Processing kit and processing method

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

[0001] The present invention relates to a processing kit and a processing method that includes a container that contains a water-absorbing polymer that absorbs water from a liquid sample containing a test substance and water, and a recovery liquid container that contains a recovery liquid containing salt, and in particular, to a processing kit and a processing method in which the recovery liquid is added after the liquid sample is placed in the container.

[0002] BACKGROUND ART Conventionally, there is known a technique 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.

[0003] Japanese Patent Application Publication No. 4-355339

[0004] The present inventors investigated a method for concentrating a liquid sample using a water-absorbent polymer, taking into account the microsample collection device described in Patent Document 1, and found that it is difficult to extract the concentrated liquid sample from the microsample collection device after concentrating the liquid sample. Specifically, from the perspective of shortening the concentration time, a larger amount of superabsorbent polymer is preferable, and even when the amount of liquid sample is large, a larger amount of superabsorbent polymer is required. A large amount of superabsorbent polymer reduces the amount of concentrated liquid, making it difficult to extract the concentrated liquid. This may result in an insufficient amount of concentrated liquid for the liquid sample being obtained. Furthermore, from the perspective of shortening the absorption time, if the saturated sample water absorption capacity of the superabsorbent polymer is greater than the amount of liquid sample, water absorption also occurs when extracting the concentrated liquid. Therefore, if it takes a long time to extract the concentrated liquid, the required amount of concentrated liquid for the liquid sample may not be obtained. Reducing the amount of water-absorbent polymer to ensure a sufficient amount of concentrated liquid reduces the concentration ratio of the concentrated liquid. Furthermore, although it is possible to extract the concentrated liquid by adding a small amount of recovery liquid after concentrating the liquid sample, increasing the amount of recovery liquid reduces the concentration ratio of the concentrated liquid. 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.

[0005] An object of the present invention is to provide a processing kit and processing method that minimizes variation in the amount of concentrated liquid collected from a liquid sample each time it is collected.

[0006] In order to achieve the above-mentioned object, invention [1] is a treatment kit comprising: a water-absorbent polymer that absorbs water from a liquid sample containing a test substance and water; a container for accommodating the water-absorbent polymer; and a recovery liquid container for accommodating a recovery liquid containing salt, the recovery liquid being added after the liquid sample is placed in the container.

[0007] 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], in which the salt content of the recovery solution is 25 mg / mL or more. Invention [5] is the treatment kit according to any one of Inventions [1] to [4], in which the liquid sample includes a biological fluid.

[0008] Invention [6] is a processing method comprising the steps of placing a liquid sample containing a test substance and water into a container containing a water-absorbent polymer, concentrating the liquid sample in the container by allowing the water contained in the liquid sample to be absorbed by the water-absorbent polymer, placing a recovery liquid containing salt into the container, and removing the concentrated liquid of the liquid sample obtained by concentration in the container from the container. Invention [7] is the processing method according to Invention [6], in which the salt contained in the recovery liquid is at least one of sodium chloride and magnesium chloride. Invention [8] is the processing kit according to Invention [6], in which the salt contained in the recovery liquid is magnesium chloride. Invention [9] is the processing method according to any one of Inventions [6] to [8], in which the salt content of the recovery liquid is 25 mg / mL or more. Invention

[10] is the processing method according to any one of Inventions [6] to [9], in which the liquid sample includes a biological fluid.

[0009] According to the present invention, it is possible to provide a processing kit and a processing method that minimize variation in the amount of concentrated liquid sample recovered each time it is recovered.

