Concentration device, method for concentrating a test body fluid, method for testing a test body fluid, and test kit

Abstract

Provided is a concentration device for concentrating a test body fluid, capable of obtaining a test body fluid concentrate at a desired concentration factor, a test body fluid concentration method using the concentration device, a test body fluid inspection method using the test body fluid concentration method, and a test kit provided with the concentration device. A concentration device for concentrating a test body fluid that is an aqueous solution containing a high molecule, includes a cylinder that contains a particulate superabsorbent polymer and a piston that can be inserted into the cylinder, the cylinder has a liquid holding portion for holding a portion of the test body fluid injected into the cylinder at a bottom portion, the superabsorbent polymer is contained in the cylinder in contact with the liquid holding portion above the liquid holding portion, and the piston has a front end portion having a smaller pore size than the particle size of the superabsorbent polymer after water absorption.

Description

TECHNICAL FIELD

[0001] The present application relates to a concentration device, a method for concentrating a test body fluid, a method for testing a test body fluid, and a test kit. BACKGROUND

[0002] Conventionally, a technique for concentrating a water solution containing a high molecule such as an antigen (hereinafter, also referred to as "test body fluid") using a super absorbent polymer is known (for example, Patent Literature 1).

[0003] PRIOR ART DOCUMENTS

[0004] PATENT LITERATURE

[0005] Patent Literature 1: Japanese Patent Application Laid-Open No. 4-355339 SUMMARY

[0006] PROBLEMS TO BE SOLVED BY THE INVENTION

[0007] In such a case, the present inventors and others have studied a concentration device for a test body fluid using a super absorbent polymer in reference to Patent Literature 1 and others, and as a result, it has been found that it is difficult to control the concentration ratio of a concentrated solution of a test body fluid (test body fluid concentrated solution). In a case where a test is performed using a test body fluid concentrated solution whose concentration ratio is not controlled, there is a problem in that a comparison obstacle is generated in test results of test body fluids with each other.

[0008] Therefore, in view of the above, an object of the present application is to provide a concentration device for concentrating a test body fluid capable of obtaining a test body fluid concentrated solution having a desired concentration ratio, a method for concentrating a test body fluid using the above concentration device, a method for testing a test body fluid using the above method for concentrating a test body fluid, and a test kit provided with the above concentration device.

[0009] MEANS FOR SOLVING THE PROBLEMS

[0010] The present inventors and others have intensively studied the above problem, and as a result, it has been found that the above problem can be solved by using a concentration device provided with a cylinder that accommodates a super absorbent polymer and has a liquid holding portion for holding a part of a test body fluid injected into the cylinder and a perforated piston, injecting a test body fluid into the cylinder of the above concentration device, almost completely absorbing water in the test body fluid by the super absorbent polymer, then adding the held test body fluid, and taking out the liquid using the perforated piston, thereby completing the present application.

[0011] That is, the present inventors and others have found that the above problem can be solved by the following structure.

[0012] (1) A concentration device provided with a cylinder that contains a particulate superabsorbent polymer and a piston that can be inserted into the cylinder, for concentrating a subject fluid that is an aqueous solution containing a polymer,

[0013] The cylinder has a liquid holding portion for holding a portion of the subject fluid injected into the cylinder at the bottom portion,

[0014] The superabsorbent polymer is contained in the cylinder in contact with the liquid holding portion above the liquid holding portion,

[0015] The piston has a front end portion having pores that are smaller than the particle size of the superabsorbent polymer after water absorption,

[0016] The superabsorbent polymer absorbs water contained in the subject fluid injected into the cylinder other than the subject fluid held in the liquid holding portion, and generates a subject fluid concentrate that is a concentrate of the subject fluid in the cylinder,

[0017] The subject fluid held in the liquid holding portion is added to the subject fluid concentrate,

[0018] A subject fluid concentrate that is a concentrated solution of the subject fluid is taken out from the pores of the front end portion of the piston by inserting the piston into the cylinder.

[0019] (2) The concentration device according to the above (1), wherein,

[0020] The liquid holding portion is a portion surrounded by the bottom portion of the cylinder and a partition wall provided on the inner circumferential surface of the cylinder in a manner that can move in the length direction of the cylinder, and the partition wall has pores that are smaller than the particle size of the superabsorbent polymer before water absorption,

[0021] The subject fluid held in the liquid holding portion is introduced above the partition wall through the pores of the partition wall by moving the partition wall to the bottom surface of the cylinder,

[0022] The subject fluid introduced above the partition wall is added to the subject fluid concentrate.

[0023] (3) The concentration device according to the above (1), wherein,

[0024] The liquid holding portion is a portion formed by the pores of a porous resin contained in the bottom portion of the cylinder, and the pores of the resin are smaller than the particle size of the superabsorbent polymer before water absorption,

[0025] The subject fluid held in the liquid holding portion is introduced above the resin by crushing the resin through the pores of the resin,

[0026] The subject fluid introduced above the resin is added to the subject fluid concentrate.

[0027] (4) The concentration device according to the above (3), wherein the porous resin is a sponge.

[0028] (5) A concentration device provided with a cylinder body that houses a particulate superabsorbent polymer and a piston that can be inserted into the cylinder body, for concentrating a subject fluid that is an aqueous solution containing a high molecule,

[0029] The piston is provided with a leading end portion having pores that are smaller than the particle size of the superabsorbent polymer after water absorption,

[0030] The cylinder body has a liquid retaining portion that retains the subject fluid present above the leading end portion of the piston among the subject fluid injected into the cylinder body, by fixing the leading end portion of the piston to a position that is lower than the liquid surface of the subject fluid injected into the cylinder body and higher than the superabsorbent polymer housed in the cylinder body,

[0031] The superabsorbent polymer is housed in the cylinder body below the liquid retaining portion via the piston,

[0032] The cylinder body and the piston are provided with a piston position fixing mechanism that fixes the leading end portion of the piston to the position against the pressure accompanying the water absorption expansion of the superabsorbent polymer,

[0033] The superabsorbent polymer absorbs water contained in the subject fluid other than the subject fluid retained in the liquid retaining portion among the subject fluid injected into the cylinder body, and generates a subject fluid concentrate that is a concentrate of the subject fluid in the cylinder body,

[0034] The piston position fixing mechanism is released and the piston is pulled up, and the subject fluid present above the leading end portion of the piston is introduced below the leading end portion of the piston through the pores of the leading end portion of the piston, whereby the subject fluid present above the piston is added to the subject fluid concentrate,

[0035] By pulling down the piston again into the cylinder body, a subject fluid concentrate that is a concentrated liquid of the subject fluid is taken out from the pores of the leading end portion of the piston.

[0036] (6) The concentration device according to any one of the above (1) to (5), wherein the cylinder body is further provided with a lid having a recovery port for recovering the subject fluid concentrate.

[0037] (7) The concentration device according to any one of (1) to (6) above, wherein the water absorption rate of the superabsorbent polymer is 0.01 g / min or more and 40 g / min or less per 1 g of the superabsorbent polymer.

[0038] (8) The concentration device according to any one of (1) to (7) above, wherein the particle diameter of the superabsorbent polymer is 5 mm or less.

[0039] (9) The concentration device according to any one of (1) to (8) above, wherein the swelling ratio of the superabsorbent polymer is greater than 0.2 g / g and less than 800 g / g.

[0040] (10) The concentration device according to any one of (1) to (9) above, wherein the test body fluid is an aqueous solution containing a high molecule contained in a biological fluid.

[0041] (11) The concentration device according to (10) above, wherein the cylinder further contains a binding substance that specifically binds to the high molecule contained in the biological fluid.

[0042] (12) The concentration device according to (11) above, wherein the binding substance is contained in the cylinder as a complex with a metal particle.

[0043] (13) The concentration device according to (11) or (12) above, wherein the high molecule contained in the biological fluid is an antigen, and the binding substance is an antibody against the antigen.

[0044] (14) The concentration device according to any one of (1) to (13) above, wherein the cylinder further contains at least one selected from the group consisting of casein and tris(hydroxymethyl)methylglycine.

[0045] (15) The concentration device according to any one of (1) to (14) above, wherein the test body fluid is urine.

[0046] (16) A method for concentrating a test body fluid, which uses the concentration device according to any one of (1) to (15) above to concentrate a test body fluid that is an aqueous solution containing a high molecule, the method for concentrating a test body fluid sequentially includes:

[0047] a test body fluid injection step of injecting the test body fluid into the cylinder while retaining a part of the test body fluid injected into the cylinder in the liquid retaining portion;

[0048] a water absorption step in which water contained in a body fluid other than the body fluid held in the liquid holding section and injected into the cylinder is absorbed by the superabsorbent polymer accommodated in the cylinder, and the body fluid concentrate is generated in the cylinder;

[0049] a liquid addition step of adding the body fluid held in the liquid holding section to the body fluid concentrate; and

[0050] a withdrawal step of inserting a piston into the cylinder, thereby withdrawing the body fluid concentrate as the concentrated liquid of the body fluid through a hole of a front end portion of the piston, the piston being capable of being inserted into the cylinder and having the front end portion having a smaller pore size than the pore size of the superabsorbent polymer after water absorption.

[0051] (17) A body fluid inspection method of detecting a macromolecule in a body fluid that is an aqueous solution containing a macromolecule, the body fluid inspection method comprising, in order:

[0052] a concentration step of obtaining the body fluid concentrate using the body fluid concentration method of (16); and

[0053] a detection step of detecting the macromolecule in the obtained body fluid concentrate.

[0054] (18) The body fluid inspection method according to (17), wherein

[0055] the body fluid is an aqueous solution capable of containing an antigen,

[0056] the concentration step is a step of obtaining an antigen concentrate by concentrating the aqueous solution capable of containing the antigen using the body fluid concentration method of (16),

[0057] the detection step is a step of detecting the antigen in the antigen concentrate by an immunochromatography method using an antigen-antibody reaction.

[0058] (19) The body fluid inspection method according to (18), wherein the detection step includes an amplification step of amplifying information of the antigen in the antigen concentrate.

[0059] (20) The body fluid inspection method according to (19), wherein the amplification step is a silver amplification step.

[0060] (21) An inspection kit for detecting a macromolecule in a body fluid that is an aqueous solution containing a macromolecule, the inspection kit comprising:

[0061] the concentration device according to any one of (1) to (15); and

[0062] A detection device that detects a high molecule in a sample fluid concentrate obtained by the sample fluid concentration method described in (16) above.

[0063] (22) The test kit according to (21) above, wherein the detection device is an immunochromatographic device.

[0064] (23) The test kit according to (21) or (22) above, wherein the detection device has a tank in which an amplification solution for amplifying a signal for detecting a high molecule in the sample fluid concentrate is enclosed.

[0065] Effects of the Invention

[0066] As described below, according to the present application, it is possible to provide a concentration device for concentrating a sample fluid that can obtain a sample fluid concentrate with a desired concentration ratio, a sample fluid concentration method using the concentration device, a sample fluid test method using the sample fluid concentration method, and a test kit having the concentration device. BRIEF DESCRIPTION OF DRAWINGS

[0067] Figure 1 is a schematic cross-sectional view of one mode of Mode Al of the concentration device of the present application.

[0068] Figure 2 is a schematic cross-sectional view of one mode of Mode A2 of the concentration device of the present application.

[0069] Figure 3 is a schematic cross-sectional view of one mode of Mode B of the concentration device of the present application.

[0070] Figure 4A is a view showing the initial state in a schematic cross-sectional view showing one mode of the sample fluid concentration method using Mode Al of the concentration device of the present application in the order of processes.

[0071] Figure 4B is a view showing the sample fluid injection process in a schematic cross-sectional view showing one mode of the sample fluid concentration method using Mode Al of the concentration device of the present application in the order of processes.

[0072] Figure 4C is a view showing the water absorption process in a schematic cross-sectional view showing one mode of the sample fluid concentration method using Mode Al of the concentration device of the present application in the order of processes.

[0073] Figure 4DFig. 1 is a diagram of an extraction liquid adding step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of a mode Al of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0074] Figure 4E Fig. 2 is a diagram of a taking-out step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of the mode Al of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0075] Figure 5A Fig. 3 is a diagram of an initial state in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of a mode A2 of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0076] Figure 5B Fig. 4 is a diagram of a body fluid injecting step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of the mode A2 of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0077] Figure 5C Fig. 5 is a diagram of a water absorbing step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of the mode A2 of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0078] Figure 5D Fig. 6 is a diagram of an extraction liquid adding step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of the mode A2 of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0079] Figure 5E Fig. 7 is a diagram of a taking-out step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of the mode A2 of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0080] Figure 6A Fig. 8 is a diagram of an initial state in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of a mode B of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0081] Figure 6B Fig. 9 is a diagram of a body fluid injecting step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of the mode B of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0082] Figure 6C Fig. 10 is a diagram of a water absorbing step in a schematic cross-sectional view of one mode of a concentrated body fluid concentrating method of the mode B of a body fluid using a concentrator device of the present application, which is shown in order of steps.

[0083] Figure 6Dis a diagram of an extraction liquid adding step in a schematic cross-sectional view showing one mode of a method for concentrating a subject fluid using a concentration device according to Mode B of the present application.

[0084] Figure 6E is a diagram of a taking-out step in a schematic cross-sectional view showing one mode of a method for concentrating a subject fluid using a concentration device according to Mode B of the present application.

[0085] Figure 7 is a partial perspective view of the concentration device 204.

[0086] Figure 8 is a partial perspective view of the concentration device 204.

[0087] Figure 9 is a mode diagram of one mode of an insoluble carrier used in the detection step of the inspection method of the present application.

[0088] Figure 10 is a perspective view showing the shape of one embodiment of an immunochromatography kit.

[0089] Figure 11 is an exploded perspective view showing the shape of one embodiment of an immunochromatography kit.

[0090] Figure 12 is a schematic side view showing the positional relationship of the test strip, the first and second tanks.

[0091] Figure 13 is a perspective view of the first convex deformation portion provided on the upper case of the immunochromatography kit shown in Figure 10

[0092] is a cross-sectional end view of the V-V' line of the first convex deformation portion shown in Figure 14 Figure 13 is a perspective view of the second convex deformation portion provided on the upper case of the immunochromatography kit shown in

[0093] Figure 15 Figure 10 is a cross-sectional end view of the VII-VII' line of the second convex deformation portion shown in

[0094] Figure 16 is a cross-sectional end view of the VII-VII' line of the second convex deformation portion shown in Figure 15

[0095] is a cross-sectional end view of the VII-VII' line of the second convex deformation portion shown in Figure 17

[0096] ​​​​Hereinafter, the present application will be described in detail.

[0097] In addition, in the present specification, a numerical range represented by "~" means a range including the lower limit value and the upper limit value of the numerical values recited before and after the "~".

[0098] Also, in the present specification, each component can be used alone or two or more components can be used at the same time. In this case, unless otherwise specified, the content of the component means the total content.

[0099] Also, in the present specification, when the sample fluid is concentrated using the concentration device of the present application, the case where a sample fluid concentrate having a desired concentration ratio can be obtained, and the case where the uniformity of the concentration of the obtained sample fluid concentrate is high, and the case where the detection sensitivity is high and the S / N ratio (signal / noise ratio) is high in the method for examining the sample fluid of the present application are also referred to as excellent effects of the present application.

[0100] [I] Concentration device

[0101] Hereinafter, the concentration device of the present application will be described.

[0102] [1] Mode A

[0103] Mode A of the concentration device of the present application is a concentration device provided with a cylinder body in which a particulate superabsorbent polymer is accommodated and a piston capable of being inserted into the above-mentioned cylinder body, for concentrating a sample fluid which is an aqueous solution containing a high molecule,

[0104] The above-mentioned cylinder body has a liquid holding portion (hereinafter, also referred to as "extraction liquid holding portion") for holding a part of the sample fluid injected into the above-mentioned cylinder body at the bottom portion,

[0105] The above-mentioned superabsorbent polymer is accommodated in the above-mentioned cylinder body in contact with the above-mentioned extraction liquid holding portion above the above-mentioned extraction liquid holding portion,

[0106] The above-mentioned piston has a leading end portion having a pore smaller than the particle diameter of the above-mentioned superabsorbent polymer after absorbing water,

[0107] The above-mentioned superabsorbent polymer absorbs water contained in the sample fluid other than the sample fluid held in the above-mentioned extraction liquid holding portion among the sample fluid injected into the above-mentioned cylinder body, and generates a sample fluid concentrate which is a concentrate of the above-mentioned sample fluid in the above-mentioned cylinder body,

[0108] The sample fluid held in the above-mentioned extraction liquid holding portion (hereinafter, also referred to as "extraction liquid") is added to the above-mentioned sample fluid concentrate,

[0109] By inserting the above-mentioned piston into the above-mentioned cylinder, a specimen liquid concentrate as the above-mentioned specimen liquid concentrate is taken out from the hole of the front end portion of the above-mentioned piston.

[0110] As a specific mode of the above-mentioned mode A, for example, mode Al and mode A2 can be cited.

[0111] [2] Mode Al

[0112] Mode Al is a mode in which, in the above-mentioned mode A,

[0113] The above-mentioned extraction liquid holding portion is a portion surrounded by the bottom portion of the above-mentioned cylinder and the partition wall, the above-mentioned partition wall is provided on the inner circumferential surface of the above-mentioned cylinder in a manner that it is movable in the length direction of the above-mentioned cylinder, and the above-mentioned partition wall has a hole smaller than the particle diameter of the above-mentioned high water absorbency polymer before water absorption,

[0114] By moving the above-mentioned partition wall to the bottom surface of the above-mentioned cylinder, the specimen liquid held in the above-mentioned extraction liquid holding portion is introduced to the upper side of the above-mentioned partition wall through the hole of the above-mentioned partition wall,

[0115] The specimen liquid introduced to the upper side of the above-mentioned partition wall is added to the above-mentioned specimen liquid concentrate.

[0116] Mode Al will be described using the drawings.

[0117] Figure 1 is a schematic cross-sectional view of one mode of mode Al.

[0118] As shown in Figure 1 , the concentration device 202 is provided with a cylinder 212 in which a high water absorbency polymer 230 is accommodated and a piston 220 which can be inserted into the above-mentioned cylinder 212. The above-mentioned piston 220 is provided with a front end portion 221 having a hole 222 smaller than the particle diameter of the above-mentioned high water absorbency polymer 230 after water absorption.

[0119] Here, the cylinder 212 is provided with a partition wall 260 which is provided on the inner circumferential surface of the cylinder 212 in a manner that it is movable in the length direction of the cylinder 212. Also, the above-mentioned partition wall 260 has a hole 262 smaller than the particle diameter of the high water absorbency polymer 230 before water absorption. Also, the above-mentioned high water absorbency polymer 230 is accommodated in the cylinder 212 in contact with the partition wall 260 on the upper side of the partition wall 260.

