Concentration jig

Abstract

The present invention addresses the problem of providing a concentration jig with little variation in concentration ratio when a specimen liquid is concentrated. A concentration jig according to the present invention is used for concentration processing in inspection for detecting a polymer contained in a liquid sample, the concentration jig including: a water-absorbing polymer for absorbing at least part of the moisture of the liquid sample; and a container which accommodates the water-absorbing polymer, into which the liquid sample is taken, and at least a portion of which is flexible, wherein the water-absorbing polymer can be pressed through the inner wall of the container, and the swelling ratio of the water-absorbing polymer is between 0.2 g / g and 800 g / g inclusive.

Description

Concentration tool

[0001] The present invention relates to a concentration tool.

[0002] Immunoassay methods (especially immunochromatography) have been frequently used in recent years due to their simple operation and rapid measurement time. For example, when detecting antigens such as influenza virus using immunochromatography, the following procedure is performed. First, a label modified with an antibody (labeled antibody) is prepared and mixed with a liquid sample containing macromolecules such as antibodies (hereinafter also referred to as "sample liquid"). The labeled antibody binds to the macromolecules to form a complex. In this state, the complex is developed on an insoluble carrier having a detection line coated with an antibody that specifically reacts with the macromolecules, where it reacts with the antibody and is captured on the detection line (test line), and detection can be confirmed visually or otherwise.

[0003] Recently, there has been a demand for immunoassay methods that can be applied to sample liquids with extremely low concentrations of macromolecules such as antigens. To address this demand, it has been proposed to concentrate sample liquids using a concentration device that includes a container containing a water-absorbent polymer (Patent Document 1).

[0004] Patent No. 7192146

[0005] In this situation, the inventors studied the concentration device described in Patent Document 1 and found that it was difficult to remove the concentrated liquid from the concentration device, and that this could result in large variations in the concentration rate.

[0006] In view of the above circumstances, an object of the present invention is to provide a concentration tool that reduces variation in concentration rate.

[0007] As a result of intensive research into the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved by making the container that houses the water-absorbent polymer a soft container and making it possible to press the water-absorbent polymer through the inner wall of the container, and have arrived at the present invention. That is, the present inventors have found that the above-mentioned problems can be solved by the following configuration.

[0008] (1) A concentration device used in a concentration process for detecting polymers contained in a liquid sample, comprising: a water-absorbing polymer for absorbing at least a portion of the water in the liquid sample; and a container that contains the water-absorbing polymer and is at least partially flexible and into which the liquid sample is taken, the concentration device being capable of pressing the water-absorbing polymer through an inner wall of the container, the water-absorbing polymer having a swelling ratio of 0.2 g / g to 800 g / g. (2) The concentration device according to (1), wherein the particle diameter of the water-absorbing polymer is 0.2 mm to 1.6 mm. (3) The concentration device according to (1) or (2), wherein the swelling ratio of the water-absorbing polymer is 10 g / g to 400 g / g. (4) The concentration device according to any one of (1) to (3), wherein the water-absorbing polymer has a water absorption rate of 0.3 g / min to 3.0 g / min per gram.

[0009] As will be described below, the present invention can provide a concentration tool with small variation in concentration rate. Furthermore, the present invention not only improves usability but also shortens the time required for users to collect the material. Furthermore, the present invention can stabilize the variation in concentration rate relative to the time required for collection, ensure robustness against environmental temperatures, and achieve stabilization of the concentration ratio (concentration rate).

[0010] FIG. 1 is a diagram conceptually showing an example of a concentration device of the present invention. FIG. 2 is a diagram for explaining the operation of the concentration device shown in FIG. 1. FIG. 3 is a diagram for explaining the operation of the concentration device shown in FIG. 1. FIG. 4 is a diagram for explaining the operation of the concentration device shown in FIG. 1. FIG. 5 is a perspective view schematically showing an example of a concentration device of the present invention. FIG. 6 is an exploded perspective view of the concentration device shown in FIG. 7. FIG. 7 is a perspective view schematically showing an example of a cap included in the concentration device of the present invention. FIG. 8 is a perspective view schematically showing another example of a container body included in the concentration device of the present invention. FIG. 9 is a perspective view schematically showing another example of a container body included in the concentration device of the present invention. FIG. 10 is a diagram for explaining the relationship between the discharge direction of a liquid sample and a flexible wall surface. FIG. 11 is a diagram for explaining the possible change in volume of a container.

[0011] The concentration tool of the present invention will be described below. In this specification, a numerical range expressed using "to" means a range that includes the numerical values ​​before and after "to" as the lower and upper limits. In this specification, each component may be used alone or in combination of two or more. When two or more components are used in combination, the content of the component refers to the total content unless otherwise specified. In this specification, the small variation in concentration rate, the ability to shorten the recovery time of the concentrated liquid, and excellent robustness against environmental temperatures are also collectively referred to as "excellent effects of the present invention."

[0012] [Concentration device] The concentration device of the present invention is a concentration device used for concentration processing in a test to detect polymers contained in a liquid sample (hereinafter also referred to as "analyte liquid"), and comprises: a water-absorbent polymer (hereinafter also referred to as "super absorbent polymer") for absorbing at least a portion of the water in the liquid sample; and a container, at least a portion of which is soft, that contains the water-absorbent polymer and into which the liquid sample is taken; the water-absorbent polymer can be pressed through the inner wall of the container; and the swelling rate of the water-absorbent polymer is 0.2 g / g or more and 800 g / g or less.

[0013] The concentration device of the present invention is a device used for concentrating a liquid sample in a test such as immunochromatography for detecting a macromolecule contained in the liquid sample.