[0010] 1 is a schematic perspective view showing a first example of a processing kit according to an embodiment of the present invention. 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. FIG. 3 is a schematic cross-sectional view showing a step of the first example of a processing method according to an embodiment of the present invention. FIG. 4 is a schematic cross-sectional view showing a step of the first example of a processing method according to an embodiment of the present invention. FIG. 5 is a schematic cross-sectional view showing a step of the first example of a processing method according to an embodiment of the present invention. FIG. 6 is a schematic cross-sectional view showing a step of the first example of a processing method according to an embodiment of the present invention. FIG. 7 is a schematic cross-sectional view showing a step of the first example of a processing method according to an embodiment of the present invention. 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 according to 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 according to the second example of the processing kit according to an embodiment of the present invention. FIG. 11 is a schematic perspective view showing another example of a container body of the container according to the second example of the processing kit according to an embodiment of the present invention. FIG. 12 is a schematic perspective view showing another example of a container body of the container according to the second example of the processing kit according to an embodiment of the present invention. FIG. 13 is a schematic view for explaining the relationship between the discharge direction of a liquid sample and a flexible wall surface. FIG. 14 is a schematic view for explaining the possible volume change amount of a container. Fig. 1 is a schematic cross-sectional view showing a step of a second example of a processing method according to an embodiment of the present invention. Fig. 2 is a schematic cross-sectional view showing a step of a second example of a processing method according to an embodiment of the present invention. Fig. 3 is a schematic cross-sectional view showing a step of a second example of a processing method according to an embodiment of the present invention.

[0011] The processing kit and processing method of the present invention will be described in detail below based on the preferred embodiments shown in the accompanying drawings. Note that the drawings described below are illustrative for explaining the present invention and are simplified for explaining the present invention. Therefore, the present invention is not limited to the drawings shown below. Note that in the following, the term "to" indicating a range of values ​​includes the values ​​written on both sides. For example, when ε is a value ε α ~Number ε β That is, the range of ε is the number ε α and the number ε β The range includes ε α ≦ε≦ε βUnless otherwise specified, the parallel and perpendicular directions include error ranges generally accepted in the relevant technical field. Furthermore, the orthogonal directions include error ranges generally accepted 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.

[0012] The processing kit and the processing method will be specifically described below.

[0013] [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. FIG. 2 is a schematic perspective view showing a modified example of the first example of a processing kit according to an embodiment of the present invention. The processing kit 10 shown in FIG. 1 includes a container 12 containing a water-absorbent polymer 26 and a recovery liquid container 14 containing a recovery liquid 15 containing salt. 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 highly water-absorbent polymer (Super Absorbent Polymer: SAP). Hereinafter, a liquid sample containing a test substance and water will also be referred to as a sample liquid. Furthermore, a concentrated liquid sample is a concentrated liquid sample, and the concentrated liquid sample and the concentrated liquid sample will also be simply referred to as a concentrated liquid. Unless otherwise specified, the term "concentrated liquid" refers to a concentrated liquid sample and a concentrated liquid sample, i.e., a concentrated sample liquid and a concentrated liquid sample.

[0014] The container 12 has, for example, a container body 20, a piston 22, and a lid 24. The container body 20 is configured as, for example, 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. A water-absorbent polymer 26 is accommodated in the interior 20c of the container body 20. A piston 22 is inserted into the interior 20c of the container body 20. An external thread 20e is provided on the outer periphery 20d of the container body 20 at the end on the opening 20a side. Note that the container body 20 is not limited to being cylindrical, as long as it is cylindrical.

[0015] The piston 22 has a tip portion 22a and a plunger 22c. The tip portion 22a is formed, for example, from a circular plate. 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-absorbing polymer 26 after absorbing water. The diameter of the circular plate constituting the tip portion 22a is equal to or smaller than the inner diameter of the opening 20a of the container body 20. The plunger 22c is, for example, two rectangular flat plates 23 crossed at right angles. The width of the plunger 22c, i.e., the width w of the flat plates 23, is equal to or smaller than the inner diameter of the opening 20a of the container body 20. The plunger 22c is provided on the surface of the tip portion 22a with the end surface 23c of the flat plates 23 in contact with the surface of the tip portion 22a. A lid 24 is disposed on the end surface 23a of the flat plates 23 opposite the end surface 23c.

[0016] The lid 24 has a lid body 24a and a nozzle 24b, and the nozzle 24b is provided with a recovery port 24c. The inside of the lid body 24a is provided with a female thread (not shown) that threads with the male thread 20e of the container body 20. The lid body 24a is threadedly engaged with the container body 20. The lid body 24a can be attached to and detached from the container body 20. The method of connecting the lid body 24a to the container body 20 is not particularly limited as long as it allows for easy attachment and detachment. The nozzle 24b is used to remove the concentrated liquid from the container 12. The container 12 is attached to the container body 20 by threading the lid body 24a onto the container body 20 with the piston 22 inserted into the interior 20c of the container body 20. In this state, the concentrated liquid is removed from the container 12 through the recovery port 24c and collected in a collection container such as a collection cup (not shown). The concentrated liquid is used, for example, in a test using an antigen-antibody reaction with an immunochromatography kit. The collection container is not limited to a collection cup.