[0120] The portion of the cylinder 212 surrounded by the bottom portion 217 and the partition wall 260 becomes an extraction liquid holding portion.

[0121] Hereinafter, a method of concentrating a specimen liquid using the above-mentioned mode Al will be described, and each component constituting the above-mentioned mode Al will also be described.

[0122] [3] The concentration method of the test fluid in method A1 was used.

[0123] A method for concentrating a test body fluid, comprising using the above-mentioned method A1 to concentrate the test body fluid as an aqueous solution containing high molecular weight, wherein the method for concentrating the test body fluid comprises:

[0124] In the sample fluid injection process, while injecting the sample fluid into the cylinder, a portion of the sample fluid injected into the cylinder is retained in the extract holding section.

[0125] In the water absorption process, the water contained in the test body fluid injected into the above-mentioned cylinder, excluding the test body fluid held in the above-mentioned extract holding section, is absorbed by the superabsorbent polymer contained in the above-mentioned cylinder, and the above-mentioned test body fluid concentrate is generated in the above-mentioned cylinder.

[0126] The liquid addition process (hereinafter also referred to as the "extraction liquid addition process") involves adding the body fluid being tested, which is held in the extraction liquid holding section, to the aforementioned body fluid concentrate; and

[0127] In the removal process, a piston is inserted into the cylinder, thereby removing the concentrated body fluid, which is the concentrated body fluid of the test sample, through a hole at the front end of the piston. The piston is insertable into the cylinder and has a front end with a hole having a smaller particle size than that of the superabsorbent polymer after water absorption.

[0128] The above-mentioned extract addition process involves moving the partition wall to the bottom of the cylinder, introducing the test fluid held in the extract holding section through the hole of the partition wall to the top of the partition wall, thereby adding the test fluid held in the extract holding section to the test fluid concentrate.

[0129] The concentration method for the test fluid using method A1 is described using the accompanying drawings.

[0130] Figure 4 Figures 4A-4E () is a schematic cross-sectional view showing one method of concentrating the tested body fluid using method A1 in the order of the process steps.

[0131] First, in the process of injecting the test fluid, the fluid is injected from the opening 216 into the cylinder 212 containing particulate superabsorbent polymer 230. Figure 4A 240 ml of the tested body fluid was injected into the sample. Figure 4B ).

[0132] Here, the cylinder 212 has a partition wall 260 provided on the inner circumferential surface of the cylinder 212 in a manner movable in the length direction of the cylinder 212. Also, the partition wall 260 has a hole 262 smaller than the particle diameter of the superabsorbent polymer 230 before water absorption. Also, the superabsorbent polymer 230 is housed in the cylinder 212 in contact with the partition wall 260 above the partition wall 260.

[0133] As described above, in the case where the test fluid 240 is injected into the cylinder 212, a part of the test fluid 240 is introduced below the partition wall 260 through the hole 262 of the partition wall 260. Also, in the water absorption process described later, water contained in the test fluid 242 present above the partition wall 260 among the test fluid 240 is absorbed by the superabsorbent polymer 230, and water contained in the test fluid 241 present below the partition wall 260 among the test fluid 240 is not absorbed by the superabsorbent polymer 230.

[0134] That is, the test fluid injection process is a process in which the test fluid 240 is injected into the cylinder 212, and a part (the test fluid 241) of the test fluid injected into the cylinder 212 is held in a part (a test fluid holding part) surrounded by the bottom 217 of the cylinder 212 and the partition wall 260 as the extraction liquid added in the extraction liquid addition process described later.

[0135] Then, in the water absorption process, water contained in the test fluid 242 present above the partition wall 260 among the test fluid 240 (the test fluid 242 among the test fluid 240 other than the test fluid 241 held in the test fluid holding part) is absorbed by the superabsorbent polymer 230, and a test fluid concentrate 246 as a concentrate of the test fluid 242 is generated in the cylinder 212 (the superabsorbent polymer 230 becomes a swollen superabsorbent polymer 232) Figure 4C ).

[0136] Next, in the extraction liquid addition process, the partition wall 260 is moved to the bottom surface 218 of the cylinder 212, and the test fluid 241 held in the test fluid holding part is introduced above the partition wall 260 through the hole 262 of the partition wall 260, whereby the test fluid 241 held in the test fluid holding part is added to the test fluid concentrate 246 Figure 4D ). In addition, in the extraction liquid addition process Figure 4DFrom the opening portion 216, a piston 220 used in a later-described extraction process is inserted into the cylinder 212, whereby the superabsorbent polymer 232 is pressed downward, and the partition wall 260 is moved to the bottom surface 218 of the cylinder 212, but the method of moving the partition wall 260 is not limited thereto, and for example, a mechanism for moving the partition wall 260 can be provided independently of the piston 220. Also, instead of moving the partition wall 260, the bottom surface 218 can be made movable in the length direction of the cylinder 212, and the bottom surface 218 is moved to the partition wall 260, and the subject fluid 241 held in the extraction liquid holding portion is introduced onto the partition wall 260 through the hole 262 of the partition wall 260, whereby the subject fluid concentrate 246 is added with the subject fluid 241 held in the extraction liquid holding portion.

[0137] Also, in the extraction process, the piston 220 is inserted into the cylinder 212, whereby the subject fluid concentrate 248, which is a concentrated solution of the subject fluid 240, is extracted through the hole 222 of the front end portion 221 of the piston 220, which is capable of being inserted into the cylinder 212 and has the hole 222 having a smaller diameter than the particle diameter of the superabsorbent polymer 230 after water absorption (the particle diameter of the swollen superabsorbent polymer 232) Figure 4E ).

[0138] Hereinafter, each process will be described.

[0139] [Subject fluid injection process]

[0140] As described above, the subject fluid injection process is a process of injecting the above-described subject fluid into the above-described cylinder while holding a part of the subject fluid injected into the above-described cylinder in the above-described extraction liquid holding portion.

[0141] [Cylinder]

[0142] The shape of the above-described cylinder is not particularly limited, and is preferably a cylindrical shape.

[0143] Generally, one end of the length direction of the above-described cylinder is closed (bottom surface), and the other end is open (opening portion).

[0144] The material of the above-described cylinder is not particularly limited, but from the viewpoint of being capable of injection molding and being capable of inexpensive and mass production, a thermoplastic resin is preferred. From the viewpoint of having a certain degree of hardness, specifically, polypropylene, acrylic acid, polyacetal, polyamide, polyethylene, polyethylene terephthalate, polycarbonate, polystyrene, polyphenylene sulfide, polybutylene terephthalate, polyvinyl chloride, ABS resin (acrylonitrile-butadiene-styrene copolymer resin), AS resin (acrylonitrile-styrene copolymer resin) are preferred.

[0145] [Superabsorbent polymer in particle form]

[0146] The particulate superabsorbent polymer (SAP) contained in the above-mentioned cylinder is not particularly limited, and from the viewpoint of more excellent effects of the present application, etc., a polymer of a polyacrylic acid type, a polyacrylamide type, a cellulose type, or a polyethylene oxide type is preferred.

[0147] <Swelling ratio>

[0148] The swelling ratio of the above-mentioned superabsorbent polymer is not particularly limited, and from the viewpoint of more excellent effects of the present application, etc., it is preferably greater than 0.2 g / g and less than 800 g / g, more preferably 1.0 g / g or greater and 600 g / g or less, further preferably 10 g / g or greater and 500 g / g or less, and particularly preferably 20 g / g or greater and 100 g / g or less.

[0149] Here, the swelling ratio is a value defined as "the mass (g) of water held by 1 g of superabsorbent polymer".

[0150] (Measurement method of swelling ratio)

[0151] The mass of the superabsorbent polymer stored at 25°C and 5% RH (relative humidity) for 10 days is measured, and then immediately immersed in a large amount of distilled water. After 120 minutes, the superabsorbent polymer is taken out, the water on the surface is removed, the mass is measured again, and the swelling ratio is measured using the following calculation formula.

[0152] {(mass after water absorption (g) - initial mass before water absorption (g)) / initial mass before water absorption (g)}

[0153] The method of adjusting the swelling ratio to the above-mentioned specific range is not particularly limited, and methods such as changing the type of polymer, changing the molecular weight of the polymer, changing the crosslinking degree, and changing the particle diameter can be mentioned.

[0154] <Water absorption speed>

[0155] The water absorption speed of the above-mentioned superabsorbent polymer is not particularly limited, but from the viewpoint of more excellent effects of the present application, etc., it is preferably 0.01 g / minute or greater and 40 g / minute or less per 1 g of superabsorbent polymer, and more preferably 0.02 g / minute or greater and 40 g / minute or less per 1 g of superabsorbent polymer.

[0156] The above-mentioned water absorption speed is measured as follows.

[0157] The mass (weight M0, unit g) of the superabsorbent polymer stored at 25°C and 5% RH (relative humidity) for 10 days is measured, and then immediately immersed in a large amount of distilled water. After 10 minutes, the superabsorbent polymer is taken out, the water on the surface is removed, and the mass (mass M 10). Immediately after the measurement of the mass, the superabsorbent polymer was again immersed in a large amount of distilled water. After 10 minutes, the superabsorbent polymer was taken out, the water on the surface was removed, and the mass was again measured (mass M 20 ). Immediately after the measurement of the mass M 20 , the superabsorbent polymer was again immersed in a large amount of distilled water. After 10 minutes, the superabsorbent polymer was taken out, the water on the surface was removed, and the mass was again measured (mass M 30 ).

[0158] The water absorption amount was defined as follows.

[0159] The water absorption amount for 10 minutes: ΔM10= (M 10 - M0) / M0 The water absorption amount for 20 minutes: ΔM20= (M 20 - M0) / M0 The water absorption amount for 30 minutes: ΔM30= (M 30 - M0) / M0

[0160] The water absorption speed was calculated using the water absorption amount defined as described above, as follows.

[0161] The water absorption amount was plotted on the X-Y plane as the horizontal axis time (x = 10, 20, 30; unit: minutes) and the vertical axis water absorption amount (y = ΔM10, ΔM20, ΔM30; unit: g water / g polymer amount), and the slope of the straight line approximation of the water absorption amount with respect to time using the least squares method was taken as the water absorption speed per unit time (minute).

[0162] <Particle diameter>

[0163] From the viewpoint of further improving the effects of the present application, the particle diameter of the superabsorbent polymer is preferably 10 mm or less, more preferably 8 mm or less, and even more preferably 5 mm or less. From the viewpoint of further improving the effects of the present application, the lower limit of the particle diameter of the superabsorbent polymer is preferably 0.01 mm or more, more preferably 0.1 mm or more, and even more preferably 1 mm or more.

[0164] Here, the particle diameter can be measured by an optical microscope to obtain the diameter of 50 particle-shaped polymers as an arithmetic mean.

[0165] [Binding substance that specifically binds to a polymer contained in a biological fluid]

[0166] From the viewpoint of further improving the effects of the present application, the cylinder preferably further contains a binding substance that specifically binds to a polymer contained in a biological fluid in a test fluid, which will be described later. In the case where the cylinder contains the binding substance, for example, in the case where an antigen-antibody reaction is performed at the same time as the concentration of the test fluid, a complex of an antigen in the test fluid and a labeled antibody is formed in a concentrated state, thereby improving the detection sensitivity.

[0167] As the above-mentioned binding substance, for example, the above-mentioned 1st binding substance (particularly, an antibody) described later can be mentioned. That is, in the present application, for the reason that the effects of the present application are more excellent and the like, it is preferred that the above-mentioned high molecule contained in the above-mentioned biological fluid be an antigen, and the above-mentioned binding substance be an antibody.

[0168] For the reason that the effects of the present application are more excellent and the like, it is preferred that the above-mentioned binding substance be contained in the above-mentioned cylinder as a complex with a labeling substance.

[0169] As the above-mentioned complex, for example, a labeled antibody can be mentioned.

[0170] Here, the labeled antibody refers to an antibody to which a detectable labeling substance is bound, and the labeling substance refers to, for example, a detectable substance, and is a substance or state which can be directly detected, such as a substance which can generate electromagnetic waves such as color, fluorescence, light, or a substance which can scatter electromagnetic waves such as color, fluorescence, light, and a substance or state which contains an enzyme or the like which forms a luminophore or a chromophore by interacting with a luminescent precursor or a color-developing precursor.

[0171] For the reason that the effects of the present application are more excellent and the like, it is preferred that the above-mentioned labeled antibody be an antibody modified with a metal particle which exhibits a bright color tone by irradiation of electromagnetic waves such as visible light. For the reason that the effects of the present application are more excellent and the like, it is more preferred that the above-mentioned metal particle be a gold particle. For the reason that the effects of the present application are more excellent and the like, it is preferred that the above-mentioned labeled antibody be an antibody labeled with a gold particle, that is, a modified gold colloid particle (a modified gold colloid particle described later) modified with an antibody.

[0172] The above-mentioned labeled antibody can also be contained in the above-mentioned cylinder as a pad (a gold colloid retaining pad) which retains a modified gold colloid particle which is a gold colloid particle modified with an antibody.

[0173] [Casein, Tris(hydroxymethyl)methylglycine]

[0174] For the reason that the effects of the present application are more excellent and the like, it is preferred that the above-mentioned cylinder further contain at least one selected from the group consisting of casein and tris(hydroxymethyl)methylglycine, and it is more preferred that the above-mentioned cylinder contain both of casein and tris(hydroxymethyl)methylglycine.

[0175] It is considered that casein has an action of inhibiting false positives. Also, in the case where the pH of a test fluid such as urine is acidic, false positives are easily generated, but it is considered that tris(hydroxymethyl)methylglycine has an action of adjusting the pH to neutral to alkaline to inhibit false positives.

[0176] [Extraction liquid retaining portion]

[0177] The above-mentioned piston is provided with an extraction liquid retaining portion.

[0178] The extraction solution holding portion is a portion surrounded by the bottom of the cylinder and the partition wall, and the partition wall is provided on the inner circumferential surface of the cylinder in a manner that it is movable in the length direction of the cylinder. The partition wall has holes smaller than the particle size of the superabsorbent polymer before water absorption.

[0179] <Partition wall>

[0180] The material of the partition wall is not particularly limited, and is preferably the same as the cylinder.

[0181] As described above, the partition wall has holes smaller than the particle size of the superabsorbent polymer before water absorption. Therefore, the superabsorbent polymer does not fall below the partition wall.

[0182] From the viewpoint of further improving the effects of the present application, the diameter of the holes of the partition wall is preferably 2 / 3 or less of the particle size of the superabsorbent polymer before water absorption.

[0183] From the viewpoint of further improving the effects of the present application, the diameter of the holes of the partition wall is preferably 0.05 to 5 mm, more preferably 0.1 to 3 mm, and further preferably 0.2 to 2 mm.

[0184] The number of the holes of the partition wall possessed by the front end portion is not particularly limited, and is preferably 10 to 100, and more preferably 20 to 50.

[0185] From the viewpoint of further improving the effects of the present application, the proportion of the total area of the holes of the partition wall to the area of the partition wall is preferably 5% or more, more preferably 10% or more, and further preferably 15% or more.

[0186] <Specimen liquid>

[0187] The specimen liquid is an aqueous solution containing a high molecule. Among them, an aqueous solution containing a high molecule contained in a biological fluid is preferable.

[0188] As specific examples of the specimen liquid, animal (particularly human) body fluids (e.g., blood, serum, plasma, cerebrospinal fluid, tears, sweat, urine, pus, nasal discharge, or sputum), mouthwash, and the like can be given. Among them, as a specimen containing an antigen as a high molecule, serum, plasma, urine, and nasal discharge are preferable, and from the viewpoint of further improving the effects of the present application, urine is particularly preferable.

[0189] <High molecule contained in a biological fluid>

[0190] As the high molecule contained in the above-mentioned biological fluid, for example, a high molecule mainly useful for the judgment of a disease, a bacterium, a bacteria (for example, Mycobacterium tuberculosis, Liparabinomannan (LAM) contained in Mycobacterium tuberculosis), a virus (for example, an influenza virus), or a nucleic protein thereof, etc., detected from the biological fluid can be mentioned. In addition, LAM is a main antigen in tuberculosis, and is a main constituent of a cell membrane and a cell wall, that is, a glycolipid.

[0191] From the reason that the effect of the present application is more excellent, etc., the high molecule contained in the above-mentioned biological fluid is preferably an antigen, more preferably a virus (especially, an influenza virus) or LAM, and further preferably LAM.

[0192] From the reason that the effect of the present application is more excellent, etc., the molecular weight of the high molecule contained in the biological fluid is preferably 1000 or more, and more preferably 2000 or more. The molecular weight is a high molecule useful for the judgment of a disease, and in the case of a high molecule of which a structural formula is known, a theoretical value calculated from the structural formula can be used. Also, in the case where the structural formula is not determined, it can be calculated by a method of comparing with a substance of a known molecular weight using an electrophoresis method, or a liquid chromatography mass spectrometry (LC-MS).

[0193] <Pre-treatment of the biological fluid to be examined>

[0194] The above-mentioned biological fluid to be examined can be used directly as the biological fluid to be examined, or in a liquid form obtained by extracting an antigen using a suitable extraction solvent, further in a form of a diluted liquid obtained by diluting the liquid extracted with a suitable diluent, or in a form obtained by concentrating the liquid extracted with a suitable method.

[0195] As the above-mentioned extraction solvent, a solvent used in a general immunological analysis method (for example, water, physiological saline, or a buffer, etc.), or a water-miscible organic solvent capable of directly performing an antigen-antibody reaction by dilution with the solvent can be used.

[0196] [Ratio of the superabsorbent polymer to the biological fluid to be examined]

[0197] The ratio of the above-mentioned superabsorbent polymer to the above-mentioned biological fluid to be examined is not particularly limited, but from the reason that the effect of the present application is more excellent, etc., it is preferably 0.01 to 100 g, and more preferably 0.1 to 50 g, per 1 mL of the biological fluid to be examined.

[0198] [Water absorption step]

[0199] As described above, the water absorption step is a step in which water contained in the specimen fluid other than the specimen fluid held in the extract liquid holding section is absorbed by the superabsorbent polymer in the cylinder, and the specimen fluid concentrate is generated in the cylinder.

[0200] In the water absorption step, generally, the water contained in the specimen fluid other than the specimen fluid held in the extract liquid holding section is almost completely absorbed by the superabsorbent polymer.

[0201] [Specimen fluid concentrate]

[0202] As described above, in the water absorption step, the specimen fluid concentrate as the concentrate of the specimen fluid is generated in the cylinder.

[0203] In the case where the specimen fluid and the superabsorbent polymer are mixed, the water in the specimen fluid is absorbed by the superabsorbent polymer, and, in contrast, the macromolecule (e.g., antigen) in the specimen fluid has a certain degree of hydrodynamic radius, and thus the mesh structure of the surface of the superabsorbent polymer produces a sieve effect, and it is difficult to be absorbed by the superabsorbent polymer. As a result, the macromolecule (e.g., antigen) in the specimen fluid is concentrated.