[0014] The concentration device of the present invention will be described below with reference to the drawings.

[0015] Fig. 1 is a diagram conceptually showing an example of the concentration device of the present invention, and Figs. 2 to 4 are diagrams for explaining the function of the concentration device of the present invention.

[0016] 1 includes a water-absorbent polymer 230 and a container 214 that contains the water-absorbent polymer 230. Although not shown, the container 214 includes an intake portion for taking in a liquid sample (hereinafter also referred to as "analyte liquid") and an exhaust portion for discharging a concentrated liquid sample (hereinafter also referred to as concentrated liquid). The specific configuration of the container 214 will be described later.

[0017] The water-absorbing polymer 230 is a superabsorbent polymer (SAP) having high water absorption properties. As shown in FIG. 1 , the water-absorbing polymer 230 is in a particulate form, and a large number of particulate water-absorbing polymers 230 are contained in a container 214. The particulate water-absorbing polymers 230 are illustrated as spherical particles of the same size, but the actual particle shape does not have to be spherical, and the size does not have to be uniform. The water-absorbing polymer 230 will be described in detail later.

[0018] As shown in Fig. 2, when a liquid sample 240 is poured into a container 214 of the concentration device 200 containing a water-absorbent polymer 230 before water absorption, the water-absorbent polymer 230 absorbs the water contained in the liquid sample 240, and the water-absorbent polymer 232 swells after water absorption, as shown in Fig. 3. After water absorption, a portion of the liquid sample (concentrated liquid) 241 that was not absorbed by the water-absorbent polymer 232 remains concentrated in the container 214. Furthermore, a specimen liquid concentrate 246, which is a concentrate of the liquid sample 240, may also be produced.

[0019] In the present invention, at least a portion of the container 214 is flexible, and the water-absorbent polymer 232 can be pressed through the inner wall of the container 214. Therefore, as shown in Fig. 4, the concentrated liquid 242 can be taken out by pressing the swollen water-absorbent polymer 232 after absorbing water through the inner wall of the container 214.

[0020] In addition, after the water-absorbing polymer 232 has absorbed water, a small amount of recovery liquid may be added, and then the swollen water-absorbing polymer 232 after absorption may be pressed through the inner wall of the container 214 to extract the concentrated liquid 242 containing the recovery liquid.

[0021] The inventors' research has revealed that with conventional concentration devices using water-absorbent polymers, it can be difficult to remove the concentrated liquid from the concentration device after concentrating a liquid sample. Specifically, a larger amount of water-absorbent polymer is preferable from the perspective of shortening the concentration time, but if the amount of water-absorbent polymer is too large, the amount of concentrated liquid becomes insufficient, making removal difficult. Although it has been considered to remove the concentrated liquid by adding a small amount of recovery liquid after concentration, if the amount of water-absorbent polymer is too large, the water-absorbent polymer swells and increases in volume after absorbing water, reducing the void space within the container, making it difficult for the recovery liquid to spread around the water-absorbent polymer, making it difficult to properly recover the sample liquid concentrate remaining near the water-absorbent polymer. Furthermore, if the amount of water-absorbent polymer is too large, water absorption may occur even during the removal operation of the concentrated liquid, potentially preventing a sufficient recovery volume. On the other hand, reducing the amount of water-absorbent polymer or increasing the amount of recovery liquid in order to ensure a sufficient amount of concentrated liquid results in a low concentration ratio of the concentrated liquid.

[0022] In contrast, in the concentration device 200 of the present invention, at least a portion of the container 214 is flexible, and the absorbent polymer 232 can be pressed through the inner wall of the container 214. Therefore, pressing the absorbent polymer 232 through the inner wall of the container 214 deforms the absorbent polymer 232, reducing the internal volume of the container 214. This creates a stirring effect, allowing a portion of the liquid sample (concentrated liquid 241) that was not absorbed and / or the recovered liquid to spread into the gaps between the absorbent polymers 232. This allows more of the concentrated liquid 241 and specimen liquid concentrate 246 remaining near the absorbent polymer 232 to be recovered, thereby increasing the concentration rate of the concentrated liquid 242. Furthermore, because the concentration device 200 of the present invention can press the absorbent polymer 232 through the inner wall of the container 214, it can directly push the contents (concentrated liquid 241) toward the discharge port. Therefore, the concentrated liquid can be more easily extracted than in a configuration in which the concentrated liquid is pushed out solely by air pressure from a pump or the like. Furthermore, since the concentrated liquid can be efficiently developed and extracted even with a small amount of concentrated liquid, the concentration ratio of the concentrated liquid 242 can be increased. This also makes it easier to ensure the necessary recovery amount of the concentrated liquid 242, and also makes it possible to keep the concentration ratio of the extracted concentrated liquid 242 constant. As a result, variation in the concentration ratio is reduced.

[0023] Furthermore, the concentration device 200 of the present invention can be deformed by pressing the container 214 with the user's fingers, which makes it easy for uneven deformation to occur and allows it to be deformed into various shapes, and since the water-absorbent polymers 232 are movable, it is possible to prevent the water-absorbent polymers 232 from being pressed, narrowing the gaps between the water-absorbent polymers 232 and preventing the concentrated liquid from moving. Therefore, even if the amount of water-absorbent polymers 232 is large, the concentrated liquid can be efficiently spread and extracted.

[0024] Furthermore, the concentration device 200 of the present invention allows the user to remove the concentrated liquid by simply pressing the container 214 with their finger, making the removal operation easy and shortening the time required for the recovery operation.

