WO2025204618A1 - Processing kit and processing method - Google Patents

Abstract

Provided are a processing kit and a processing method with which there is little variation in the amount of collected liquid for each collection of concentrated liquid of a liquid sample. The processing kit comprises: a water-absorbent polymer that absorbs water from a liquid sample that contains an analyte and water; a container that accommodates the water-absorbent polymer; and a recovery liquid container that accommodates a recovery liquid containing a salt. The recovery liquid is added after the liquid sample is placed into the container.

Description

Processing kit and processing method

The present invention relates to a processing kit and processing method that includes a container for containing a water-absorbing polymer that absorbs water from a liquid sample containing a test substance and water, and a recovery liquid container for containing a recovery liquid containing salt. In particular, the present invention relates to a processing kit and processing method in which the recovery liquid is added after the liquid sample is placed in the container.

Conventionally, there is known technology for concentrating a liquid sample containing a test substance and water using a water-absorbent polymer (water-absorbent material) (see, for example, Patent Document 1). The test substance is, for example, a polymer such as an antigen.

Japanese Patent Application Publication No. 4-355339

The present inventors have studied a method for concentrating a liquid sample using a water-absorbent polymer, with reference to the trace specimen collection device of Patent Document 1, and have found that it is difficult to extract the concentrated liquid sample from the trace specimen collection device after concentrating the liquid sample.
Specifically, from the viewpoint of shortening the concentration time, a larger amount of superabsorbent polymer is preferable, and a larger amount of superabsorbent polymer is also required when the amount of liquid sample is large. If the amount of superabsorbent polymer is large, the amount of concentrate becomes small, making it difficult to extract the concentrate. As a result, there is a possibility that the required amount of concentrate of the liquid sample cannot be obtained.
Furthermore, from the viewpoint of shortening the absorption time, if the saturated water absorption capacity of the superabsorbent polymer is greater than the volume of the liquid sample, water absorption also occurs when extracting the concentrated solution. Therefore, if it takes a long time to extract the concentrated solution, it may not be possible to obtain the required amount of concentrated solution for the liquid sample. If the amount of water-absorbent polymer is reduced to ensure the required volume of concentrated solution, the concentration ratio of the concentrated solution will decrease.
Furthermore, after concentrating the liquid sample, it is possible to add a small amount of recovery liquid and extract the concentrated liquid, but if the amount of recovery liquid is increased, the concentration ratio of the concentrated liquid will decrease.
Furthermore, if a recovery liquid is added after concentrating the liquid sample, the recovery liquid may be absorbed by the water-absorbent polymer, making it impossible to recover test substances such as antigens and other macromolecules contained in the liquid sample. This can lead to variations in the amount of concentrated liquid recovered each time the liquid sample is recovered, resulting in poor repeatability in the recovery of the concentrated liquid.

The object of the present invention is to provide a processing kit and processing method that minimizes variation in the amount of concentrated liquid sample recovered each time it is collected.

In order to achieve the above-mentioned objectives, invention [1] is a processing kit that includes a water-absorbing polymer that absorbs water from a liquid sample containing a test substance and water, a container that houses the water-absorbing polymer, and a recovery liquid container that houses a recovery liquid containing salt, and the recovery liquid is added after the liquid sample is placed in the container.

Invention [2] is the treatment kit according to invention [1], in which the salt contained in the recovery solution is at least one of sodium chloride and magnesium chloride.
Invention [3] is the treatment kit according to invention [1], in which the salt contained in the recovery solution is magnesium chloride.
Invention [4] is the treatment kit according to any one of inventions [1] to [3], wherein the salt content of the recovery solution is 25 mg/mL or more.
Invention [5] is a treatment kit according to any one of inventions [1] to [4], wherein the liquid sample includes a biological fluid.

Invention [6] is a processing method comprising the steps of: placing a liquid sample containing a test substance and water in a container containing a water-absorbent polymer; concentrating the liquid sample in the container by allowing the water-absorbent polymer to absorb the water contained in the liquid sample; placing a recovery liquid containing salt into the container; and removing the concentrated liquid of the liquid sample obtained by concentrating it in the container from the container.
Invention [7] is the treatment method according to invention [6], wherein the salt contained in the recovered liquid is at least one of sodium chloride and magnesium chloride.
Invention [8] is the treatment kit according to invention [6], in which the salt contained in the recovery solution is magnesium chloride.
Invention [9] is the treatment method according to any one of Inventions [6] to [8], wherein the salt content of the recovered solution is 25 mg/mL or more.
Invention [10] is the processing method according to any one of Inventions [6] to [9], wherein the liquid sample includes a biological fluid.

The present invention provides a processing kit and processing method that minimizes variation in the amount of concentrated liquid sample recovered each time it is collected.

1 is a schematic perspective view showing a first example of a processing kit according to an embodiment of the present invention. FIG. 10 is a schematic perspective view showing a modified example of the first example of the processing kit according to the embodiment of the present invention. 1 is a schematic cross-sectional view showing one step of a first example of a processing method according to an embodiment of the present invention. 1 is a schematic cross-sectional view showing one step of a first example of a processing method according to an embodiment of the present invention. 1 is a schematic cross-sectional view showing one step of a first example of a processing method according to an embodiment of the present invention. 1 is a schematic cross-sectional view showing one step of a first example of a processing method according to an embodiment of the present invention. 1 is a schematic cross-sectional view showing one step of a first example of a processing method according to an embodiment of the present invention. FIG. 10 is a schematic perspective view showing a second example of a processing kit according to an embodiment of the present invention. FIG. 10 is an exploded perspective view showing an example of a container in a second example of a processing kit according to an embodiment of the present invention. 10 is a schematic cross-sectional view showing an example of a cap of a container in a second example of a treatment kit according to an embodiment of the present invention. FIG. FIG. 10 is a schematic perspective view showing another example of the container body of the container of the second example of the processing kit according to the embodiment of the present invention. FIG. 10 is a schematic perspective view showing another example of the container body of the container of the second example of the processing kit according to the embodiment of the present invention. FIG. 10 is a schematic perspective view showing another example of the container body of the container of the second example of the processing kit according to the embodiment of the present invention. FIG. 10 is a schematic diagram for explaining the relationship between the discharge direction of the liquid sample and the flexible wall surface. FIG. 10 is a schematic diagram for explaining the amount of change in the volume of a container. 5A to 5C are schematic cross-sectional views showing a step of a second example of a processing method according to an embodiment of the present invention. 5A to 5C are schematic cross-sectional views showing a step of a second example of a processing method according to an embodiment of the present invention. 5A to 5C are schematic cross-sectional views showing a step of a second example of a processing method according to an embodiment of the present invention. 5A to 5C are schematic cross-sectional views showing a step of a second example of a processing method according to an embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The processing kit and processing method of the present invention will be described in detail below based on preferred embodiments shown in the accompanying drawings.
The drawings described below are merely illustrative and simplified for the purpose of explaining the present invention, and therefore the present invention is not limited to the drawings shown below.
In the following, the term "to" indicating a range of values includes the values written on both sides. For example, if ε is a value _εα to a value _εβ , the range of ε includes the values _εα and _εβ , and expressed in mathematical notation as _εα ≦ε≦ _εβ .
Unless otherwise specified, the parallel and perpendicular directions include a generally accepted error range in the relevant technical field. Similarly, the orthogonal directions include a generally accepted error range in the relevant technical field unless otherwise specified.
Unless otherwise specified, the temperature and time include error ranges generally accepted in the relevant technical field.

The processing kit and processing method are explained in detail below.

[First example of processing kit]
Fig. 1 is a schematic perspective view showing a first example of a processing kit according to an embodiment of the present invention, and Fig. 2 is a schematic perspective view showing a modified example of the first example of the processing kit according to an embodiment of the present invention.
1 includes a container 12 containing a water-absorbent polymer 26 and a recovery liquid container 14 containing a salt-containing recovery liquid 15. The water-absorbent polymer 26 absorbs water from a liquid sample containing a test substance and water. The water-absorbent polymer 26 contained in the container is, for example, a super absorbent polymer (SAP) that has high water absorption properties.
Hereinafter, a liquid sample containing a test substance and water will also be referred to as a specimen liquid. A concentrated liquid sample is a concentrated liquid sample, but a concentrated liquid sample and a concentrated liquid sample will also be simply referred to as a concentrated liquid. Unless otherwise specified, a concentrated liquid refers to a concentrated liquid sample and a concentrated liquid sample, i.e., a concentrated specimen liquid and a concentrated liquid of a specimen liquid.