[0017] The recovery liquid container 14 is used to add the salt-containing recovery liquid 15 to the container 12 containing the water-absorbent polymer 26, i.e., the interior 20c of the container body 20, after a liquid sample has been placed therein. The recovery liquid 15 is added after the liquid sample has been placed in the container 12. The recovery liquid container 14 is not particularly limited in configuration as long as it can accommodate the salt-containing recovery liquid 15 and add the recovery liquid 15 to the container 12. The amount of recovery liquid 15 added by the recovery liquid container 14 is less than that 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, or a pipette. The recovery liquid container 14 may be made of, for example, polyethylene (PE), polypropylene (PP), or the like.

[0018] (Variation of the First Example of the Processing Kit) The configuration of the container 12 of the processing kit 10 is not limited to the configuration shown in FIG. 1 and may be, for example, the configuration of the container 13 of the processing kit 11 shown in FIG. 2. The container 13 shown in FIG. 2 differs in the configuration of the container body 20 and the piston 22, but otherwise has the same configuration as the container 12 of the 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 continuously with the first linear portion 25a. The second linear portion 25b is bent 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 flat plate 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 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 circumferentially 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, by engaging the protrusion 23d of the piston 22 with the guide groove 25 of the container body 20, the position of the tip 22a of the piston 22 can be maintained against pressure caused by the water-absorbing and expanding water-absorbent polymer 26.

[0019] [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 may also be used, or a processing kit with another configuration may also be used. Here, FIGS. 3 to 7 are schematic cross-sectional views showing the process sequence of a first example of a processing method according to an embodiment of the present invention. Note that in FIGS. 3 to 7, components that are the same as those in processing kit 10 shown in FIG. 1 are assigned the same reference numerals, and detailed descriptions thereof will be omitted.

[0020] In the processing 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). Next, as shown in FIG. 4, a step of pouring a liquid sample 30 containing a test substance and water into the container body 20 of the container 12 (see FIG. 1) containing the water-absorbent polymer 26 is carried out. Specifically, the liquid sample 30 containing the test substance and water is poured into the interior 20c of the container body 20 through the opening 20a of the container body 20. When pouring the liquid sample 30 into the interior 20c of the container body 20, the liquid sample 30 is poured from a storage container (not shown) while being stored in the storage container, for example. The storage container is not particularly limited, and for example, a cup with a spout or the like can be 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.

[0021] Next, a step of concentrating the liquid sample 30 in the container 12 by having the water-absorbent polymer 26 absorb the water contained in the liquid sample is carried out. Specifically, in the water-absorbing step of having the water-absorbent polymer absorb the water contained in the liquid sample, as shown in FIG. 5 , the water contained in the liquid sample 30 (see FIG. 4 ) is absorbed by the water-absorbent polymer 26, concentrating the liquid sample 30 and producing a concentrate 28 of the liquid sample 30 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 described above, a step of pouring the recovery liquid 15 containing salt into the container 12 is carried out. Specifically, as shown in FIG. 6 , the recovery liquid 15 containing salt is poured from the recovery liquid container 14 into the interior 20c of the container body 20.

[0022] After the step of introducing the salt-containing recovery liquid 15 into the container 12, the 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 water absorption, 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 pressed 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 concentrate 34 removed from the container 12 is stored in a collection container, such as a collection cup (not shown).

[0023] The recovery liquid 15 containing the salt described above is not easily absorbed by the water-absorbent polymer 26, so a decrease in the amount of the concentrated liquid 34 can be suppressed. Therefore, when recovering the concentrated liquid 34, variation in the amount of the concentrated liquid 34 recovered each time can be suppressed. Furthermore, because the recovery liquid 15 is not easily absorbed by the water-absorbent polymer 26, the concentrate 28 can be transferred to the concentrated liquid 34. This makes it possible to maintain the concentration of the concentrate 28 in the concentrated liquid 34, and to maintain a predetermined concentration ratio. The concentration ratio of the concentrated liquid is the amount of liquid sample divided by the amount of concentrated liquid.