[0204] The specimen fluid concentrate generally exists in the vicinity of the superabsorbent polymer in the form of a precipitate of the macromolecule or a high-concentration solution of the macromolecule dissolved in a trace amount of residual liquid.

[0205] [Extract liquid addition step]

[0206] As described above, the extract liquid addition step is a step in which the specimen fluid held in the extract liquid holding section is added to the specimen fluid concentrate generated in the water absorption step.

[0207] The extract liquid has an effect of extracting (taking out) the specimen fluid concentrate generated in the water absorption step.

[0208] As described above, the method of adding the extract liquid can be exemplified by a method of pressing the superabsorbent polymer 232 downward to move the partition wall to the bottom surface of the cylinder 212 by inserting a piston used in a later-described taking-out step into the cylinder from the opening section of the cylinder, a method of providing a mechanism of moving the partition wall independently of the piston, a method of moving the bottom surface 218 to the partition wall 260 instead of moving the partition wall, and the like.

[0209] The ratio of the amount of extract (the body fluid held in the extract holding section) to the amount of body fluid injected into the cylinder (extract / body fluid) should be less than 100% by volume. However, for reasons of superiority such as the effect of the present invention, it is preferable to be 30% or less, more preferably 20% or less, and even more preferably 1% or more and 10% or less.

[0210] [Removal Process]

[0211] As described above, the extraction process involves inserting a piston into the cylinder after the water absorption process, thereby extracting the concentrated body fluid of the test fluid as a concentrated body fluid through the hole at the front end of the piston. The piston can be inserted into the cylinder and has a front end with a hole that is smaller than the particle size of the superabsorbent polymer after water absorption.

[0212] During the extraction process, the piston is inserted into the cylinder, and the perforated front end is pressed into the superabsorbent polymer. At this time, as the extract moves uniformly within the gaps in the superabsorbent polymer and gathers upwards, a uniform concentrate of the tested body fluid can be obtained through the stirring effect.

[0213] 〔piston〕

[0214] The piston described above can be inserted into the cylinder and has a front end with a hole that is smaller than the particle size of the superabsorbent polymer after water absorption.

[0215] There are no particular restrictions on the material of the piston, and its preferred method is the same as that of the cylinder.

[0216] As described above, the front end of the piston has pores smaller than the particle size of the superabsorbent polymer after water absorption. Furthermore, the particle size of the superabsorbent polymer after water absorption can be determined by measuring the diameter of 50 polymer particles and calculating their arithmetic mean.

[0217] From the perspective of superior effects of the present invention, the diameter of the hole at the aforementioned front end is preferably less than 1 / 2 of the particle size of the superabsorbent polymer after water absorption, more preferably less than 1 / 5, and even more preferably less than 1 / 10.

[0218] From the perspective of superior effects of the present invention, the diameter of the pore at the aforementioned front end is preferably smaller than the particle size of the superabsorbent polymer before water absorption.

[0219] From the perspective of superior effects of the present invention, the diameter of the hole at the front end is preferably 0.01 to 5 mm, more preferably 0.1 to 2 mm.

[0220] The number of holes at the aforementioned front end is not particularly limited, but is preferably 10 to 100, more preferably 20 to 50.

[0221] The ratio of the total area of the holes of the front end portion to the area of the front end portion is preferably 5% or more, more preferably 10% or more, and further preferably 15% or more, from the viewpoint of further improving the effects of the present application.

[0222] [Concentrate of a test body fluid]

[0223] As described above, the concentrate of the test body fluid can be obtained in the extraction process. The amount of the concentrate of the test body fluid is substantially the amount of the extraction liquid. That is, the concentration ratio of the concentrate of the test body fluid is substantially the test body fluid / extraction liquid. Therefore, by making the amounts of the test body fluid and the extraction liquid (the test body fluid held in the extraction liquid holding portion) constant (making the amount of the test body fluid injected into the cylinder and the amount of the extraction liquid holding portion constant), the concentrate of the test body fluid having the desired concentration ratio can be obtained.

[0224] [4] Mode A2

[0225] Mode A2 is a mode in which, in Mode A described above,

[0226] The extraction liquid holding portion is a portion formed by the holes of the porous resin housed in the bottom portion of the cylinder, and the holes of the resin are smaller than the particle diameter of the superabsorbent polymer before water absorption,

[0227] By crushing the resin, the test body fluid held in the extraction liquid holding portion is introduced into the resin above the resin through the holes of the resin,

[0228] The test body fluid introduced into the resin above the resin is added to the concentrate of the test body fluid.

[0229] Mode A2 will be described using the drawings.

[0230] Figure 2 is a schematic cross-sectional view of one mode of Mode A2.

[0231] As Figure 2 shown, the concentration device 203 is provided with a cylinder 213 in which a superabsorbent polymer 230 is housed, and a piston 220 that can be inserted into the cylinder 213. The piston 220 is provided with a front end portion 221 having holes 222 that are smaller than the particle diameter of the superabsorbent polymer 230 after water absorption.

[0232] Here, a porous synthetic resin 270 is housed in the bottom portion 217 of the cylinder 213. Also, the holes (not shown) of the synthetic resin 270 are smaller than the particle diameter of the superabsorbent polymer 230 before water absorption. Also, the superabsorbent polymer 230 is housed in the cylinder 213 in contact with the synthetic resin 270 above the synthetic resin 270.

[0233] The hole of the synthetic resin 270 becomes an extract liquid holding portion.

[0234] Next, a method for concentrating a subject fluid using the above-described manner A2 will be described, and each component of the above-described manner A2 will be described.

[0235] [5] Method for concentrating a subject fluid using the above-described manner A2

[0236] A method for concentrating a subject fluid using the above-described manner A2 to concentrate a subject fluid which is an aqueous solution containing a high molecule, the method for concentrating a subject fluid sequentially includes:

[0237] a subject fluid injection process of injecting the subject fluid into the cylinder while retaining a part of the subject fluid injected into the cylinder in the extract liquid holding portion;

[0238] a water absorption process of absorbing water contained in the subject fluid injected into the cylinder except for the subject fluid retained in the extract liquid holding portion by the superabsorbent polymer accommodated in the cylinder to generate the subject fluid concentrate in the cylinder;

[0239] a liquid addition process (hereinafter, also referred to as an "extract liquid addition process") of adding the subject fluid retained in the extract liquid holding portion to the subject fluid concentrate; and

[0240] a taking-out process of inserting a piston into the cylinder to thereby take out a subject fluid concentrate as a concentrated liquid of the subject fluid through a hole of a front end portion of the piston, the piston being capable of being inserted into the cylinder and having a front end portion having a hole smaller than a particle size after water absorption of the superabsorbent polymer,

[0241] the extract liquid addition process is a process of crushing the resin and introducing the subject fluid retained in the extract liquid holding portion above the resin through the hole of the resin to thereby add the subject fluid retained in the extract liquid holding portion to the subject fluid concentrate.

[0242] A method for concentrating a subject fluid using the above-described manner A2 will be described using the drawings.

[0243] FIG. 5 Figures 5A-5E is a schematic cross-sectional view of one manner of the manner A2, which shows a process sequence.

[0244] First, in the subject fluid injection process, the subject fluid is injected from the opening portion 216 into the cylinder 213 Figure 5A containing the particulate superabsorbent polymer 230. Figure 5B

[0245] ​Here, a porous synthetic resin 270 is contained in the bottom 217 of the cylinder 213. The pores (not shown) of the synthetic resin 270 are smaller than the particle size of the superabsorbent polymer 230 before water absorption. Furthermore, the superabsorbent polymer 230 is contained in the cylinder 213 above and in contact with the synthetic resin 270.

[0246] As described above, when the test fluid is injected into the cylinder 213, a portion of the test fluid is introduced into the pores of the synthetic resin 270 (the synthetic resin 270 becomes the test fluid 241 (not shown) which is introduced into the pores as part of the test fluid 241). Furthermore, in the water absorption process described later, the water contained in the test fluid 242, which exists only above the synthetic resin 270, is absorbed by the superabsorbent polymer 230, while the water contained in the test fluid 241, which exists within the pores of the synthetic resin 270, is not absorbed by the superabsorbent polymer 230.

[0247] That is, the test fluid injection process is a process in which, while injecting the test fluid into the cylinder 213, a portion of the test fluid injected into the cylinder 213 (test fluid 241) is used as an extractant added in the extractant addition process described later, and is held in the pores (extractant holding part) of the porous synthetic resin 270 contained in the bottom 217 of the cylinder 213.

[0248] Then, in the water absorption process, the water contained in the body fluid 242 (the body fluid 242 in the body fluid 240 that exists only above the synthetic resin 270, excluding the body fluid 241 held in the extract holding section) is absorbed by the superabsorbent polymer 230, and a body fluid concentrate 246 is generated in the cylinder 213 as a concentrate of the body fluid 242 (the superabsorbent polymer 230 becomes a swollen superabsorbent polymer 232). Figure 5C ).

[0249] Next, in the extract addition step, the synthetic resin 270 is crushed, and the test fluid 241 held in the extract holding section is introduced through the holes of the synthetic resin 270 to the top of the synthetic resin 270, thereby adding the test fluid 241 held in the extract holding section to the test fluid concentrate 246. Figure 5D Additionally, in Figure 5D In this process, the piston 220 used in the removal process described later is inserted into the cylinder 213 through the opening 216, thereby pressing the superabsorbent polymer 232 downward and crushing the synthetic resin 270. However, the method of crushing the synthetic resin 270 is not limited to this. For example, a mechanism for crushing the synthetic resin 270 may be provided independently of the piston 220.

[0250] Also, in the extracting step, the piston 220 is inserted into the cylinder 213, whereby the specimen fluid concentrate 248, which is the specimen fluid 240, is extracted through the hole 222 of the front end portion 221 of the piston 220, which is capable of being inserted into the cylinder 213 and has the hole 222 having a smaller diameter than the particle diameter of the water-absorbed superabsorbent polymer 230 (the particle diameter of the swollen superabsorbent polymer 232) Figure 5E

[0251] [Specimen fluid injection step]

[0252] The specimen fluid injection step is the same as the specimen fluid injection step of the specimen fluid concentration method using the above-described mode Al, except that the extract solution holding portion has the following structure.

[0253] [Extract solution holding portion]

[0254] The above-described piston has an extract solution holding portion.

[0255] The above-described extract solution holding portion is a portion formed by the hole of the porous resin housed in the bottom portion of the above-described cylinder. The hole of the above-described resin is smaller than the particle diameter of the superabsorbent polymer before water absorption. Therefore, the superabsorbent polymer does not enter the resin.

[0256] <Resin>

[0257] As the above-described resin, any one of the resins existing in nature or synthetic resins can be used, but from the viewpoint of ease of molding or mass production at low cost, a synthetic resin is preferable.

[0258] The material of the above-described synthetic resin is not particularly limited, and as a specific example, polyvinyl alcohol (PVA) can be given.

[0259] From the viewpoint of more excellent reasons of effects of the present application, the above-described resin is preferably a sponge.

[0260] The hole of the above-described resin is smaller than the particle diameter of the superabsorbent polymer before water absorption. Therefore, the superabsorbent polymer does not enter the resin.

[0261] The porosity (volume of voids / volume of resin containing voids) of the above-described resin is not particularly limited, and from the viewpoint of more excellent reasons of effects of the present application, it is preferably 50% or more, more preferably 70% or more and 99% or less, and further preferably 70% or more and 98% or less.

[0262] [Water absorption step]

[0263] The water absorption step is the same as the water absorption step of the specimen fluid concentration method using the above-described mode Al.

[0264] ​[extraction liquid addition step]

[0265] As described above, the extraction liquid addition step is a step of adding the specimen liquid held in the extraction liquid holding section to the specimen liquid concentrate generated in the water absorption step.

[0266] The extraction liquid has a function of extracting (taking out) the specimen liquid concentrate generated in the water absorption step.

[0267] As described above, methods of adding the extraction liquid include a method of inserting a piston used in a later-described taking-out step into a cylinder from an opening section, pressing down the superabsorbent polymer, and crushing the porous resin, and a method of providing a mechanism for crushing the porous resin independently of the piston.

[0268] The ratio of the amount of the extraction liquid (the specimen liquid held in the extraction liquid holding section) to the amount of the specimen liquid injected into the cylinder (extraction liquid / specimen liquid) is the same as that of the extraction liquid addition step of the specimen liquid concentration method using the above-described mode Al.

[0269] [extraction liquid addition step]

[0270] The taking-out step is the same as that of the specimen liquid concentration method using the above-described mode Al.

[0271] [6] Mode B

[0272] Mode B of the concentration device of the present application is a concentration device that has a cylinder that accommodates a superabsorbent polymer in the form of particles and a piston that can be inserted into the cylinder, and is used to concentrate a specimen liquid that is an aqueous solution containing a high molecule,

[0273] The above-described piston has a tip portion having pores that are smaller than the particle diameter of the superabsorbent polymer after water absorption,

[0274] The above-described cylinder has a liquid holding section (hereinafter also referred to as "extraction liquid holding section"), and the above-described liquid holding section holds the specimen liquid present above the tip portion of the above-described piston in the specimen liquid injected into the above-described cylinder by fixing the tip portion of the above-described piston to a position (hereinafter also referred to as "position A") that is lower than the liquid surface of the specimen liquid injected into the above-described cylinder and higher than the superabsorbent polymer accommodated in the above-described cylinder,

[0275] The above-described superabsorbent polymer is accommodated in the above-described cylinder below the above-described extraction liquid holding section via the above-described piston,

[0276] The above-described cylinder and the above-described piston have a piston position fixing mechanism that fixes the tip portion of the above-described piston to the above-described position against the pressure accompanying the water absorption expansion of the above-described superabsorbent polymer,

[0277] The water contained in the subject fluid other than the subject fluid held in the extraction fluid holding section among the subject fluid injected into the cylinder is concentrated in the cylinder to generate a subject fluid concentrate as a concentrate of the subject fluid,

[0278] The subject fluid (hereinafter, also referred to as "extraction fluid") present above the front end section of the piston is introduced below the front end section of the piston through the hole of the front end section of the piston by pulling up the piston to release the piston position fixing mechanism and pulling up the piston, thereby adding the subject fluid present above the piston to the subject fluid concentrate,

[0279] The subject fluid concentrate as a concentrate of the subject fluid is taken out from the hole of the front end section of the piston by pulling down the piston again into the cylinder.

[0280] The method B will be described using the drawings.

[0281] Figure 3 is a schematic cross-sectional view of one mode of the method B.

[0282] As shown in Figure 3 , the concentration device 204 is provided with a cylinder 214 in which a superabsorbent polymer 230 is accommodated and a piston 224 which can be inserted into the cylinder 214. The piston 220 has a hole smaller than the particle size of the superabsorbent polymer 230 after water absorption. The piston 224 is provided with a front end section 221 having a hole 222 smaller than the particle size of the superabsorbent polymer 230 after water absorption. The cylinder 214 and the piston 224 are provided with a piston position fixing mechanism (not shown) which fixes the front end section 221 of the piston 224 to a position A against the pressure accompanying the water absorption expansion of the superabsorbent polymer 230.

[0283] In a case where the subject fluid is injected into the cylinder 214, the subject fluid present above the front end section 221 of the piston 220 among the subject fluid injected into the cylinder 214 is held by fixing the front end section 221 of the piston 220 to the position A. That is, the cylinder 214 has an extraction fluid holding section which holds a part of the subject fluid injected into the cylinder 214.

[0284] Hereinafter, a method of concentrating a subject fluid using the above-described method B will be described, and each component constituting the above-described method B will be described.

[0285] [7] Method of concentrating a subject fluid using the method B

[0286] A method of concentrating a subject fluid using the above-described method B to concentrate a subject fluid which is an aqueous solution containing a high molecule, the method of concentrating the subject fluid sequentially includes:

[0287] a subject fluid injection process of injecting the subject fluid into the cylinder while retaining a part of the subject fluid injected into the cylinder in the extract liquid retaining portion;

[0288] a water absorbing process of absorbing water contained in the subject fluid injected into the cylinder except for the subject fluid retained in the extract liquid retaining portion by the superabsorbent polymer accommodated in the cylinder, to generate the subject fluid concentrate in the cylinder;

[0289] a liquid addition process (hereinafter, also referred to as "extract liquid addition process") of adding the subject fluid retained in the extract liquid retaining portion to the subject fluid concentrate; and

[0290] a taking-out process of inserting the piston into the cylinder to thereby take out the subject fluid concentrate as the concentrated liquid of the subject fluid through the hole of the front end portion of the piston, the piston being capable of being inserted into the cylinder and having the front end portion having a hole smaller than the particle diameter of the superabsorbent polymer after water absorption,

[0291] the subject fluid injection process is a process of injecting the subject fluid into the cylinder while inserting the piston into the cylinder and fixing the piston at a position (position A) lower than the liquid surface of the subject fluid injected into the cylinder and higher than the superabsorbent polymer accommodated in the cylinder, thereby retaining the subject fluid existing above the piston among the subject fluid injected into the cylinder in the cylinder,

[0292] the extract liquid addition process is a process of pulling up the piston to introduce the subject fluid existing above the piston below the piston through the hole of the piston, thereby adding the subject fluid existing above the piston to the subject fluid concentrate.

[0293] A method of concentrating a subject fluid using Mode B will be described using the drawings.

[0294] FIG. 6 Figures 6A-6E is a schematic cross-sectional view showing one mode of Mode B in the order of processes.

[0295] First, in the subject fluid injection process, the subject fluid is injected from the opening portion 216 into the cylinder 214 in which the particulate superabsorbent polymer 230 is accommodated Figure 6A) while the subject fluid 240 is being injected into the cylinder 214, the piston 224 is inserted into the cylinder 214, and the front end portion 221 of the piston 224 is fixed to a position (position A) lower than the liquid surface 244 of the subject fluid 240 injected into the cylinder 214 and higher than the superabsorbent polymer 230 accommodated in the cylinder 214, the piston 224 being insertable into the cylinder 214 and having the front end portion 221 with the pores 222 smaller than the particle diameter of the superabsorbent polymer 230 after water absorption Figure 6B ). In addition, the cylinder 214 and the piston 224 have a piston position fixing mechanism (not shown) that fixes the front end portion 221 of the piston 224 to the position A against the pressure accompanying the water absorption expansion of the superabsorbent polymer 230.