The container 12 includes, for example, a container body 20 , a piston 22 , and a lid 24 .
The container body 20 is configured, for example, as a cylinder having a bottom 20b. In this case, one longitudinal end of the container body 20 is closed and the other end is open. The container body 20 has an opening 20a facing the bottom 20b. The water-absorbent polymer 26 is contained in an interior 20c of the container body 20. A piston 22 is inserted into the interior 20c of the container body 20.
A male screw portion 20e is provided at the end on the opening 20a side of the outer periphery 20d of the container body 20. Note that the container body 20 is not limited to a cylindrical shape as long as it is cylindrical.

The piston 22 has a tip portion 22a and a plunger 22c. The tip portion 22a is formed, for example, from a disk. The tip portion 22a is provided with a plurality of holes 22b penetrating the tip portion 22a in the thickness direction. The diameter of the holes 22b is smaller than the particle diameter of the water-absorbent polymer 26 after absorbing water.
The diameter of the disk that constitutes the tip portion 22 a is equal to or smaller than the inner diameter of the opening 20 a of the container body 20 .
The pusher 22c is, for example, two rectangular flat plates 23 that intersect at right angles. The width of the pusher 22c, i.e., the width w of the flat plate 23, is equal to or less than the inner diameter of the opening 20a of the container body 20. The pusher 22c is provided on the surface of the tip portion 22a with the end face 23c of the flat plate 23 in contact with the surface of the tip portion 22a. The lid 24 is disposed on the end face 23a of the flat plate 23 opposite to the end face 23c.

The lid 24 has a lid body 24a and a nozzle 24b, and a recovery port 24c is provided in the nozzle 24b. A female thread portion (not shown) that threads onto the male thread portion 20e of the container body 20 is provided on the inside of the lid body 24a. The lid body 24a is threaded onto the container body 20. The lid body 24a can be freely attached to and detached from the container body 20. The method of connecting the lid body 24a and the container body 20 is not particularly limited as long as the lid body 24a can be freely attached and detached.
The nozzle 24b is for taking out the concentrated liquid to the outside.
With the piston 22 inserted into the interior 20c of the container body 20, the lid body 24a of the container 12 is screwed onto the container body 20, and the lid 24 is attached to the container body 20. In this state, the concentrated liquid is removed from the container 12 through the collection port 24c and stored in a collection container such as a collection cup (not shown). The concentrated liquid is used, for example, in a test utilizing an antigen-antibody reaction using an immunochromatography kit. The collection container is not limited to a collection cup.

The recovery liquid container 14 is for adding a recovery liquid 15 containing salt into the container 12 containing the water-absorbent polymer 26, i.e., into the interior 20c of the container body 20, after the liquid sample has been placed therein. The recovery liquid 15 is added after the liquid sample has been placed in the container 12.
The configuration of the recovery liquid container 14 is not particularly limited as long as it can accommodate the recovery liquid 15 containing salt and can add the recovery liquid 15 to the container 12. The amount of recovery liquid 15 added by the recovery liquid container 14 is smaller than the amount of the liquid sample.
The recovery liquid container 14 may be, for example, a container with a spout, a container with a nozzle, a dropper, a pipette, etc. The recovery liquid container 14 is made of, for example, polyethylene (PE), polypropylene (PP), etc.

(Modification of the first example of the processing kit)
The configuration of container 12 of processing kit 10 is not limited to the configuration shown in Fig. 1, and may be, for example, the configuration of container 13 of processing kit 11 shown in Fig. 2. Container 13 shown in Fig. 2 differs in the configuration of container body 20 and piston 22, but otherwise has the same configuration as container 12 of processing kit 10 shown in Fig. 1.
The container body 20 has a guide groove 25 at the end of the outer periphery 20d on the opening 20a side. The guide groove 25 penetrates from the outer surface of the container body 20 to the interior 20c. The guide groove 25 has a first linear portion 25a extending from the opening 20a toward the bottom 20b of the container body 20, and a second linear portion 25b provided continuous with the first linear portion 25a. The second linear portion 25b is provided so as to bend in the circumferential direction relative to the first linear portion 25a.
The piston 22 has a protrusion 23d provided on a side surface 23b in the width direction of one of the flat plates 23. The protrusion 23d engages with the guide groove 25 when the piston 22 is inserted into the container body 20.
With the piston 22 inserted into the interior 20c of the container body 20, the lid body 24a of the container 13 is screwed onto the container body 20, and the lid 24 is attached to the container body 20. At this time, the protrusion 23d of the piston 22 is guided into the first linear portion 25a of the guide groove 25, and then the piston 22 is rotated in the circumferential direction to guide the protrusion 23d into the second linear portion 25b. This engages the piston 22 with the container body 20. In this state, the concentrated liquid is removed from the container 12 through the recovery port 24c and stored in a recovery container such as a recovery cup (not shown).
In the container 13, the position of the tip 22a of the piston 22 can be maintained against the pressure caused by the water-absorbing expansion of the water-absorbent polymer 26 by engaging the protrusion 23d of the piston 22 with the guide groove 25 of the container body 20.

[First example of processing method]
Next, a processing method will be described using processing kit 10 shown in Fig. 1. Note that the processing method is not particularly limited to being performed using processing kit 10 shown in Fig. 1, and processing kit 11 shown in Fig. 2 or a processing kit with another configuration may also be used.
3 to 7 are schematic cross-sectional views showing a first example of a processing method according to an embodiment of the present invention in the order of steps. In FIGS. 3 to 7, the same components as those in the processing kit 10 shown in FIG. 1 are designated by the same reference numerals, and detailed descriptions thereof will be omitted.

In the treatment method, first, as shown in Fig. 3, a container 12 (see Fig. 1) containing particulate water-absorbent polymer 26 is prepared. The water-absorbent polymer 26 is contained in the interior 20c of the container body 20 of the container 12 (see Fig. 1).
4, a step is carried out in which a liquid sample 30 containing a test substance and water is poured into the container body 20 of the container 12 (see FIG. 1) containing the water-absorbent polymer 26. Specifically, the liquid sample 30 containing the test substance and water is poured into the interior 20c of the container body 20 from the opening 20a of the container body 20.
When the liquid sample 30 is poured into the interior 20c of the container body 20, the liquid sample 30 is poured from a storage container (not shown) in a state where the liquid sample 30 is stored in the storage container. The storage container is not particularly limited, and for example, a cup with a spout or the like is used. The cup with a spout is made of, for example, paper or plastic.
The amount of liquid sample 30 injected is determined appropriately depending on the capacity of the container body 20, the amount of water-absorbent polymer 26, the target amount of concentrated liquid to be recovered, and the like, and is, for example, several tens of mL.

Next, a step of concentrating the liquid sample 30 in the container 12 by absorbing the water contained in the liquid sample 30 into the water-absorbing polymer 26 is carried out.
Specifically, in the water absorption step in which the water contained in the liquid sample is absorbed by the water-absorbent polymer, as shown in Fig. 5, the water contained in the liquid sample 30 (see Fig. 4) is absorbed by the water-absorbent polymer 26, the liquid sample 30 is concentrated, and a concentrate 28 of the liquid sample 30 is produced in the interior 20c of the container body 20. At this time, the water-absorbent polymer 26 absorbs water and becomes a swollen water-absorbent polymer 27.
After the step of concentrating the liquid sample 30 in the container 12, a step of pouring the recovery liquid 15 containing salt into the container 12 is carried out. Specifically, as shown in Figure 6, the recovery liquid 15 containing salt is poured from the recovery liquid container 14 into the interior 20c of the container body 20.

After the step of placing the salt-containing recovery liquid 15 into the container 12, a step of removing the concentrated liquid of the liquid sample obtained by concentration in the container 12 from the container is then carried out. Specifically, as shown in FIG. 7 , a piston 22 is inserted into the interior 20c of the container body 20 through the opening 20a. As described above, the hole 22b of the tip 22a of the piston 22 is smaller than the particle diameter of the water-absorbent polymer 26 after absorbing water, i.e., the particle diameter of the swollen water-absorbent polymer 27. Therefore, by inserting the piston 22 into the interior 20c of the container body 20, the swollen water-absorbent polymer 27 is pushed down, and the concentrated liquid 34 of the liquid sample 30 passes through the hole 22b and is positioned on the surface of the tip 22a.
With the concentrated liquid 34 in the state shown in Fig. 7, the lid body 24a shown in Fig. 1 is screwed onto the container body 20 to attach the lid 24 to the container body 20. In this state, the concentrated liquid 34 is removed from the container 12 through the recovery port 24c of the nozzle 24b of the lid 24 of the container 12 shown in Fig. 1. In this case, the concentrated liquid 34 removed from the container 12 is stored in a recovery container such as a recovery cup (not shown).