[0024] In the above-described treatment method, the water in the liquid sample (analyte liquid) is absorbed by the water-absorbent polymer. The sample is typically 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, resulting in the formation of a concentrate in the container body. When the liquid sample is mixed with the water-absorbent polymer, the water in the liquid sample is absorbed by the water-absorbent polymer. However, the 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 difficult to absorb by the water-absorbent polymer. As a result, the macromolecules, such as antigens, in the liquid sample are concentrated. The concentrate typically 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. To extract the concentrate, after the above-described water absorption process, a recovery liquid is added, and then a piston is inserted into the container and its tip is pressed against the water-absorbent polymer, extracting the concentrate through holes smaller than the particle size. At this time, the recovered liquid moves thoroughly through the gaps between the water-absorbing polymers 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.

[0025] [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 container cap of the second example of the processing kit according to an embodiment of the present invention. In FIGS. 8 to 10, components identical to those of the processing kit 10 shown in FIG. 1 are designated by the same reference numerals, and detailed descriptions 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 otherwise has the same configuration as 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.

[0026] A container 42 of a processing kit 40 shown in FIGS. 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 detachably provided on the opening 45 of the container body 44 .

[0027] The container body 44 of the container 42 shown in Figures 8 and 9 comprises 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 substantially 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 communicates with 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.

[0028] The neck portion 44b is a generally cylindrical portion having an opening 45 penetrating from one bottom surface (end) to the other bottom surface (end). In the illustrated example, the neck portion 44b 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 accommodation portion 44a. The neck portion 44b also has a male thread portion 45a on its outer circumferential surface.

[0029] The area of ​​the housing 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 housing 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 housing portion 44a at the connection position between the housing portion 44a and the neck portion 44b is larger than the area of ​​the neck portion 44b. Hereinafter, the bottom surface of the housing portion 44a to which the neck portion 44b is connected is also referred to as the shoulder portion.

[0030] Furthermore, at least a portion of the storage portion 44a is flexible, and the water-absorbent polymer stored in the storage portion 44a can be pressed via the inner wall of the storage portion 44a. In the illustrated example, it is preferable that at least a portion of the circumferential surface of the storage portion 44a is flexible, and the entire storage portion 44a may be flexible.

[0031] In the example shown in Figures 8 and 9, the cap 46 is a member that closes the opening 45 of the neck portion 44b of the container body 44. Figure 10 shows a cross-sectional view of the cap 46. As shown in Figures 8, 9, and 10, the cap 46 is a cylindrical member that has one bottom surface and is provided with 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, allowing the cap 46 to be freely attached to and detached from the container body 44.

[0032] 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 is provided, and this through-hole serves as a discharge portion 46b.

[0033] 10, in a preferred embodiment, a filter 47 is disposed on the bottom side inside the cap 46. The filter 47 is a filter that 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.

[0034] 8 and 9, the container 42 having a container body 44 and a cap 46 can have the cap 46 removed from the container body 44, and the water-absorbent polymer 26 (see FIG. 1) before water absorption can be placed in the storage section 44a through the opening 45 of the neck section 44b. Also, the liquid sample 30 (see FIG. 4) can be placed through the opening 45 of the neck section 44b. In other words, the opening 45 of the container body 44 is an intake section for taking in the liquid sample.

[0035] After the liquid sample is introduced, the cap 46 is attached to the container body 44. Over a predetermined time, the water-absorbent polymer absorbs the moisture from 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 introduced into the container 42 through the opening 45 of the neck 44b, i.e., the recovery liquid 15 is introduced into the container body 44. The concentrated liquid is then discharged from the discharge port 46b provided on the nozzle 46a of the cap 46. At this time, at least a portion of the container body 44 is flexible, allowing the water-absorbent polymer to be pressed through the inner wall of the container body 44. Therefore, the concentrated liquid can be removed from the container body 44 by pressing the swollen water-absorbent polymer through the inner wall of the container body 44.

