Assay Device

Abstract

An assay device comprises: an inlet (2); an internal flow path (31, 32) through which liquid introduced via the inlet (2) flows; and a liquid absorbing material (4) which absorbs the liquid that has passed through the internal flow path (31, 32). The internal flow path (31, 32) includes a micro flow path (31) that has an assay region (31c) and a separation flow path (32) that is provided between the micro flow path (31) and the liquid absorbing material (4) and that is for separating liquid inside when introduction of the liquid is stopped. The separation flow path (32) has a narrow portion (321) at which the width of the flow path becomes narrow.

Description

[Technical Field]

[0001] The present invention relates to an assay device, and more particularly to an assay device capable of performing an assay using a small amount of liquid. [Background technology]

[0002] One known example of this type of conventional assay device is the assay device described in Patent Document 1. The assay device described in Patent Document 1 includes a microchannel configured to allow a fluid to flow, an absorbent porous medium disposed at an interval from one end of the microchannel located on one end side of the fluid flow direction, a separation space disposed between the one end of the microchannel and the absorbent porous medium, and two side air passages adjacent to the microchannel on both sides in a width direction perpendicular to the flow direction so as to communicate with the microchannel and allowing air to circulate. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2020 / 045551 Summary of the Invention [Problem to be solved by the invention]

[0004] In the assay device described in Patent Document 1, when a microchannel is filled with a first liquid, a second liquid is injected into the microchannel in an amount that exceeds the amount of the first liquid, thereby replacing the liquid in the microchannel with the second liquid, i.e., liquid exchange within the microchannel is possible.

[0005] However, if the interfacial tension of the liquid is low, the liquid may not be able to stably remain in the microchannel. If the liquid does not stably remain in the microchannel, it becomes difficult for the liquid to maintain a stable shape within the microchannel. As a result, air may get mixed into the microchannel, preventing stable liquid exchange within the microchannel.

[0006] Here, sample liquids (extracts, etc.) used in biochemical tests often contain relatively large amounts of surfactants, and their interfacial tension tends to be low due to the influence of blocking agents used in blocking treatments on the surface of microchannels. Furthermore, processing sample liquids in biochemical tests may require multi-step reactions, such as ELISA (Enzyme-Linked ImmunoSorbent Assay). For these reasons, stable liquid exchange within microchannels is required, especially when sample liquids used in biochemical tests are used.

[0007] This demand is not limited to cases where a sample liquid is used in a biochemical test, but is common to cases where a liquid with a relatively low interfacial tension is used.

[0008] Therefore, the present invention aims to provide an assay device that enables stable liquid exchange within a microchannel, even for liquids with relatively low interfacial tension or microchannels where the interfacial tension has been weakened by surface treatment such as blocking. [Means for solving the problem]

[0009] According to one aspect of the present invention, there is provided an assay device having an injection port, an internal flow path through which a liquid injected from the injection port flows, and a liquid absorbent material that absorbs the liquid that has passed through the internal flow path. In the provided assay device, the internal flow path includes a microflow path having an assay region, and a separation flow path that is provided between the microflow path and the liquid absorbent material and that separates the liquid in the internal flow path when the injection of the liquid is stopped, and the separation flow path has a narrow portion where the flow path width is narrowed. The internal flow path is formed by stacking an upper flow path-forming member on which the injection port and an upper wall portion constituting the upper wall of the internal flow path are formed, a lower flow path-forming member on which a lower wall portion constituting the lower wall of the internal flow path is formed, and an intermediate member that functions as a spacer between the upper flow path-forming member and the lower flow path-forming member, and a pair of lateral spaces adjacent to and communicating with the microflow path are provided on both sides in the width direction of the microflow path, and a pair of openings located above and communicating with the pair of lateral spaces are formed in the upper flow path-forming member. [Effects of the Invention]

[0010] According to the present invention, an assay device can be provided that enables stable liquid exchange within a microchannel, even for liquids with relatively low interfacial tension or microchannels where the interfacial tension has been weakened by surface treatment such as blocking. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a perspective view of an assay device according to a first embodiment. [Figure 2] FIG. 1 is a cross-sectional view of an assay device according to a first embodiment. [Figure 3] FIG. 1 is an exploded perspective view of an assay device according to a first embodiment. [Figure 4] 1A is a top view of the upper flow path forming member; FIG. 1B is a side view of the upper flow path forming member; FIG. 1C is a bottom view of the upper flow path forming member. [Figure 5] 1A and 1B are diagrams showing a lower flow path forming member, in which (a) is a top view of the lower flow path forming member, (b) is a side view of the lower flow path forming member, (c) is a bottom view of the lower flow path forming member, and (d) is a cross-sectional view taken along the line AA in (a). [Figure 6] 1A and 1B are diagrams showing an intermediate member disposed between an upper flow path forming member and a lower flow path forming member, in which FIG. 1A is a top view of the intermediate member, and FIG. 1B is a side view of the intermediate member. [Figure 7]1A and 1B are diagrams for explaining an internal flow path and an internal ventilation space, in which FIG. 1A mainly shows the upper part of the internal flow path, and FIG. 1B mainly shows the lower part of the internal flow path. [Figure 8] FIG. 10 is a diagram showing the assay device before the upper cover is attached and when a blocking treatment is performed on the internal flow path. [Figure 9] FIG. 2 is a diagram for explaining the movement of a first liquid injected into the assay device, and is a diagram schematically showing the internal flow paths and the like when the assay device is viewed from above. [Figure 10] FIG. 10 is a diagram for explaining the movement of the first liquid and the second liquid when the injection of the first liquid into the assay device is stopped and then the second liquid is injected, and is a diagram that schematically shows the internal flow paths, etc. when the assay device is viewed from above. [Figure 11] FIG. 10 is a diagram for explaining a modified example of the assay device according to the first embodiment. [Figure 12] FIG. 10 is a perspective view of an assay device according to a second embodiment. [Figure 13] FIG. 10 is an exploded perspective view of an assay device according to a second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0012] An assay device according to an embodiment of the present invention will now be described.

[0013] The assay device according to the embodiment is a device capable of performing an assay using a minute amount of liquid. The liquid that can be used in the assay device according to the embodiment is not particularly limited as long as it can flow through a flow path (internal flow path) provided in the assay device. Such a liquid is typically an aqueous solution. Furthermore, the liquid that can be used in the assay device according to the embodiment includes not only chemically pure liquids but also liquids in which gases, other liquids, or solids are dissolved, dispersed, or suspended.

[0014] For example, biologically derived liquids may be used. When biologically derived liquids are used, the assay device can measure diagnostically useful analytes in the liquid for applications such as pregnancy tests, urine tests, stool tests, adult disease tests, allergy tests, infectious disease tests, drug tests, and cancer tests. Food suspensions, drinking water, river water, and soil suspensions may also be used. When these are used, the assay device can measure pathogens in food or drinking water, or contaminants in river water or soil.

[0015] As used herein, the term "analyte" refers to a compound or composition that is detected or measured primarily using a liquid. Examples of "analyte" include sugars (e.g., glucose), cells, proteins or peptides (e.g., serum proteins, hormones, enzymes, immunomodulators, lymphokines, monokines, cytokines, glycoproteins, vaccine antigens, antibodies, growth factors), fats, amino acids, nucleic acids, steroids, vitamins, pathogens or their antigens, natural or synthetic chemicals, pollutants, therapeutic or illicit drugs, or metabolites or antibodies of these substances.

[0016] In addition, in this specification, the term "microchannel" refers to a channel within an assay device that enables detection or measurement of a sample using a minute amount of liquid on the order of μl (microliter), i.e., a minute amount of liquid of 1 μl or more but less than 1000 μl.

[0017] [First embodiment] 1 to 3 show an assay device 1 according to a first embodiment. Fig. 1 is a perspective view of the assay device 1, Fig. 2 is a cross-sectional view of the assay device 1, and Fig. 3 is an exploded perspective view of the assay device 1.

[0018] First, the basic configuration of the assay device 1 will be described.

[0019] The assay device 1 is formed as a roughly rectangular parallelepiped overall, and has an inlet 2 through which a liquid is injected (mainly dropwise injection) at one end side (the right side in FIG. 2) in the longitudinal direction L. The inlet 2 is formed in a circular shape and opens on the top surface of the assay device 1. However, the shape of the inlet 2 is not limited to a circle, and can be any shape such as an oval or polygon.