The recovered liquid 15 containing the salt described above is not easily absorbed by the water-absorbing polymer 26, which can prevent a decrease in the amount of the concentrated liquid 34. Therefore, when the concentrated liquid 34 is recovered, variation in the amount of the concentrated liquid 34 recovered each time can be reduced.
Furthermore, since the recovery liquid 15 is not easily absorbed by the water-absorbing polymer 26, the concentrate 28 can be transferred to the concentrate 34. This allows the concentration of the concentrate 28 in the concentrate 34 to be maintained at a predetermined concentration ratio. The concentration ratio of the concentrate is the volume of the liquid sample divided by the volume of the concentrate.

In the above-described treatment method, the water in the liquid sample (analyte liquid) is absorbed by the water-absorbent polymer, and the liquid sample is usually left to stand until the water in the liquid sample is almost completely absorbed by the water-absorbent polymer. The water is absorbed by the water-absorbent polymer, and a concentrate that is a concentrate of the liquid sample is produced in the container body.
When a liquid sample is mixed with a water-absorbent polymer, the water in the liquid sample is absorbed by the water-absorbent polymer, whereas macromolecules in the liquid sample, such as antigens, have a certain hydrodynamic radius, and therefore the mesh structure on the surface of the water-absorbent polymer creates a sieving effect, making them less likely to be absorbed by the water-absorbent polymer. As a result, macromolecules such as antigens in the liquid sample are concentrated. The concentrate usually exists near the water-absorbent polymer as a precipitate of the polymer or as a highly concentrated solution of the polymer dissolved in a trace amount of residual liquid.
When extracting the concentrated liquid, after the above-mentioned water absorption step, the recovered liquid is added, and then a piston is inserted into the container and the tip is pressed against the water-absorbing polymer, thereby extracting the concentrated liquid through holes smaller than the particle diameter. At this time, the recovered liquid moves thoroughly through the gaps between the water-absorbing polymer and collects at the top, and the stirring effect at this time allows a uniform concentrated liquid containing the above-mentioned concentrate to be obtained.

[Second Example of Processing Kit]
Fig. 8 is a schematic perspective view showing a second example of a processing kit according to an embodiment of the present invention. Fig. 9 is an exploded perspective view showing an example of a container of the second example of the processing kit according to an embodiment of the present invention. Fig. 10 is a schematic cross-sectional view showing an example of a cap of the container of the second example of the processing kit according to an embodiment of the present invention.
8 to 10, the same components as those in the processing kit 10 shown in FIG. 1 are denoted by the same reference numerals, and detailed description thereof will be omitted.
The processing kit 40 shown in Fig. 8 differs from the processing kit 10 shown in Fig. 1 in the configuration of the container 42, but other configurations are similar to those of the processing kit 10 shown in Fig. 1. The container body 44 of the container 42 has lower rigidity and is softer than the container body 20 of the processing kit 10 shown in Fig. 1.

The container 42 of the processing kit 40 shown in Figures 8 and 9 has a container body 44 that is at least partially flexible and has an opening 45, and a cap 46 that is removably attached to the opening 45 of the container body 44.

The container body 44 of the container 42 shown in Figures 8 and 9 consists of a storage section 44a that stores a water-absorbent polymer, and a neck section 44b that has an opening 45. In the illustrated example, the storage section 44a is approximately cylindrical in shape with a bottom surface, and forms an internal space capable of storing the water-absorbent polymer. The neck section 44b is connected to one of the bottom surfaces, and the opening 45 of the neck section 44b is connected to the internal space of the storage section 44a. In the example shown in Figures 8 and 9, the storage section 44a has a tapered section 44c at the end on the neck section 44b side that tapers in diameter toward the neck section 44b.

The neck portion 44b is a generally cylindrical portion having an opening 45 that penetrates from one bottom surface (end) to the other bottom surface (end). In the illustrated example, the neck portion 44b is positioned so that its central axis (the central axis of the cylinder) roughly coincides with the central axis (the central axis of the cylinder) of the storage portion 44a. In addition, the neck portion 44b has a male thread portion 45a on its outer circumferential surface.

The area of the storage portion 44a in a cross section perpendicular to the central axis is larger than the area of the neck portion 44b. In the illustrated example, the diameter of the storage portion 44a in a cross section perpendicular to the central axis is larger than the diameter of the neck portion 44b. Therefore, the area of the storage portion 44a at the connection position between the storage portion 44a and the neck portion 44b is larger than the area of the neck portion 44b. Hereinafter, the bottom surface of the storage portion 44a to which the neck portion 44b is connected is also referred to as the shoulder portion.

Furthermore, at least a portion of the storage section 44a is flexible, and the absorbent polymer stored in the storage section 44a can be pressed through the inner wall of the storage section 44a. In the illustrated example, it is preferable that at least a portion of the circumferential surface of the storage section 44a is flexible, and the entire storage section 44a may be flexible.

In the example shown in FIGS. 8 and 9, the cap 46 is a member that closes the opening 45 of the neck portion 44 b of the container body 44 .
Fig. 10 shows a cross-sectional view of the cap 46. As shown in Figs. 8, 9, and 10, the cap 46 is a cylindrical member having one bottom surface and a female thread portion 46c on its inner circumferential surface. The female thread portion 46c is threadedly engaged with the male thread portion 45a of the neck portion 44b of the container body 44, thereby enabling the cap 46 to be freely attached to and detached from the container body 44.

The cap 46 also has a nozzle 46a that protrudes outward from the bottom surface, and a through-hole that passes through the nozzle 46a serves as the discharge portion 46b.

10, in a preferred embodiment, a filter 47 is disposed on the bottom side inside the cap 46. The filter 47 allows the concentrated liquid to pass through but does not allow the water-absorbing polymer to pass through.
The filter 47 is not particularly limited as long as it allows the concentrated liquid to pass through but does not allow the water-absorbing polymer to pass through. For example, a membrane filter is used as the filter 47.

In the container 42 shown in Figures 8 and 9, which has a container body 44 and a cap 46, the cap 46 can be removed from the container body 44, and the water-absorbent polymer 26 (see Figure 1) before absorption can be placed into the storage section 44a through the opening 45 of the neck 44b. A liquid sample 30 (see Figure 4) can also be placed through the opening 45 of the neck 44b. In other words, the opening 45 of the container body 44 is an intake section for taking in a liquid sample.

After the liquid sample is taken in, the cap 46 is attached to the container body 44. After a predetermined time has passed, the water-absorbent polymer absorbs the water in the liquid sample, concentrating the liquid sample. Thereafter, the concentrated liquid is stirred in the container 42 as needed.
Next, using the recovery liquid container 14 (see FIG. 8), the recovery liquid 15 (see FIG. 8) is poured into the container 42 from the opening 45 of the neck portion 44b, i.e., the recovery liquid 15 is poured into the container body 44, and then the concentrated liquid is discharged from the discharge portion 46b provided on the nozzle 46a of the cap 46. At this time, at least a part of the container body 44 is soft, and the water-absorbent polymer can be pressed through the inner wall of the container body 44. Therefore, the concentrated liquid can be taken out of the container body 44 by pressing the swollen water-absorbent polymer through the inner wall of the container body 44.

After the water-absorbing polymer has absorbed the moisture from the liquid sample, recovery liquid 15 is poured into recovery liquid container 14 through opening 45 of neck 44b. Next, cap 46 is attached. Thereafter, the recovery liquid may be stirred in container 42 as needed, and the concentrated liquid may be taken out from outlet 46b provided on nozzle 46a of cap 46.
Furthermore, when stirring at least one of the concentrated liquid and the recovered liquid, a cap without a nozzle 46a (discharge portion 46b) may be used to seal the inside of the container 42 and perform stirring, and then, when discharging the concentrated liquid, the cap may be replaced with a cap 46 with a nozzle 46a to remove the concentrated liquid.

8 and 9, the area of the storage portion 44a at the connection position between the storage portion 44a and the neck portion 44b is larger than the area of the neck portion 44b, and the storage portion 44a has a shoulder, but this is not limited to this. For example, as shown in Fig. 11, the storage portion 44d may have a configuration in which the end of the storage portion 44d of the container body 48 on the neck portion 44b side has a tapered portion 44e that tapers toward the neck portion 44b to the same diameter as the neck portion 44b, and the storage portion 44d is connected to the neck portion 44b. That is, the example shown in Fig. 11 is an example in which the area (diameter) of the storage portion 44d at the connection position between the storage portion 44d and the neck portion 44b is equal to the area (diameter) of the neck portion 44b, and the storage portion 44d does not have a shoulder.
FIG. 11 is a schematic perspective view showing another example of the container body of the container of the second example of the processing kit according to the embodiment of the present invention.