[0036] After the water-absorbing polymer has absorbed the moisture from the liquid sample, the recovery liquid 15 is introduced into the recovery liquid container 14 through the opening 45 of the neck 44b. Next, the cap 46 is attached. Thereafter, if necessary, the recovery liquid may be stirred in the container 42, and the concentrated liquid may be removed from the outlet 46b provided on the nozzle 46a of the cap 46. Furthermore, when performing at least one of stirring the concentrated liquid and stirring the recovery liquid, a cap without a nozzle 46a (outlet 46b) may be used to seal the inside of the container 42 and perform stirring, and then, when discharging the concentrated liquid, the cap 46 may be replaced with a cap with a nozzle 46a to remove the concentrated liquid.

[0037] In the examples shown in Figures 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 Figure 11, the storage portion 44d may have a reduced diameter portion 44e at the end of the storage portion 44d on the neck portion 44b side of the container body 48, which reduces in diameter 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 Figure 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. Note that Figure 11 is a schematic perspective view showing another example of a container body of a container of a second example of a processing kit according to an embodiment of the present invention.

[0038] In addition, 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.

[0039] 8 and 9, the end portion of the container body 44 adjacent to the neck 44b has a reduced diameter portion 44c, but the container body 44 may have no reduced diameter portion 44c. A configuration having a reduced diameter portion 44c at the end portion of the neck 44b is preferable because it facilitates the removal of the concentrated liquid. In the example shown in FIGS. 8 and 9, the storage portion 44a of the container body 44 is generally cylindrical, but this is not limiting. For example, the storage portion 44a may be a polygonal cylinder, such as a triangular or rectangular cylinder, or an elliptical cylinder.

[0040] 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.

[0041] 13, the container body 48b may have a neck portion 44b having an opening 45 to which the cap 46 can be attached and detached, and a bag-shaped container portion 49 for containing a water-absorbent polymer. The bag-shaped 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.

[0042] In the above example, the container bodies 44, 48, 48a, 48b and the cap 46 are configured to be threaded together using the male thread portion 45a and the female thread portion 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 threading. One of the container bodies 44, 48, 48a, 48b and the cap 46 may have a protrusion and the other a recess, and the recess and the protrusion may be engaged. Any known detachable fastening method may be used to attach the container bodies 44, 48, 48a, 48b and the cap 46, as appropriate.

[0043] 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, in addition to the above materials, a composite material may be used that contains a material that has necessary functions such as low moisture permeability, gas barrier properties, light blocking properties, and decorative properties. From the viewpoints of high flexibility, relatively high strength, chemical resistance, cost, etc., the resin material of the flexible portion of the container is preferably either polyethylene (PE) or polypropylene (PP).

[0044] 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. The lower limit is not particularly limited, but is preferably 20 μm or more.

[0045] Here, it is preferable that the wall surface of the discharge section of the container, which is parallel to the discharge direction of the concentrated liquid sample (concentrated liquid), is flexible. This point will be explained using FIG. 14 . FIG. 14 is a schematic diagram for explaining the relationship between the discharge direction of the liquid sample and the flexible wall surface. FIG. 14 conceptually shows a cross-sectional view of a container 50 included in a processing kit. In the container 50 shown in FIG. 14 , a discharge section 46 b is provided on the upper surface of the container 50 in the figure. That is, in the illustrated example, the direction of conveyance of the concentrated liquid from the discharge section 46 b is upward in the figure, as indicated by arrow D. Therefore, it is preferable that the wall surface 52 of the container 50, which is parallel to this arrow D, is flexible.

[0046] 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, allowing the container 50 to be pressed in a direction approximately 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 making it easier to remove. For example, in the example of the 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 circumferential surface of the storage portion 44a of the container body 44 is flexible, and more preferably that the entire circumferential surface is flexible.

[0047] Furthermore, it is preferable that the amount of change in the volume of the container is larger than the difference δ 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. 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 the container, conceptually showing the container 42 shown in FIGS. 8 and 9 . 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 water absorption is Vp, and the volume of the liquid sample 30 to be placed in the container 50 is Vs, the difference δ (=V−(Vs+Vp)) between the volume V of the container and 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.