[0025] As described above, the concentration device 200 of the present invention takes in the liquid sample 240 into the container 214 and discharges the concentrated liquid 242. Therefore, the container 214 has an inlet for taking in the liquid sample 240 and an outlet for discharging the concentrated liquid 242. The inlet is not particularly limited, and various configurations can be used as long as it can take in the liquid sample 240 into the container 214. Similarly, the outlet is not particularly limited, and various configurations can be used as long as it can discharge the concentrated liquid 242 from the container 214. Furthermore, the inlet and outlet may be a common device. However, the inlet preferably has a relatively large opening so that the liquid sample 240 can be easily taken into the container 214 and the water-absorbent polymer before water absorption can be placed in the container 214, and the opening is preferably larger than the particle diameter of the water-absorbent polymer before water absorption. On the other hand, it is preferable that the discharge portion be a relatively large opening that is smaller than the particle diameter of the absorbent polymer after absorption, in order to enable the concentrated liquid to be discharged without discharging the absorbent polymer after absorption, and to prevent air from leaking and making it difficult to remove the concentrated liquid 242 when the container 214 is pressed to discharge the concentrated liquid 242.

[0026] The specific configuration of the container will be described below with reference to the drawings.

[0027] [Container] Fig. 5 is a perspective view schematically showing an example of the concentration device of the present invention, and Fig. 6 is an exploded perspective view of the container shown in Fig. 5.

[0028] The container 214a shown in FIGS. 5 and 6 has a container body 210a, at least a portion of which is flexible and has an opening 216, and a cap 212 that is detachably provided on the opening 216 of the container body 210a.

[0029] 5 and 6, the container body 210a of the container 214a comprises a storage section 211a for storing a water-absorbent polymer and a neck section 215 having an opening 216. In the illustrated example, the storage section 211a is substantially cylindrical in shape with a bottom surface and forms an internal space capable of storing the water-absorbent polymer. The neck section 215 is connected to one of the bottom surfaces, and the opening 216 of the neck section 215 communicates with the internal space of the storage section 211a. In the example shown in FIGS. 5 and 6, the storage section 211a has a tapered section 217a at the end on the neck section 215 side, the diameter of which tapers toward the neck section 215.

[0030] The neck portion 215 is a generally cylindrical portion having an opening 216 penetrating from one bottom surface to the other. In the illustrated example, the neck portion 215 is disposed so that its central axis (the central axis of the cylinder) substantially coincides with the central axis (the central axis of the cylinder) of the storage portion 211a. The neck portion 215 also has a male thread on its outer circumferential surface.

[0031] The area of ​​storage portion 211a in a cross section perpendicular to the central axis is larger than the area of ​​neck portion 215. In the illustrated example, the diameter of storage portion 211a in a cross section perpendicular to the central axis is larger than the diameter of neck portion 215. Therefore, the area of ​​storage portion 211a at the connection position between storage portion 211a and neck portion 215 is larger than the area of ​​neck portion 215. Hereinafter, the bottom surface of storage portion 211a to which neck portion 215 is connected is also referred to as the shoulder portion.

[0032] Furthermore, at least a portion of the storage portion 211a is flexible, and the water-absorbing polymer stored in the storage portion 211a can be pressed via the inner wall of the storage portion 211a. In the illustrated example, it is preferable that at least a portion of the circumferential surface of the storage portion 211a is flexible, and the entire storage portion 211a may be flexible.

[0033] In the example shown in Figures 5 and 6, the cap 212 is a member that closes the opening 216 of the neck portion 215 of the container body 210a. Figure 7 shows a cross-sectional view of the cap 212. As shown in Figures 5, 6, and 7, the cap 212 is a cylindrical member that has one bottom surface and is provided with a female thread on its inner circumferential surface. The cap 212 can be attached to and detached from the container body 210 by threading this female thread into the male thread of the neck portion 215 of the container body 210.

[0034] The cap 212 also has a nozzle 213 that protrudes outward from the bottom surface, and a through-hole that passes through the nozzle 213 is provided, and this through-hole serves as a discharge portion 219 .

[0035] 7, in a preferred embodiment, a filter 220 is disposed on the bottom side inside the cap 212. The filter 220 allows the concentrated liquid to pass through but does not allow the water-absorbing polymer to pass through.

[0036] In the container 214a having such a container body 210a and cap 212, the cap 212 can be removed from the container body 210a, and the water-absorbent polymer 230 before absorbing water can be placed in the storage portion 211a through the opening 216 of the neck portion 215. Also, a liquid sample 240 can be placed through the opening 216 of the neck portion 215. In other words, the opening 216 of the container body 210a is an intake portion for taking in a liquid sample.

[0037] After the liquid sample is taken in, the cap 212 is attached. After a predetermined time has passed, the water-absorbent polymer absorbs the moisture in the liquid sample, concentrating the liquid sample. Thereafter, the concentrated liquid may be stirred in the container 214a as needed, and the concentrated liquid may be discharged from the discharge portion 219 provided on the nozzle 213 of the cap 212. At this time, since at least a portion of the container body 210a is soft and the water-absorbent polymer can be pressed via the inner wall of the container body 210a, the concentrated liquid can be removed by pressing the swollen water-absorbent polymer after absorbing water via the inner wall of the container body 210a.

[0038] Alternatively, after the absorbent polymer has absorbed the water content of the liquid sample, recovery liquid may be added through the opening 216 of the neck 215, and then the cap 212 may be attached. If necessary, the recovery liquid may be stirred in the container 214a, and the concentrated liquid may be removed from the discharge port 219 provided on the nozzle 213 of the cap 212.