In order to prevent deformation of the neck portion 44b to which the cap 46 is attached when the storage portion 44a is pressed to remove the concentrated liquid from the container body 44, it is preferable that the storage portion 44a has a shoulder portion, i.e., the area of the storage portion 44a at the connection position between the storage portion 44a and the neck portion 44b is larger than the area of the neck portion 44b.

8 and 9, the end portion on the neck portion 44b side has the reduced diameter portion 44c, but the end portion on the neck portion 44b side may not have the reduced diameter portion 44c. The reduced diameter portion 44c on the end portion on the neck portion 44b side is preferable because it makes it easier to remove the concentrated liquid.
8 and 9, the storage section 44a of the container body 44 has a substantially cylindrical shape, but this is not limiting. For example, the storage section 44a may have a polygonal cylindrical shape such as a triangular cylindrical shape or a square cylindrical shape, or may have an elliptical cylindrical shape.

Furthermore, the storage section 44a is not limited to a generally cylindrical shape and may have various shapes. For example, as shown in Fig. 12, the storage section 44f of the container body 48a may have a generally circular cross-sectional shape on the neck 44b side and a shape that flattens and reduces in cross-sectional area toward the opposite side from the neck 44b.
FIG. 12 is a schematic perspective view showing another example of the container body of the container of the second example of the processing kit according to the embodiment of the present invention.

13, a container body 48b may have a neck 44b having an opening 45 to which a cap 46 can be attached or detached, and a bag-like container 49 for containing a water-absorbent polymer. Note that a bag-like container refers to a container made of a material that is not self-supporting.
FIG. 13 is a schematic perspective view showing another example of the container body of the container of the second example of the processing kit according to the embodiment of the present invention.

In addition, in the above example, the container bodies 44, 48, 48a, 48b and the cap 46 are configured to be threaded together using male threads 45a and female threads 46c, respectively, but this is not limited to this. The container bodies 44, 48, 48a, 48b and the cap 46 may be attached to each other by fitting instead of by threading. One of the container bodies 44, 48, 48a, 48b and the cap 46 may have a convex portion and the other a concave portion, with the concave portion engaging with the convex portion. Any known detachable fastening method can be used to attach the container bodies 44, 48, 48a, 48b and the cap 46, as appropriate.

Here, "at least a portion of the container is flexible" means that the flexible portion of the container is made of a resin material such as polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), or acrylic resin (PMMA), or an elastomer material, and has a thickness of 1000 μm or less. Furthermore, the flexible portion may be a composite material containing the above-mentioned materials and other materials having required functions such as low moisture permeability, gas barrier properties, light blocking properties, and decorative properties.
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.

The thickness of the flexible portion of the container is preferably 1000 μm or less, more preferably 800 μm or less, and even more preferably 600 μm or less. There is no particular lower limit, but it is preferably 20 μm or more.

Here, it is preferable that the wall surface of the container, which is parallel to the direction in which the concentrated liquid sample (concentrated liquid) is discharged at the discharge part, is soft. This point will be explained using FIG.
14 is a schematic diagram for explaining the relationship between the discharge direction of the liquid sample and the soft wall surface. FIG. 14 conceptually shows a cross-sectional view of a container 50 included in the processing kit.
14, a discharge portion 46b is provided on the upper surface of the container 50 in the figure. That is, in the illustrated example, the direction in which the concentrated liquid is discharged from the discharge portion 46b is upward in the figure, as indicated by arrow D. Therefore, it is preferable that the wall surface 52 of the container 50 parallel to this arrow D is flexible.

The container 50 has a flexible wall surface 52 parallel to the direction in which the concentrated liquid is discharged from the discharge portion 46b, so that the container 50 can 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, so the concentrated liquid (recovered liquid) can be efficiently spread and easily removed.
For example, in the example of container 42 shown in Figure 8, 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 44a of the container body 44 is soft, and it is more preferable that the entire peripheral surface is soft.

Furthermore, it is preferable that the amount of change in the volume of the container is greater than the difference δ between the volume V of the container and the volume Vp of the water-absorbent polymer contained in the container, Vs. This point will be explained using Figure 15. The difference δ is expressed as δ = V - (Vs + Vp).
FIG. 15 is a schematic diagram for explaining the amount of change in the volume of a container, and conceptually shows the container 42 shown in FIGS.
As shown in FIG. 15 , if the total volume of the container 50 is V, the total volume of all the water-absorbent polymers 26 in the container 50 before absorbing water is Vp, and the volume of the liquid sample 30 to be put into the container 50 is Vs, the difference δ (=V−(Vs+Vp)) between the volume V of the container, the volume Vp of the water-absorbent polymer 26, and the volume Vs of the liquid sample 30 is the volume Va of the space in the container 50 that is not filled with the water-absorbent polymer 26 and/or the liquid sample 30.

The sum of the volume of the 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 absorbent polymer 26 before absorbing water and the volume Vs of the liquid sample 30. Therefore, by making the amount of volume change possible for the container 50 greater than the difference δ (= V - (Vs + Vp)), that is, by making it greater than the volume Va of the space in the container 50 before deformation that is not filled with the absorbent polymer 26 and/or liquid sample 30, i.e., the void volume within the container 50, the concentrated liquid can be more reliably discharged even if at least some of the air within the container 50 is discharged when discharging the concentrated liquid from the container 50.

Furthermore, it is preferable that the ratio of the surface area _S2 of the flexible wall to the total surface area _S1 of the container wall is 50% or more. By making the ratio of the surface area _S2 of the flexible wall to the total surface area _S1 of the container wall 50 to be 50% or more, the amount of volume change that can be made in the container can be increased, and the concentrated liquid can be more reliably discharged when it is discharged from the container 50.

When the container 42 has a container body 44 and a cap 46 as shown in Figure 8, it is preferable that at least a portion of the circumferential surface of the storage portion 44a of the container body 44 is flexible, and it is more preferable that the entire circumferential surface is flexible. The entire storage portion 44a may also be flexible. The neck portion 44b and the cap 46 may be either flexible or not, but it is preferable that they are not flexible. When the storage portion 44a and neck portion 44b shown in Figure 9 are integrally formed from the same material, the storage portion 44a can be made flexible and the neck portion 44b can be made not flexible by making the thicknesses different. The storage portion 44a and neck portion 44b may also be formed from different materials.

Furthermore, in a direction parallel to the direction in which the concentrated liquid is discharged, the distance from the tip of the discharge portion of the container to the soft wall surface (i.e., the part that is pressed) 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 more reliably discharged from the container.

Furthermore, the ratio of the width in the direction perpendicular to the height direction (the diameter of the cross section if cylindrical) 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. There are no particular restrictions on the lower limit of this ratio, but it is preferably 0.5 or more. This allows the concentrated liquid to be discharged more reliably when it is discharged from the container.

[Second example of processing method]

16 to 19 are schematic cross-sectional views showing the process sequence of a second example of the processing method according to the embodiment of the present invention. In Figs. 16 to 19, the same components as those in the processing kit 40 shown in Fig. 8 are designated by the same reference numerals, and detailed descriptions thereof will be omitted.
16, a container 42 containing a water-absorbent polymer 26 is prepared. The water-absorbent polymer 26 is contained in an interior 42c of the container 42. Although not shown, the container 42 has an intake part for taking in a liquid sample (analyte liquid) therein and an outlet part for discharging a concentrated liquid sample (concentrated liquid).
The water-absorbing polymer 26 has the same structure as the water-absorbing polymer shown in Fig. 1 and is a super absorbent polymer (SAP) that has high water absorption. The water-absorbing polymer will be described later.

Next, a process is carried out in which the liquid sample 30 is placed in a container 42 containing a water-absorbing polymer 26, and then a process is carried out in which the water contained in the liquid sample 30 is absorbed by the water-absorbing polymer 26, thereby concentrating the liquid sample 30 in the container 42.
Specifically, as shown in FIG. 17, the liquid sample 30 is poured into the interior 42c of the container 42 containing the water-absorbent polymer 26 before absorbing water.
The method of injecting the liquid sample 30 is the same as in the first example of the processing method described above. The amount of the liquid sample 30 injected is determined appropriately depending on the capacity of the container 42, the amount of the water-absorbent polymer 26, the target amount of the concentrated liquid to be recovered, and the like, and is, for example, several tens of mL.
When the liquid sample 30 is injected, the water-absorbent polymer 26 absorbs the water contained in the liquid sample 30 and swells. As shown in Figure 18, the water-absorbent polymer 26 absorbs water and swells to become the water-absorbent polymer 27. The portion of the liquid sample 30 that is not absorbed by the water-absorbent polymer 27 is concentrated, and a concentrated liquid 34 accumulates in the interior 42c of the container 42, producing a concentrate 28 that is a concentrate of the liquid sample 30.
After the step of concentrating the liquid sample 30 in the container 42 described above, a predetermined amount of recovery liquid 15 containing salt is then injected from the recovery liquid container 14 into the interior 42c of the container 42.