[0296] As described above, in the case where the piston 224 is inserted into the cylinder 214 while the subject fluid 240 is being injected into the cylinder 214, and the front end portion 221 of the piston 224 is fixed to the position A, a part of the subject fluid is introduced above the front end portion 221 of the piston 224 through the pores 222 of the front end portion 221 of the piston 224. Also, in the water absorption process described later, water contained in the subject fluid 242 present below the front end portion 221 of the piston 224 among the subject fluid 240 is absorbed by the superabsorbent polymer 230, and water contained in the subject fluid 241 present above the front end portion 221 of the piston 224 among the subject fluid 240 is not absorbed by the superabsorbent polymer.

[0297] That is, the subject fluid injection process is a process of inserting the piston 224 into the cylinder 214, fixing the front end portion 221 of the piston 224 to the position A, and thereby retaining the subject fluid 241 present above the front end portion 221 of the piston 224 among the subject fluid 240 injected into the cylinder 214 as the extraction liquid to be added in the extraction liquid addition process described later.

[0298] Then, in the water absorption process, water contained in the subject fluid 242 present below the front end portion 221 of the piston 224 among the subject fluid 240 (the subject fluid 242 other than the subject fluid 241 retained as the extraction liquid among the subject fluid 240) is absorbed by the superabsorbent polymer 230, and the subject fluid concentrate 246 as a concentrate of the subject fluid 242 is generated in the cylinder 214 (the superabsorbent polymer 230 becomes the swollen superabsorbent polymer 232) Figure 6C ).

[0299] Next, in the extraction liquid addition step, the piston 224 is pulled up, and the specimen liquid 241 present above the front end portion 221 of the piston 224 is introduced below the front end portion 221 of the piston 224 through the hole 222 of the front end portion 221 of the piston 224, whereby the specimen liquid 241 present above the front end portion 221 of the piston 224 is added to the specimen liquid concentrate 246. Figure 6D

[0300] Also, in the extraction step, the piston 224 is inserted into the cylinder 214, whereby the specimen liquid concentrate 248 as the concentrated liquid of the specimen liquid 240 is extracted through the hole 222 of the front end portion 221 of the piston 224. Figure 6E

[0301] [Specimen Liquid Injection Step]

[0302] The specimen liquid injection step is the same as the specimen liquid injection step of the specimen liquid concentration method using the above-described mode Al except that the extraction liquid holding portion has the following structure.

[0303] [Extraction Liquid Holding Portion]

[0304] In the case where the specimen liquid is injected into the above-described cylinder, the specimen liquid present above the front end portion of the piston is held in the specimen liquid injected into the piston by fixing the front end portion of the piston to the position A. That is, the cylinder has an extraction liquid holding portion which holds a part of the specimen liquid injected into the cylinder.

[0305] [Water Absorption Step]

[0306] The water absorption step is the same as the water absorption step of the specimen liquid concentration method using the above-described mode Al.

[0307] [Extraction Liquid Addition Step]

[0308] As described above, the extraction liquid addition step is a step of adding the specimen liquid held in the above-described extraction liquid holding portion to the specimen liquid concentrate generated in the above-described water absorption step.

[0309] The extraction liquid has a function of extracting (extracting) the specimen liquid concentrate generated in the water absorption step.

[0310] As described above, methods of adding the extraction liquid include a method of pulling up the piston, introducing the specimen liquid present above the front end portion of the piston below the front end portion of the piston through the hole of the front end portion of the piston, and the like.

[0311] The ratio of the amount of the extraction liquid (the specimen liquid held in the extraction liquid holding portion) to the amount of the specimen liquid injected into the cylinder (extraction liquid / specimen liquid) is the same as that of the extraction liquid addition step of the specimen liquid concentration method using the above-described mode Al.​​

[0312] [extraction process]

[0313] The extraction process is the same as that of the concentration method of a test body fluid using the above-described mode A1.

[0314] [piston position fixing mechanism]

[0315] As described above, in the above-described mode B, the above-described cylinder and the above-described piston are provided with a piston position fixing mechanism that fixes the front end portion of the above-described piston to the above-described position A against the pressure accompanying the water absorption expansion of the above-described superabsorbent polymer.

[0316] The above-described piston position fixing mechanism is not particularly limited, and for example, a mechanism as shown in Embodiment 3 (described later) can be cited: the cylinder is provided with a notch, and the piston is provided with a protrusion, the piston is inserted into the cylinder, and the protrusion of the piston is hung on the notch of the cylinder, whereby the front end portion of the piston can be fixed to the position A against the pressure accompanying the water absorption expansion of the superabsorbent polymer. Figure 8

[0317] [8] cap having a recovery port

[0318] From the viewpoint of more excellent reasons of effects and the like of the present application, the concentration device (mode A, mode B) of the present application preferably further has a cap having a recovery port for recovering the above-described test body fluid concentrate.

[0319] As a specific mode of the above-described cap, for example, the cap used in Embodiment 1 (described later) can be cited. Figure 7

[0320] [II] concentration method of a test body fluid

[0321] The concentration method of a test body fluid of the present application (hereinafter, also referred to as “the concentration method of the present application”) is as described above.

[0322] [III] test method of a test body fluid of the present application

[0323] The test method of a test body fluid of the present application (hereinafter, also referred to as “the test method of the present application”) detects a high molecule in a test body fluid that is an aqueous solution containing a high molecule, and sequentially includes:

[0324] a concentration process of obtaining the above-described test body fluid concentrate using the above-described concentration method of a test body fluid of the present application (the above-described concentration method of the present application); and

[0325] a detection process of detecting a high molecule in the obtained above-described test body fluid concentrate.

[0326] ​​In the examination method of the present application, since the detection of the high molecule is performed using the specimen fluid concentrate obtained by the above-described concentration method of the present application, high detection sensitivity can be obtained.

[0327] [Concentration Step]

[0328] The method of obtaining the specimen fluid concentrate using the concentration method of the present application is as described above.

[0329] [Detection Step]

[0330] The detection step is a step of detecting the high molecule in the specimen fluid concentrate.

[0331] From the viewpoint of further excellence of the effects of the present application and the like, the detection step is preferably a method using an antigen-antibody reaction, and as such a method, for example, enzyme immunoassay (EIA), solid-phase enzyme immunoassay (ELISA), radioimmunoassay (RIA), fluorescence immunoassay (FIA), Western blotting, immunochromatography, and the like can be given. Among them, from the viewpoint of further excellence of the effects of the present application and the like, immunochromatography is preferred.

[0332] [Preferred Mode]

[0333] From the viewpoint of further excellence of the effects of the present application and the like, the examination method of the present application is preferably an examination method in which:

[0334] the above-described specimen fluid is an aqueous solution capable of containing an antigen (high molecule),

[0335] the above-described concentration step is a step of concentrating the aqueous solution capable of containing the above-described antigen using the above-described concentration method of the present application to obtain an antigen concentrate (specimen fluid concentrate),

[0336] the above-described detection step is a step of detecting the antigen in the above-described antigen concentrate by immunochromatography using an antigen-antibody reaction.

[0337] Here, from the viewpoint of further excellence of the effects of the present application and the like, the above-described detection step preferably includes:

[0338] a development step of developing on an insoluble carrier having a reaction site at which a second binding material capable of binding to the above-described antigen is fixed, in a state in which a gold particle complex is formed as a complex of the antigen in the above-described antigen concentrate and a modified gold particle using a first binding material capable of binding to the above-described antigen to modify the gold particle, that is, a modified gold particle; and

[0339] a capturing step of capturing the above-described gold particle complex at the reaction site of the above-described insoluble carrier.

[0340] From the viewpoint of further improving the effects of the present application, the above detection step preferably further includes a silver amplification step of performing silver amplification on the gold particle complex captured in the above capture step.

[0341] Here, from the viewpoint of further improving the effects of the present application, at least one of the above first binding substance and the above second binding substance is preferably a monoclonal antibody, and more preferably both of the above first binding substance and the above second binding substance are monoclonal antibodies.

[0342] In addition, impurities such as salts are sometimes contained in the test body fluid. For example, in the case where the test body fluid is urine, impurities of low molecular components such as urea are contained. According to the research by the present inventors and the like, it has been found that, in the case where these impurities are concentrated together with the high molecular contained in the biological fluid, the antigen-antibody reaction is sometimes hindered, resulting in a decrease in detection sensitivity. That is, it has been found that the improvement effect of the detection sensitivity by concentration is sometimes not sufficiently obtained.

[0343] Therefore, in the above concentrator device of the present application used in the above concentration step, the swelling ratio of the superabsorbent polymer is preferably within the above preferable range in which impurities and the like can be sufficiently absorbed. If it is within the above range, these impurities are absorbed together with water by the superabsorbent polymer, and a decrease in detection sensitivity as described above is difficult to occur, and as a result, it is considered that extremely high detection sensitivity can be achieved for the high molecular contained in the biological fluid.

[0344] Hereinafter, each step included in the above preferable mode (hereinafter, also referred to as "the method of the present application") will be described.

[0345] [Development Step]

[0346] The development step is a step of developing on an insoluble carrier having a reaction site at which a second binding substance capable of binding to the above antigen is fixed, in a state where a gold particle complex of a complex of an antigen in the antigen concentrated solution obtained in the above concentration step and a gold particle modified with a first binding substance capable of binding to the above antigen, i.e., a modified gold particle, is formed.

[0347] <Gold Particle Complex>

[0348] As described above, in the development step, first, a gold particle complex of a complex of an antigen in the antigen concentrated solution obtained in the above concentration step and a gold particle modified with a first binding substance capable of binding to the above antigen, i.e., a modified gold particle, is formed. In addition, in the case where a complex of an antigen in the test body fluid and a labeled antibody is formed at the same time as the concentration of the test body fluid, the antigen concentrated solution can be directly developed on the insoluble carrier.

[0349] (Modified Gold Particle)

[0350] The gold particles are gold particles modified with a first binding substance capable of binding to the antigen.

[0351] (1) Gold particles

[0352] The gold particles are not particularly limited, but from the viewpoint of more excellent effects and the like of the present application, gold colloidal particles are preferred.

[0353] In the case where the method of the present application includes a silver amplification process described later, the gold particles function as a catalyst for reducing silver ions in the silver amplification process.

[0354] The particle diameter of the gold particles is preferably 500 nm or less, more preferably 300 nm or less, further preferably 200 nm or less, and particularly preferably 100 nm or less, from the viewpoint of more excellent effects and the like of the present application.

[0355] The lower limit of the particle diameter of the gold particles is not particularly limited, but is preferably 1 nm or more, more preferably 2 nm or more, and further preferably 5 nm or more, from the viewpoint of more excellent effects and the like of the present application.

[0356] In addition, the particle diameter can be measured using a commercially available particle size distribution meter or the like. As a method for measuring the particle size distribution, optical microscope method, confocal laser microscope method, electron microscope method, atomic force microscope method, static light scattering method, laser diffraction method, dynamic light scattering method, centrifugal sedimentation method, electric pulse measurement method, chromatography method, ultrasonic wave attenuation method, and the like are known, and devices corresponding to each principle are commercially available. As a method for measuring the particle diameter, from the viewpoint of the range of the particle diameter and the ease of measurement, the dynamic light scattering method can be preferably used. As a commercially available measuring device using the dynamic light scattering, NANOTRAC UPA (Nikkiso Co., Ltd.), dynamic light scattering type particle size distribution measuring device LB-550 (HORIBA, Ltd.), and dense particle analyzer FPAR-1000 (OTSUKA ELECTRONICS Co., Ltd.) can be mentioned, and in the present application, the value of the median particle diameter (d=50) measured at a measuring temperature of 25°C is obtained.

[0357] (2) First binding substance

[0358] The first binding substance is not particularly limited as long as it can bind to the antigen, but from the viewpoint of more excellent effects and the like of the present application, a protein is preferred, and an antibody (for example, polyclonal antibody or monoclonal antibody) is more preferred, and from the viewpoint of achieving higher detection sensitivity, a monoclonal antibody is further preferred.

[0359] The above antibody is not particularly limited, and for example, an antiserum prepared from serum of an animal immunized with an antigen or an immunoglobulin fraction purified from the antiserum can be used, and a monoclonal antibody obtained by cell fusion using spleen cells of an animal immunized with an antigen, or a fragment thereof [for example, F(ab')2, Fab, Fab', or Fv] can be used. The preparation of these antibodies can be performed by a conventional method.

[0360] As an example of the first binding substance when the antigen is an influenza virus, commercially available antibodies can be used, and for example, Anti-Influenza A SPTN-5 7307 (Medix Biochemica) or Anti-Influenza A Monoclonal Antibody (Bios Pacific Inc., clone number: A60010044P) can be mentioned.

[0361] Further, as an example of the first binding substance when the antigen is LAM, the A194-01 antibody described in International Publication No. 2017 / 139153 can be mentioned. The contents described in International Publication No. 2017 / 139153 regarding the A194-01 antibody are all incorporated into the present specification as a part of the disclosure of the present specification.

[0362] As another example of the first binding substance when the antigen is LAM, an antibody having the sequence described as MoAb1 in paragraph

[0080] of International Publication No. 2013 / 129634 can be mentioned. The contents described in International Publication No. 2013 / 129634 regarding the MoAb1 antibody are all incorporated into the present specification as a part of the disclosure of the present specification.

[0363] (3) Method for producing modified gold particles

[0364] The method for producing the above modified gold particles is not particularly limited, and a publicly known method can be used.

[0365] For example, a chemical bonding method in which an SH group is introduced to an antibody by chemical bonding of gold with the SH group, and then fixed by Au-S bonds generated on the Au surface at the time of proximity with gold particles, and the like can be mentioned.

[0366] <Insoluble carrier>

[0367] The aforementioned insoluble carrier (porous carrier) is an insoluble carrier having a reaction site (test line) on which a second binding substance capable of binding to the aforementioned antigen is immobilized. The insoluble carrier can have multiple test lines depending on the type of antigen (e.g., test lines for influenza A virus and test lines for influenza B virus). Furthermore, to confirm the development of the aforementioned gold particle complex, the insoluble carrier may have a control line downstream of the test line. Moreover, in the case where a reducing agent solution is used in the silver amplification process described later, a chromogenic reagent immobilization line may be provided downstream of the test line to detect the reducing agent solution.

[0368] Specific examples of the aforementioned insoluble carriers include, for instance, those mentioned above. Figure 9 The nitrocellulose membrane 300 shown has a gold colloid holding pad 301, a test line 302, a control line 303, and a colorimetric reagent immobilization line 304 from the upstream side. Here, the gold colloid holding pad 301 is a pad that holds gold particles modified with a first binding substance (modified gold particles), the test line 302 is a line with a second binding substance immobilized, the control line 303 is a line used to confirm the development, and the colorimetric reagent immobilization line 304 is a line used to detect the reducing agent solution described later. Here, "upstream side" and "downstream side" refer to the direction of development from the upstream side to the downstream side during the development of the gold particle complex.

[0369] As a more specific example of the aforementioned insoluble carrier (or immunochromatographic kit having the insoluble carrier), the insoluble carrier and immunochromatographic kit described in Japanese Patent No. 5728453 can be cited, and the entire contents of Japanese Patent No. 5728453 concerning the insoluble carrier and immunochromatographic kit are incorporated herein by reference as part of the disclosure of this specification.

[0370] (Insoluble carrier)

[0371] The insoluble carrier is preferably a porous carrier. In particular, for reasons of superior performance of the present invention, nitrocellulose membranes, cellulose membranes, acetylcellulose membranes, polysulfone membranes, polyethersulfone membranes, nylon membranes, glass fibers, nonwoven fabrics, cloths, or filaments are preferred, and nitrocellulose membranes are even more preferred.

[0372] (Second binding substance)

[0373] There are no particular restrictions on the second binding substance as long as it can bind to the aforementioned antigens.

[0374] Examples of the second binding substance and preferred modes thereof include the same examples and preferred modes as those described above for the first binding substance. The second binding substance can be the same as or different from the first binding substance, but from the viewpoint of more excellent effects of the present application, it is preferred that the second binding substance be different from the first binding substance.

[0375] Also, in the case where the first binding substance and the second binding substance are antibodies, from the viewpoint of more excellent effects of the present application, it is preferred that the antibody as the first binding substance and the antibody as the second binding substance be different.

[0376] Also, in the case where the first binding substance and the second binding substance are antibodies, from the viewpoint of more excellent effects of the present application, it is preferred that the epitope of the first binding substance (a part of an antigen recognized by the first binding substance) and the epitope of the second binding substance (a part of an antigen recognized by the second binding substance) be different. The difference in the epitope of the antibody can be confirmed by, for example, ELISA (Enzyme-Linked Immuno Sorbent Assay).

[0377] <Development>

[0378] The method of developing on the insoluble support having the test line in the state of the gold particle complex is not particularly limited, and includes, for example, a method of preparing the nitrocellulose membrane 300 (or an immunochromatography kit having the nitrocellulose membrane 300) as described above Figure 9 and dropping the antigen concentrate obtained in the above concentration process onto the gold colloid holding pad, and moving it from the upstream side to the downstream side using the capillary phenomenon as described in Figure 9

[0379] [Capture Process]

[0380] The capture process is a process of capturing the gold particle complex on the reaction site of the insoluble support.

[0381] As described above, since the second binding substance capable of binding to the antigen is immobilized on the reaction site of the insoluble support, the gold particle complex (a complex of the antigen and the modified gold particle) developed on the insoluble support in the above development process is captured on the reaction site (test line) of the insoluble support.

[0382] Since the captured gold particle complex is colored by the surface plasmon of the gold particle or the like, it can be visually recognized. Also, the concentration of the captured complex can be estimated using an image analysis device or the like. In this way, the antigen in the sample can be detected.

[0383] ​In addition, when the sample does not contain antigen, the aforementioned gold particle complex is not formed, so it is not captured at the reaction site of the insoluble carrier and is not stained.

[0384] [Silver Amplification Process]

[0385] The silver amplification process is a process of amplifying the gold particle complex captured in the above-mentioned capture process.

[0386] The silver amplification process involves imparting silver ions to the insoluble support following the capture process, thereby forming large silver particles within the gold particle complex captured at the reaction site of the insoluble support. More specifically, it involves using the gold particles of the aforementioned gold particle complex as a catalyst to reduce silver ions, forming silver particles (e.g., with a diameter of 10 μm or more).

[0387] As a result, the detection sensitivity of the captured gold particle complex is significantly improved.

[0388] Alternatively, the silver amplification process can be performed together with the development process, and the silver amplification process can also serve as the development process.

[0389] <Preferred Method>

[0390] There are no particular limitations on the method of imparting silver ions to the insoluble carrier after the above-mentioned capture process, but considering the superior effects of the present invention, the method of using the following reducing agent solution and the following silver amplification solution is preferred.

[0391] Furthermore, in addition to reducing agents and silver amplification solutions, cleaning solutions can also be used to clean complexes remaining in the insoluble carrier through specific binding reactions. The aforementioned reducing solutions can also be used as cleaning solutions.