[0048] 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 26 before absorbing water and the volume Vs of the liquid sample 30, by making the amount of change in volume of the container 50 larger than the difference δ (= V - (Vs + Vp)), that is, by making it larger than the volume Va of the space in the container 50 before deformation that is not filled with the water-absorbent polymer 26 and / or the liquid sample 30, that is, the volume Va of the void portion in the container 50, the concentrated liquid can be more reliably discharged when discharging the concentrated liquid from the container 50, even if at least a portion of the air in the container 50 is discharged.

[0049] 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 equal to or greater than 50%, the amount of volume change of the container can be increased, and the concentrated liquid can be more reliably discharged when it is discharged from the container 50.

[0050] When the container 42 has a container body 44 and a cap 46 as shown in FIG. 8, it is preferable that at least a portion of the circumferential surface of the container portion 44a of the container body 44 is flexible, and more preferably that the entire circumferential surface is flexible. The entire container portion 44a may be flexible. The neck portion 44b and the cap 46 may be flexible or not, but are preferably not flexible. When the container portion 44a and the neck portion 44b shown in FIG. 9 are integrally formed from the same material, the container portion 44a and the neck portion 44b can be made flexible and the neck portion 44b can be made non-flexible by making their thicknesses different. The container portion 44a and the neck portion 44b may also be formed from different materials.

[0051] Furthermore, the distance from the tip of the discharge portion of the container to the soft wall surface (i.e., the pressing portion) in a direction parallel to the direction of discharge of the concentrated liquid is preferably 70 mm or less, more preferably 50 mm or less, and even more preferably 30 mm or less. The lower limit is not particularly limited, but is preferably 1 mm or more. This allows the concentrated liquid to be more reliably discharged from the container.

[0052] Furthermore, 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. The lower limit of the ratio is not particularly limited, but is preferably 0.5 or more. This allows the concentrated liquid to be discharged more reliably when it is discharged from the container.

[0053] [Second example of processing method]

[0054] 16 to 19 are schematic cross-sectional views showing the steps of a second example of a processing method according to an embodiment of the present invention. In FIGS. 16 to 19, components identical to those in the processing kit 40 shown in FIG. 8 are designated by the same reference numerals, and detailed descriptions thereof will be omitted. As shown in FIG. 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 section for taking in a liquid sample (analyte liquid) and an outlet section for discharging a concentrated liquid sample (concentrated liquid). The water-absorbent polymer 26 has the same configuration as the water-absorbent polymer shown in FIG. 1 and is a highly water-absorbent superabsorbent polymer (SAP). The water-absorbent polymer will be described later.

[0055] Next, a step of placing the liquid sample 30 into a container 42 containing a water-absorbent polymer 26 is performed, followed by a step of concentrating the liquid sample 30 in the container 42 by allowing the water-absorbent polymer 26 to absorb the water contained in the liquid sample 30. Specifically, as shown in FIG. 17 , the liquid sample 30 is injected into the interior 42c of the container 42 containing the water-absorbent polymer 26 before water absorption. The injection method for the liquid sample 30 is the same as that of the first example of the treatment method described above. The injection amount of the liquid sample 30 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 milliliters. 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 FIG. 18 , the water-absorbent polymer 26 absorbs water and becomes a swollen water-absorbent polymer 27. A 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 poured from the recovery liquid container 14 into the interior 42c of the container 42.

[0056] After the step of placing the above-described salt-containing recovery liquid 15 into the container 42, a step of removing from the container 42 a concentrated liquid 34 of the liquid sample 30 obtained by concentration in the container 42 is then carried out. Here, at least a portion of the container 42 is soft, and the water-absorbent polymer 27 can be pressed through the inner wall of the container 42. Therefore, as shown in FIG. 19 , the water-absorbent polymer 27 that has swollen after absorbing water can be pressed through the inner wall of the container 42, and the concentrated liquid 34 containing the recovery liquid 15 can be removed 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).

[0057] Since the recovered liquid 15 containing the salt is not easily absorbed by the water-absorbent polymer 26, the second example of the treatment method can also prevent a decrease in the amount of the concentrated liquid 34, as in the first example of the treatment method. Therefore, when recovering the concentrated liquid 34, variation in the amount of the concentrated liquid 34 recovered each time can be reduced. Furthermore, since the recovered liquid 15 is not easily absorbed by the water-absorbent polymer 26, the concentrate 28 can be moved to the concentrated liquid 34. As a result, the concentration of the concentrate 28 in the concentrated liquid 34 can be maintained, and a predetermined concentration ratio can be maintained, also in the second example of the treatment method.