[0039] In addition, when stirring the concentrated liquid and / or recovered liquid, a cap without a nozzle 213 (discharge portion 219) may be used to seal the inside of container 214a and stir the liquid, and then when discharging the concentrated liquid, the cap may be replaced with cap 212 having a nozzle 213 to remove the concentrated liquid.

[0040] 5 and 6, the area of ​​the storage portion 211a at the connection position between the storage portion 211a and the neck portion 215 is larger than the area of ​​the neck portion 215, and the storage portion 211a has a shoulder, but this is not limited to this. For example, as shown in the example of Fig. 8, the end of the storage portion 211b of the container body 210b on the neck portion 215 side may have a reduced diameter portion 217b that reduces in diameter toward the neck portion 215 to the same diameter as the neck portion 215, and be connected to the neck portion 215. That is, the example shown in Fig. 8 is an example in which the area (diameter) of the storage portion 211b at the connection position between the storage portion 211b and the neck portion 215 is equal to the area (diameter) of the neck portion 215, and the storage portion 211b does not have a shoulder.

[0041] In addition, in order to prevent deformation of neck portion 215 to which cap 212 is attached when storage portion 211a is pressed to extract the concentrated liquid, it is preferable that storage portion 211a has a shoulder portion, i.e., the area of ​​storage portion 211a at the connection position between storage portion 211a and neck portion 215 is larger than the area of ​​neck portion 215.

[0042] 5 and 6, the end portion on the neck portion 215 side has a reduced diameter portion 217a, but the end portion on the neck portion 215 side does not have to have a reduced diameter portion 217a. The configuration having a reduced diameter portion 217a on the end portion on the neck portion 215 side is preferable because it makes it easier to remove the concentrated liquid.

[0043] 5 and 6, the storage section 211a of the container body 210 has a substantially cylindrical shape, but this is not limiting. For example, the storage section 211a may have a polygonal cylindrical shape such as a triangular cylindrical shape or a square cylindrical shape, or may have an elliptical cylindrical shape.

[0044] Furthermore, the storage section 211a is not limited to a substantially cylindrical shape, and may have various shapes. For example, as shown in the example of Fig. 9, the storage section 211c of the container body 210c may have a substantially circular cross-sectional shape on the neck 215 side and a shape that flattens and reduces in cross-sectional area toward the opposite side from the neck 215.

[0045] 10, the container body 210d may have a neck 215 having an opening 216 to which the cap 212 can be attached or detached, and a bag-like container 218 for containing the water-absorbent polymer. Note that the bag-like container refers to a container made of a material that is not self-supporting.

[0046] Furthermore, in the above example, the container body 210 (210a to 210d) and the cap 212 each have a male thread and a female thread and are configured to be screwed together, but this is not limited to this, and they may be configured to be fixed by various known detachable fixing methods, such as a method of attaching by fitting, or a method of having one side with a convex portion and the other with a concave portion and engaging the concave portion with the convex portion.

[0047] Here, in the present invention, "at least a portion of a container is flexible" means that the flexible portion of the container is made of a resin or elastomer material such as polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), or acrylic resin (PMMA), and has a thickness of 1000 μm or less. Furthermore, in addition to the above materials, the container may be a composite material containing a material that has the necessary functions such as low moisture permeability, gas barrier properties, light blocking properties, and decorative properties. Hereinafter, a container that is at least partially flexible will also be referred to as a "flexible container."

[0048] The resin material of the soft portion of the container is preferably either polyethylene (PE) or polypropylene (PP) from the viewpoints of high flexibility, relatively high strength, chemical resistance, cost, etc.

[0049] The thickness of the flexible portion of the container is preferably 1000 μm or less, more preferably 800 μm or less, even more preferably 600 μm or less, and particularly preferably 400 μm or less, for reasons of better effects of the present invention, etc. There is no particular lower limit, but for reasons of better effects of the present invention, the thickness is preferably 20 μm or more, more preferably 100 μm or more.

[0050] In the present invention, it is preferable that the wall surface of the container in the outlet portion, which is parallel to the direction in which the concentrated liquid sample (concentrated liquid) is discharged, is soft. This point will be explained using FIG.

[0051] 11 is a conceptual cross-sectional view of a container 214 included in the concentration device of the present invention. In the container 214 shown in FIG. 11, a discharge part 219 is provided on the upper surface of the container 214 in the drawing. That is, in the illustrated example, the direction in which the concentrated liquid is discharged from the discharge part 219 is upward in the drawing, as indicated by arrow D. Therefore, it is preferable that the wall surface 221 of the container 214 parallel to this arrow D is flexible.

[0052] The container 214 has a flexible wall surface 221 parallel to the direction in which the concentrated liquid is discharged from the discharge portion 219, and this allows the container 214 to be pressed in a direction substantially perpendicular to the direction in which the concentrated liquid is discharged. This prevents the water-absorbent polymer from being pressed, narrowing the gaps between the water-absorbent polymers and preventing the concentrated liquid (recovered liquid) from moving, thereby allowing the concentrated liquid (recovered liquid) to be efficiently spread and facilitating the removal of the concentrated liquid.

[0053] For example, in the example shown in Figure 5, the direction in which the concentrated liquid is discharged is upward in the figure, so it is preferable that at least a portion of the peripheral surface of the storage section 211a of the container body 210a is soft, and it is more preferable that the entire peripheral surface is soft.

[0054] In the present invention, the amount of change in the volume of the container is preferably greater than the difference V-(Vs+Vp) between the volume V of the container and the volume Vs of the liquid sample and the volume Vp of the water-absorbent polymer contained in the container. This point will be explained using FIG. 12.