After the step of placing the above-mentioned salt-containing recovery liquid 15 into the container 42, a step of removing the concentrated liquid 34 of the liquid sample 30 obtained by concentration in the container 42 from the container 42 is then carried out.
Here, at least a portion of the container 42 is flexible, and it is possible to press the water-absorbent polymer 27 through the inner wall of the container 42. Therefore, as shown in Fig. 19, it is possible to press the swollen water-absorbent polymer 27 after absorbing water through the inner wall of the container 42, and to remove the concentrated liquid 34 containing the recovery liquid 15 from the container 42. The concentrated liquid 34 removed from the container 42 is stored in a recovery container such as a recovery cup (not shown), for example.

The recovered liquid 15 containing the salt is not easily absorbed by the water-absorbent polymer 26, and therefore, in the second example of the treatment method, as in the first example of the treatment method, it is possible to prevent the amount of the concentrated liquid 34 from decreasing. Therefore, when the concentrated liquid 34 is recovered, it is possible to prevent variation in the amount of the concentrated liquid 34 recovered each time.
Furthermore, since the recovered liquid 15 is not easily absorbed by the water-absorbing polymer 26, the concentrate 28 can be transferred to the concentrate 34. As a result, in the second example of the treatment method, the concentration of the concentrate 28 in the concentrate 34 can be maintained, and the predetermined concentration ratio can be maintained.

As described above, the inventors' investigations have revealed that with conventional treatment kits using water-absorbent polymers, it is difficult to remove the concentrated liquid from the treatment kit, i.e., the container, after concentrating the liquid sample. Specifically, from the viewpoint of shortening the concentration time, a larger amount of water-absorbent polymer is preferable, but if the amount of water-absorbent polymer is large, the amount of concentrated liquid decreases, making it difficult to remove the concentrated liquid. As a result, there is a possibility that the required amount of concentrated liquid of the liquid sample cannot be obtained.
Furthermore, if the saturated water absorption capacity of the superabsorbent polymer is greater than the volume of the liquid sample, water absorption also occurs when extracting the concentrated solution. This may result in an insufficient volume of concentrated liquid from the liquid sample. On the other hand, if the amount of water-absorbent polymer is reduced or the volume of the collected liquid is increased to ensure a sufficient volume of concentrated solution, the concentration ratio of the concentrated solution will decrease. A lower concentration ratio also reduces the amount of test substance, such as antigen, in the concentrated solution, which is undesirable because it can cause a decrease in the detection accuracy of antigens, etc.

In contrast, the container 42 of the present invention is at least partially flexible, allowing pressure to be applied to the absorbent polymer 27 via the inner wall of the container 42. Pressing the absorbent polymer 27 via the inner wall of the container 42 deforms the absorbent polymer 27, reducing the internal volume of the container 42 and creating a stirring effect that allows the remaining liquid sample (concentrated liquid 34) and recovered liquid 15 to be dispersed into the gaps between the absorbent polymers 27. This allows more of the concentrate 28 remaining near the absorbent polymer 27 to be recovered, increasing the concentration ratio of the concentrate 34. Furthermore, because the container 42 is capable of pressing the absorbent polymer 27 via the inner wall, the contents (concentrated liquid 34) can be directly pushed toward the discharge port. This makes it easier to remove the concentrate than with a configuration in which the concentrate is pushed out solely by air pressure, such as with a pump. Furthermore, because the concentrate can be efficiently dispersed even with a small amount of concentrate and efficiently removed from the container 42, the concentration ratio of the concentrate 34 can be increased. It also makes it easier to ensure the necessary recovery volume of concentrated liquid 34, and makes it possible to maintain a constant concentration ratio for the extracted concentrated liquid 34.

Furthermore, because the container 42 can be deformed, for example, by being pressed with the user's finger, it is easy for uneven deformation to occur and it can be deformed into various shapes. Furthermore, because the water-absorbent polymer 27 is movable, it is possible to prevent the water-absorbent polymer 27 from being pressed, narrowing the gaps between the water-absorbent polymers 27 and preventing the concentrated liquid 34 from moving. Therefore, even if the amount of water-absorbent polymer 27 is large, the concentrated liquid 34 can be efficiently spread and efficiently removed from the container 42.

Furthermore, the concentrated liquid can be removed from the container 42 by simply pressing the container 42 with the user's finger, making the removal operation easy and reducing the time required for the recovery operation.

As described above, the liquid sample 30 is introduced into the container 42 and the concentrated liquid 34 is discharged. Therefore, the container 42 has an inlet for introducing the liquid sample 30 and an outlet for discharging the concentrated liquid 34. The inlet is not particularly limited, and various configurations can be used as long as it can introduce the liquid sample 30 into the container 42. Similarly, the outlet is not particularly limited, and various configurations can be used as long as it can discharge the concentrated liquid 34 from the container 42. Furthermore, the inlet and outlet may be a common unit. However, the inlet preferably has a relatively large opening so that the liquid sample 30 can be easily introduced into the container 42 and the water-absorbent polymer before water absorption can be placed into the container 42, 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 smaller than the particle diameter of the water-absorbent polymer after absorption, in order to enable the concentrated liquid to be discharged without discharging the water-absorbent polymer after absorption, and to prevent air from leaking, which makes it difficult to remove the concentrated liquid 34, when the container 42 is pressed to discharge the concentrated liquid 34.
The configuration of the processing kit will be described in more detail below.

[Container body]
1 and 2 is not particularly limited, thermoplastic resin is preferred because it can be injection molded and mass-produced at low cost. Specific examples of materials that have a certain degree of hardness include polypropylene, acrylic, polyacetal, polyamide, polyethylene, polyethylene terephthalate, polycarbonate, polystyrene, polyphenylene sulfide, polybutylene terephthalate, polyvinyl chloride, ABS resin (acrylonitrile-butadiene-styrene copolymer resin), and AS resin (acrylonitrile-styrene copolymer resin).

As described above, the container bodies 44, 48, 48a, and 48b shown in Figures 8, 11, 12, and 13 have soft portions made of resin materials or elastomer materials such as polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), and acrylic resin (PMMA), and have a thickness of 1000 μm or less.
The resin material of the soft portion of the container is preferably either polyethylene (PE) or polypropylene (PP) from the viewpoints of high flexibility and relatively high strength as described above, chemical resistance, cost, etc.

[Water-absorbent polymer]
The water-absorbing polymer contained in the container is, for example, a super absorbent polymer (SAP). The water-absorbing polymer is in particulate form, and a large number of particulate water-absorbing polymers are contained in the container. The particulate water-absorbing polymer is illustrated schematically as a spherical shape of uniform size, but the actual particle shape does not have to be spherical, and the particle size may not be uniform but may be heterogeneous.
The composition of the water-absorbing polymer is not particularly limited, and various known water-absorbing polymers such as polyacrylic acid-based, polyacrylamide-based, cellulose-based, or polyethylene oxide-based polymers can be used as appropriate.

<Swelling rate>
The swelling rate of the water-absorbing polymer is not particularly limited, but is preferably more than 0.2 g/g and less than 800 g/g, more preferably 1.0 g/g or more and 600 g/g or less, further preferably 10 g/g or more and 500 g/g or less, and particularly preferably 20 g/g or more and 100 g/g or less.
Here, the swelling ratio is a value defined as "the mass (g) of water held by 1 g of water-absorbing polymer."

(Method for measuring swelling ratio)
The mass of the water-absorbing polymer stored at 25°C and 5%RH (relative humidity) for 10 days is measured, and then it is immediately immersed in a large amount of distilled water. After 120 minutes, the water-absorbing polymer is taken out, the water on the surface is removed, the mass is measured again, and the swelling ratio is calculated using the following formula.
Swelling ratio = {(mass after water absorption (g) - initial mass before water absorption (g)) / initial mass before water absorption (g)}

There are no particular limitations on the method for adjusting the swelling ratio to the specific range mentioned above, but examples include changing the type of polymer, changing the molecular weight of the polymer, changing the degree of crosslinking, or changing the particle size.