[0020] The assay device 1 also has an internal flow path 3 through which liquid injected from the injection port 2 flows, and a first liquid absorbent 4 that absorbs the liquid that has passed through the internal flow path 3. The internal flow path 3 extends in the longitudinal direction L inside the assay device 1. The first liquid absorbent 4 is made of a porous material or the like that can absorb liquid, and is housed in a housing space 5 provided at the other end side in the longitudinal direction L of the assay device 1 (the left side in Figure 2). In other words, the longitudinal direction L is also the direction in which liquid flows inside the assay device 1. In this case, the end side in the longitudinal direction L where the injection port 2 is located is the upstream side, and the other end side in the longitudinal direction L where the first liquid absorbent 4 is located is the downstream side.

[0021] In this embodiment, the first liquid absorbent 4 is composed of an upper absorbent 4a and a lower absorbent 4b. However, this is not limited to this, and the first liquid absorbent 4 may be composed of one absorbent material, or three or more absorbent materials.

[0022] In this embodiment, the internal flow path 3 has an upper wall and a lower wall, as is clear from Fig. 2. Furthermore, in this embodiment, the internal flow path 3 is defined by the upper wall and the lower wall and does not have a side wall. The internal flow path 3 also includes a microflow path 31 and a separation flow path 32.

[0023] The microchannel 31 constitutes the upstream channel of the internal channel 3, i.e., the channel close to the injection port 2. The base end (upstream end) 31a of the microchannel 31 is located near the injection port 2, specifically, in a range that can receive the liquid injected from the injection port 2. Preferably, the base end 31a of the microchannel 31 is located below (or directly below) the injection port 2. The microchannel 31 extends approximately horizontally from the base end 31a toward the other end in the longitudinal direction L, and the tip end (downstream end) 31b of the microchannel 31 is located approximately in the center of the assay device 1 in the longitudinal direction L.

[0024] An assay region 31c is provided in the middle of the microchannel 31, i.e., between the base end 31a and the tip end 31b of the microchannel 31. One or more assay reagents may be disposed in the assay region 31c. The assay reagent may be any substance that produces a detectable result by reacting with a liquid or a sample contained therein, and may be, for example, an antibody or an antigen. The detectable result is preferably visible to the naked eye of an observer, but is not limited to this. The detectable result may also be visible to an observer using a predetermined device. The detectable result may include color development, absorbance, luminescence, fluorescence, etc.

[0025] In this embodiment, the first assay reagent 6a and the second assay reagent 6b are arranged in the assay region 31c, spaced apart from each other in the longitudinal direction L. Specifically, in this embodiment, the first assay reagent 6a and the second assay reagent 6b are fixed to either the lower wall or the upper wall of the microchannel 31, or to both the lower wall and the upper wall. However, this is not limitative. The first assay reagent 6a and / or the second assay reagent 6b may be supported on a porous material that allows liquid to pass through, and the porous material (support) may be placed in the assay region 31c.

[0026] The separation channel 32 constitutes a downstream channel of the internal channel 3, i.e., a channel on the side closer to the first liquid absorbent material 4. One end (upstream end) of the separation channel 32 is connected to the tip end (downstream end) 31b of the microchannel 31. The separation channel 32 extends from the one end connected to the tip end 31b of the microchannel 31 toward the other end in the longitudinal direction L, and the other end (downstream end) of the separation channel 32 is in contact with the first liquid absorbent material 4.

[0027] That is, in this embodiment, the first liquid absorbent 4 is provided at a distance from the tip portion (downstream end) 31b of the microchannel 31 in the longitudinal direction L, and the separation channel 32 is provided between (the tip portion 31b of) the microchannel 31 and the first liquid absorbent 4. As will be described later, the separation channel 32 is configured to separate the liquid in the internal channel 3 when the injection of liquid into the inlet 2 is stopped, in other words, when the supply of liquid to the internal channel 3 is stopped. Specifically, when the injection of liquid into the inlet 2 is stopped, the liquid in the internal channel 3 is separated in the separation channel 32, a part of which is absorbed by the first liquid absorbent 4, and the remainder remains (is retained) in the microchannel 31.

[0028] Furthermore, an internal ventilation space 7 communicating with the outside of the assay device 1 is provided inside the assay device 1. The internal ventilation space 7 is formed to surround most of the microchannel 31. More specifically, the internal ventilation space 7 is formed to surround most of the periphery of the microchannel 31, excluding the tip 31b of the microchannel 31 to which the one end (upstream end) of the separation channel 32 is connected, when viewed from above. As described above, in this embodiment, the internal channel 3 does not have a sidewall. Therefore, the internal ventilation space 7 also communicates with the microchannel 31. In this embodiment, the internal ventilation space 7 includes a pair of side spaces 7a (only one of which is shown by a dashed line in FIG. 2) and a connecting space 7b connecting the pair of side spaces 7a. The pair of side spaces 7a are adjacent to the microchannel 31 on both sides in the short direction (hereinafter referred to as the "width direction") W and communicate with the microchannel 31. The connecting space 7b is formed in an arc shape so as to extend along the outer edge of the injection port 2, with one end of the connecting space 7b connected to one of the side spaces 7a and the other end of the connecting space 7b connected to the other side space 7a. The communication between the internal ventilation space 7 and the outside will be described later.

[0029] 2, in this embodiment, the upper and lower walls of the microchannel 31 extend substantially horizontally, and the height of the microchannel 31, i.e., the distance between the upper and lower walls of the microchannel 31 in the height direction H, is constant (it does not need to be strictly constant, as long as it is approximately constant; the same applies below). The height of the microchannel 31 is determined so as to generate interfacial tension of the liquid that prevents leakage of the liquid into the internal ventilation space 7 (particularly, the pair of side spaces 7a, 7a on both sides of the microchannel 31) when the liquid flows through the microchannel 31. On the other hand, the upper wall of the separation channel 32 is formed by directly extending the upper wall of the microchannel 31 and extends substantially horizontally, but the lower wall of the separation channel 32 is inclined downward so that the height position decreases as it moves away from (the tip 31b of) the microchannel 31, i.e., as it approaches the first liquid absorbent 4. The downward inclination angle of the lower wall of the separation channel 32 can be set arbitrarily within the range of 1° to 45° with respect to the horizontal, but is preferably set to 2° to 10°.

[0030] Here, although not particularly limited, the height of the microchannel 31 can be set in the range of, for example, 1 μm to 1 mm, the width (dimension in the width direction W) of the microchannel 31 can be set in the range of, for example, 100 μm to 1 cm, and the length (dimension in the longitudinal direction L) of the microchannel 31 can be set in the range of, for example, 10 μm to 10 cm.

[0031] In particular, when the liquid is a sample liquid for biochemical testing, it is preferable to subject the surface of the internal channel 3 (microchannel 31 and separation channel 32) that comes into contact with the liquid to a blocking treatment or plasma treatment to prevent nonspecific adsorption of biological substances, antigens, antibodies, etc. Blocking agents used in the blocking treatment include commercially available blocking agents, bovine serum albumin, casein, skim milk, gelatin, surfactants, polyvinyl alcohol, globulin, serum (e.g., fetal bovine serum or normal rabbit serum), ethanol, MPC polymer, etc. Commercially available blocking agents include Immunoblock, Block Ace, Pierce Examples include, but are not limited to, Blocking Buffer, StartingBlock, StabilGuard, StabilBrock, StabilCoat, and ChonBlock.

[0032] The internal flow path 3 and the internal ventilation space 7 will be further described.

[0033] In this embodiment, the internal flow path 3 and the internal ventilation space 7 are formed by stacking an upper flow path forming member 11, a lower flow path forming member 12, and an intermediate member 13 that functions as a spacer between them. Below, the upper flow path forming member 11, the lower flow path forming member 12, and the intermediate member 13 will be described in order.

[0034] Fig. 4 shows the upper flow path forming member 11. Fig. 4(a) is a top view of the upper flow path forming member 11, Fig. 4(b) is a side view of the upper flow path forming member 11, and Fig. 4(c) is a bottom view of the upper flow path forming member 11.