[0055] Fig. 12 is a diagram conceptually showing the concentration device 200 of the present invention. As shown in Fig. 12, if the total volume of the container 214 is V, the total volume of all the water-absorbent polymers 230 in the container 214 before absorbing water is Vp, and the volume of the liquid sample 240 to be placed in the container 214 is Vs, the difference V-(Vs+Vp) between the volume V of the container, the volume Vp of the water-absorbent polymers 230, and the volume Vs of the liquid sample 240 is the volume Va of the space in the container 214 that is not filled with the water-absorbent polymers 230 and / or the liquid sample 240.

[0056] Since the sum of the volume of the water-absorbent polymer after absorbing water and the volume of the remaining concentrated liquid is approximately equal to the sum of the volume Vp of the water-absorbent polymer 230 before absorbing water and the volume Vs of the liquid sample 240, by making the amount of change in volume of the container 214 larger than the difference V-(Vs+Vp), that is, by making it larger than the volume Va of the space in the container 214 before deformation that is not filled with the water-absorbent polymer 230 and / or liquid sample 240, i.e., the void portion in the container 214, the concentrated liquid can be more reliably discharged when discharging the concentrated liquid from the container 214, even if at least a portion of the air in the container 214 is discharged.

[0057] In the present invention, the total surface area S of the container wall １ The surface area of ​​the flexible wall S ２ It is preferable that the ratio of the total surface area S of the container wall is 50% or more. １ The surface area of ​​the flexible wall S ２ By making the ratio of the volumetric capacity of the container 214 50% or more, the volumetric capacity of the container 214 can be increased, and the concentrated liquid can be discharged more reliably when the concentrated liquid is discharged from the container 214 .

[0058] As in the example shown in FIG. 5 , when the container 214 has a container body 210 and a cap 212, it is preferable that at least a portion of the circumferential surface of the storage portion 211 of the container body 210 is flexible, and it is more preferable that the entire circumferential surface is flexible. The entire storage portion 211 may be flexible. The neck portion 215 and the cap 212 may be either flexible or non-flexible, but non-flexible is preferable. When the storage portion 211 and the neck portion 215 are integrally formed from the same material, the storage portion 211 can be flexible and the neck portion 215 can be non-flexible by making the thicknesses different. The storage portion 211 and the neck portion 215 may also be formed from different materials.

[0059] In the present invention, the distance from the tip of the discharge part of the container to the soft wall surface (i.e., the pressing part) in a direction parallel to the direction in which the concentrated liquid is discharged is preferably 70 mm or less, more preferably 50 mm or less, and even more preferably 30 mm or less. There is no particular lower limit, but it is preferably 1 mm or more. This allows the concentrated liquid to be discharged more reliably when it is discharged from the container.

[0060] In the present invention, the ratio of the width in the direction perpendicular to the height direction (the diameter of the cross section in the case of a cylindrical shape) of the container's storage section that stores the water-absorbent polymer to the height in the direction in which the concentrated liquid is discharged is preferably 8 or less, more preferably 5 or less, and even more preferably 3 or less, and although there is no particular restriction on the lower limit of the ratio, it is preferably 0.5 or more. This allows the concentrated liquid to be discharged more reliably when it is discharged from the container.

[0061] [Specific Superabsorbent Polymer] The water-absorbing polymer used in the concentration device of the present invention is a superabsorbent polymer (SAP) that is contained in a container and absorbs moisture from a liquid sample. In the example shown in FIG. 1 etc., the water-absorbing polymer is shown schematically as spherical particles of uniform size, but is not limited thereto. The swelling ratio of the water-absorbing polymer used in the concentration device of the present invention is 0.2 g / g or more and 800 g / g or less. Hereinafter, a water-absorbing polymer having a swelling ratio of 0.2 g / g or more and 800 g / g or less will also be referred to as a "specific superabsorbent polymer."

[0062] The specific highly water-absorbent polymer is not particularly limited as long as the swelling ratio is within the above-mentioned range, and various known water-absorbent polymers such as polyacrylic acid-based, polyacrylamide-based, cellulose-based, polyethylene oxide-based, etc. Among them, polyacrylic acid-based and polyacrylamide-based polymers are more preferred because they provide better effects of the present invention.

[0063] <Swelling ratio> The swelling ratio of the specific superabsorbent polymer is 0.2 g / g or more and 800 g / g or less. For reasons such as better effects of the present invention, the swelling ratio is more preferably 1.0 g / g or more and 600 g / g or less, even more preferably 10 g / g or more and 400 g / g or less, and particularly preferably 20 g / g or more and 200 g / g or less. Here, the swelling ratio is a value defined as "the mass (g) of water held by 1 g of water-absorbent polymer."

[0064] (Method for measuring swelling ratio) The mass of a water-absorbent polymer stored at 25°C and 5% RH (relative humidity) for 10 days is measured, and immediately thereafter, the polymer is immersed in a large amount of distilled water. After 120 minutes, the water-absorbent 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 formula: {(mass after water absorption (g) - initial mass before water absorption (g)) / initial mass before water absorption (g)}

[0065] The method for adjusting the swelling ratio to the above-mentioned specific range is not particularly limited, and examples thereof include changing the type of polymer, changing the molecular weight of the polymer, changing the degree of crosslinking, and changing the particle size.