[0392] (Reducing agent solution)

[0393] The aforementioned reducing agent solution contains a reducing agent capable of reducing silver ions. Any inorganic or organic material or mixture thereof can be used as the reducing agent, as long as it can reduce silver ions to silver. As an inorganic reducing agent, Fe is a preferred example. 2+ V 2+ and Ti 3+ Reducing metal salts and reducing metal complexes are metals whose oxidation states can be altered by metal ions. When using inorganic reducing agents, it is necessary to remove or neutralize the oxidized ions by complexing or reducing them. For example, when using Fe... 2+ In systems where citric acid or ethylenediaminetetraacetic acid (EDTA) is used as a reducing agent, Fe can be formed as an oxide. 3+ The complex is made harmless. In this invention, such an inorganic reducing agent is preferably used; as a more preferred embodiment of the invention, Fe is preferably used.2+ metal salt of gallic acid as a reducing agent.

[0394] Further, as the developing main agent used in the wet silver halide photographic light-sensitive material (e.g., a salt of methyl gallate, a hydroquinone, a substituted hydroquinone, 3-pyrazolidinones, p-aminophenols, p-phenylenediamines, hindered phenols, amidoximes, azines, catechols, pyrogallols, ascorbic acid (or a derivative thereof), and leuco dyes), and other materials obvious to those skilled in the art, such as the materials described in U.S. Patent No. 6,020,117, and capable of being used as a reducing agent.

[0395] As the reducing agent, an ascorbic acid reducing agent is also preferable. Useful ascorbic acid reducing agents include ascorbic acid and its analogs, isomers, and derivatives, and examples of which can preferably be selected from D- or L-ascorbic acid and its sugar derivatives (e.g., gamma-lactobionic acid ascorbic acid, gluconic acid ascorbic acid, alginic acid ascorbic acid, glucoheptonic acid ascorbic acid, maltobionic acid ascorbic acid), sodium salts of ascorbic acid, potassium salts of ascorbic acid, erythorbic acid (or L-erythromycin ascorbic acid) and its salts (e.g., alkali metal salts, ammonium salts, or salts known in the art), enediol-type ascorbic acid, enaminol-type ascorbic acid, thioenol-type ascorbic acid, and the like, with D, L, or D, L-ascorbic acid (and alkali metal salts thereof) or erythorbic acid (or alkali metal salts thereof) being particularly preferable, with sodium salts being preferable. If desired, mixtures of these reducing agents can be used.

[0396] For the reason that the effects of the present application are more excellent, the reducing agent solution preferably flows in a manner such that the angle between the development direction in the development step and the development direction of the reducing agent solution becomes 0 degrees to 150 degrees, and more preferably in a manner such that the angle between the development direction in the development step and the development direction of the reducing agent solution becomes 0 degrees to 135 degrees.

[0397] Further, as a method of adjusting the angle between the development direction in the development step and the development direction of the reducing agent solution, for example, the method described in the examples of Japanese Patent Application Publication No. 2009-150869 can be cited.

[0398] (Silver amplification solution)

[0399] The silver amplification solution described above is a liquid containing a compound containing a silver ion. As the compound containing silver, for example, an organic silver salt, an inorganic silver salt, or a silver complex can be used. Preferable examples include silver nitrate, silver acetate, silver lactate, silver butyrate, and silver thiosulfate, which are compounds containing a silver ion having high solubility in a solvent such as water. Silver nitrate is particularly preferable. As the silver complex, a silver complex coordinated to a ligand having a water-soluble group such as a hydroxyl group and a sulfone group can be cited, and examples include a hydroxyl sulfide silver complex.

[0400] The organic silver salt, the inorganic silver salt, or the silver complex is contained in the silver amplification solution as silver at a concentration of 0.001 mol / L to 5 mol / L, preferably at a concentration of 0.005 mol / L to 3 mol / L, and more preferably at a concentration of 0.01 mol / L to 1 mol / L.

[0401] As an aid of the silver amplification solution, a buffer, a preservative such as an antioxidant or an organic stabilizer, a speed modifier, and the like can be given. As the buffer, for example, acetic acid, citric acid, sodium hydroxide, or one of these salts, a buffer using tris(hydroxymethyl)aminomethane, or other buffers commonly used in chemical experiments can be used. By appropriately using these buffers, it is possible to adjust the pH to be most suitable for the amplification solution thereof. Also, as an antifogging agent, an alkylamine can be used as an aid, and a dodecylamine is particularly preferable. Also, in order to improve the solubility of these aids, a surfactant can be used, and a C9H 19 -C6H4-O-(CH2CH2O) 50 H.

[0402] From the viewpoint of more excellent reasons of effects of the present application, the silver amplification solution is preferably flowed from a direction opposite to the above-described development process, and more preferably flowed in a manner that an angle between a development direction in the development process and a development direction of the reducing agent solution becomes 45 degrees to 180 degrees.

[0403] In addition, as a method of adjusting the angle between the development direction in the development process and the development direction of the silver amplification solution, for example, a method described in the examples of Japanese Patent Application Publication No. 2009-150869, and the like can be given.

[0404] [IV] Test kit

[0405] The test kit of the present application for detecting a high molecule in a test object liquid which is an aqueous solution containing a high molecule has:

[0406] The above-described concentrator (mode A, mode B) of the present application; and

[0407] A detection device that detects a high molecule in a test object liquid concentrate obtained by using the above-described concentration method of the present application.

[0408] [1] Concentrator

[0409] The concentrator (mode A, mode B) of the present application is as described above.

[0410] [2] Detection device

[0411] From the viewpoint of more excellent reasons of effects of the present application, the above-described detection device is preferably an immunochromatographic instrument.

[0412] From the perspective of superior effects of the present invention, the detection device described above preferably comprises:

[0413] The test strip includes an insoluble carrier having a test region for detecting high molecular weights contained in biological fluids; a first canister and a second canister, respectively sealed with a first amplification solution and a second amplification solution for amplifying the test signal in the test region; and a casing containing the test strip, the first canister, and the second canister.

[0414] [Preferred method]

[0415] From the perspective of superior effects of the present invention, the above-described detection device is preferably an immunochromatographic reagent kit (hereinafter also referred to as "the immunochromatographic reagent kit of the present invention" or simply "immunochromatographic reagent kit"):

[0416] An immunochromatographic reagent kit for detecting a target substance (a macromolecule contained in biological body fluids) in a sample solution (body fluid being tested), comprising:

[0417] Test strips for testing contain an insoluble carrier that allows the sample solution to spread and has a test area containing the substance being tested;

[0418] The first and second containers are respectively sealed with a first amplification solution and a second amplification solution for amplifying detection signals in the inspection area, and each has a side with a sheet component; and

[0419] The outer casing contains test strips, canister 1, and canister 2.

[0420] The outer casing comprises the following components: a lower casing with a receiving portion for holding test strips; an upper casing joined to the lower casing at its periphery; and an intermediate component disposed between the upper and lower casings.

[0421] The intermediate component has a fracture portion that causes the sheet component of the first can to break, and the fracture portion faces the sheet component of the first can.

[0422] The upper shell is composed of the following components: a first convex deformable portion, which deforms the first can side by applying pressure from the outside to the portion opposite to the first can, and breaks the sheet component of the first can by using the fracture portion of the intermediate component; and a second convex deformable portion, which deforms towards the second can side by applying pressure from the outside to the portion opposite to the second can, and breaks the sheet component of the second can.

[0423] In the immunochromatographic kit of the present invention, preferably, the first convex deformable portion is moved to the position where the sheet component is broken by the fracture portion of the intermediate component by applying pressure.

[0424] At this time, it is preferable that the upper case have two protruding portions that stand toward the first tank side and abut against the first tank and move it when a pressing force is applied to the first convexly deformed portion.

[0425] In the immunochromatography kit of the present application, it is preferable that the first convexly deformed portion have a mountain shape that is centrally symmetrical.

[0426] Also at this time, it is preferable that the two protruding portions be symmetrically arranged with respect to the top of the mountain shape.

[0427] Also, it is preferable that the two protruding portions be formed independently of each other on the inclined surface sandwiching the top of the mountain shape.

[0428] In the immunochromatography kit of the present application, when the first convexly deformed portion has the above two protruding portions, it is preferable that the two protruding portions be symmetrically arranged with respect to the center of the abutting surface of the first tank.

[0429] Also, it is preferable that the two protruding portions be arranged on the end portion side more than halfway from the center to the end portion of the abutting surface of the first tank.

[0430] In the present specification, the convexly deformed portion refers to a convex shape when viewed from the outside of the immunochromatography kit, and likewise, the mountain shape refers to a mountain shape when viewed from the outside.

[0431] In the immunochromatography kit of the present application, when the first convexly deformed portion has the above two protruding portions, it can be configured such that the leading ends of the two protruding portions each abut against the first tank, slowly displace toward the end portion side, and move the first tank.

[0432] In the immunochromatography kit of the present application, it is preferable that the flexural modulus of the material constituting the first convexly deformed portion be 50 MPa to 350 MPa.

[0433] Also, it is preferable that the flexural modulus of the material constituting the upper case be 50 MPa to 350 MPa, and the flexural modulus of the material constituting the lower case be 500 MPa to 900 MPa.

[0434] In the immunochromatography kit of the present application, it is preferable that the upper case be integrally formed with the first convexly deformed portion and the second convexly deformed portion by injection molding.

[0435] In the immunochromatography kit of the present application, the upper case has a first convex deformation portion that deforms to the first tank side by applying a pressing force from the outside to a portion opposite the first tank, and breaks the sheet member of the first tank using a breaking portion of the intermediate member, and a second convex deformation portion that deforms to the second tank side by applying a pressing force from the outside to a portion opposite the second tank, and breaks the sheet member of the second tank, and by applying a pressing force to the two convex deformation portions with a finger or the like, the sheet member of the tank can be broken, and the amplification solution can be supplied to the test strip, so that the amplification reaction can be normally performed even without a dedicated analysis device that requires a power source. Therefore, the immunochromatography kit of the present application is particularly useful in an emergency, a disaster, or the like, in which a dedicated analysis device is not available, or an analysis device cannot be used.

[0436] Hereinafter, an embodiment of the immunochromatography kit of the present application will be described using the drawings, but the immunochromatography kit of the present application is not limited thereto. In addition, the scale and the like of each component in the drawings are appropriately changed from the actual situation so as to be easily visually recognized.

[0437] Figure 10 is a schematic perspective view of the immunochromatography kit 100 according to the embodiment of the present application, Figure 11 is a schematic perspective view of the immunochromatography kit 100 according to the embodiment of the present application, Figure 10 is an exploded schematic perspective view of the immunochromatography kit 100 according to the embodiment of the present application.

[0438] As shown in Figs. 1 and 2, the immunochromatography kit 100 according to the embodiment of the present application contains the following components in the case 9: a test strip 1 including an insoluble carrier 2 having a test region in which a sample solution is spread and a substance to be detected is present; and a first tank 40 and a second tank 45 each of which has a sheet member and in which a first amplification solution 41 and a second amplification solution 46 for amplifying a detection signal in the test region are respectively sealed. Figure 10 Figure 11 The case 9 has the following components: a lower case 20 having an insoluble carrier housing portion 21 in which the test strip 1 is disposed; an upper case 10 that is joined to the lower case 20 at the periphery; and an intermediate member 30 disposed between the upper case 10 and the lower case 20. In addition, in the description of the immunochromatography kit 100, the upper case 10 side is defined as the upper side, and the lower case 20 side is defined as the lower side.

[0439] ​The intermediate member 30 has a tank housing portion 32 that houses the first tank 40 and is provided with an amplification solution filling hole on the bottom surface for dropping the first amplification solution 41 onto the insoluble carrier 2. Also, a protrusion-shaped breaking portion 34 that breaks the sheet member 43 of the first tank 40 is provided at a position of the sheet member 43 facing the first tank 40 in the tank housing portion 32. In this example, the first tank 40 is disposed above the tank housing portion 32 with the face having its sheet member 43 as the lower surface, and the breaking portion 34 is provided on the bottom surface of the tank housing portion 32 opposite the sheet member 43 (see FIG. 2). Figure 12

[0440] Also, a flow path forming portion 35 that extends to the downstream side of the bottom surface of the tank housing portion 32 of the intermediate member 30 is provided. The flow path forming portion 35 is disposed so as to coincide with the upper positions of the inspection region LI, the confirmation region L2, and the amplification index region L3, and is formed of a transparent material in order to enable visual recognition of these regions LI to L3.

[0441] The upper case 10 has a first convex deformation portion 12 that deforms to the first tank 40 side by applying a pressing force from the outside to a portion opposite the first tank 40, and breaks the sheet member 43 of the first tank 40 using the breaking portion 34 of the intermediate member 30. Also, the upper case 10 has a second convex deformation portion 14 at a portion opposite the second tank 45 that deforms to the second tank 45 side by applying a pressing force from the outside, thereby breaking the sheet member 48 of the second tank 45.

[0442] Also, a sample liquid dropping opening 16 is provided on the upper case 10, and sample liquid is dropped onto the marker holding pad 3 of the test strip 1 from the sample liquid dropping opening 16. The position of the marker holding pad 3 is adjusted so as to coincide with the position of the sample liquid dropping opening 16, whereby sample liquid can be reliably dotted onto the marker holding pad 3. Also, the upper case 10 has an observation window 18 for visually recognizing the three regions LI to L3 at a position corresponding to the flow path forming portion 35 of the intermediate member 30.

[0443] On the lower case 20, an insoluble carrier housing portion 21 that places the insoluble carrier 2 and an absorbent pad housing portion 22 that places the absorbent pad 6 on the downstream side thereof are provided as housing portions that place the test strip 1. Also, a second tank housing portion 24 that houses the second tank 45 is provided on the upstream side of the insoluble carrier housing portion 21.

[0444] Figure 12 is a schematic cross-sectional view showing the positional relationship of the test strip 1, the intermediate member 30, and the two tanks 40, 45. As Figure 12 ​As shown, the test strip 1 for inspection has: an insoluble carrier 2 that spreads a sample liquid; a label holding pad 3 that contains a label substance modified with a first substance capable of binding to a target substance fixed to the insoluble carrier 2; a liquid delivery pad 4 that delivers a second amplification liquid 46 disposed in contact with one end of the insoluble carrier 2 to the insoluble carrier 2; and an absorption pad 6 disposed in contact with the other end of the insoluble carrier 2. The insoluble carrier 2 is fixed and supported on a back adhesive sheet 7. Also, the insoluble carrier 2 has, in order from the label holding pad 3 side between the label holding pad 3 and the absorption pad 6, a test region LI containing a second substance that binds to the target substance, a confirmation region L2 containing a substance capable of binding to the first substance, and an amplification indicator region L3 containing a substance that reacts with the second amplification liquid.

[0445] In addition, in the present specification, the insoluble carrier 2 formed with the test region LI, the confirmation region L2, and the amplification indicator region L3 is sometimes referred to as a chromatographic carrier. Also, in the present specification, as described in the Figure 12 In the present specification, the side of the liquid delivery pad 4 is defined as the upstream, and the side of the absorption pad 6 is defined as the downstream.

[0446] The intermediate member 30 is located on the upper portion of the downstream end side of the test strip 1 for inspection, and the first tank 40 is disposed in the tank housing portion 32 of the intermediate member 30 with the sheet member 43 facing downward. The second tank 45 is housed below the upstream end of the test strip 1 for inspection of the lower housing 20 with the sheet member 48 facing upward.

[0447] As shown in Figure 12 A gap (void) D is formed between the back surface 36 of the flow path forming portion 35 of the intermediate member 30 and the insoluble carrier 2 of the test strip 1 for inspection. The gap D is preferably in the range of 0.01 mm to 1 mm. If it is 0.01 mm or more, the amplification liquid or the like can be sufficiently infiltrated, and if it is 1 mm or less, the capillary force is exerted, and the insoluble carrier 2 and the gap of the intermediate member 30 can be uniformly filled with the first amplification liquid 41.

[0448] The first tank 40 in which the first amplification liquid 41 is enclosed, for example, has the first amplification liquid 41 filled in a container 42 composed of a resin material and having an opening on one side, and the opening of the container 42 is covered and sealed by a sheet member 43 that can be broken.

[0449] The second tank 45 in which the second amplification liquid 46 is enclosed is also the same, for example, has the second amplification liquid 46 filled in a container 47 composed of a resin material and having an opening on one side, and the opening of the container 47 is covered and sealed by a sheet member 48 that can be broken.

[0450] As the sheet members 43, 48 that can be broken in the first tank 40 and the second tank 45, a laminated film such as an aluminum foil or an aluminum laminate sheet is preferably used. Here, the broken state means a state that does not regenerate after breaking.

[0451] The convex deformation portions 12, 14 at two places of the upper case will be described in detail.

[0452] Figure 13 is a perspective view of the first convex deformation portion 12, Figure 14 is Figure 13 a V-V' line cut end face view of Figure 14 A of Figure 14 B of

[0453] The first convex deformation portion 12 moves the first tank 40 to a position at which the sheet member 43 is broken by the breaking portion 34 of the intermediate member 30 by being pressed. Specifically, the first convex deformation portion 12 is configured to be pressed downward by being pressed with a finger or the like, and by deforming the first convex deformation portion 12 in a manner of being convex downward (in a recessed shape when viewed from the outside), the first tank 40 is moved toward the breaking portion 34 until the sheet member 43 of the first tank 40 is broken by the breaking portion 34 inside the tank housing portion 32 of the intermediate member 30. Thereby, the breaking portion 34 pierces the sheet member 43 of the first tank 40, and the first amplification solution 41 can be supplied to the outside. The first amplification solution 41 is dropped from the amplification solution filling hole provided to the bottom surface of the tank housing portion 32 of the intermediate member 30 to the upper portion of the insoluble carrier 2, and the first amplification solution 41 can be supplied to the inspection region LI, the confirmation region L2, and the amplification index region L3 on the insoluble carrier. In addition, at this time, the first amplification solution 41 dropped from the amplification solution filling hole to the upper portion of the insoluble carrier 2 fills the gap between the intermediate member 30 and the insoluble carrier 2, is supplied to the upper side of the inspection region LI, the confirmation region L2, and the amplification index region L3 through the gap, and slowly infiltrates into the insoluble carrier 2.

[0454] As shown in Figure 14 , the first convex deformation portion 12 has two protrusion portions 12b that are vertically provided toward the first tank 40 at positions opposite to the first tank 40. The two protrusion portions 12b are configured to abut against the first tank 40 to move the first tank 40 when the first convex deformation portion 12 is deformed by being pressed.

[0455] The first convex deformation portion 12 has a mountain shape that is centrally symmetrical, and the two protrusion portions 12b are symmetrically arranged with respect to the top portion 12a of the mountain shape and are independently formed below (at the back of) the inclined surface 12c sandwiching the top portion 12a.