<Water absorption rate>
The water absorption rate of the water-absorbing polymer is not particularly limited, but is preferably 0.01 g/min or more and 40 g/min or less per 1 g of water-absorbing polymer, and more preferably 0.02 g/min or more and 40 g/min or less per 1 g of water-absorbing polymer.

The above-mentioned water absorption rate is measured as follows.
A water-absorbent polymer stored at 25°C and 5% RH (relative humidity) for 10 days is weighed (weight M0, unit: g) and immersed in a large amount of distilled water. After time T1 has elapsed, the water-absorbent polymer is removed, the surface water is removed, and the mass is measured (mass _M1 ). Similarly, the mass after time T2 has elapsed from immersion and the mass after time T3 have elapsed are measured, respectively, to obtain _M2 and _M3 . Here, time T1, time T2, and time T3 are set to the same interval, and time T3 is set to a range that is shorter than the water absorption saturation time Ts of the superabsorbent polymer and can be considered to be constant in water absorption per unit time. For example, time T3 = Ts/2.

The water absorption is defined as follows:
Water absorption amount after time T1: ΔM1 = (M ₁ - _{M 0} )/M ₀
Water absorption amount after time T2: ΔM2 = (M ₂ -M ₀ )/M ₀
Water absorption amount after time T3: ΔM3 = (M ₃ -M ₀ )/M ₀
Using the amount of water absorption defined above, the water absorption rate is calculated as follows.
Three points are plotted on an XY plane with time (x = T1, T2, T3; unit: minutes) on the horizontal axis and water absorption (y = ΔM1, ΔM2, ΔM3; unit: g water/g polymer amount) on the vertical axis, and the slope of the linear approximation of water absorption versus time using the least squares method is taken as the water absorption rate per unit time (minute).

<Particle size>
The particle size of the water-absorbing polymer is preferably 10 mm or less, more preferably 5 mm or less, and even more preferably 2 mm or less. The lower limit of the particle size of the water-absorbing polymer is preferably 0.01 mm or more, more preferably 0.1 mm or more, and even more preferably 0.5 mm or more.
The particle size of the water-absorbent polymer is generally not uniform but has a distribution. The particle size of the water-absorbent polymer described above can be determined by measuring the diameters of 50 particulate water-absorbent polymers using an optical microscope and calculating the arithmetic mean value.

[Binding substances that specifically bind to macromolecules contained in biological fluids]
In order to enhance the detection sensitivity when a test is performed using a concentrated liquid obtained by concentrating a liquid sample, the container preferably further contains a binding substance that specifically binds to a macromolecule contained in the biological fluid in the sample liquid, as described below. When the container contains the above-mentioned 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.

The binding substance mentioned above can be, for example, the 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 mentioned above is an antigen, and the binding substance mentioned above is an antibody.

The above-mentioned binding substance is preferably contained in the container as a complex with a labeling substance. An example of the above-mentioned complex is a labeled antibody. Here, a labeled antibody is an antibody bound to a detectable labeling substance, and a labeling substance is, for example, a substance that can be detected, 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 even a substance or state that includes an enzyme that forms a luminescent or chromogenic body by interacting with a luminescent precursor or chromogenic precursor.

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 antibodies (modified colloidal gold particles, described below).
The above-mentioned labeled antibody may be contained in a container as a pad (colloidal gold-holding pad) holding modified colloidal gold particles, which are colloidal gold particles modified with the antibody.

[Casein, Tricin]
In order to increase the detection sensitivity when testing using a concentrated solution obtained by concentrating a liquid sample, it is preferable that the container further contains at least one substance selected from the group consisting of casein and tricine, and it is more preferable that the container contains both casein and tricine.
Casein is thought to have the effect of suppressing false positives. Furthermore, when the pH (hydrogen ion exponent) of a sample liquid such as urine is on the acidic side, false positives tend to occur, but tricine is thought to have the effect of suppressing false positives by adjusting the pH to neutral or alkaline.

[Liquid sample (analyte liquid)]
The liquid sample (analyte liquid) contains a test substance and water. The liquid sample (analyte liquid) may be collected from a living body, in which case the liquid sample contains a biological fluid. The liquid sample is preferably an aqueous solution containing a polymer contained in the biological fluid. The water contained in the liquid sample may be water contained in the biological fluid.
Specific examples of liquid samples include animal (particularly human) body fluids (e.g., blood, serum, plasma, cerebrospinal fluid, tears, sweat, urine, pus, nasal discharge, or sputum), gargle, etc. Among these, serum, plasma, urine, and nasal discharge are preferred as specimens containing antigens as macromolecules, and urine is particularly preferred because it can be suitably used in a treatment kit and treatment method.
The liquid sample may also be an artificial imitation of a biological fluid, such as artificial urine.

<Biofluids>
Biofluids are biological or bioorganic fluids produced by living organisms. Biofluids are liquids that living organisms have in some form within their bodies.
As the biological fluid, any liquid collected from a living body can be used as is, such as blood, tissue fluid, body cavity fluid, digestive fluid, urine, saliva, sweat, tears, nasal discharge, semen, lymphatic fluid, vaginal fluid, amniotic fluid, milk, cerebrospinal fluid, synovial fluid, and cell suspension. Alternatively, a biological sample from which cellular components have been previously disrupted or removed may be used. Among biological fluids, blood, saliva, sweat, tears, and urine are easily obtained.

<Polymers contained in biological fluids>
Examples of the polymers (particularly antigens) contained in the biological fluids mentioned above are polymers that are primarily useful for diagnosing diseases and are detected in biological fluids, such as fungi, bacteria (e.g., Mycobacterium tuberculosis, lipoarabinomannan (LAM) contained in Mycobacterium tuberculosis), bacteria, viruses (e.g., influenza virus), and their nucleoproteins. LAM is a major antigen in tuberculosis and is a glycolipid that is a major component of cell membranes and cell walls.
The macromolecules contained in the biological fluid are preferably antigens, more preferably viruses (particularly influenza viruses) or LAM, and even more preferably LAM.
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).

<Pretreatment of liquid samples>
The above-mentioned liquid sample can be used as it is, or in the form of a liquid obtained by extracting the antigen using an appropriate extraction solvent, or in the form of a diluted liquid obtained by diluting the extracted liquid with an appropriate diluent, or in the form of a liquid obtained by concentrating the extracted liquid using an appropriate method.
The extraction solvent may be a solvent used in a conventional immunological analysis (e.g., water, physiological saline, or a buffer solution), or a water-miscible organic solvent that can be used to directly carry out an antigen-antibody reaction by diluting the sample with such a solvent.

[Ratio of water-absorbing polymer to liquid sample]
The ratio of the water-absorbing polymer to the liquid sample is not particularly limited, but is preferably 0.01 to 100 g, more preferably 0.01 to 1 g, per 1 mL of the liquid sample, from the viewpoint that the liquid sample can be concentrated to an appropriate concentration and the concentrated liquid can be easily extracted.

[Recovered liquid]
The recovery liquid contains a salt. The recovery liquid contains a solvent used in a conventional immunological analysis method or a water-miscible organic solvent that can be used to directly carry out an antigen-antibody reaction by diluting the solution with such a solvent. Examples of solvents used in conventional immunological analysis methods include water, physiological saline, and a buffer solution.
Furthermore, the recovery liquid can be made functional by adding a buffer, a surfactant, and other additives as necessary. The recovery liquid is preferably a buffer solution, more preferably PBS (Phosphate Buffered Salts). A part of the sample liquid may also be used as the recovery liquid. The recovery liquid may contain a preservative, such as Proclin 950 (trade name, manufactured by Sigma-Aldrich Japan Partnership).

The salt contained in the recovery liquid is a compound consisting of anions and cations. The salt contained in the recovery liquid is, for example, an inorganic salt. The inorganic salt is, for example, an alkali metal salt or an alkaline earth salt. An example of the alkali metal salt is sodium chloride. An example of the alkaline earth salt is magnesium chloride.
The salt contained in the recovered solution is preferably sodium chloride or magnesium chloride because the variation in the recovered amount of the concentrated solution is small. Of sodium chloride and magnesium chloride, magnesium chloride is more preferred because the variation in the recovered amount of the concentrated solution is even smaller.

The salt content of the recovery liquid is preferably 25 mg/mL (milliliter) or more.
When the salt content of the recovered liquid is 25 mg/mL or more, the recovered liquid can be prevented from being absorbed by the water-absorbent polymer, and the variation in the recovered amount of concentrated liquid can be reduced.
It has been confirmed that the water absorption rate of the water-absorbent polymer becomes constant when the salt content of the recovery solution is 25 mg/mL or more. When the salt content of the recovery solution is 25 mg/mL or more, depending on the type of salt, the detection sensitivity may change when the concentrated solution is used in an immunochromatography kit. For this reason, the upper limit of the salt content of the recovery solution is preferably 100 mg/mL or less.
The salt content of the recovered liquid is the mass of the salt as a solute relative to the amount of solvent in the recovered liquid, and is the mass of the salt in the recovered liquid converted into mass per milliliter.