[0066] <Water absorption rate> The water absorption rate of the specific superabsorbent polymer is not particularly limited, but for reasons such as better effects of the present invention, it is preferably 0.01 g / min or more and 40 g / min or less per 1 g of the specific superabsorbent polymer, more preferably 0.1 g / min or more and 10.0 g / min or less per 1 g of the specific superabsorbent polymer, and even more preferably 0.3 g / min or more and 3.0 g / min or less per 1 g of the specific superabsorbent polymer.

[0067] The water absorption rate is measured as follows. The mass (M0, unit: g) of a water-absorbent polymer stored at 15 to 30°C and 5% RH (relative humidity) for 10 days or more is measured, and then the polymer is immersed in a large amount of artificial urine (JIS T3214). After immersion for 10 minutes, the water-absorbent polymer is removed, the water on the surface is removed, and the mass is measured. The mass of the water-absorbent polymer removed after 10 minutes is designated as M10, and the amount of water absorption (ΔM) is defined as follows: ΔM = (M10 - M0) / M0 From the above, the water absorption rate (V) per unit time (minute) is defined as follows: V = ΔM / 10

[0068] <Particle size> The particle size of the specific superabsorbent polymer is preferably 5 mm or less, more preferably 3 mm or less, and even more preferably 1.5 mm or less, because the effects of the present invention are more excellent. The lower limit of the particle size of the specific superabsorbent polymer is preferably 0.01 mm or more, more preferably 0.1 mm or more, and even more preferably 0.2 mm or more, because the effects of the present invention are more excellent. The particle size is generally not uniform but has a distribution. The particle size can be determined by measuring the diameter of 50 particulate polymers using an optical microscope and calculating the arithmetic average value.

[0069] <Amount> The amount of the specific superabsorbent polymer is not particularly limited, but in order to obtain better effects of the present invention, the amount is preferably 0.01 to 100 g, and more preferably 0.1 to 1 g, per mL of the sample liquid.

[0070] [Binding substance that specifically binds to macromolecules contained in biological fluids] In order to increase the detection sensitivity when performing a test using a concentrate obtained using the concentrating device of the present invention, it is preferable that the container further contains a binding substance that specifically binds to macromolecules contained in the biological fluid in the sample liquid described below. When the container contains the binding substance, for example, an antigen-antibody reaction proceeds simultaneously with the concentration of the sample liquid, and a complex between the antigen in the sample liquid and the labeled antibody is formed in a concentrated state, leading to improved detection sensitivity.

[0071] The binding substance may be, for example, a first binding substance (particularly an antibody) described below. That is, in the present invention, it is preferable that the macromolecule contained in the biological fluid is an antigen and the binding substance is an antibody.

[0072] The binding substance is preferably contained in the container as a complex with a labeling substance. Examples of the complex include a labeled antibody. Here, the labeled antibody refers to an antibody bound to a detectable labeling substance, and the labeling substance refers to, for example, a detectable substance, such as a substance that can be directly detected, for example, a substance that can generate electromagnetic waves such as color, fluorescence, or light, or a substance that can scatter electromagnetic waves such as color, fluorescence, or light, or a substance or state that includes an enzyme or the like that forms a luminescent or chromogenic body by interacting with a luminescent precursor or a chromogenic precursor.

[0073] The labeled antibody is preferably an antibody modified with metal particles that exhibit a vivid color when irradiated with electromagnetic waves such as visible light. The metal particles are more preferably gold particles. The labeled antibody is preferably an antibody labeled with gold particles, i.e., gold particles modified with an antibody (modified gold particles, described below). The labeled antibody may be contained in a container as a pad (gold colloid-holding pad) holding modified gold colloid particles, which are gold colloid particles modified with an antibody.

[0074] [Casein, Tricine] In view of increasing the detection sensitivity when testing is performed using a concentrate concentrated using the concentration device of the present invention, it is preferable that the container further contains at least one selected from the group consisting of casein and tricine, and it is more preferable that the container contains both casein and tricine.

[0075] Casein is thought to have the effect of suppressing false positives. Furthermore, when the pH of a sample liquid, such as urine, is on the acidic side, false positives tend to occur, but tricin is thought to have the effect of suppressing false positives by adjusting the pH to neutral or alkaline.

[0076] [Method of Use] The method of using the concentration jig is not particularly limited, but examples include the following. First, a sample liquid is placed into the intake portion of the concentration jig and left to absorb for a predetermined time. During the absorption process, macromolecules such as antigens in the sample liquid remain without being absorbed by the polymer. Then, the sample liquid (concentrated liquid) that has not been absorbed by the water-absorbent polymer is removed from the discharge portion of the concentration jig. This is a mechanism by which the target macromolecules such as antigens are concentrated in proportion to the amount absorbed by the water-absorbent polymer. As mentioned above, a small amount of recovery liquid may be added to the concentration jig, and a concentrated liquid containing the recovery liquid may be removed.

[0077] [Specimen Liquid (Liquid Sample)] The specimen liquid (liquid sample) is a liquid sample containing a polymer, and is preferably an aqueous solution containing a polymer contained in a biological fluid.

[0078] Specific examples of the sample liquid include animal (particularly human) body fluids (e.g., blood, serum, plasma, cerebrospinal fluid, tears, sweat, urine, pus, nasal mucus, or sputum), gargle, etc. Among these, serum, plasma, urine, and nasal mucus are preferred as samples containing antigens as macromolecules, and urine is particularly preferred because it allows for more suitable use of the concentration device of the present invention.