[0456] And, as shown in Figure 14 A, the first convex deformation portion 12 is formed on the upper case 10 in a manner that the two protrusion portions 12b are centrally located at symmetrical positions with respect to the abutting surface of the first tank 40 before deformation. And, as shown inFigure 14 The broken portion 34 of the intermediate member 30 is located below the sheet member 43 of the first tank 40 as indicated by a broken line. When the first convexly deformed portion 12 is deformed by being pressed, the two protruding portions 12b (the leading ends of the two protruding portions 12b, respectively) abut against the first tank 40, slowly displace toward the end portion side, and move the first tank 40. Also, as shown in B of FIG. 10, after deformation of the first convexly deformed portion 12, the two protruding portions 12b are spaced apart, and the leading ends of the two protruding portions 12b are located on the end portion side more than halfway from the central portion to the end portion of the abutting surface of the first tank 40. In the present embodiment, the two protruding portions 12b are independently provided, and a gap is provided between the protruding portions 12b (the back surface of the top portion 12a), and the first convexly deformed portion 12 is formed of a soft material, whereby the gap between the two protruding portions 12b is greatly enlarged, and the first tank 40 is pressed. Figure 14

[0457] The shape or arrangement of the protruding portions 12b is not limited to the above-described shape, and for example, the two protruding portions 12b can be provided on the end portion side more than halfway from the central portion to the end portion of the abutting surface of the first tank 40 before deformation.

[0458] The first convexly deformed portion 12, which moves the first tank 40, has the two protruding portions 12b, whereby the first tank 40 can be pressed at two places equally, and thus the first tank 40 can be moved in parallel.

[0459] The first convexly deformed portion 12 is easily deformed by being pressed with a finger or the like, and the first convexly deformed portion 12 becomes convex downward (concave). It is preferable that the concave shape not be restored after the pressing, and the state of pressing the first tank 40 can be maintained. The first convexly deformed portion 12 is configured to press the top portion 12a, but can also be deformed by the elasticity of the first convexly deformed portion 12 by pressing the inclined surface of the mountain shape.

[0460] Figure 15 is a perspective view of the second convexly deformed portion 14, Figure 16 is a sectional view taken along the line VII-VII' of FIG. 11, Figure 15 is a sectional view taken along the line VII-VII' of FIG. 11, Figure 16 A of FIG. 12 indicates the second convexly deformed portion 14 before deformation, Figure 16 B of FIG. 12 indicates the second convexly deformed portion 14 after deformation, and is a view that collectively indicates the positional relationship with the second tank 45.

[0461] The second convexly deformed portion 14 breaks the sheet member 48 of the second tank 45 by being pressed. As shown in A of FIG. 12, the second convexly deformed portion 14 is provided with two protruding portions 14b, and the two protruding portions 14b are spaced apart from each other. The two protruding portions 14b are located on the end portion side more than halfway from the central portion to the end portion of the abutting surface of the second tank 45. Figure 16 ​As shown in A, the second convex deformation portion 14 has one protrusion portion 14b that stands up toward the second tank 45 at a position opposite the second tank 45. Further, a pad 4 for sending liquid is disposed between the second tank 45 and the test paper strip 1 for inspection. The second convex deformation portion 14 is pressed to protrude toward the second tank 45, that is, to be deformed into a concave shape when viewed from the outside, as shown in B. Figure 16 As shown in B, the protrusion portion 14b abuts against the surface of the pad 4 for sending liquid, and punctures the sheet member 48 of the second tank 45, and presses the pad 4 for sending liquid into the second tank 45. As shown in C, the second convex deformation portion 14 is configured to have a mountain shape having a top portion 14a on the slightly upstream side in a cross section along the upstream and downstream directions, and when deformed, the protrusion portion 14b is inclined toward the downstream side to puncture the sheet member 48. Figure 16

[0462] By this operation, the pad 4 for sending liquid is dipped in the second amplification solution 46 in the second tank 45, and the second amplification solution 46 can be soaked into the pad 4 for sending liquid by capillary phenomenon and supplied to the insoluble carrier 2.

[0463] The second convex deformation portion 14 is also easily deformed into a concave shape by pressing with a finger or the like. It is preferable to be configured so that the concave shape is not restored after the pressing, and the state of pressing the pad 4 for sending liquid into the second tank 45 can be maintained.

[0464] The present application does not use a device connected to a power source to deform the first and second convex deformation portions, and supply amplification solution to achieve high-sensitivity analysis. As one mode, a mode in which a person deforms it by hand is assumed. Therefore, it is preferable to design so that amplification solution does not be mistakenly leaked to the outside, and it is preferable that the first and second convex deformation portions 12, 14 provided on the upper housing 10 are integrally formed with no gap with other parts of the upper housing 10. It is preferable that the convex deformation portions 12, 14 are made of a material that can be stretched and contracted to be engaged with other parts of the upper housing 10 in a sealed state. It is also possible to make the first and second convex deformation portions 12, 14 and other parts of the upper housing 10 separately and then engage them with each other, but it is preferable to make the first and second convex deformation portions 12, 14 as a part of the upper housing 10, and integrally mold them as one continuous member without an engagement site in the middle by injection molding.

[0465] The first and second convex deformation portions 12, 14 need to have flexibility to be easily deformed by a person's finger or the like. The bending elastic modulus of the material constituting the convex deformation portions 12, 14 is preferably 50 MPa or more and 350 MPa or less, and more preferably 70 MPa or more and 150 MPa or less.

[0466] Further, in the case of fitting only when the upper housing 10 and the lower housing 20 are combined, liquid sometimes comes out from the gap, and therefore it is preferable to adhere the fitting part of the upper housing 10 and the lower housing 20 in a sealed state.​

[0467] As the bonding method of the upper case 10 and the lower case 20, ultrasonic welding is preferably used. As generally known as ultrasonic welding, if the components to be welded are not the same material, it is not easy to weld, and the combination of the upper case / lower case is preferably polyethylene / polyethylene, polypropylene / polypropylene, or ABS (acrylonitrile-butadiene-styrene copolymer) / ABS.

[0468] On the other hand, in order to fix the test strip 1 for inspection or the second tank 45, the lower case 20 preferably has rigidity. Specifically, the bending elastic modulus of the material constituting the upper case 10 is preferably 50 MPa or more and 350 MPa or less, and more preferably 70 MPa or more and 150 MPa or less. The bending elastic modulus of the material constituting the lower case 20 is preferably 500 MPa or more and 900 MPa, and particularly preferably 650 MPa or more and 750 MPa or less.

[0469] In addition, the bending elastic modulus is a value calculated by Formula (1) below in an environment at a temperature of 20°C, according to the measurement method of ISO 178.

[0470] For the material to measure the bending elastic modulus, a test piece in the shape of a plate having a width b (mm) and a thickness h (mm) is prepared, and the test piece is supported at two support points with a support point distance of L (mm). A load of F (N) is applied to the center between the support points, and the deflection amount (mm) in the direction of the applied load is measured. A deflection-load curve is prepared with the horizontal axis as the deflection S (mm) and the vertical axis as the load F (N). The tangent line at the origin of the curve is found, and the slope thereof (when the change amount of the load ΔF (N) and the change amount of the deflection ΔS (mm) are assumed, (ΔF / ΔS)) is calculated, and the bending elastic modulus E (MPa) can be calculated using the following formula.

[0471] Bending elastic modulus E = (L 3 / (4bh 3 )) x (ΔF / ΔS) Formula (1)

[0472] Therefore, the combination of the upper case / lower case is most preferably a combination of polypropylene to which a softening agent is added / polypropylene. Here, the softening agent used in the polypropylene to which a softening agent is added is preferably an olefin-based elastomer, and the concentration of the olefin-based elastomer with respect to the polypropylene is preferably 20% by mass or more and 60% by mass or less, and particularly preferably 40% by mass or more and 55% by mass or less. As a specific softening agent, TAFSELEN (registered trademark) manufactured by Sumitomo Chemical Co., Ltd. can be given.

[0473] In addition, the immunochromatography kit of the present application can have two or more convex deformations, and in the case where three or more kinds of solutions are to be supplied to the test strip, the kit can have three or more convex deformations corresponding thereto.

[0474] As the insoluble carrier (porous carrier) 2, for example, a nitrocellulose membrane or the like can be used. Further, the adhesive sheet 7 that fixes the back surface of the insoluble carrier 2 is a sheet-shaped substrate having an adhesive surface to which the insoluble carrier 2 is attached.

[0475] The marker holding pad 3 is fixed to the central portion in the longitudinal direction of the insoluble carrier 2. As the marker substance, for example, a gold colloid having a diameter of 50 nm (EM.GC50, manufactured by BBI Co., Ltd.) can be used. By modifying the surface of the marker substance with a substance that binds to the test substance, a complex with the test substance can be formed.

[0476] The marker substance is not limited to the above, and a metal sulfide that can be used in general chromatography, a colored particle used in an immune agglutination reaction, or the like can be used, and a metal colloid is particularly preferable. As the metal colloid, a gold colloid, a silver colloid, a platinum colloid, an iron colloid, an aluminum hydroxide colloid, and a complex colloid thereof, or the like can be given, and among them, a gold colloid is most preferable.

[0477] In the case where the sample solution to be added is prepared by a process in which a substance that binds to the test substance on the surface of the marker substance is bound to the test substance in the sample solution in advance, it is preferable that the marker holding pad 3 does not contain the marker substance. In this case, the marker holding pad 3 functions as a pad that indicates the position at which the sample solution containing the marker substance is added.

[0478] In addition, the test strip 1 is positioned so that the sample solution addition opening 16 of the upper housing 10 and the marker holding pad 3 are aligned.

[0479] The test region LI contains a second substance that binds to the test substance, and is a marker substance capturing region that captures the marker substance that binds to the test substance via the test substance. For example, in the case where it is intended to detect an influenza A virus or a biomarker thereof as the test substance, it is preferable that the test region LI is constituted by, for example, an antibody immobilized line in which an anti-influenza A monoclonal antibody (Anti-Influenza A SPTN-5 7307, manufactured by Medix Biochemica Co., Ltd.) is fixed in a line shape by physical adsorption.

[0480] When the labeling substance reaches the inspection region Ll via the complex of the substance to be detected and the first substance, the second substance specifically binds to the substance to be detected, and the labeling substance is captured via the substance to be detected and the first substance. On the other hand, the labeling substance that does not form a complex with the substance to be detected is not captured and passes through the inspection region Ll.

[0481] The confirmation region L2 contains a substance capable of binding to the first substance, is a region in which the labeling substance captured via the first substance by the inspection region Ll is spread in the insoluble carrier 2 from the labeling holding pad 3 together with the sample liquid, and is used to confirm completion of spreading of the sample liquid. For example, in a case where it is intended to detect an influenza A virus or a biomarker thereof as the substance to be detected, an anti-mouse IgG antibody (Anti-Mouse IgG (H+L), Rabbit F(ab')2, Product No. 566-70621, manufactured by FUJIFILM Wako Pure Chemical Corporation) is preferably fixed in a line shape, for example, by physical adsorption.

[0482] The amplification indicator region L3 contains a substance that reacts with the second amplification liquid 46, is a region in which color development or color change occurs by reaction with the second amplification liquid 46, indicates that the second amplification liquid 46 has spread to the region, and becomes an indicator of the timing at which the first amplification liquid 41 is added. For example, in a case where a mixed aqueous solution of an aqueous ferric nitrate solution and citric acid (manufactured by FUJIFILM Wako Pure Chemical Corporation, 038-06925) is used as the second amplification liquid, it is preferable that the amplification indicator region L3 be constituted by a line of a color developing reagent in which bromocresol green (manufactured by FUJIFILM Wako Pure Chemical Corporation) is fixed in a line shape. At this time, when the second amplification liquid 46 reaches the amplification indicator region L3, the region L3 changes from green to orange. This color change can be captured as an indicator that the inspection region Ll and the confirmation region L2 are sufficiently filled with the second amplification liquid 46.

[0483] As a method of amplifying the signal of the metal-based labeling substance such as a metal colloid, a method in which silver ions and a reducing agent for silver ions are brought into contact with the labeling substance, the silver ions are reduced by the reducing agent to generate silver particles, the silver particles are deposited on the labeling substance with the labeling substance as a nucleus, and thus the signal of the labeling substance is amplified (hereinafter, referred to as silver amplification) is preferable.

[0484] In order to achieve silver amplification, it is sufficient that a solution containing silver ions be used as the first amplification liquid 41 and a reducing agent liquid containing a reducing agent for silver ions be used as the second amplification liquid 46.

[0485] (First amplification liquid)

[0486] As the solution containing silver ions used as the first amplification solution 41, a solution in which a compound containing silver ions is dissolved in a solvent is preferable. As the compound containing silver ions, an organic silver salt, an inorganic silver salt, or a silver complex can be used. An inorganic silver salt or a silver complex is preferable. As the inorganic silver salt, a compound containing silver ions having high solubility in a solvent such as water can be used, and silver nitrate, silver acetate, silver lactate, silver butyrate, silver thiosulfate, and the like can be mentioned. Silver nitrate is particularly preferable. As the silver complex, a silver complex coordinated to a ligand having a water-soluble group such as a hydroxyl group and a sulfone group is preferable, and a hydroxyl sulfide silver and the like can be mentioned.

[0487] (Second amplification solution)

[0488] As the reducing agent used in the reducing agent solution containing a reducing agent capable of reducing silver ions used as the second amplification solution 46, any material of inorganic or organic or a mixture thereof can be used as long as it is a substance capable of reducing silver ions to silver. As the inorganic reducing agent, a reducing metal salt in which a metal ion such as Fe 2+ , V 2+ or Ti 3+ can change the valence, a reducing metal complex salt can be preferably mentioned. In the case of using an inorganic reducing agent, it is necessary to complex the oxidized ion to form or to remove or make harmless by reduction. For example, in the case of using Fe 2+ as the reducing agent, citric acid or EDTA (ethylenediaminetetraacetic acid) can be used to form a complex of Fe 3+ as an oxide, and to make it harmless. In the present system, it is preferable to use such an inorganic reducing agent, and more preferably a metal salt of Fe 2+ .

[0489] In addition, a developing main agent (for example, a gallate salt, a hydroquinone, a substituted hydroquinone, a 3-pyrazolidone, a p-aminophenol, a p-phenylenediamine, a hindered phenol, an amidoxime, an azine, a catechol, a pyrogallol, an ascorbic acid (or a derivative thereof), and a leuco dye) used in a wet silver halide photographic photosensitive material and other materials obvious to those skilled in the art, for example, the materials described in U.S. Patent No. 6,020,117 can also be used.

[0490] As the reducing agent, ascorbic acid reducing agents are also preferable. Useful ascorbic acid reducing agents include ascorbic acid and analogs, isomers, and derivatives thereof, and examples include D- or L-ascorbic acid and sugar derivatives thereof (e.g., gamma-lactobionic acid ascorbic acid, gluconic acid ascorbic acid, alginic acid ascorbic acid, glucoheptonic acid ascorbic acid, maltobionic acid ascorbic acid), sodium salts of ascorbic acid, potassium salts of ascorbic acid, erythorbic acid (or L-erythorbic acid ascorbic acid) and salts thereof (e.g., alkali metal salts, ammonium salts, or salts known in the art), enediol-type ascorbic acid, enaminol-type ascorbic acid, thioenol-type ascorbic acid, and the like, with D, L, or D, L-ascorbic acid (and alkali metal salts thereof) or erythorbic acid (or alkali metal salts thereof) being particularly preferable, with sodium salts being preferable. Mixtures of these reducing agents can be used as needed.

[0491] Further, in the present embodiment, the first convex deformation portion 12 moves the first tank 40 toward the breaking portion 34 provided in the intermediate member 30, but the first convex deformation portion 12 can be any structure that can break the sheet member 43 of the first tank 40 using the breaking portion 34 in conjunction with deformation thereof.

[0492] The structure of the first tank 40 and the tank housing portion 32 that houses the first tank 40 is not limited to the structure of the present embodiment, as long as the sheet member 43 of the first tank 40 can be broken and the first amplification solution 41 that flows out of the first tank 40 can be dropped onto the insoluble carrier 2 from the amplification solution filling hole in the bottom surface of the tank housing portion 32.

[0493] Further, the protruding portion of the first convex deformation portion has two or more, and can move the first tank 40 without tilting and in parallel, and is therefore preferable. However, the first convex member can have one protruding portion having the same shape as the second convex deformation portion of the above-described embodiment. A convex deformation portion having the same shape as the second convex deformation portion can also be used as the first convex deformation portion that moves the first tank 40.

[0494] Figure 17 is the same cutaway end view as Figure 16 , showing the state when the first tank 40 is moved using a convex deformation portion 114 having the same shape as the second convex deformation portion.

[0495] As shown in A of Figure 17 , before deformation, the first tank 40 is disposed below the protruding portion 114b of the convex deformation portion 114. Further, the breaking portion 34 of the intermediate member 30 is disposed below the first tank 40. By pressing the top portion 114a of the convex deformation portion 114, the protruding portion 114b presses against the upper surface of the first tank 40, and the first tank 40 is pressed downward. As a result, the breaking portion 34 pierces the sheet member 43 of the first tank 40, and the first amplification solution 41 enclosed in the first tank 40 flows out of the first tank and is supplied to the test strip 1.

[0496] Thus, even if the protrusion provided to the convex deformation portion 114 is one, the tank can be moved.

[0497] In addition, the immunochromatography kit of the present application can also include a tank containing a sample extraction solution containing an auxiliary medicine or the like for assisting extraction of a sample, a tank containing a sample dilution solution, a desiccant or deoxidizer for facilitating preservation of the kit, a package insert such as an instruction manual, and a sample collection tool such as a cotton swab, or one or a part of the equipment required for the examination.

[0498] If the immunochromatography kit of the present application is used, it is possible to perform the examination with high precision using only the kit alone without using a dedicated analysis device or the like.

[0499] <Immunochromatography examination method>

[0500] The immunochromatography examination method using the above-described immunochromatography kit 100 will be briefly described.

[0501] The sample solution is dropped onto the label holding pad 3 using the opening 16. In the case where the sample solution contains a sample substance, in the label holding pad 3, a complex of the sample substance and the label substance via the first substance is formed by the sample substance binding to the first substance, and this complex spreads toward the absorbent pad 6 side using the capillary phenomenon by the suction force of the absorbent pad 6 together with the sample solution. In the case where the complex of the sample substance and the label substance in the sample solution is formed in advance, it is preferable that the label substance is not contained on the label holding pad 3 in a manner that the preformed complex spreads toward the absorbent pad 6 side. At the same time or after the sample solution is dropped, the second convex deformation portion 14 is pressed to displace the pad 4 for liquid transfer and to break the sheet member 48 of the second tank 45, and the pad 4 for liquid transfer is immersed in the second amplification solution 46 to transfer the second amplification solution 46 to the insoluble carrier 2. In addition, the timing at which the second convex deformation portion 14 is pressed is preferably within 30 seconds from the time when the sample solution is dropped, and particularly preferably immediately after the sample solution is dropped.