[0035] In this embodiment, the upper flow path forming member 11 is made of a transparent synthetic resin and is formed to have a certain degree of flexibility. Preferably, the upper flow path forming member 11 is made of a molded product of a transparent synthetic resin. Examples of such synthetic resins include, but are not limited to, PS resin (polystyrene), PMMA (acrylic resin), PC (polycarbonate), COP (cycloolefin polymer), COC (cycloolefin copolymer), ABS resin, AS resin, and silicone resin. Furthermore, although not particularly limited, it is preferable that the contact angle of the surface of the upper flow path forming member 11 with respect to water is 90 degrees or less.

[0036] 4(a) to 4(c), the upper flow path forming member 11 has an outer shape that is rectangular when viewed from above. In addition, the upper flow path forming member 11 has a predetermined range on the one end side in the longitudinal direction L that is larger in the height direction H than other portions, in other words, is formed to have a thicker wall thickness. Hereinafter, the portion on the one end side in the longitudinal direction L that is larger in the height direction H (thicker wall thickness) will be referred to as the thick portion 11a, and the remaining portion that is thinner in thickness than the thick portion 11a will be referred to as the thin portion 11b.

[0037] An injection port 2 is formed in the thick portion 11a of the upper flow path forming member 11. The injection port 2 penetrates the thick portion 11a in the height direction H. That is, one end of the injection port 2 opens to the upper surface of the thick portion 11a of the upper flow path forming member 11, and the other end opens to the lower surface (bottom surface) of the thick portion 11a. When viewed from above, the injection port 2 is formed in the center of the thick portion 11a in the width direction W and at a position closer to the thin portion 11b.

[0038] The thin-walled portion 11b of the upper flow path forming member 11 is provided with an upper wall portion 111 that, together with a part of the thick-walled portion 11a (the portion surrounding the injection port 2), forms the upper wall of the internal flow path 3, and a pair of first openings 112, 112 that sandwich the upper wall portion 111 in the width direction W. The upper wall portion 111 extends from the end of the thin-walled portion 11b on the thick-walled portion 11a side (the boundary with the thick-walled portion 11a), that is, from the vicinity of the injection port 2 toward the other end in the longitudinal direction L. The pair of first openings 112, 112 are formed symmetrically. Each of the pair of first openings 112, 112 extends in the longitudinal direction L along the side edge of the upper wall portion 111 and penetrates the thin-walled portion 11b of the upper flow path forming member 11 in the height direction. In other words, a pair of first openings 112, 112 that are spaced apart in the width direction W and penetrate the thin portion 11b in the height direction H of the upper flow path forming member 11 are formed in the thin portion 11b of the upper flow path forming member 11, and the area between the pair of first openings 112, 112 in the thin portion 11b of the upper flow path forming member 11 constitutes the upper wall portion 111.

[0039] In this embodiment, the upper wall portion 111 has, in order from the one end side in the longitudinal direction L, i.e., the side closer to the injection port 2, an upper tapered portion 111a, a first upper straight portion 111b, an upper narrow portion 111c, and a second upper straight portion 111d.

[0040] Upper tapered portion 111a extends from the end of thin portion 11b on the thick portion 11a side, i.e., from the vicinity of injection port 2, toward the other end in longitudinal direction L. Upper tapered portion 111a is tapered so that its width gradually narrows (the dimension in width direction W gradually decreases) with increasing distance from injection port 2. Although not particularly limited, the taper angle of upper tapered portion 111a is set to 1° to 20°, preferably 2° to 16°. In other words, the angle that each of both side portions of upper tapered portion 111a makes with a line parallel to longitudinal direction L is set to 0.5° to 10°, preferably 1° to 8°. Alternatively, the ratio of the width W dimension of the upper tapered portion 111a on the injection port 2 side to the width W dimension of the upper tapered portion 111a on the first upper straight portion 111b side, i.e., the width W dimension ratio between the upstream and downstream portions of the upper tapered portion 111a, is set to 1:0.99 to 1:0.2.

[0041] The first upper straight portion 111b has the same width as the tip of the upper tapered portion 111a and extends linearly from the tip of the upper tapered portion 111a toward the other end in the longitudinal direction L. The width of the first upper straight portion 111b is constant. The tip of the first upper straight portion 111b is located approximately in the center in the longitudinal direction L.

[0042] The upper narrow width portion 111c is a portion where the width of the upper wall portion 111 narrows. In this embodiment, the upper narrow width portion 111c connects the first upper straight portion 111b and the second upper straight portion 111d. Specifically, in this embodiment, the second upper straight portion 111d is formed to be narrower than the first upper straight portion 111b. The upper narrow width portion 111c is formed in a tapered shape in which its width gradually narrows from the width of the first upper straight portion 111b to the width of the second upper straight portion 111d, connecting the first upper straight portion 111b and the second upper straight portion 111d. The taper angle of the upper narrow width portion 111c can be set arbitrarily, but is preferably set to be equal to or smaller than the taper angle of the upper tapered portion 111a. However, this is not limited to this. The upper narrow portion 111c may be any portion where the width of the upper wall portion 111 is narrowed, and may be configured, for example, as one or more stepped shapes or multiple tapered shapes.

[0043] As described above, the second upper straight portion 111d is formed to be narrower than the first upper straight portion 111b, and extends linearly from the upper narrow portion 111c toward the other end in the longitudinal direction L. The width of the second upper straight portion 111d is constant.

[0044] Furthermore, rectangular through-holes 113, 113 that are long in the width direction W are formed in the thin-walled portion 11b of the upper flow path forming member 11. The through-holes 113, 113 are provided spaced apart from each other in the longitudinal direction L at positions spaced apart from the tip end of (the second upper straight portion 111d of) the upper wall portion 111 toward the other end in the longitudinal direction L.

[0045] Fig. 5 shows the lower flow path forming member 12. Fig. 5(a) is a top view of the lower flow path forming member 12, Fig. 5(b) is a side view of the lower flow path forming member 12, Fig. 5(c) is a bottom view of the lower flow path forming member 12, and Fig. 5(d) is a cross-sectional view taken along line AA in Fig. 5(a).

[0046] In this embodiment, the lower flow path-forming member 12, like the upper flow path-forming member 11, is made of a transparent synthetic resin and is formed to have a certain degree of flexibility. The lower flow path-forming member 12 is preferably formed as a molded product of a transparent synthetic resin. The lower flow path-forming member 12 is preferably formed of the same synthetic resin as the upper flow path-forming member 11, but may be formed of a different synthetic resin. Although not particularly limited, the contact angle of the surface of the lower flow path-forming member 12 with respect to water is preferably 90 degrees or less, like that of the upper flow path-forming member 11.

[0047] 5(a) to 5(c), the lower flow-path forming member 12 is formed to have a rectangular outer shape in a top view so as to correspond to the upper flow-path forming member 11. Furthermore, the lower flow-path forming member 12 has a lower wall portion 121 that constitutes the lower wall of the internal flow path 3, formed so as to correspond to the injection port 2 and upper wall portion 111 formed in the upper flow-path forming member 11. In other words, the lower wall portion 121 is formed so as to be located below the injection port 2 and upper wall portion 111 of the upper flow-path forming member 11 when the upper flow-path forming member 11, the lower flow-path forming member 12, and the intermediate member 13 are stacked. The lower wall portion 121, like the upper wall portion 111, extends from the one end side to the other end side in the longitudinal direction L.

[0048] In this embodiment, the lower wall portion 121 has, in order from the one end side in the longitudinal direction L, a semicircular portion 121a, a lower tapered portion 121b, a first lower straight portion 121c, a lower narrow portion 121d, and a second lower straight portion 121e.

[0049] The semicircular portion 121a is a portion corresponding to the injection port 2 of the upper flow path forming member 11. The semicircular portion 121a is concentric with the injection port 2 of the upper flow path forming member 11 indicated by the two-dot chain line in FIG. 5(a), and has a diameter larger than that of the injection port 2.

[0050] The lower tapered portion 121b is a portion corresponding to the upper tapered portion 111a of the upper flow path forming member 11. The lower tapered portion 121b extends from the semicircular portion 121a toward the other end in the longitudinal direction L. The lower tapered portion 121b is formed in a tapered shape such that its width gradually narrows with increasing distance from the semicircular portion 121a. The lower tapered portion 121b is designed to be able to overlap with the upper tapered portion 111a in a top view, and has the same taper angle as the upper tapered portion 111a.