[0079] <Polymers contained in biological fluids> Examples of polymers (particularly antigens) contained in biological fluids are polymers that are primarily useful for diagnosing diseases, and include bacteria, germs (e.g., Mycobacterium tuberculosis, lipoarabinomannan (LAM) contained in Mycobacterium tuberculosis), bacteria, viruses (e.g., influenza virus), and their nucleoproteins that are detected in biological fluids. LAM is a major antigen in tuberculosis and is a glycolipid that is a major component of cell membranes and cell walls.

[0080] The polymer contained in the biological fluid is preferably an antigen, more preferably a virus (particularly influenza virus) or LAM, and even more preferably LAM, for reasons such as better effects of the present invention.

[0081] The molecular weight of the polymer contained in the biological fluid is preferably 1,000 or more, and more preferably 2,000 or more. When the structural formula of the polymer is known and the polymer is useful for diagnosing a disease, the theoretical value calculated from the structural formula can be used. When the structural formula is not determined, the molecular weight can be calculated by comparison with substances of known molecular weight using electrophoresis, or by liquid chromatography mass spectrometry (LC-MS).

[0082] [Recovery liquid] The recovery liquid may be a solvent used in a typical immunological analysis (e.g., water, physiological saline, buffer solution, etc.), or a water-miscible organic solvent that can be diluted with such a solvent to directly carry out an antigen-antibody reaction. Furthermore, the recovery liquid may be provided with functionality by adding a buffer, a surfactant, or other additives, as necessary. The recovery liquid is preferably a buffer, and more preferably PBS (phosphate buffered salts). Alternatively, a portion of the sample liquid may be used as the recovery liquid.

[0083] The recovery liquid preferably contains a salt. Specifically, the recovery liquid preferably contains either sodium chloride or magnesium chloride. The concentration of the salt in the recovery liquid is preferably 25 mg / mL or more. Adding a certain amount or more of salt to the recovery liquid can prevent the recovery liquid from being absorbed by the water-absorbent polymer, thereby reducing variation in the recovery amount of the concentrated liquid.

[0084] The volume of the recovery liquid is smaller than the volume of the specimen liquid poured into the container in order to concentrate the specimen liquid. The volume ratio of the recovery liquid to the volume of the specimen liquid poured into the container (recovery liquid / specimen liquid) may be less than 100% by volume, preferably 30% or less, more preferably 20% or less, and even more preferably 0.01% to 10%.

[0085] [Testing] A liquid sample (analyte liquid) concentrated using the concentration device of the present invention is used in a test method for detecting macromolecules in the sample liquid, which is an aqueous solution containing macromolecules. Macromolecules in the concentrate obtained by concentrating the sample liquid using the concentration device can be detected by various known methods.

[0086] The concentrate obtained by using the concentrating device of the present invention can be concentrated at a high concentration rate and can be reliably extracted, resulting in high detection sensitivity.

[0087] The method for detecting a polymer in a concentrated solution is preferably a method using an antigen-antibody reaction, and examples of such methods include enzyme immunoassay (EIA), enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), fluorescent immunoassay (FIA), Western blotting, immunochromatography, etc. Among these, the concentration device of the present invention can be suitably used for concentrating a sample solution for immunochromatography.

[0088] Specific methods for detecting polymers in concentrated solutions and the configuration of test kits for detecting polymers in sample solutions (concentrated solutions) containing polymers are described, for example, in JP 2009-150869 A and WO 2021 / 065300.

[0089] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0090] [1] Preparation of concentration jig

[0091] Examples 1 to 3 Concentration jigs as shown in Figures 5 to 7 were fabricated. Here, the container body 210a (capacity: 15 mL) was made of polyethylene. The thickness of the storage section 211a was 200 µm. Therefore, the storage section 211a was flexible. The storage section 211a contained 3.0 g of SAP Sphere 1.0 mm manufactured by M2 Polymer Technologies Inc. (not shown). As described above, because the storage section 211a was flexible, it was possible to press the SAP through the inner wall of the container.

[0092] [Examples 4 to 7]

[0093] [Classification of SAP Particles] SAP particles were obtained by classifying AQUALIC CA H2 manufactured by Nippon Shokubai Co., Ltd. Specifically, the classification method used two sieves with different mesh sizes, and the SAP that passed through the larger mesh size sieve and did not pass through the smaller mesh size sieve was used. In this case, four types of SAP particles with different particle sizes were obtained by classifying using sieves with mesh sizes of 1.0 mm and 0.65 mm, 0.65 mm and 0.44 mm, 0.44 mm and 0.33 mm, and 0.33 mm and 0.15 mm. The particle sizes of the SAP obtained by the above classification were 0.83 mm, 0.54 mm, 0.38 mm, and 0.25 mm.

[0094] Example 4 A concentration device was produced in the same manner as in Examples 1 to 3, except that the above-mentioned SAP particles (particle diameter: 0.83 mm) were used as the SAP.

[0095] Example 5 A concentration device was produced in the same manner as in Examples 1 to 3, except that the above-mentioned SAP particles (particle diameter: 0.54 mm) were used as the SAP.

[0096] Example 6 A concentration tool was produced in the same manner as in Examples 1 to 3, except that the above-mentioned SAP particles (particle diameter: 0.38 mm) were used as the SAP.

[0097] Example 7 A concentration device was produced in the same manner as in Examples 1 to 3, except that the above-mentioned SAP particles (particle diameter: 0.25 mm) were used as the SAP.

[0098] Examples 8 and 9 Concentration jigs were prepared in the same manner as in Examples 1 to 3, except that highly water-absorbent polymer particles (model number 197-12451) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. were used as the SAP.