[0502] The complex reaching the examination region LI is captured by binding to the second substance of the examination region LI. Also, the first substance not binding to the sample substance reaches the confirmation region L2 through the examination region LI, and is captured by binding to the substance of the confirmation region L2 binding to the first substance.

[0503] The second amplification solution 46 reaches the amplification index region L3 through the examination region LI and the confirmation region L2. At this time, the color of the amplification index region L3 is changed by the passage of the second amplification solution 46, and the passage of the second amplification solution 46 to the amplification index region L3 can be visually recognized. After confirming the color change of the amplification index region L3, the first amplification solution 41 is supplied to the insoluble carrier 2 by pressing the first convex deformation portion 12.

[0504] After supplying the first amplification solution 41 to the insoluble carrier 2, waiting for the reaction to end, and confirming the color development of the inspection area LI and the confirmation area L2 from the observation window 18. The presence or absence of the inspection substance and the concentration thereof can be confirmed by the color development of the inspection area LI, and whether the inspection of the inspection substance was successful can be confirmed by the color development of the confirmation area L2. The color development in the inspection area LI and the confirmation area L2 is obtained by the signal of the amplification label, and high-sensitivity inspection can be achieved.

[0505] Examples

[0506] Hereinafter, the present application will be further described in detail by examples, but the present application is not limited thereto.

[0507] [Preparation of a test body fluid]

[0508] A liparabomannan (LAM) (02249-61, Nacalai Tesque Inc.) (antigen) extracted from Mycobacterium tuberculosis was added to a urine test body (Bioreclamation IVT Inc.) of a healthy person, and a test body fluid having the LAM concentration described in Table 1 was prepared.

[0509] [Production of an anti-liparabomannan (LAM) monoclonal antibody-modified gold colloid holding pad]

[0510] To 9 mL of a solution containing gold colloid particles (particle diameter: 50 nm) (product number: EM.GC50, manufactured by BBI Co.), 1 mL of a 50 mmol / L KH2PO4 buffer (pH 8.0) was added to adjust the pH. To the above solution in which the pH was adjusted, 1 mL of a 20 μg / mL solution containing an anti-LAM monoclonal antibody was added, and stirred for 10 minutes. Then, after standing for 10 minutes, 550 μL of a 1 mass% aqueous solution containing polyethylene glycol (PEG (Mw: 20,000, product number: 168-11285, manufactured by FUJIFILM Wako Pure Chemical Corporation)) was added, stirred for 10 minutes, and then 1.1 mL of a 10 mass% aqueous solution of bovine serum albumin (BSA (Fraction V, product number: A-7906, manufactured by Sigma Corporation)) was added, and stirred for 10 minutes. Using a centrifugal separator (himac CF16RX, manufactured by Hitachi, Ltd.), the solution was centrifuged at 8000 x g at 4°C for 30 minutes. 1 mL was left at the bottom of the container, and the supernatant was removed, and the gold colloid particles contained in the 1 mL of liquid left at the bottom of the container were redispersed using an ultrasonic cleaner. Then, this was dispersed in 20 mL of a gold colloid storage solution (20 mmol / L Tris-HCl buffer (pH 8.2), 0.05% PEG (Mw. 20000), 150 mmol / L NaCl, 1% BSA), and again centrifuged under the same conditions using the same centrifugal separator, the supernatant was removed, and after ultrasonic dispersion, dispersed in the gold colloid storage solution, to obtain a solution of modified gold colloid particles (labeled antibody) which are gold colloid particles (particle diameter: 50 nm) modified with an anti-LAM monoclonal antibody. The obtained solution was diluted with water so that the concentration of the Tris-HCl buffer (pH 8.2) became 20 mmol / L, the concentration of PEG (Mw. 20000) became 0.05 mass%, the concentration of sucrose became 5 mass%, and the optical density of gold colloid at 520 nm when the optical path length was 10 mm became 0.1, and 1 mL was uniformly applied to each of 5 mm x 30 cm glass fiber pads (Merck Co. GFDX203000), and then dried for 15 hours using a vacuum drier, and the pads were cut, to thereby obtain pads (gold colloid retaining pads) (5 mm x 4 mm) retaining the modified gold colloid particles (labeled antibody) which are gold colloid particles modified with an anti-LAM monoclonal antibody.

[0511] [Manufacture of immunochromatography kit]

[0512] An immunochromatographic test kit was produced as follows.

[0513] 〔Production of the chromatography carrier〕

[0514] A nitrocellulose membrane (with a plastic liner, HiFlow Plus HF135 (capillary flow rate = 135 seconds / cm, manufactured by Millipore Corporation) cut to 60 mm x 300 mm was used as a porous carrier, and a test region, a confirmation region, and an amplification indicator region were formed on the membrane by the following method to produce a chromatography carrier.

[0515] An anti-LAM antibody solution prepared to be 1.5 mg / mL was applied in a line at a position 15 mm from the downstream side in the 60 mm short side of the nitrocellulose membrane as the test region. Also, an anti-human IgG antibody (anti-human IgG (H+L), rabbit F(ab')2, product number 309-006-003, manufactured by FUJIFILM Wako Pure Chemical Corporation) solution prepared to be 0.5 mg / mL was applied in a line at a position 11 mm from the downstream side in the 60 mm short side as the confirmation region. Also, bromocresol green (manufactured by FUJIFILM Wako Pure Chemical Corporation) was applied in a line to be 30 mmol / L at a position 9 mm from the downstream side in the 60 mm short side as the amplification indicator region. After the respective applications, the nitrocellulose membrane was dried with a warm air dryer at 50°C for 30 minutes. After the drying was completed, the nitrocellulose membrane dried as described above was dipped in a tank containing 500 mL of a blocking solution (50 mmol / L boric acid buffer (pH 8.5) containing 0.5 mass% casein (derived from milk, product number 030-01505, manufactured by FUJIFILM Wako Pure Chemical Corporation)), and left in this state for 30 minutes. Then, the nitrocellulose membrane was taken out, dipped in 500 mL of a washing / stabilizing solution (50 mmol / L Tris-HCl (pH 7.5) buffer containing 0.5 mass% sucrose and 0.05 mass% sodium cholate) prepared in another tank, and left in this state for 30 minutes. Then, the nitrocellulose membrane was taken out of the solution and dried in an environment at 25°C for 24 hours.

[0516] The portion to which the anti-LAM antibody is immobilized corresponds to an inspection region containing the second substance bound to the test substance, the portion to which the anti-mouse IgG antibody is immobilized corresponds to a confirmation region containing a substance capable of binding to the first substance, and the portion to which bromocresol green is immobilized corresponds to an amplification indicator region containing a substance that reacts with the amplification solution (reducing agent solution) enclosed in the second tank.

[0517] [Manufacture of test strips]

[0518] The chromatography carrier manufactured as described above was attached to an adhesive-backed sheet (60 mm x 300 mm (manufactured by Adhesives Research)). Next, a double-sided tape (Nitto Denko Corporation) having a width of 3 mm was immobilized at a position 26 mm from the downstream side in the short side of the chromatography carrier. Then, the downstream end of the double-sided tape was overlapped with the downstream end of a glass fiber pad (Glass Fiber Conjugate Pad, manufactured by Millipore) cut to 8 mm x 300 mm, and a pad (5 mm x 30 cm) before cutting was immobilized on the chromatography carrier without retaining the gold colloid. A pad for liquid delivery (a glass fiber pad (Glass Fiber Conjugate Pad, manufactured by Millipore) cut to 25 mm x 300 mm) was attached to the upstream side of the chromatography carrier so that the pad for liquid delivery and the chromatography carrier were overlapped by 7 mm. The member thus manufactured was cut with a guillotine cutter (CM4000, manufactured by NIPPTECH Cluster, Inc.) so that the direction perpendicular to the 300 mm long side was parallel and the width was 5 mm, and 60 test strips (not including the absorbent pad) were manufactured.

[0519] [Manufacture of the amplification solution (reducing agent solution) enclosed in the second tank]

[0520] 23.6 mL of a 1 mol / L ferric nitrate aqueous solution (prepared by dissolving ferric nitrate(III) nonahydrate (manufactured by FUJIFILM Wako Pure Chemical Corporation, 095-00995) in water) and 13.1 g of citric acid (manufactured by FUJIFILM Wako Pure Chemical Corporation, 038-06925) were dissolved in 290 g of water. After complete dissolution, 36 mL of nitric acid (10% by weight) solution and 60.8 g of ferric ammonium sulfate(II) hexahydrate (manufactured by FUJIFILM Wako Pure Chemical Corporation, 091-00855) were added while stirring. This solution was used as the second amplification solution, i.e., the reducing agent solution, sealed in the second tank.

[0521] [Preparation of the amplification solution (silver ion solution) to be sealed in the first container]

[0522] 8 mL of silver nitrate solution (containing 10 g of silver nitrate) and 24 mL of 1 mol / L ferric nitrate aqueous solution were added to 66 g of water. Furthermore, this solution was mixed with 5.9 mL of nitric acid (10 wt%), 0.1 g of dodecaneamine (manufactured by FUJIFILM Wako Pure Chemical Corporation, 123-00246), and surfactant C. 12 H 25 -C6H4-O-(CH2CH2O) 50 A solution of 0.1g of H dissolved in 47.6g of water was mixed, and this mixture was used as the first amplification solution, namely the silver ion solution, to be sealed in the first tank.

[0523] [Making Absorbent Pads]

[0524] Prepare 60 glass fiber pads (glass filter paper, manufactured by Advantech Co., Ltd.) cut into 12mm×10mm pieces to serve as absorbent pads.

[0525] [Preparation of Immunochromatographic Reagent Kit Components]

[0526] Using polypropylene as the material, injection molding is used to produce products such as... Figures 10-12The lower case 20, the upper case 10, the intermediate member 30, the first tank 40, and the second tank 45 that constitute the immunochromatography kit 100 are shown. Polypropylene containing 50 mass% of an olefin-based elastomer, TAFSEL EN (registered trademark) manufactured by Sumitomo Chemical Co., Ltd., was used as a material, and the upper case was produced by injection molding. In addition, the upper case 10 has two deformable portions (a first convex deformation portion and a second convex deformation portion), and the two deformation portions are not separated from the upper case 10, and are produced as a part of the upper case 10 by injection molding at all boundary portions.

[0527] In addition, the upper case of the embodiment is configured as follows. Figure 10 and Figure 11 The first convex deformation portion 12 has two protruding portions, and the second convex deformation portion 14 has one protruding portion.

[0528] [Production of the immunochromatography kit]

[0529] The lower case 20, the test strip 1 produced as described above, and the absorbent pad 6 produced as described above were fixed as shown. Figures 10-12 Next, the first amplification solution 41 produced as described above was filled in the first tank 40, and the second amplification solution 46 produced as described above was filled in the second tank 45, and the second tank 45 was sealed with an aluminum foil as a sheet member 48, and the first tank 40 was sealed with an aluminum foil as a sheet member 43, as shown. Figures 10-12 The second tank 45 was installed in the lower case 20 with the sheet member 48 provided above, and the first tank 40 was installed in the intermediate member 30 with the sheet member 43 provided below. Then, the upper case 10 and the lower case 20 were fitted to each other with the outer periphery in contact with each other, and the contact portions of the upper case and the lower case were joined by ultrasonic welding. At this time, it was confirmed that the welding portions were uniformly welded in a sealed state at all portions. In this way, the immunochromatography kit was produced.

[0530] [Example 1]

[0531] [Production of the concentration device]

[0532] A concentration device 202 was produced as shown. Figure 1 and Figure 7 In addition, the concentration device 202 of the embodiment has a lid 280 having a recovery port 282, as shown. Figure 7 Figure 7

[0533] ​​Specifically, in a cylinder 212 (12 mm inner diameter, 60 mm depth, cylindrical shape, with external threads on the top), 50 μL of an 800 mmol / L Tricine buffer (pH 8.5) (347-02844, FUJIFILM Wako Pure Chemical Corporation) containing 0.2% by mass casein (030-01505, manufactured by FUJIFILM Wako Pure Chemical Corporation) and 2% by mass Tween40 (T2531, manufactured by Tokyo Chemical Industry Co., Ltd.) was added. The solution was dried for 3 days at 25°C and below 10% Rh (relative humidity), followed by vacuum drying for 24 hours to solidify it, thus producing a drying reagent. Furthermore, one gold colloidal retaining pad (5 mm × 4 mm) and 700 mg of superabsorbent polymer 230 (described later) were added.

[0534] Furthermore, a piston 220 with a front end 221 having holes 222 (1 mm in diameter, 24 holes) smaller than the water-absorbing particle size of the superabsorbent polymer 230 after water absorption, and a cap 280 (with internal threads) having a hose 281 with a retraction port 282 are prepared and combined with the cylinder 212 to complete the concentration device 202.

[0535] Here, the cylinder 212 has a partition wall 260 at a position 3.5 mm from the bottom surface 218. This partition wall 260 is disposed on the inner circumferential surface of the cylinder 212 in a manner that allows it to move along the length of the cylinder 212. The partition wall 260 has pores 262 (pore diameter 1 mm, number of pores 24) smaller than the particle size of the superabsorbent polymer 230 before water absorption. The portion (400 μL) surrounded by the bottom 217 and the partition wall 260 corresponds to the extract holding portion described above. The partition wall 260 is positioned by a protrusion (not shown) formed on the inner circumferential surface at a position 3.5 mm from the bottom surface of the cylinder 212, but by applying pressure from above, it can penetrate the extract holding portion beyond the protrusion.

[0536] In addition, such as Figure 1 As shown, in the concentrator 202, the superabsorbent polymer 230 is contained in the cylinder 212 above and in contact with the partition wall 260.

[0537] <Superabsorbent polymer>

[0538] A commercially available superabsorbent polymer particle (manufactured by M2 Polymer Technologies Inc.; SAPSphere 2.5 mm) 700 mg was fractionated to produce a superabsorbent polymer 230 used in the examples and the like. The superabsorbent polymer 230 had a particle diameter of 2.5 mm, a swelling ratio of 13 g / g, and a water absorption rate of 0.5 g / min.

[0539] 〔Concentration of the test body fluid〕

[0540] The obtained concentration device 202 was used to concentrate the above-described test body fluid as shown in FIG. 4.

[0541] <Injection of the test body fluid>

[0542] First, the cap 280 and the piston 220 were removed from the concentration device 202. Then, 4.5 mL of the above-described test body fluid was injected into the cylinder 212 from the opening 216, and the test body fluid was stirred. At this time, a part of the test body fluid (test body fluid 241: 400 μL) was introduced into the lower portion of the partition wall 260 through the hole 262 of the partition wall 260. Figure 4B ).

[0543] <Absorption>

[0544] Then, the concentration device 202 was left to stand for 60 minutes. During this period, water contained in the test body fluid 242 (the test body fluid 242 in the test body fluid 240 other than the test body fluid 241 held in the extract liquid holding portion) present only in the upper portion of the partition wall 260 was almost completely absorbed by the superabsorbent polymer 230, and the test body fluid concentrate 246 as a concentrate of the test body fluid 242 was generated in the cylinder 212 (the superabsorbent polymer 230 became the swollen superabsorbent polymer 232) Figure 4C ). In addition, as described above, since the gold colloid holding pad was contained in the cylinder 212, the antigen-antibody reaction was performed at the same time as the concentration, and the gold particle complex as a complex of LAM contained in the test body fluid and the gold colloid particle modified with the anti-LAM monoclonal antibody contained in the cylinder, i.e., the modified gold colloid particle (labeled antibody) was formed. That is, in the obtained test body fluid concentrate 246, LAM formed the gold particle complex as a complex with the modified gold colloid particle (labeled antibody).

[0545] <Addition of the extract liquid>

[0546] Next, the piston 220 is inserted into the cylinder 212 from the opening portion 216, and the superabsorbent polymer 232 is pressed downward, thereby moving the partition wall 260 to the bottom surface 218 of the cylinder 212, and introducing the subject fluid 241 held in the extraction liquid holding portion into the upper portion of the partition wall 260 through the hole 262 of the partition wall 260. Thus, the subject fluid concentrate 246 to which the subject fluid 241 held in the extraction liquid holding portion is added Figure 4D

[0547] <Extraction Process>

[0548] Further, the piston 220 is inserted into the cylinder 212 from the opening portion 216, and the cap 280 is fastened from the upper portion of the piston 220. By fastening the cap 280 by screwing, the piston 220 is pressed downward, and the subject fluid concentrate 248 as a concentrated solution of the subject fluid is obtained through the hole 222 of the front end portion 221 of the piston 220 Figure 4E The concentrator 202 is reversed, and the obtained subject fluid concentrate 248 is moved to the hose 281, and the subject fluid concentrate 248 is extracted from the recovery port 282 by pressing the hose 281. Further, as described above, in the subject fluid concentrate 248, the LAM forms a gold particle complex, like the subject fluid concentrate 246 obtained in the water absorption process.

[0549] [Detection of LAM]

[0550] The obtained subject fluid concentrate 248 (24 μL) is dropped into the immunochromatography kit prepared as described above. Immediately after dropping, the second convex deformation portion 14 is pressed, thereby breaking the sheet member 48, i.e., the aluminum foil, which seals the second amplification solution 46 enclosed in the second tank 45, and the liquid delivery pad 4 is dipped in the second tank 45, thereby supplying the second amplification solution 46 to the porous carrier 2 by capillary phenomenon.

[0551] After the amplification indicator region L3 changes from green to orange, the first convex deformation portion 12 is pressed, and the first tank 40 is moved toward the broken portion 34 of the tank housing portion 32 of the intermediate member 30, thereby breaking the sheet member 43, i.e., the aluminum foil, which seals the first tank 40, through the broken portion 34, and supplying the first amplification solution 41, i.e., the silver ion solution, from the opening portion of the intermediate member 30 to the porous carrier 2, and performing a silver amplification reaction. The silver amplification reaction is completed within several tens of seconds.

[0552] After the silver amplification reaction is completed, coloring is visually confirmed. The results are shown in Table 1.

[0553] +: coloring

[0554] -: no coloring

[0555] [Example 2]

[0556] ​Manufacture of the concentration device

[0557] A concentration device 203 as shown in Figure 2 and Figure 7 was manufactured. In addition, the concentration device 203 of Example 2 was the same as the concentration device 202 of Example 1 except that the cylinder 212 was replaced by a cylinder 213.