The amount of recovery liquid is less than the amount of liquid sample injected into the container, in order to concentrate the liquid sample (analyte liquid). The ratio of the amount of recovery liquid to the amount of liquid sample injected into the container (amount of recovery liquid/amount of liquid sample (analyte liquid)) should be less than 100% by volume, preferably 30% or less, more preferably 20% or less, and even more preferably 0.01% to 10%.

The salts contained in the recovery solution are required not to inhibit the antigen-antibody reaction in immunochromatography. We investigated the effects of salts contained in the recovery solution on the antigen-antibody reaction of the immunochromatography kit.
Four types of recovery liquids containing sodium chloride, calcium chloride, magnesium chloride, or citric acid as additives were used.
To evaluate the effect on the antigen-antibody reaction, an immunochromatographic kit for detecting Mycobacterium tuberculosis antigens was used to detect lipoarabinomannan antigens as the test substance described in WO 2020/045625. The immunochromatographic kit was configured as shown in Figures 1 to 3 of WO 2020/045625.
The sample solution used was artificial urine (JIS (Japanese Industrial Standards) T3214) containing LAM (lipoarabinomannan) antigen and BSA (bovine serum albumin) at a concentration of 1 mg/mL. The LAM concentration was diluted to 200 pg/mL. The recovery solution was added to the sample solution to examine its effect.

According to the operating method of the immunochromatography kit described in WO 2020/045625, 200 μL of the sample solution to which the recovery solution was added was placed in a tube, and the sample solution to which the recovery solution was added was then immersed in a pad and left to stand for 40 minutes to allow the gold colloid to react with the antigen. Then, the sample was spotted on an immunochromatography kit to evaluate the effect on the antigen-antibody reaction. The evaluation results of the effect on the antigen-antibody reaction are shown in Table 1 below.
The effects on the antigen-antibody reaction were evaluated in terms of the effect on the surface condition, sensitivity, and false positives.
The effect on the surface condition was confirmed by visually observing the surface condition through the observation window of the immunochromatography kit.
The effects on sensitivity and false positives were evaluated by increasing the additive content and visually checking the color of the test line and the line indicating a positive result that appeared on the surface observed through the observation window of the immunochromatography kit. The easier the test line and the line indicating a positive result were to be visually observed, the higher the S/N ratio (signal/noise ratio), the higher the sensitivity, and the lower the possibility of a false positive.
On the other hand, if the test line and the line indicating a positive result are difficult to see, the signal-to-noise ratio will be low, the sensitivity will be low, and there will be a high possibility of a false positive.
As calcium chloride and citric acid showed poor results in the evaluation of their effect on the surface condition, as described below, their effects on sensitivity and false positives were not examined. For this reason, a "-" is entered in the "Effect on sensitivity and false positives" column in Table 1 below.

When calcium chloride and citric acid were used as additives to the recovery solution, the surface observed through the observation window of the immunochromatography kit turned black, making it impossible to determine whether the result was positive or negative.
When sodium chloride and magnesium chloride are used as additives to the recovery solution, they have little effect on the surface observed through the observation window of the immunochromatography kit, so sodium chloride and magnesium chloride are preferred. It has been found that magnesium chloride is even more preferred because it has little effect on sensitivity and false positives.
From the viewpoint of the influence on the surface state observed through the observation window and the influence on false positive sensitivity, the salt contained in the recovery liquid is preferably sodium chloride or magnesium chloride, and more preferably magnesium chloride.
The surface refers to the immunochromatographic reaction area (the member holding the various lines) that can be seen through the observation window.
Furthermore, regarding the effect on the surface condition, "small effect on the surface condition" means that there is little discoloration such as blackening, and that there is little effect on the positive/negative judgment due to discoloration. "Low effect on the surface condition" and "little effect on the surface condition" are synonymous.

〔piston〕
As described above, the piston has a plurality of holes at the tip end that are smaller than the particle size of the water-absorbing polymer after absorbing water.
The diameter of the hole at the tip is preferably 1/2 or less, more preferably 1/5 or less, and even more preferably 1/10 or less of the particle diameter of the water-absorbent polymer after absorbing water.
The diameter of the hole at the tip is preferably smaller than the particle diameter of the water-absorbent polymer before it absorbs water, and is preferably 0.01 to 5 mm, more preferably 0.1 to 2 mm.
The number of holes in the tip is not particularly limited, but is preferably 10 to 100, and more preferably 20 to 50.
The ratio of the total area of the holes in the tip to the area of the tip is preferably 5% or more, more preferably 10% or more, and even more preferably 15% or more.
The material of the piston is not particularly limited, and the same material as that of the container body 20 shown in FIGS. 1 and 2 can be used.

A liquid sample (analyte liquid) concentrated using the treatment kit and treatment method is used in a test method for detecting macromolecules in the sample liquid, which is an aqueous solution containing macromolecules. The macromolecules in the concentrate obtained by concentrating the sample liquid can be detected by various known methods.
The concentrated solution can be concentrated at a high concentration rate, can be extracted reliably, and the variation in the amount recovered each time is small, resulting in high detection sensitivity and high repeatability of detection.

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-linked immunosorbent assay (EIA), enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), fluorescent immunoassay (FIA), Western blotting, immunochromatography, etc. In particular, the treatment kit and treatment method can be suitably used for concentrating a liquid sample (analyte liquid) for performing immunochromatography.
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.

The present invention is basically configured as described above. The processing kit and processing method of the present invention have been described in detail above, but the present invention is not limited to the above-described embodiments, and various improvements and modifications may of course be made without departing from the spirit of the present invention.

The features of the present invention will be explained in more detail below with reference to examples. The materials, reagents, amounts and proportions of substances, and procedures shown in the following examples can be changed as appropriate without departing from the spirit of the present invention. Therefore, the scope of the present invention is not limited to the following examples.
In this example, the variation in the recovery amount was evaluated using the containers of Examples 1 to 12 and Comparative Examples 1 to 4. The variation in the recovery amount will be explained below.

(Variation in recovery amount)
Regarding the variation in the recovered amount, the concentrated solution was recovered 30 times.
For each collection, the amount of the concentrated liquid that was not absorbed by the superabsorbent polymer and could be removed was weighed.
The standard deviation (σ) and average value were calculated from the recovered amount of concentrated solution for 30 runs, and the coefficient of variation was calculated. The coefficient of variation is (standard deviation (σ)/average value) × 100 (%). The coefficient of variation (unit: %) was evaluated based on the following evaluation criteria. The results are shown in Table 2 below.
Evaluation criteria: A: Coefficient of variation is less than 5%. B: Coefficient of variation is 5% or more but less than 10%. C: Coefficient of variation is 10% or more but less than 15%. D: Coefficient of variation is 15% or more but less than 20%. E: Coefficient of variation is more than 20%. If the evaluation is A, the repeatability of the recovered amount of concentrated liquid is very good and there is very little variation in the recovered amount.
If the evaluation is B, the reproducibility of the recovered amount of concentrated liquid is good and the variation in the recovered amount is small.
If the evaluation is C, the variation in the amount of recovered concentrated liquid is kept low and is practically acceptable.
If the evaluation is D, the variation in the amount of recovered concentrate cannot be suppressed to a low level, which is not practically acceptable.
If the evaluation is E, the recovered amount of the concentrated liquid varies greatly, which is not practically acceptable.

Examples 1 to 12 and Comparative Examples 1 to 4 will be described below.
Example 1
In Example 1, a rigid container was used, and the container 12 shown in FIG. 1 was used.
The container body 20 has a cylindrical shape with an inner diameter of 12 mm and a height of 60 mm, and is configured to have a male screw portion on the top.
The piston 22 has a tip 22a with 24 holes 22b each having a diameter of 1 mm and smaller than the particle diameter of the superabsorbent polymer after absorbing water.
A lid 24 (with a female screw) equipped with a nozzle 24b having a recovery port 24c was prepared. By connecting it to the container body 20, the container 12 was completed.
The container body 20, piston 22 and lid 24 were made of polyethylene terephthalate.
In Example 1, 3.0 g of superabsorbent polymer was placed inside the container body. 20 mL of artificial urine prepared in accordance with JIS T 3214 was placed as a liquid sample (analyte liquid) and allowed to stand for 10 minutes to allow the superabsorbent polymer to absorb water. Then, 3 mL (milliliters) of recovery liquid was added, and a concentrated liquid recovery operation was performed. The mass of the recovered concentrated liquid was measured.
This recovery operation was carried out 30 times, and the mass of the recovered concentrate was measured for each recovery, a total of 30 times. The masses of the recovered concentrates from the 30 times were used to evaluate the variation in the recovery amount as described above.
The superabsorbent polymer used was superabsorbent polymer particles (SAP Sphere manufactured by M2 Polymer Technologies Inc.) The particle diameter of the superabsorbent polymer was 2.5 mm, the swelling ratio was 13 g/g, and the water absorption rate was 0.5 g/min.
The recovery solution was an aqueous solution of pure water and salt. NaCl (sodium chloride) was used as the salt. The salt content of the recovery solution was 20 mg/mL. Proclin 950 (trade name, manufactured by Sigma-Aldrich Japan G.K.) was added to the recovery solution as a preservative.

