A Bottom surface, 7B Wall surface, 11 X-axis table, 12 Y-axis table, 13 Z-axis table, 14 Coating mechanism, 15 Observation optical system, 16 Camera, 17 Operation panel, 18 Monitor, 19 Control computer, 20 Coating needle holder, 21 Coating needle, 22 Coating material container, 41 Servo motor, 42 Stand, 43 Cam, 44 Bearing, 45 Cam connecting plate, 46 Movable part, 47 Coating needle holder fixing part, 48 Coating needle holder storage part, 49 Linear guide, 50 Spring, 51, 52 Fixed pins, 70 Coating material, 100, 100A, 100C, 101, 102, 103 Immunochromatographic test kit.

Claims

1. In a method for manufacturing an immunochromatographic test kit comprising a sample dropping part on a porous member where a sample is dropped, a conjugate part to which a labeled antibody having a property of binding to a detection target in the sample adheres, and at least one detection part to which a capture antibody having a property of binding to the detection target adheres, the method includes a step of forming the at least one detection part by applying the capture antibody to the porous member using at least one application needle holding the capture antibody at its tip, In the step of forming the at least one detection part, when the at least one application needle contacts the upper surface of the porous member and is further pushed into the porous member to form a recess in the porous member, the capture antibody is applied to the bottom surface of the recess. A method for manufacturing an immunochromatographic test kit.

2. The method further includes a step of preparing an application device, The application device includes an application mechanism, The application mechanism includes the at least one application needle and a servo motor having a rotation shaft, In the step of forming the at least one detection part, the depth of the bottom surface of the recess changes according to the rotation amount of the rotation shaft of the servo motor. The method for manufacturing an immunochromatographic test kit according to Claim 1.

3. The depth of the recess is 10 μm or more. The method for manufacturing an immunochromatographic test kit according to Claim 1 or 2.

4. The outer diameter of the tip of the at least one application needle is less than 1 mm. The method for manufacturing an immunochromatographic test kit according to any one of Claims 1 to 3.

5. In the step of forming and applying the at least one detection part, the capture antibody is applied in a dot shape by the at least one application needle. The method for manufacturing an immunochromatographic test kit according to any one of Claims 1 to 4.

6. In the step of forming the at least one detection part, a plurality of application needles are used to apply the capture antibody at intervals in one dimension or two dimensions to form a plurality of detection parts. The method for manufacturing an immunochromatographic test kit according to any one of Claims 1 to 5.

7. The plurality of application needles include a first application needle holding a first capture antibody having a property of binding to a first detection target at its tip, and a second application needle holding a second capture antibody having a property of binding to a second detection target at its tip. In the step of forming the plurality of detection units, the first capture antibody is applied to the first region using the first application needle to form a first detection unit, and the second capture antibody is applied to the second region using the second application needle to form a second detection unit. The method for manufacturing an immunochromatographic test kit according to claim 6.

8. The plurality of application needles include a first application needle holding a first capture antibody having a property of binding to a first type of analyte at its tip, a second application needle holding a second capture antibody having a property of binding to a second type of analyte at its tip, and a third application needle holding a third capture antibody having a property of binding to a third type of analyte at its tip. In the step of forming the plurality of detection units, the first capture antibody is applied to the first region using the first application needle to form a first detection unit, the second capture antibody is applied to the second region using the second application needle to form a second detection unit, and the third capture antibody is applied to the third region using the third application needle to form a third detection unit. The method for manufacturing an immunochromatographic test kit according to claim 6.

9. The method for manufacturing an immunochromatographic test kit according to any one of claims 1 to 8, wherein the sample dropping portion, the conjugate portion, and the at least one detection unit are formed on a single porous member.

10. The method for manufacturing an immunochromatographic test kit according to any one of claims 1 to 8, wherein the sample dropping portion, the conjugate portion, and the at least one detection unit are formed on a plurality of porous members.

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