[0099] Comparative Example 1 A concentration jig as shown in FIG. 2 of WO 2021 / 065300 was prepared. Here, the cylinder 10 was made of polypropylene. The thickness of the cylinder 10 was 1.1 mm. Therefore, the cylinder 10 was not flexible. The cylinder 10 also contained 3.0 g of SAP Sphere 1.0 mm manufactured by M2 Polymer Technologies Inc. as a specific superabsorbent polymer 30 (SAP). As described above, because the cylinder 10 was not flexible, the SAP could not be pressed through the inner wall of the container.

[0100] Comparative Example 2 A concentration jig was produced in the same manner as in Comparative Example 1, except that highly water-absorbent polymer particles (model number 197-12451) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. were used as the SAP.

[0101] Comparative Example 3 A concentration jig as shown in FIG. 4 of International Publication No. 2021 / 065300 was prepared. Here, the tube portion 70 was made of polypropylene. The thickness of the tube portion 70 was 1.1 mm. Therefore, the tube portion 70 was not flexible. The tube portion 70 contained 3.0 g of SAP Sphere 1.0 mm manufactured by M2 Polymer Technologies Inc. as a specific superabsorbent polymer 30 (SAP). As described above, since the tube portion 70 was not flexible, the SAP could not be pressed through the inner wall of the container.

[0102] Comparative Example 4 A concentration jig was produced in the same manner as in Comparative Example 3, except that highly water-absorbent polymer particles (model number 197-12451) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. were used as the SAP.

[0103] [2] Concentration of Sample Liquid The sample liquid was concentrated using the prepared concentration device. Specifically, 12 mL of artificial urine (JIS T3214) was added to the concentration device as the sample liquid and allowed to stand for 10 minutes. After standing, the SAP was pressed through the inner wall of the soft container of the concentration device to recover the sample liquid (concentrated liquid) that was not absorbed by the SAP from the concentration device. This recovery took the time listed in the "Recovery Time" column in Table 1. The weight of the recovered concentrated liquid was then measured, and the weight of the sample liquid added divided by the weight of the concentrated liquid was used as the concentration rate. For each example, similar concentration was performed 10 times, and the coefficient of variation (1 SD / average value) of the concentration rate was calculated. The results are shown in Table 1. In practice, a coefficient of variation of 0.40 or less is preferable. Note that the sample liquid does not contain polymers such as LAM. However, if a polymer is present, the polymer will be difficult to absorb into the SAP, and the polymer will be concentrated in proportion to the amount of sample liquid absorbed into the SAP. Therefore, the concentration rate is approximately the same as the concentration rate when the sample liquid contains a polymer.

[0104]

[0105] In Table 1, the columns "Particle size," "Swelling ratio," and "Water absorption rate" respectively indicate the particle size, swelling ratio, and water absorption rate of the superabsorbent polymer used in each example. Furthermore, all of the superabsorbent polymers listed in Table 1 have a swelling ratio of 0.2 g / g or more and 800 g / g or less, and therefore all fall under the above-mentioned specific superabsorbent polymers.

[0106] As can be seen from Table 1, when the sample liquid was concentrated using the concentration jigs of Examples 1 to 9, which had a specific superabsorbent polymer and a soft container to contain it and were capable of pressing the specific superabsorbent polymer through the inner wall of the container, the coefficient of variation of the concentration rate was small.

[0107] On the other hand, when the sample liquid was concentrated using the concentration devices of Comparative Examples 1 to 4, which used containers other than soft containers, the coefficient of variation of the concentration rate was large.

[0108] Furthermore, a comparison of Examples 1 to 9 shows that Examples 1 to 7, in which the particle size of the specific superabsorbent polymer was 0.2 mm or more, had a smaller coefficient of variation in the concentration rate. It is thought that the large particle size of the specific superabsorbent polymer made it difficult for the particles to aggregate, making it easier to recover the concentrated liquid. However, since such a tendency was not clearly observed in a comparison of Comparative Examples 1 to 4, it is thought that the effect of reducing the coefficient of variation in the concentration rate by setting the particle size to 0.2 mm or more can only be achieved by combining it with a flexible container.

[0109] 200 Concentration jig 210, 210a, 210b, 210c, 210d Container body 211, 211a, 211b, 211c Storage section 212 Cap 213 Nozzle 214, 214a Container 215 Neck section 216 Opening 217a, 217b Diameter-reduced section 218 Bag-shaped storage section 219 Discharge section 220 Filter 221 Wall surface 230 Water-absorbent polymer (water-absorbent polymer before water absorption) 232 Water-absorbent polymer (water-absorbent polymer after water absorption, swollen water-absorbent polymer) 240 Liquid sample (analyte liquid) 241 Concentrated liquid 242 Removed concentrated liquid 246 Concentrated sample liquid

Claims

1. A concentration device used in a concentration process for a test to detect macromolecules contained in a liquid sample, comprising: a water-absorbing polymer for absorbing at least a portion of the water in the liquid sample; and a container, at least a portion of which is soft, that contains the water-absorbing polymer and into which the liquid sample is taken, wherein the water-absorbing polymer can be pressed through the inner wall of the container, and the swelling rate of the water-absorbing polymer is 0.2 g / g or more and 800 g / g or less.

2. The concentration jig according to claim 1, wherein the particle diameter of the water-absorbent polymer is 0.2 mm or more and 1.6 mm or less.

3. A concentration jig according to claim 1 or 2, wherein the swelling rate of the water-absorbent polymer is 10 g / g or more and 400 g / g or less.

4. A concentration jig according to claim 1 or 2, wherein the water absorption rate of the water-absorbent polymer is 0.3 g / min or more and 3.0 g / min or less per gram.

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