[0051] The first lower straight portion 121c is a portion corresponding to the first upper straight portion 111b of the upper flow path forming member 11. The first lower straight portion 121c has the same width as the tip end of the lower tapered portion 121b, and extends linearly from the tip end of the lower tapered portion 121b toward the other end in the longitudinal direction L. The first lower straight portion 121c has the same width as the first upper straight portion 111b.

[0052] In this embodiment, a substantially U-shaped recessed groove portion 122 with an open portion facing the other end side in the longitudinal direction L is formed on the upper surface of the lower flow path forming member 12 closer to the one end side in the longitudinal direction L than the center part in the longitudinal direction L. The inner part of the recessed groove portion 122 in the lower flow path forming member 12 constitutes a semicircular portion 121a, a lower tapered portion 121b, and a first lower straight portion 121c.

[0053] The lower narrow width portion 121d is a portion corresponding to the upper narrow width portion 111c of the upper flow path forming member 11, and is a portion where the width of the lower wall portion 121 narrows. In the present embodiment, the lower narrow width portion 121d connects the first lower straight portion 121c and the second lower straight portion 121e. Specifically, in the present embodiment, the second lower straight portion 121e is narrower than the first lower straight portion 121c and has the same width as the second upper straight portion 111d of the upper flow path forming member 11. The lower narrow width portion 121d is formed in a tapered shape in which its width gradually narrows from the width of the first lower straight portion 121c to the width of the second lower straight portion 121e, connecting the first lower straight portion 121c and the second lower straight portion 121e. Lower narrow portion 121d has the same taper angle as upper narrow portion 111c. If upper narrow portion 111c is configured with, for example, one or more step shapes or multiple tapered shapes, lower narrow portion 121d will also be configured with one or more step shapes or multiple tapered shapes accordingly.

[0054] The second lower straight portion 121e is a portion corresponding to the second upper straight portion 111d of the upper flow path forming member 11. As described above, the second lower straight portion 121e is formed to be narrower than the first lower straight portion 121c (having the same width as the second upper straight portion 111d), and extends linearly from the lower narrow portion 121d toward the other end in the longitudinal direction L.

[0055] In this embodiment, a substantially U-shaped cutout hole 123 with its open portion facing the one end in the longitudinal direction L is formed in the lower flow path forming member 12, closer to the other end in the longitudinal direction L than the center of the lower flow path forming member 12 in the longitudinal direction L. The inner portion of the cutout hole 123 in the lower flow path forming member 12 constitutes the lower narrow portion 121d and the second lower straight portion 121e. The upper surfaces of the lower narrow portion 121d and the second lower straight portion 121e are inclined so that their height positions gradually decrease with increasing distance from the tip end of the first lower straight portion 121c. As will be described later, the lower narrow portion 121d and the second lower straight portion 121e constitute the lower wall of the separation flow path 32. Therefore, the inclination angle of the upper surfaces of the lower narrow portion 121d and the second lower straight portion 121e is set to a range of 1° to 45°, preferably 2° to 10°, with respect to the horizontal. A part of the other end side of the cutout hole 123 in the longitudinal direction L forms an accommodating space 5 in which the first liquid absorbent material 4 is accommodated.

[0056] A recess 124 is formed on the lower surface of the lower flow path forming member 12, closer to the one end in the longitudinal direction L than the center in the longitudinal direction L. The recess 124 has a size that can accommodate at least most of the lower tapered portion 121b of the lower wall portion 121, as viewed from above. A back plate 15, which will be described later, is housed in this recess 124.

[0057] Furthermore, a plurality of (six in this case) pins 125 are provided at intervals from one another to protrude from the peripheral edge of the lower surface of the lower flow path forming member 12. Although six pins 125 are provided in this case, the number of pins 125 can be set arbitrarily.

[0058] Fig. 6 shows the intermediate member 13. Fig. 6(a) is a top view of the intermediate member 13, and Fig. 6(b) is a side view of the intermediate member 13.

[0059] 6(a) and 6(b), the intermediate member 13 has a rectangular outer shape in a top view so as to correspond to the upper flow path forming member 11 and the lower flow path forming member 12. The intermediate member 13 has a small dimension in the height direction H (i.e., thickness) and has a second opening 13a penetrating the intermediate member 13 in the height direction H on the inside. The dimension (thickness) of the intermediate member 13 in the height direction H can be set according to the required height of the microchannel 31. The second opening 13a has a size sufficient to accommodate the injection port 2, the upper wall portion 111, the pair of first openings 112, 112, and the through-holes 113, 113 formed in the upper flow path forming member 11, in a top view. The upper and lower surfaces of the intermediate member 13 are formed as adhesive surfaces. As an example, the intermediate member 13 can be formed by arranging double-sided adhesive sheets on the upper and lower surfaces of a sheet material. In this case, for example, by appropriately selecting a sheet material having an arbitrary thickness, it is possible to freely change the dimension of the intermediate member 13 in the height direction H, and therefore the height of the microchannel 31. Furthermore, it is only necessary that the intermediate member 13 does not allow liquid to penetrate at least the portion that functions as a spacer (spacer portion), and it is also possible to freely change the shape and type of the intermediate member 13.

[0060] Then, the lower surface of the upper flow path-forming member 11 is joined to the upper surface of the intermediate member 13, and the upper surface of the lower flow path-forming member 12 is joined to the lower surface of the intermediate member 13, so that the upper flow path-forming member 11, the lower flow path-forming member 12, and the intermediate member 13 are stacked and integrated, thereby forming the internal flow path 3 and the internal ventilation space 7. Here, in actual assembly, when the upper flow path-forming member 11, the lower flow path-forming member 12, and the intermediate member 13 are integrated, the lower absorbent 4b of the first liquid absorbent 4 is accommodated in a predetermined position (accommodation space 5) of the cutout hole 123 of the lower flow path-forming member 12.

[0061] 7A and 7B are diagrams illustrating the internal flow path 3 and the internal ventilation space 7. Fig. 7A is a view of the upper flow path-forming member 11 and the intermediate member 13 viewed from the lower flow path-forming member 12 side, and mainly shows the upper part of the internal flow path 3. Fig. 7B is a view of the lower flow path-forming member 12 viewed from the intermediate member 13 side, and mainly shows the lower part of the internal flow path 3. The two-dot chain lines in the figure indicate the first liquid absorbent material 4 (upper absorbent material 4a, lower absorbent material 4b) and the assay region 31c.

[0062] In this embodiment, the upper tapered portion 111a and the first upper straight portion 111b of the upper wall portion 111 of the upper flow path forming member 11 form the upper wall of the microflow path 31 in the internal flow path 3, and the semicircular portion 121a, the lower tapered portion 121b and the first lower straight portion 121c of the lower wall portion 121 of the lower flow path forming member 12 form the lower wall of the microflow path 31 in the internal flow path 3. Furthermore, the upper narrow portion 111c and the second upper straight portion 111d of the upper wall portion 111 of the upper flow path forming member 11 form the upper wall of the separation flow path 32 in the internal flow path 3, and the lower narrow portion 121d and the second lower straight portion 121e of the lower wall portion 121 of the lower flow path forming member 12 form the lower wall of the separation flow path 32 in the internal flow path 3.

[0063] That is, the microchannel 31 extends from a position corresponding to the inlet 2, i.e., a position below the inlet 2 where the microchannel 31 can receive a liquid injected through the inlet 2, toward the separation channel 32, and is formed as a channel having a tapered channel section 311 whose channel width gradually narrows with increasing distance from the inlet 2. More specifically, in this embodiment, the microchannel 31 is formed as a channel having the tapered channel section 311 and a first straight channel section 312 of a constant channel width that extends from the tip of the tapered channel section 311 to the separation channel 32. Here, the tapered channel section 311 is defined by an upper tapered section 111a and a lower tapered section 121b, and has a taper angle of 1° to 20°, preferably 2° to 16°. The first straight channel section 312 is defined by a first upper straight section 111b and a first lower straight section 121c. Although not particularly limited, the channel width near the inlet of the microchannel 31 (i.e., near the injection port 2) may be, for example, 2 mm or more and 10 mm or less, preferably 4 mm or more and 10 mm or less, and the channel width near the outlet of the microchannel 31 (i.e., near the separation channel 32) may be, for example, 1 mm or more and 6 mm or less, preferably 3 mm or more and 6 mm or less.