Example 2
Example 2 differs from Example 1 in that the salt content of the recovery solution was 28 mg/mL.
Example 3
Example 3 differs from Example 1 in that MgCl ₂ (magnesium chloride) was used as the salt. Other than that, Example 3 was the same as Example 1.
Example 4
Example 4 differs from Example 3 in that the salt content of the recovery solution was set to 28 mg/mL.

Example 5
Example 5 is different from Example 1 in that a soft container was used, and the container 42 shown in Figures 8 and 9 was used.
In Example 5, the container body 44 of the container 42 had an overall height of 65 mm, an inner diameter of 12 mm up to the reduced diameter portion 44c, and a height of 60 mm. The cap 46 and the container body 44 were joined to complete the container 42. The container body 44 and the cap 46 were made of polypropylene.
In Example 5, 3.0 g of superabsorbent polymer was placed inside the container body in the same manner as in Example 1. 20 mL of artificial urine, which was a liquid sample (analyte liquid), was placed inside the container body and allowed to stand for 10 minutes to allow the superabsorbent polymer to absorb the water. 3 mL (milliliters) of recovery liquid was then placed inside the container body, and the concentrated liquid was then recovered. The mass of the recovered concentrated liquid was measured.
This recovery operation was carried out 30 times, and the mass of the recovered concentrate was measured for each recovery, a total of 30 times. The masses of the recovered concentrates from the 30 times were used to evaluate the variation in the recovery amount as described above.

Example 6
Example 6 differs from Example 5 in that the salt content of the recovery solution was 28 mg/mL.
Example 7
Example 7 differs from Example 5 in that the salt content of the recovery solution was 100 mg/mL.

(Example 8)
Example 8 differs from Example 5 in that MgCl ₂ (magnesium chloride) was used as the salt and the salt content of the recovery liquid was 15 mg/mL.
Example 9
Example 9 differs from Example 8 in that the salt content of the recovery solution was 28 mg/mL. Other than that, Example 9 was the same as Example 8.
Example 10
Example 10 differs from Example 8 in that the salt content of the recovery solution was 36 mg/mL.
Example 11
Example 11 differs from Example 8 in that the salt content of the recovery solution was 100 mg/mL. Other than that, Example 11 was the same as Example 8.
Example 12
Example 12 differs from Example 8 in that NaCl (sodium chloride) and MgCl ₂ (magnesium chloride) were used as salts. Other than that, Example 12 was the same as Example 8. In Example 12, the content of NaCl (sodium chloride) was 125 mg/mL, and the content of MgCl ₂ (magnesium chloride) was 60 mg/mL.

(Comparative Example 1)
Comparative Example 1 differs from Example 1 in that no recovery liquid was used. Other than that, it was the same as Example 1. For Comparative Example 1, "-" is entered in the columns of "Presence or Absence of Salt,""Type of Salt," and "Salt Content" in Table 2.
(Comparative Example 2)
Comparative Example 2 differs from Example 1 in that the recovery liquid does not contain salt, and only pure water is used as the recovery liquid. Other than that, Comparative Example 2 is the same as Example 1. For Comparative Example 2, "-" is entered in the "Salt type" and "Salt content" columns in Table 2.
(Comparative Example 3)
Comparative Example 3 differs from Example 5 in that no recovery liquid was used. Other than that, it was the same as Example 5. For Comparative Example 3, "-" is entered in the columns of "Presence or Absence of Salt,""Type of Salt," and "Salt Content" in Table 2.
(Comparative Example 4)
Comparative Example 4 differs from Example 5 in that the recovery liquid did not contain salt, but pure water was used. Other than that, the comparison was the same as Example 1. For Comparative Example 4, "-" is entered in the "Salt type" and "Salt content" columns of Table 2.

As shown in Table 2, Examples 1 to 12 have smaller variations in the recovery amounts than Comparative Examples 1 to 4.
From Examples 1 to 12, when the salt content is 25 mg/mL or more, the variability in the recovery amount is smaller. In addition, when comparing sodium chloride and magnesium chloride, magnesium chloride has a smaller variability in the recovery amount.

In Examples 1 to 12, an immunochromatographic kit for detecting Mycobacterium tuberculosis antigens was used as the test substance for detecting lipoarabinomannan antigens described in WO 2020/045625. The immunochromatographic kit had the configuration shown in Figures 1 to 3 of WO 2020/045625.
The liquid sample (analyte solution) used was artificial urine (JIS T3214) containing LAM (lipoarabinomannan) antigen at a concentration of 1 mg/mL and BSA (Bovine Serum Albumin). It was diluted to a LAM concentration equivalent to 200 pg/mL. The above-mentioned concentrate was obtained in the same manner as in Examples 1 to 12, except for using this liquid sample.
The obtained concentrate was placed in a tube in 200 μL in accordance with the operating method of the immunochromatography kit described in International Publication No. 2020/045625. The concentrate was then immersed in a pad and left to stand for 40 minutes to allow the gold colloid and antigen to react. The concentrate was then applied to the immunochromatography kit to evaluate its effect on the antigen-antibody reaction. As a result, sodium chloride had an effect on the surface when the content exceeded 100 mg/mL. On the other hand, magnesium chloride did not have an effect on the surface even when the content exceeded 100 mg/mL. Thus, it was confirmed that the detection sensitivity of magnesium chloride was not affected by the content, compared to sodium chloride.

10, 11, 40 Processing kit 12, 13, 42 Container 14 Recovery liquid container 15 Recovery liquid 20, 48, 48a, 48b Container body 20a Opening 20b Bottom 20c Interior 20d Outer periphery 20e, 45a Male threaded portion 22 Piston 22a Tip 22b Hole 22c Pusher 23 Flat plate 23a End face 23b Side face 23c End face 23d Protrusion 24 Lid 24a Lid body 24b, 46a Nozzle 24c Recovery port 25 Guide groove 25a First straight portion 25b Second straight portion 26, 27 Water-absorbing polymer 28 Concentrate 30 Liquid sample 34 Concentrated liquid 42c Interior 44 Container body 44a Storage portion 44b Neck portion 44c, 44e Diameter-reduced portion 44d, 44f, 49 Storage portion 45 Opening 46 Cap 46b Discharge portion 46c Female thread portion 47 Filter 50 Container 52 Wall surface D Arrow

Claims (10)

a water-absorbing polymer that absorbs water from a liquid sample containing a test substance and water;
A container containing the water-absorbing polymer;
a recovery liquid container for containing a recovery liquid containing salt,
A processing kit, wherein the recovery liquid is added after the liquid sample is placed in the container. The processing kit of claim 1, wherein the salt contained in the recovery solution is at least one of sodium chloride and magnesium chloride. The processing kit of claim 1, wherein the salt contained in the recovery solution is magnesium chloride. The processing kit described in any one of claims 1 to 3, wherein the salt content of the recovery solution is 25 mg/mL or more. The processing kit according to any one of claims 1 to 3, wherein the liquid sample includes a biological fluid. A step of placing a liquid sample containing a test substance and water into a container containing a water-absorbent polymer;
a step of concentrating the liquid sample in the container by absorbing the water contained in the liquid sample into a water-absorbing polymer;
placing a recovery solution containing salt into the container;
and removing the concentrated liquid of the liquid sample obtained by concentrating the liquid sample in the container from the container. The treatment method described in claim 6, wherein the salt contained in the recovered liquid is at least one of sodium chloride and magnesium chloride. The treatment method described in claim 6, wherein the salt contained in the recovered liquid is magnesium chloride. The processing method described in any one of claims 6 to 8, wherein the salt content of the recovery liquid is 25 mg/mL or more. The processing method described in any one of claims 6 to 8, wherein the liquid sample includes a biological fluid.