[0058] As described above, the inventors' investigations 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, a larger amount of water-absorbent polymer is preferable from the standpoint of shortening the concentration time, but a larger amount of water-absorbent polymer reduces the amount of concentrated liquid, making it difficult to remove the concentrated liquid. This may result in an insufficient amount of concentrated liquid from the liquid sample being 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 removing the concentrated liquid. This may result in an insufficient amount of concentrated liquid from the liquid sample being obtained. On the other hand, reducing the amount of water-absorbent polymer or increasing the volume of recovery liquid to ensure a sufficient amount of concentrated liquid reduces the concentration ratio of the concentrated liquid. A lower concentration ratio also reduces the amount of test substance, such as an antigen, in the concentrated liquid, which is undesirable because it reduces the amount of antigen detection accuracy.

[0059] 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 the recovered liquid 15 to be dispersed into gaps between the absorbent polymers 27. This allows a larger amount of the concentrate 28 remaining near the absorbent polymer 27 to be recovered, thereby 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 allows the concentrate to be more easily removed than in a configuration in which the concentrate is pushed out solely by air pressure, such as with a pump. Furthermore, the concentrate can be efficiently dispersed even with a small amount of concentrate, and can be efficiently removed from the container 42, thereby increasing the concentration ratio of the concentrate 34. Furthermore, it becomes easy to ensure the necessary amount of concentrated liquid 34 to be recovered, and it becomes possible to keep the concentration rate of the extracted concentrated liquid 34 constant.

[0060] Furthermore, because the container 42 can be deformed by, for example, being pressed by the user's finger, it is easy for uneven deformation to occur and it can be deformed into various shapes, and because the water-absorbent polymers 27 are movable, it is possible to prevent the water-absorbent polymers 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 polymers 27 is large, the concentrated liquid 34 can be efficiently spread and can be efficiently taken out of the container 42.

[0061] 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.

[0062] 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, the discharge part is preferably a relatively large opening that is smaller than the particle size of the water-absorbent polymer after absorption, from the viewpoints of enabling the concentrated liquid to be discharged without discharging the water-absorbent polymer after absorption, and suppressing the occurrence of air leakage that makes it difficult to take out the concentrated liquid 34 when the container 42 is pressed to discharge the concentrated liquid 34, etc. The configuration of the treatment kit will be described in more detail below.

[0063] 1 and 2 is not particularly limited, but is preferably a thermoplastic resin 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).

[0064] 8, 11, 12, and 13, 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), acrylic resin (PMMA), or an elastomer material, and has a thickness of 1000 μm or less. From the viewpoints of high flexibility and relatively high strength, chemical resistance, cost, etc., as described above, the resin material of the flexible portion of the container is preferably either polyethylene (PE) or polypropylene (PP).

[0065] [Water-absorbent polymer] The water-absorbent polymer contained in the container is, for example, a super absorbent polymer (SAP). The water-absorbent polymer is in particulate form, and a large number of particulate water-absorbent polymers are contained in the container. The particulate water-absorbent polymer is illustrated 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 or may be heterogeneous. The composition of the water-absorbent polymer is not particularly limited, and various known water-absorbent polymers such as polyacrylic acid-based, polyacrylamide-based, cellulose-based, or polyethylene oxide-based polymers can be appropriately used.

[0066] <Swelling ratio> The swelling ratio of the water-absorbent 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, even more 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-absorbent polymer."

[0067] (Method for measuring swelling ratio) The mass of a water-absorbent polymer stored at a temperature of 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: Swelling ratio = {(mass after water absorption (g) - initial mass before water absorption (g)) / initial mass before water absorption (g)}

[0068] 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.

[0069] <Water absorption rate> The water absorption rate of the water-absorbent 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-absorbent polymer, and more preferably 0.02 g / min or more and 40 g / min or less per 1 g of water-absorbent polymer.