[0064] Furthermore, the separation channel 32 is formed as a channel extending from the microchannel 31 toward the first liquid absorbent 4, and has a narrow width portion 321 where the channel width narrows. The narrow width portion 321 is provided contiguous to or adjacent to the microchannel 31. Here, "provided adjacent to the microchannel 31" means being provided in the immediate vicinity of the microchannel 31, and includes the case where a portion that does not significantly affect the flow of liquid is interposed between the microchannel 31 and the narrow width portion 321. More specifically, in this embodiment, the separation channel 32 is formed as a channel having the narrow width portion 321 provided contiguous to or adjacent to the microchannel 31, and a second straight channel portion 322 that extends from the narrow width portion 321 to reach the first liquid absorbent 4 and has a channel width narrower than the first straight channel portion 312 of the microchannel 31. In this embodiment, the narrow width portion 321 is formed in a tapered shape such that the channel width gradually narrows from the channel width of the first straight channel portion 312 of the microchannel 31 to the channel width of the second straight channel portion 322. The lower wall of the separation channel 32 is inclined downward so that the height position decreases as it approaches the first liquid absorbent 4. The narrow width portion 321 is defined by the upper narrow width portion 111c and the lower narrow width portion 121d, and the second straight channel portion 322 is defined by the second upper straight portion 111d and the second lower straight portion 121e. Although not particularly limited, the channel width near the inlet of the narrow width portion 321 may be the same as the channel width near the outlet of the microchannel 31. That is, the channel width near the inlet of the narrow width portion 321 may be, for example, 1 mm to 6 mm, preferably 3 mm to 6 mm. The width of the flow path near the outlet of the narrow portion 321 may be, for example, 0.5 mm or more and 5 mm or less, and preferably 1 mm or more and 4 mm or less.

[0065] Furthermore, an internal ventilation space 7 (side spaces 7a, 7a and connecting space 7b) is formed by a substantially U-shaped recessed groove portion 122 formed in the upper surface of the lower flow-path forming member 12 closer to the one end in the longitudinal direction L than the center in the longitudinal direction L, and the space above the recessed groove portion 122. A pair of first openings 112, 112 formed in the upper flow-path forming member 11 are located above the side spaces 7a, 7a of the internal ventilation space 7 and communicate with the side spaces 7a, 7a.

[0066] Next, other configurations of the assay device 1 will be described with reference to FIGS.

[0067] In addition to the above-mentioned first liquid absorbent 4 (upper absorbent 4a and lower absorbent 4b), upper flow path forming member 11, lower flow path forming member 12, and intermediate member 13, the assay device 1 further has an upper cover 14, a back panel 15, a second liquid absorbent 16, and a lower case 17.

[0068] The upper cover 14 is made of, for example, synthetic resin and formed in a flat plate shape. Preferably, the upper cover 14 is a molded product of synthetic resin. The upper cover 14 is attached (adhered) to the upper surface of the upper flow path forming member 11 (the thin portion 11b thereof) via a double-sided adhesive sheet 18 formed in substantially the same shape as the upper cover 14.

[0069] The upper cover 14 has ventilation holes 141, 141 that connect the internal ventilation space 7 with the outside. The ventilation holes 141, 141 are arranged above a pair of first openings 112, 112 of the upper flow path forming member 11 that communicate with the internal ventilation space 7 (side spaces 7a, 7a).

[0070] Additionally, the upper cover 14 is formed with observation windows 142, 142 through which an observer can observe (the detectable result occurring in) the assay region 31c of the microchannel 31. The observation windows 142, 142 are disposed above the assay region 31c of the microchannel 31, more specifically, above the first assay reagent 6a and the second assay reagent 6b.

[0071] Furthermore, the upper cover 14 is formed with confirmation / ventilation windows 143, 143 that connect the storage space 5 that stores the first liquid absorbent material 4 with the outside and that allow the state (liquid absorption status, etc.) of the first liquid absorbent material 4 to be confirmed. The confirmation / ventilation windows 143, 143 are arranged above the first liquid absorbent material 4 and above the two through holes 113, 113 of the upper flow path forming member 11.

[0072] The back plate 15 is made of a white or black synthetic resin and is preferably a molded synthetic resin. The back plate 15 is accommodated in a recess 124 formed in the lower surface of the lower flow-path forming member 12. As described above, in this embodiment, the upper flow-path forming member 11 and the lower flow-path forming member 12 that form the internal flow path 3 are formed to be transparent. The recess 124 formed in the lower surface of the lower flow-path forming member 12 is large enough to accommodate most of the lower tapered portion 121b of the lower wall portion 121 that forms the lower wall of the microflow path 31. Therefore, by being accommodated in the recess 124 formed in the lower surface of the lower flow-path forming member 12, the back plate 15 is positioned below the assay region 31c of the microflow path 31. The back plate 15 accommodated in the recess 124 provides a white or black background for the assay region 31c, thereby facilitating an observer's observation of the assay region 31c (the detectable result occurring therein) through the observation windows 142.

[0073] Therefore, it is preferable that the color of the back plate 15 be appropriately selected depending on the detectable result occurring in the assay region 31 c. For example, when an observer needs to observe color development, absorbance, or the like through the observation windows 142, 142, a white back plate 15 is selected, and when an observer needs to observe luminescence, fluorescence, or the like through the observation windows 142, 142, a black back plate 15 is selected.

[0074] The second liquid absorbent 16 is formed of a porous material capable of absorbing liquid, similar to the first liquid absorbent 4. The second liquid absorbent 16 is formed larger than the first liquid absorbent 4 and is disposed below the first liquid absorbent 4 and the lower flow path forming member 12. The second liquid absorbent 16 absorbs liquid mainly via the first liquid absorbent 4.

[0075] The lower case 17 is made of, for example, synthetic resin, and is preferably a molded product of synthetic resin. The lower case 17 has an upper opening containing section 171 for containing the second liquid absorbent 16, and a support surface 172 for supporting the lower surface of the back plate 15 contained in a recess 124 formed in the lower surface of the lower flow path forming member 12. In addition, six pin holes 173 are formed on the periphery of the upper surface of the lower case 17, into which six pins 125 protruding from the lower surface of the lower flow path forming member 12 are fitted.

[0076] Next, we will briefly explain an example of an assembly method (manufacturing method) of the assay device 1. In this embodiment, the first assay reagent 6a and the second assay reagent 6b are assumed to be fixed to desired positions on the upper wall portion 111 (upper tapered portion 111a) of the upper flow path forming member 11 and / or the lower wall portion 121 (lower tapered portion 121b) of the lower flow path forming member 12 using a known immobilization technique, i.e., they are assumed to be placed in the assay region 31c, and therefore a description thereof will be omitted here.

[0077] First, the second liquid absorbent material 16 is housed in the housing portion 171 of the lower case 17 .

[0078] Next, the pin 125 of the lower flow path forming member 12 is fitted into the pin hole 173 of the lower case 17, thereby attaching the lower flow path forming member 12 to the lower case 17. At this time, the lower absorbent 4b of the first liquid absorbent 4 is accommodated in the other end side (accommodation space 5) in the longitudinal direction L of the cutout hole 123 of the lower flow path forming member 12, and the back plate 15 is accommodated in the recess 124 formed in the lower surface of the lower flow path forming member 12. Here, although not shown in the drawings, instead of or in addition to fitting the pin 125 into the pin hole 173, the lower flow path forming member 12 may be attached to the lower case 17 using a double-sided adhesive sheet or the like.

[0079] Next, the upper absorbent material 4a of the first liquid absorbent material 4 is accommodated in the other end side (accommodation space 5) in the longitudinal direction L of the cutout hole 123 of the lower flow path forming member 12. In other words, the upper absorbent material 4a is placed on the lower absorbent material 4b.