[0558] Specifically, the cylinder 213 (inner diameter 12 mm, depth 60 mm, cylindrical, upper portion provided with external threads) was used in place of the cylinder 212, and the concentration device (concentration device 203) was manufactured in the same manner as in Example 1.

[0559] Here, a porous synthetic resin 270 (sponge made of PVA (polyvinyl alcohol)) (void ratio 90%) was contained in the bottom portion 217 (4 mm from the bottom surface 218) of the cylinder 213. The pores (not shown) of the synthetic resin 270 were smaller than the particle diameter of the superabsorbent polymer 230 before water absorption. The pores of the synthetic resin 270 corresponded to the above-mentioned extract liquid holding portion.

[0560] In addition, as shown in Figure 2 , in the concentration device 203, the superabsorbent polymer 230 was contained in the cylinder 213 in contact with the synthetic resin 270 above the synthetic resin 270.

[0561] Concentration of the test body fluid

[0562] The concentration device 203 obtained was used to concentrate the above-mentioned test body fluid as shown in Fig. 5.

[0563] <Injection of the test body fluid>

[0564] First, the cap 280 and the piston 220 were removed from the concentration device 203. Then, 4.5 mL of the above-mentioned test body fluid was injected into the cylinder 213 from the opening portion 216, and stirring was performed. At this time, a portion of the test body fluid (test body fluid 241: 400 μL) was introduced into the pores of the synthetic resin 270 (the synthetic resin 270 became a synthetic resin 272 into which the test body fluid 241, which was a portion of the test body fluid 240, was introduced into the pores) Figure 5B ).

[0565] <Water absorption>

[0566] Then, the condensing device 203 was left for 60 minutes. During this period, water contained in the subject fluid 242 (the subject fluid 242 in the subject fluid 240 other than the subject fluid 241 held in the extract liquid holding section) present only above the synthetic resin 270 was almost completely absorbed by the superabsorbent polymer 230, and the subject fluid condensate 246 as a condensate of the subject fluid 242 (the superabsorbent polymer 230 became the swollen superabsorbent polymer 232) was generated in the cylinder 213. Figure 5C ) In addition, as in Example 1, in the obtained subject fluid condensate 246, LAM formed gold particle complexes as complexes with the modified gold colloid particles (labeled antibodies).

[0567] <Extract liquid addition step>

[0568] Next, the piston 220 was inserted into the cylinder 213 from the opening section 216, and the superabsorbent polymer 232 was pressed downward, whereby the synthetic resin 270 was crushed, and the subject fluid 241 held in the extract liquid holding section was introduced onto the synthetic resin 270 through the hole of the synthetic resin 270. Thus, the subject fluid 241 held in the extract liquid holding section was added to the subject fluid condensate 246. Figure 5D

[0569] <Taking-out step>

[0570] Also, the subject fluid condensate 248 was taken out in the same procedure as in Example 1.

[0571] [Detection of LAM]

[0572] The obtained subject fluid condensate 248 (24 μL) was subjected to detection of LAM in the same procedure as in Example 1. The results are shown in Table 1.

[0573] [Example 3]

[0574] [Manufacture of condensing device]

[0575] A condensing device 204 was manufactured as shown in Figs. 9 and 10. In addition, the condensing device 204 of Example 3 was the same as the condensing device 202 of Example 1 except that the cylinder 212 was the cylinder 214 and the piston 220 was the piston 224. Figure 3 Figures 7-8 Specifically, the cylinder 214 (inner diameter 12 mm, depth 60 mm, cylindrical, upper portion provided with external threads) was used instead of the cylinder 212, and the piston 224 was used instead of the piston 220, and the condensing device (condensing device 204) was manufactured in the same procedure as in Example 1 except for this.

[0576] Specifically, the cylinder 214 (inner diameter 12 mm, depth 60 mm, cylindrical, upper portion provided with external threads) was used instead of the cylinder 212, and the piston 224 was used instead of the piston 220, and the condensing device (condensing device 204) was manufactured in the same procedure as in Example 1 except for this. ​​

[0577] Here, the cylinder 214 and the piston 224 are provided with a piston position fixing mechanism that fixes the front end portion 221 of the piston 224 to the above-mentioned position A (specifically, a position 3.5 mm lower than the liquid surface 244 of the subject fluid 240 injected into the cylinder 214 in the subject fluid injection process described later) against the pressure accompanying the water absorption expansion of the superabsorbent polymer 230.

[0578] More specifically, as shown in Figure 8 the cylinder 214 is provided with a notch 215, and the piston 224 is provided with a protrusion 223. By inserting the piston 224 into the cylinder 214 and hanging the protrusion 223 of the piston 224 on the notch 215 of the cylinder 214, it is possible to fix the front end portion 221 of the piston 224 to the position A against the pressure accompanying the water absorption expansion of the superabsorbent polymer 230.

[0579] [Concentration of subject fluid]

[0580] Using the obtained concentration device 204, the above-mentioned subject fluid is concentrated as shown in Fig. 6.

[0581] <Subject fluid injection process>

[0582] First, the cap 280 and the piston 220 are removed from the concentration device 204. Then, 4.5 mL of the above-mentioned subject fluid is injected into the cylinder 214 from the opening portion 216, stirred, and the piston 224 is inserted into the cylinder 214, and the protrusion 223 of the piston 224 is hung on the notch 215 of the cylinder 214, thereby fixing the front end portion 221 of the piston 224 to the above-mentioned position A. At this time, a part of the subject fluid (subject fluid 241: 400 μL) is introduced above the front end portion 221 of the piston 224 through the hole 222 of the front end portion 221 of the piston 224. Figure 6B

[0583] <Water absorption process>

[0584] Then, the concentration device 204 is left for 60 minutes. During this period, the water contained in the subject fluid 242 (the subject fluid 242 in the subject fluid 240 other than the subject fluid 241 held in the extract liquid holding portion) present only below the front end portion 221 of the piston 224 in the subject fluid 240 is almost completely absorbed by the superabsorbent polymer 230, and the subject fluid concentrate 246 as a concentrate of the subject fluid 242 is generated in the cylinder 214 (the superabsorbent polymer 230 becomes the swollen superabsorbent polymer 232). Figure 6C In addition, as in Example 1, in the obtained subject fluid concentrate 246, LAM forms a gold particle complex as a complex with the modified gold colloid particle (labeled antibody). ​

[0585] <extraction liquid addition step>

[0586] Next, the subject fluid 241 present above the front end portion 221 of the piston 224 is introduced below the front end portion 221 of the piston 224 through the hole 222 of the front end portion 221 of the piston 224, whereby the subject fluid 241 present above the front end portion 221 of the piston 224 is added to the subject fluid concentrate 246. Figure 6D ).

[0587] <extraction step>

[0588] Also, the subject fluid concentrate 248 was taken out in the same manner as in Example 1.

[0589] [Detection of LAM]

[0590] The detection of LAM was performed on the obtained subject fluid concentrate 248 (24 μL) in the same manner as in Example 1. The results are shown in Table 1.

[0591] [Comparative Example 1]

[0592] A concentration device (Comparative Device 1) was produced in the same manner as in Example 1 except that the superabsorbent polymer 230 was not added to the cylinder 212 (in which the partition wall 260 was not provided).

[0593] When the concentration of the subject fluid was performed in the same manner as in Example 1 except that the obtained Comparative Device 1 was used, the subject fluid itself was not concentrated and was taken out. Also, the detection of LAM was performed on the taken-out subject fluid in the same manner as in Example 1. The results are shown in Table 1.

[0594] [Example 4]

[0595] A concentration device 202 was produced in the same manner as in Example 1 except that 300 mg of the superabsorbent polymer 230 was added to the cylinder 211.

[0596] The detection of LAM was performed on the taken-out subject fluid concentrate in the same manner as in Example 1 except that the obtained concentration device 202 was used. The results are shown in Table 1.

[0597] [Comparative Example 2]

[0598] The subject fluid injection step, the water absorption step, and the extraction liquid addition step were performed in the same manner as in Example 1. Then, when the subject fluid concentrate was taken out by tilting the cylinder 212 without using the piston 220, the subject fluid concentrate could not be taken out.

[0599] [Comparative Example 3]

[0600] A concentrator (comparative device 2) was produced in the same manner as in Example 1, except that the cylinder 212 in which the partition wall 260 was not provided was used as the cylinder 212.

[0601] The sample fluid injection step (however, a portion of the sample fluid was not held) and the water absorption step were performed in the same manner as in Example 1 using the obtained comparative device 2. Then, when the eluent was not added and the withdrawal step was performed in the same manner as in Example 1, the sample fluid concentrate could not be withdrawn.

[0602] [Table 1]

[0603]

[0604] In the case where the sample fluid was concentrated using the concentrators of Examples 1 to 4 which are the concentrators according to the present application, a sample fluid concentrate having a desired concentration ratio could be obtained. On the other hand, in Comparative Example 1 in which the superabsorbent polymer was not used, the sample fluid could not be concentrated. Also, in Comparative Example 2 in which the prescribed piston was not used, the sample fluid concentrate could not be withdrawn. Also, in Comparative Example 3 in which the eluent was not added, the sample fluid concentrate (sample fluid concentrate) could not be withdrawn.

[0605] Explanation of symbols

[0606] 1 Test strip for inspection

[0607] 2 Insoluble carrier (porous carrier)

[0608] 3 Mark holding pad (glass fiber pad)

[0609] 4 Pad for sending liquid

[0610] 6 Absorbent pad

[0611] 7 Back adhesive sheet

[0612] 9 Housing

[0613] 10 Upper housing

[0614] 12 First convex deformation portion

[0615] 12a Top portion of the first convex deformation portion

[0616] 12b Protruding portion of the first convex deformation portion

[0617] 12c Inclined surface of the first convex deformation portion

[0618] 14 Second convex deformation portion

[0619] 14a Top portion of the second convex deformation portion

[0620] 14b protruding portion of the second convexly deformed portion

[0621] 16 sample droplet addition opening

[0622] 18 observation window

[0623] 20 lower case

[0624] 21 insoluble carrier accommodating portion (porous carrier accommodating portion)

[0625] 22 absorbent pad accommodating portion

[0626] 24 second tank accommodating portion

[0627] 30 intermediate member

[0628] 32 first tank accommodating portion

[0629] 34 breaking portion

[0630] 35 flow path forming portion

[0631] 36 back surface of the flow path forming portion 35

[0632] 40 first tank for first amplification solution

[0633] 41 first amplification solution

[0634] 42 tank container

[0635] 43 sheet member

[0636] 45 second tank for second amplification solution

[0637] 46 second amplification solution

[0638] 47 tank container

[0639] 48 sheet member

[0640] 100 immunochromatographic kit

[0641] 114 convexly deformed portion

[0642] 114a top portion of the convexly deformed portion 114

[0643] 114b protruding portion of the convexly deformed portion 114

[0644] 202, 203, 204 concentration device

[0645] 212, 213, 214 cylinder

[0646] 215 cutout

[0647] 216 opening portion

[0648] 217 bottom

[0649] 218 bottom surface

[0650] 220, 224 piston

[0651] 221 front end portion

[0652] 222 hole of front end portion

[0653] 223 protrusion

[0654] 230 superabsorbent polymer (before water absorption)

[0655] 232 superabsorbent polymer (after water absorption) (swollen superabsorbent polymer)

[0656] 240, 241, 242 test body fluid

[0657] 244 liquid surface of test body fluid

[0658] 246 test body fluid concentrate

[0659] 248 test body fluid concentrate

[0660] 250 extraction liquid

[0661] 260 partition

[0662] 262 hole of partition

[0663] 270 synthetic resin

[0664] 272 synthetic resin into which test body fluid is introduced into hole

[0665] 280 cap having recovery port

[0666] 281 flexible tube

[0667] 282 recovery port

[0668] 300 nitrocellulose membrane

[0669] 301 gold colloid holding pad

[0670] 302 test line

[0671] 303 control line

[0672] 304 color developing reagent immobilized line

Claims

1. A concentration device provided with a cylinder that contains a particulate superabsorbent polymer and a piston that can be inserted into the cylinder, for concentrating a subject fluid that is an aqueous solution containing a high molecule, the cylinder has a liquid holding portion for holding a portion of the subject fluid injected into the cylinder at a bottom portion, the superabsorbent polymer is contained in the cylinder in contact with the liquid holding portion above the liquid holding portion, the piston has a front end portion having a hole smaller than a particle size of the superabsorbent polymer after water absorption, the superabsorbent polymer absorbs water contained in the subject fluid injected into the cylinder other than the subject fluid held in the liquid holding portion, to generate a subject fluid concentrate that is a concentrate of the subject fluid in the cylinder, the subject fluid held in the liquid holding portion is added to the subject fluid concentrate, a subject fluid concentrate that is a concentrated liquid of the subject fluid is taken out from the hole of the front end portion of the piston by inserting the piston into the cylinder.

2. The concentration device according to claim 1, wherein the liquid holding portion is a portion surrounded by the bottom portion of the cylinder and a partition wall provided on an inner peripheral surface of the cylinder in a manner movable in a length direction of the cylinder, the partition wall having a hole smaller than a particle size of the superabsorbent polymer before water absorption, the subject fluid held in the liquid holding portion is introduced above the partition wall through the hole of the partition wall by moving the partition wall to a bottom surface of the cylinder, the subject fluid introduced above the partition wall is added to the subject fluid concentrate.

3. The concentration device according to claim 1, wherein the liquid holding portion is a portion formed by a hole of a porous resin contained in the bottom portion of the cylinder, the hole of the resin being smaller than a particle size of the superabsorbent polymer before water absorption, the subject fluid held in the liquid holding portion is introduced above the resin through the hole of the resin by crushing the resin, the subject fluid introduced above the resin is added to the subject fluid concentrate.

4. The concentration device according to claim 3, wherein the porous resin is a sponge.

5. A concentration device provided with a cylinder that contains a particulate superabsorbent polymer and a piston that can be inserted into the cylinder, for concentrating a subject fluid that is an aqueous solution containing a high molecule, the piston has a front end portion having a hole smaller than a particle size of the superabsorbent polymer after water absorption, the cylinder has a liquid holding portion that holds a portion of the subject fluid injected into the cylinder present above the front end portion of the piston by fixing the front end portion of the piston to a position lower than a liquid surface of the subject fluid injected into the cylinder and higher than the superabsorbent polymer contained in the cylinder, the superabsorbent polymer is contained in the cylinder below the liquid holding portion via the piston, the subject fluid held in the liquid holding portion is added to the subject fluid concentrate. The cylinder and the piston are provided with a piston position fixing mechanism that fixes the front end portion of the piston at the position against pressure accompanying water absorption expansion of the superabsorbent polymer, The superabsorbent polymer absorbs water contained in a subject fluid other than the subject fluid held in the liquid holding portion among the subject fluid injected into the cylinder, and generates a subject fluid concentrate as a concentrate of the subject fluid in the cylinder, The piston position fixing mechanism is released, and the piston is pulled up to introduce the subject fluid present above the front end portion of the piston through the hole of the front end portion of the piston to below the front end portion of the piston, thereby adding the subject fluid present above the piston to the subject fluid concentrate, The subject fluid concentrate as a concentrated solution of the subject fluid is taken out from the hole of the front end portion of the piston by pulling down the piston into the cylinder again.

6. The concentration device according to any one of claims 1 to 5, wherein The cylinder further has a lid having a recovery port for recovering the subject fluid concentrate.

7. The concentration device according to any one of claims 1 to 5, wherein The water absorption speed of the superabsorbent polymer is 0.01 g / min or more and 40 g / min or less per 1 g of the superabsorbent polymer.

8. The concentration device according to any one of claims 1 to 5, wherein The particle diameter of the superabsorbent polymer is 5 mm or less.

9. The concentration device according to any one of claims 1 to 5, wherein The swelling ratio of the superabsorbent polymer is greater than 0.2 g / g and less than 800 g / g.

10. The concentration device according to any one of claims 1 to 5, wherein The subject fluid is an aqueous solution containing a high molecule contained in a biological fluid.

11. The concentration device according to claim 10, wherein The cylinder further contains a binding substance that specifically binds to the high molecule contained in the biological fluid.

12. The concentration device according to claim 11, wherein The binding substance is contained in the cylinder as a complex with a metal particle.

13. The concentration device according to claim 11, wherein The high molecule contained in the biological fluid is an antigen, and the binding substance is an antibody against the antigen.

14. The concentration device according to any one of claims 1 to 5, wherein The cylinder further contains at least one selected from the group consisting of casein and tris(hydroxymethyl)methylglycine.

15. The concentration device according to any one of claims 1 to 5, wherein The subject fluid is urine.

16. A method for concentrating a subject fluid as an aqueous solution containing a high molecule using the concentration device according to any one of claims 1 to 15, the method for concentrating a subject fluid successively comprising: a subject fluid injection step of injecting the subject fluid into the cylinder while holding a part of the subject fluid injected into the cylinder in the liquid holding portion; a water absorption step of absorbing water contained in a body fluid other than the body fluid held in the liquid holding section in the body fluid injected into the cylinder, using a superabsorbent polymer housed in the cylinder, to generate the body fluid concentrate in the cylinder; a liquid addition step of adding the body fluid held in the liquid holding section to the body fluid concentrate; and a withdrawal step of inserting a piston into the cylinder to withdraw a body fluid concentrate as the concentrated liquid of the body fluid, using a hole of a front end portion of the piston, the piston being insertable into the cylinder and having the front end portion having a hole smaller than a particle size of the superabsorbent polymer after water absorption.

17. A body fluid examination method of detecting a macromolecule in a body fluid as an aqueous solution containing a macromolecule, the body fluid examination method comprising, in order: a concentration step of obtaining the body fluid concentrate using the body fluid concentration method of claim 16; and a detection step of detecting the macromolecule in the obtained body fluid concentrate.

18. The body fluid examination method according to claim 17, wherein the body fluid is an aqueous solution capable of containing an antigen, the concentration step is a step of obtaining an antigen concentrate by concentrating the aqueous solution capable of containing the antigen using the body fluid concentration method of claim 16, the detection step is a step of detecting the antigen in the antigen concentrate by an immunochromatography method using an antigen-antibody reaction.

19. The body fluid examination method according to claim 18, wherein the detection step includes an amplification step of amplifying information of the antigen in the antigen concentrate.

20. The body fluid examination method according to claim 19, wherein the amplification step is a silver amplification step.

21. An examination kit for detecting a macromolecule in a body fluid as an aqueous solution containing a macromolecule, the examination kit comprising: the concentration device of any one of claims 1 to 15; and a detection device of detecting a macromolecule in a body fluid concentrate obtained using the body fluid concentration method of claim 16.

22. The examination kit according to claim 21, wherein the detection device is an immunochromatography device.

23. The examination kit according to claim 21 or 22, wherein the detection device includes a tank in which an amplification solution for amplifying a signal of detecting a macromolecule in the body fluid concentrate is enclosed.

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