[0080] Next, the intermediate member 13 and the upper flow path-forming member 11 are placed on the lower flow path-forming member 12 while being aligned. That is, the lower surface (adhesion surface) of the intermediate member 13 is joined to the upper surface of the lower flow path-forming member 12, and the lower surface of the upper flow path-forming member 11 is joined to the upper surface (adhesion surface) of the intermediate member 13. Alternatively, the upper flow path-forming member 11 is first joined to the upper surface of the intermediate member 13, and then the lower surface of the intermediate member 13 is joined to the upper surface of the lower flow path-forming member 12. As a result, the upper flow path-forming member 11, the lower flow path-forming member 12, and the intermediate member 13 are integrated in a stacked state, and the internal flow path 3 and the internal ventilation space 7 are formed. This state is shown in FIG. 8.

[0081] Next, a blocking treatment is performed on the internal flow channel 3. In this embodiment, a predetermined amount of blocking agent is injected dropwise into the injection port 2, followed by incubation for a predetermined time (for example, 1 hour). The blocking agent used is not particularly limited, but may be a diluted or undiluted solution of the above-mentioned commercially available blocking agent. Here, since the blocking agent may reduce the interfacial tension of the liquid in the microflow channel 31, it is preferable to remove any excess blocking agent from the injected blocking agent.

[0082] In this regard, in this embodiment, as shown in Fig. 8, when a blocking treatment is performed on the internal flow path 3, a pair of first openings 112, 112 formed in the upper flow path forming member 11 are exposed on the upper surface. The pair of first openings 112, 112 are located above and communicate with the side spaces 7a, 7a of the internal ventilation space 7, and the side spaces 7a, 7a of the internal ventilation space 7 are adjacent to and communicate with the microflow path 31 on both sides in the width direction of the microflow path 31. Therefore, by inserting the tip nozzle of a suction machine or the like into the first openings 112 and performing suction, it is possible to easily and effectively remove excess blocking agent.

[0083] After the blocking process for the internal flow path 3 is completed, the upper cover 14 is attached (pasted) to the upper surface of the thin-walled portion 11b of the upper flow path forming member 11 using a double-sided adhesive sheet 18 or the like, thereby completing the assay device 1 (see FIG. 1).

[0084] Next, the movement of the liquid in the assay device 1 will be described with reference to FIGS.

[0085] 9 is a diagram for explaining the movement of a liquid (hereinafter referred to as "first liquid LQ1") injected into the assay device 1, and shows a schematic diagram of the internal flow path 3 and the like when the assay device 1 is viewed from above. In FIG. 9, the first liquid LQ1 is indicated by hatching.

[0086] 9(a), the first liquid LQ1 enters (is supplied to) the microchannel 31. Here, the microchannel 31 has a tapered channel section 311 in which the channel width gradually narrows from the vicinity of the injection port 2 toward the separation channel 32. Therefore, the first liquid LQ1 that enters the microchannel 31 flows smoothly toward the separation channel 32.

[0087] As the injection of the first liquid LQ1 continues and an amount of the first liquid LQ1 supplied to the microchannel 31 exceeds its capacity, the first liquid LQ1 flows into the separation channel 32. Here, the bottom wall of the separation channel 32 is inclined downward so that the height position becomes lower the closer it is to the first liquid absorbent material 4. For this reason, as shown in FIG. 9(b), the first liquid LQ1 that has flowed into the separation channel 32 flows through the separation channel 32 toward the first liquid absorbent material 4 and comes into contact with the first liquid absorbent material 4. The first liquid LQ1 is then absorbed into the first liquid absorbent material 4 by the capillary force of the first liquid absorbent material 4.

[0088] Thereafter, when the injection of the first liquid LQ1 is stopped, the first liquid LQ1 from the injection port 2 flows through the microchannel 3 (towards the liquid absorbent 4), and then the first liquid LQ1 in the microchannel 31 stops flowing into the separation channel 32. At this time, the capillary force of the first liquid absorbent 4 acts on the first liquid LQ1, and so the first liquid LQ1 is pulled by the microchannel 31 and the first liquid absorbent 4, as shown by the arrows in Figure 9(c).

[0089] Here, in this embodiment, the separation channel 32 located between the microchannel 31 and the first liquid absorbent 4 has a narrow width portion 321 where the channel width is narrowed. Furthermore, the narrow width portion 321 is provided continuous with or adjacent to the microchannel 31. For this reason, the first liquid LQ1 in the microchannel 31 on the upstream side of the narrow width portion 321 is strongly retained in the microchannel 31 due to interfacial tension, and the first liquid LQ1 in the microchannel 31 is prevented from passing over the narrow width portion 321 and flowing downstream. On the other hand, the first liquid LQ1 on the downstream side of the narrow width portion 321 is sucked in by the capillary force of the first liquid absorbent 4. As a result, the first liquid LQ1 in the internal flow channel 3 is divided by the narrow portion 321 of the separation flow channel 32, and as shown in FIG. 9(d), a portion of it (the portion on the downstream side of the narrow portion 321) is absorbed by the first liquid absorbent 4, while the remainder is retained on the upstream side of the narrow portion 321, that is, mainly within the microflow channel 31. As a result, the first liquid LQ1 in the internal flow channel 3 is separated into a portion absorbed by the first liquid absorbent 4 and a portion retained within the microflow channel 31. As such, in this embodiment, the provision of the narrow portion 321 in the separation flow channel 32 prevents the first liquid LQ1, which has a small (weak) interfacial tension, from being sucked from the microflow channel 31 into the first liquid absorbent 4 due to the capillary force of the first liquid absorbent 4. As a result, the first liquid LQ1 in the internal flow channel 3 is stably divided by the separation flow channel 32; in other words, the first liquid LQ1 can be stably retained within the microflow channel 31. Then, as the first liquid LQ1 remains in the assay region 31c, the first assay reagent 6a and / or the second assay reagent 6b react with the first liquid LQ1 or the sample contained therein, producing the detectable result. In other words, an assay is performed in the assay region 31c.

[0090] 10 is a diagram for explaining the movements of the first liquid LQ1 and the second liquid LQ2 when a new liquid (hereinafter referred to as the "second liquid LQ2") is injected after the injection of the first liquid LQ1 into the assay device 1 has stopped, and it schematically shows the internal flow path 3 and the like when viewed from above the assay device 1. In Fig. 10, the first liquid LQ1 is shown with the same hatching as in Fig. 9, and the second liquid LQ2 is shown with hatching different from that of the first liquid LQ1.

[0091] 10(a), when the second liquid LQ2 is injected after the injection of the first liquid LQ1 is stopped, the second liquid LQ2 enters (is supplied to) the microchannel 31 and flows toward the separation channel 32, just as in the case of the first liquid LQ1. Here, as described above, the first liquid LQ1 is retained in the microchannel 31. The first liquid LQ1 retained in the microchannel 31 is pushed out of the microchannel 31 by the newly injected second liquid LQ2, flows through the separation channel 32, and comes into contact with the first liquid absorbent 4, where it is absorbed by the first liquid absorbent 4.

[0092] As the injection of the second liquid LQ2 continues, and an amount of the second liquid LQ2 that exceeds the capacity of the microchannel 31 is supplied, in other words, an amount of the second liquid LQ2 that exceeds the amount of the first liquid LQ1 that had been retained in the microchannel 31, all of the first liquid LQ1 that had been retained in the microchannel 31 is pushed out of the microchannel 31. As a result, the first liquid LQ1 is replaced with the second liquid LQ2 in the microchannel 31. In other words, liquid exchange occurs in the microchannel 31. Then, as the second liquid LQ2 is further injected, the second liquid LQ2 flows from the microchannel 31 into the separation channel 32, and flows through the separation channel 32 toward the first liquid absorbent 4, coming into contact with the first liquid absorbent 4. As a result, the second liquid LQ2, following the first liquid LQ1, is absorbed by the first liquid absorbent 4 due to the capillary force of the first liquid absorbent 4.

[0093] Thereafter, when the injection of the second liquid LQ2 is stopped, the second liquid LQ2 from the injection port 2 flows through the microchannel 3 (towards the liquid absorbent 4), and then the second liquid LQ2 in the microchannel 31 stops flowing into the separation channel 32. At this time, the capillary force of the first liquid absorbent 4 acts on the second liquid LQ2, and therefore, as shown in FIG. 10( c), the microchannel 31 and the first liquid absorbent 4 pull on the second liquid LQ2, similar to the case of the first liquid LQ1. Then, similar to the case of the first liquid LQ1, the second liquid LQ2 in the microchannel 31 on the upstream side of the narrow portion 321 is strongly retained in the microchannel 31 by interfacial tension, and the second liquid LQ2 in the microchannel 31 is prevented from passing over the narrow portion 321 and flowing downstream. On the other hand, the second liquid LQ2 on the downstream side of the narrow portion 321 is sucked in by the capillary force of the first liquid absorbent 4. 10(d), a portion of the second liquid LQ2 (the portion on the downstream side of the narrow portion 321) is absorbed by the first liquid absorbent material 4, and the remainder is retained on the upstream side of the narrow portion 321, that is, mainly within the microchannel 31. Furthermore, as the second liquid LQ2 remains within the microchannel 31, an assay is carried out in the assay region 31c, just as in the case of the first liquid LQ1.

[0094] In this way, in the assay device 1, because the separation channel 32 is provided with the narrow width portion 321, even if the liquid has a small (weak) interfacial tension, the liquid in the internal channel 3 is stably separated by the separation channel 32 after the injection of the liquid is stopped, and can stably remain in the microchannel 31. Then, when a liquid (for example, the first liquid LQ1) is retained in the microchannel 31, new liquid (for example, the second liquid LQ2) is injected in an amount that exceeds the amount of the liquid (for example, the first liquid LQ1) retained in the microchannel 31, thereby performing liquid exchange in the microchannel 31. In other words, the assay device 1 can stably perform liquid exchange in the microchannel 31 even for liquids with a small (weak) interfacial tension. Such stable liquid exchange can facilitate the generation of multistage antigen-antibody reactions in ELISA and other methods.

[0095] The assay device 1 according to the embodiment provides the following effects.

[0096] In the assay device 1 according to the embodiment, the separation channel 32 is provided adjacent to or continuous with the microchannel 31 and has a narrow portion 321 where the channel width is narrowed.

[0097] In the assay device 1, when the injection of liquid is stopped, the liquid in the injection port 2 flows toward the first liquid absorbent 4, and then the microchannel 31 and the first liquid absorbent 4 start to pull on each other (see FIGS. 9(c) and 10(c)). At this time, due to the presence of the narrow portion 321, the liquid in the microchannel 31 tries to remain in the microchannel 31 strongly due to its own interfacial tension. Therefore, even if the interfacial tension of the liquid is small, the liquid in the microchannel 31 is prevented from being sucked in by the capillary force of the first liquid absorbent 4 and flowing out of the microchannel 31. As a result, even if the interfacial tension of the liquid is small, the liquid in the internal channel 3 is stably separated at the narrow portion 321 of the separation channel 32, and the liquid can be stably retained in the microchannel 31. Therefore, there is almost no risk of air being mixed into the microchannel 31, and liquid exchange in the microchannel 31 is stably performed, allowing the assay in the microchannel 31 to proceed stably.

[0098] Here, an example of a liquid with low interfacial tension is a liquid containing a relatively large amount of surfactant. The inventors conducted experiments and confirmed that, in the assay device 1 according to the embodiment, a liquid containing a larger amount of surfactant is separated at the narrow portion 321 of the separation channel 32 and remains sufficiently within the microchannel 31 compared to conventional assay devices. Some of these examples are shown below.

[0099] When the surfactant is a polyoxyethylene sorbitan fatty acid ester such as Tween 20 (usage concentration: 0.05 to 1 wt%), conventional assay devices may not be able to retain a liquid containing 0.5 wt% or more of the surfactant sufficiently within the microchannel. In contrast, the assay device 1 according to the embodiment is able to retain a liquid containing 5 to 10 wt% of the surfactant sufficiently within the microchannel 31. In other words, the assay device 1 according to the embodiment can perform an assay using a liquid containing the surfactant without any problems in practical use.

[0100] Furthermore, when the surfactant is a polyoxyethylene alkylphenyl ether such as Triton X-100 (usage concentration: 0.1 to 2.0 wt%), conventional assay devices may not be able to retain a liquid containing 0.5 wt% or more of the surfactant sufficiently within the microchannel. In contrast, the assay device 1 according to the embodiment is able to retain a liquid containing 2.0 wt% of the surfactant sufficiently within the microchannel 31. In other words, the assay device 1 according to the embodiment can perform an assay using a liquid containing the surfactant without any problems in practical use.

[0101] Furthermore, when the surfactant is a polyethylene glycol surfactant such as PEIS-8 (polyethylene glycol monoisostearate), conventional assay devices may not be able to retain a liquid containing 0.05 wt% or more of the surfactant in the microchannel 31. In contrast, the assay device 1 according to the embodiment was able to retain a liquid containing 1.0 wt% of the surfactant in the microchannel 31.

[0102] To summarize, the assay device 1 of the embodiment is capable of performing assays using liquids containing 1.0 wt% or more surfactant, which was not possible to perform stably with conventional assay devices.

[0103] In the assay device 1 according to the embodiment, the microchannel 31 has a tapered channel section 311 that extends from the vicinity of the inlet 2, more specifically, from a position that can receive the liquid injected from the inlet 2, toward the separation channel 32, and whose channel width gradually narrows as it moves away from the inlet 2.

[0104] Therefore, the liquid injected from the injection port 2 moves smoothly through the microchannel 31 toward the separation channel 32, and the reaction in the assay region 31c can also be carried out stably.

[0105] In the assay device 1 according to the embodiment, the narrow section 321 of the separation channel 32 is formed in a tapered shape in which the channel width gradually narrows from the channel width of the first straight channel section 312 of the microchannel 31 to the channel width of the second straight channel section 322, which is narrower than the channel width of the first straight channel section 312.

[0106] Therefore, the liquid in the internal flow path 3 can be stably separated at the narrow width portion 321, and the liquid is prevented from accumulating in the narrow width portion 321.

[0107] In the assay device 1 according to the embodiment, the internal flow path 3 (micro flow path 31 and separation flow path 32) is formed by stacking an upper flow path forming member 11 having an injection port 2 and an upper wall portion 111 that forms the upper wall of the internal flow path 3, a lower flow path forming member 12 having a lower wall portion 121 that forms the lower wall of the internal flow path 3, and an intermediate member 13 that functions as a spacer between the upper flow path forming member 11 and the lower flow path forming member 12.

[0108] This facilitates the formation of an internal flow path 3 with an appropriate height, and in turn the manufacture of the assay device 1. At least the upper flow path forming member 11 and the lower flow path forming member 12 can be made of molded synthetic resin, which reduces manufacturing costs. Furthermore, because no seams are created between the injection port 2 and the internal flow path 3 (microflow path 31) or along the internal flow path 3, the movement of the liquid injected into the injection port 2 into the internal flow path 3 (microflow path 31) and within the internal flow path 3 can be ensured.

[0109] In the assay device 1 according to the embodiment, a pair of lateral spaces 7a, 7a adjacent to and communicating with the microchannel 31 are provided on both sides of the width direction W of the microchannel 31, and a pair of first openings 112, 112 located above and communicating with the pair of lateral spaces 7a, 7a are formed in the upper channel forming member 11.

[0110] Therefore, for example, when performing a blocking treatment on the internal flow channel 3, the pair of first openings 112, 112 can be used to easily suck and remove excess blocking agent. This can prevent the interfacial tension of the liquid in the microflow channel 31 from decreasing due to the influence of the blocking agent. Furthermore, because the blocking agent can be sucked through the pair of first openings 112, 112, it is possible to avoid performing a blocking treatment on the separation flow channel 32. In this way, the surface of the separation flow channel 32 does not become hydrophilic, making it easier to stably separate the liquid in the internal flow channel 3 at the separation flow channel 32.

[0111] In the assay device 1 according to the embodiment, the upper flow path forming member 11 and the lower flow path forming member 12 are transparent. The assay device 1 according to the embodiment further includes observation windows 142, 142 provided above the assay region 31c of the microflow path 31 for observing the assay region 31c from the outside, and a white or black back panel 15 located below the assay region 31c of the microflow path 31. More specifically, the observation windows 142, 142 are located above the first assay reagent 6a and the second assay reagent 6b.

[0112] Therefore, when an observer observes the assay region 31c with the naked eye or using a predetermined device through the observation windows 142, 142, the background of the assay region 31c may appear white or black, which makes it possible to detect the detectable result relatively easily even if it is a weak signal (such as luminescence or fluorescence).

[0113] In the above-described embodiment, the microchannel 31 has the tapered channel portion 311 and the first straight channel portion 312. However, this is not limitative. The entire microchannel 31 may be formed as a straight channel with a constant channel width.

[0114] In this case, as shown in Figure 11(a) corresponding to Figure 4(a), the upper tapered portion 111a is omitted from the upper wall portion 111 of the upper flow path forming member 11, and a first upper straight portion 111b is formed so as to extend from the end of the thin portion 11b on the thick portion 11a side, i.e., from the vicinity of the injection port 2, toward the upper narrow portion 111c. Also, as shown in Figure 11(b) corresponding to Figure 5(a), the lower tapered portion 121b is omitted from the lower wall portion 121 of the lower flow path forming member 12, and a first lower straight portion 121c is formed so as to extend from the semicircular portion 121a toward the lower narrow portion 121d. The first upper straight portion 111b of the upper wall portion 111 of the upper flow path forming member 11 constitutes the upper wall of the microflow path 31 in the internal flow path 3, and the semicircular portion 121a and the first lower straight portion 121c of the lower wall portion 121 of the lower flow path forming member 12 constitute the lower wall of the microflow path 31 in the internal flow path 3. The upper narrow portion 111c and the second upper straight portion 111d of the upper wall portion 111 of the upper flow path forming member 11 constitute the upper wall of the separation flow path 32 in the internal flow path 3, and the lower narrow portion 121d and the second lower straight portion 121e of the lower wall portion 121 of the lower flow path forming member 12 constitute the lower wall of the separation flow path 32 in the internal flow path 3. In other words, the microchannel 31 is defined by the first upper straight portion 111b and the first lower straight portion 121c, and the separation channel 32 has a narrow portion defined by the upper narrow portion 111c and the lower narrow portion 121d, and a straight channel portion defined by the second upper straight portion 111d and the second lower straight portion 121e.

[0115] Alternatively, the entire microchannel 31 may be formed as a tapered channel. Although not shown in the drawings, in this case, the first upper straight portion 111b is omitted from the upper wall portion 111 of the upper channel-forming member 11, and, for example, the upper narrow portion 111c is formed with a taper angle larger than the taper angle of the upper tapered portion 111a. Similarly, the first lower straight portion 121c is omitted from the lower wall portion 121 of the lower channel-forming member 12, and, for example, the lower narrow portion 121d is formed with a taper angle larger than the taper angle of the lower tapered portion 121b.

[0116] Furthermore, in the above-described embodiment, the narrow width portion 321 of the separation channel 32 is provided continuous with or adjacent to the microchannel 31. However, this is not limited to this. The narrow width portion 321 of the separation channel 32 may be provided at a position separated from the microchannel 31. However, from the viewpoint of efficiently exchanging liquid within the microchannel 31, it is preferable that the narrow width portion 321 of the separation channel 32 is provided continuous with or adjacent to the microchannel 31, particularly continuous with the microchannel 31, as in the above-described embodiment.

[0117] Furthermore, in the above-described embodiment, the upper flow-path-forming member 11 and the lower flow-path-forming member 12 are transparent, the observation windows 142, 142 are provided above the assay region 31c of the microchannel 31, and a white or black back plate 15 is disposed below the assay region 31c of the microchannel 31. However, this is not limited to this. The upper flow-path-forming member 11 may be transparent, while the lower flow-path-forming member 12 may be formed in white or black. That is, the upper flow-path-forming member 11 may be formed from a transparent synthetic resin, and the lower flow-path-forming member 12 may be formed from a white or black synthetic resin. In this case, the back plate 15 is not necessary. Furthermore, the color of the lower flow-path-forming member 12 is selected according to the detectable result occurring in the assay region 31c, as in the case of the back plate 15. This configuration also achieves the same effects as the above-described embodiment.

[0118] [Second embodiment] Figures 12 and 13 show an assay device 10 according to a second embodiment. Figure 12 is a perspective view of the assay device 10, and Figure 13 is an exploded perspective view of the assay device 10. In Figures 12 and 13, elements common to the assay device 1 according to the first embodiment are designated by the same reference numerals and their description will be omitted.

[0119] The main difference between the assay device 1 according to the first embodiment and the assay device 10 according to the second embodiment is that the assay device 1 according to the first embodiment is provided with one injection port 2 and one internal flow path 3, whereas the assay device 10 according to the second embodiment is provided with multiple injection ports 2 and multiple internal flow paths 3 (three of each in this case), and accordingly, additional features such as an air vent 141 and an observation window 142 are also provided. Other configurations are basically the same.

[0120] The assay device 10 according to the second embodiment also provides the same effects as the assay device 1 according to the first embodiment. Furthermore, the assay device 10 according to the second embodiment can simultaneously and parallelly assay a plurality of liquids. Note that the modified examples of the first embodiment can also be applied to the second embodiment.

[0121] The above describes an embodiment of the present invention and its modified examples, but the present invention is not limited to the above-described embodiment, and it goes without saying that modifications and changes can be made based on the technical concept of the present invention. [Explanation of symbols]

[0122] DESCRIPTION OF SYMBOLS 1, 10... assay device, 2... inlet, 3... internal flow path, 4... first liquid absorbent, 4a... upper absorbent, 4b... lower absorbent, 5... storage space, 6a... first assay reagent, 6b... second assay reagent, 7... internal ventilation space, 7a... side space, 7b... connecting space, 11... upper flow path forming member, 12... lower flow path forming member, 13... intermediate member, 14... upper cover, 15... rear panel, 16... second liquid absorbent, 17... lower case, 31... micro flow path, 31c... assay region, 32... separation flow path, 111... upper wall portion, 121... lower wall portion, 142... observation window, 311... tapered flow path portion, 312... first straight flow path portion, 321... narrow width portion, 322... second straight flow path portion, LQ1... first liquid, LQ2... second liquid

Claims

1. An inlet; an internal flow path through which the liquid injected from the injection port flows; a liquid absorbent material that absorbs liquid that has passed through the internal flow path; 1. An assay device comprising: The internal flow path is a microchannel having an assay region; a separation flow path provided between the micro flow path and the liquid absorbent material, for separating the liquid in the internal flow path when the injection of the liquid is stopped; Including, the separation channel has a narrow portion where the channel width is narrowed, the internal flow path is formed by stacking an upper flow path-forming member on which the injection port and an upper wall portion constituting an upper wall of the internal flow path are formed, a lower flow path-forming member on which a lower wall portion constituting a lower wall of the internal flow path is formed, and an intermediate member that functions as a spacer between the upper flow path-forming member and the lower flow path-forming member, a pair of side spaces adjacent to and communicating with the microchannel are provided on both sides of the microchannel in a width direction; The upper flow path forming member has a pair of openings formed therein that are located above and communicate with the pair of side spaces. Assay device.

2. The narrow width portion is provided continuous with or adjacent to the microchannel. The assay device of claim 1 .

3. the microchannel extends from a position capable of receiving a liquid injected from the injection port toward the separation channel, and has a tapered channel portion whose channel width gradually narrows as it extends away from the injection port; The assay device of claim 1 .

4. the microchannel has the tapered channel section and a first straight channel section having a constant channel width that extends from a tip end of the tapered channel section to the separation channel, the separation flow path has the narrow width portion and a second straight flow path portion that extends from the narrow width portion to the liquid absorbent material and has a constant flow path width that is narrower than the flow path width of the first straight flow path portion, the narrow width portion is formed in a tapered shape in which the flow path width gradually narrows from the flow path width of the first straight flow path portion to the flow path width of the second straight flow path portion. The assay device of claim 3 .

5. the upper flow path forming member and the lower flow path forming member are transparent, an observation window provided above the assay region of the microchannel for observing the assay region from outside; a white or black back plate disposed below the assay region of the microchannel; further comprising The assay device of claim 1 .

6. the upper flow path forming member is transparent, The lower flow path forming member is formed in white or black, The assay region may further include an observation window provided above the assay region of the microchannel for observing the assay region from the outside. The assay device of claim 1 .

7. The assay area has disposed therein at least one assay reagent that reacts with the liquid or the analyte contained therein. The assay device according to any one of claims 1 to 6.

8. The injection port and the internal flow path are provided in plural. The assay device according to any one of claims 1 to 6.

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