[0070] The water absorption rate is measured as follows. A water-absorbent polymer stored at a temperature of 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 a time T1 has elapsed, the water-absorbent polymer is taken out, the water on the surface is removed, and the mass is measured (mass M １ Similarly, the mass after time T2 and time T3 from the immersion are measured. ２ and M ３ Here, the time T1, the time T2, and the time T3 are set to be equal intervals, and the time T3 is set to be shorter than the water absorption saturation time Ts of the superabsorbent polymer and within a range in which the amount of water absorption per unit time can be considered constant. For example, the time T3 may be set to Ts / 2.

[0071] The amount of water absorption is defined as follows: Amount of water absorption after time T1 has elapsed: 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 has elapsed: ΔM3 = (M ３ -M ０ ) / M０ Using the water absorption amount defined above, the water absorption rate is calculated as follows: Three points are plotted on the X-Y plane with time (x = T1, T2, T3; unit: minutes) on the horizontal axis and water absorption amount (y = ΔM1, ΔM2, ΔM3; unit: g water / g polymer amount) on the vertical axis, and the slope of the linear approximation of the water absorption amount versus time using the least squares method is taken as the water absorption rate per unit time (minute).

[0072] <Particle size> The particle size of the water-absorbent 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-absorbent 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 can be determined by measuring the diameters of 50 particulate water-absorbent polymers using an optical microscope and calculating the arithmetic average value.

[0073] [Binding substance that specifically binds to macromolecules contained in biological fluid] From the viewpoint of increasing detection sensitivity when a test is performed using a concentrated solution obtained by concentrating a liquid sample, it is preferable that the container further contains a binding substance that specifically binds to macromolecules contained in the biological fluid in the specimen solution, which will be described later. When the container contains the above-mentioned binding substance, for example, an antigen-antibody reaction proceeds simultaneously with the concentration of the specimen solution, and a complex between the antigen in the specimen solution and the labeled antibody is formed in a concentrated state, leading to improved detection sensitivity.

[0074] The binding substance may 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 is an antigen and the binding substance is an antibody.

[0075] 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.

[0076] 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 labeled antibody may be contained in a container as a pad (colloidal gold-retaining pad) holding modified colloidal gold particles, which are gold colloidal particles modified with antibodies.

[0077] [Casein, Tricine] From the viewpoint of increasing detection sensitivity when performing a test using a concentrated solution obtained by concentrating a liquid sample, the container preferably further contains at least one selected from the group consisting of casein and tricine, and more preferably contains both casein and tricine. Casein is thought to have the function 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 are likely to occur, and tricine is thought to have the function of adjusting the pH to neutral to alkaline, thereby suppressing false positives.

[0078] [Liquid Sample (Specimen Liquid)] The liquid sample (specimen liquid) contains a test substance and water. The liquid sample (specimen 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 (e.g., 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 polymers, and urine is particularly preferred because it can be suitably used in treatment kits and treatment methods. The liquid sample may also be an artificial imitation of a biological fluid, such as artificial urine.

[0079] <Biological fluids> Biological fluids are biological or bioorganic fluids produced by living organisms. Biological fluids are liquids that living organisms have in some form within their bodies. Any liquid collected from a living organism 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 suspensions. 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 easy to obtain.

[0080] <Polymers Contained in Biological Fluids> Examples of polymers (particularly antigens) contained in the above-mentioned biological fluids are polymers that are primarily useful for diagnosing diseases and are detected in biological fluids, such as bacteria, germs (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 polymer contained in the above-mentioned biological fluid is preferably an antigen, more preferably a virus (particularly influenza virus) 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. In the case of a polymer that is useful for diagnosing diseases and has a known structural formula, the theoretical value calculated from the structural formula can be used for the molecular weight. Furthermore, in cases where the structural formula is not determined, the molecular weight can be determined by a method of calculating the molecular weight by comparison with a substance of known molecular weight using electrophoresis, or by liquid chromatography mass spectrometry (LC-MS).

[0081] <Pretreatment of Liquid Samples> The liquid sample described above can be used as 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 solution obtained by diluting the extracted liquid with an appropriate diluent, or in the form of a liquid obtained by concentrating the extracted liquid by an appropriate method. The extraction solvent described above can be a solvent used in conventional immunological analysis methods (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.

[0082] [Ratio of water-absorbent polymer to liquid sample] The ratio of the water-absorbent 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.

[0083] [Recovery Solution] The recovery solution contains a salt. The recovery solution contains a solvent used in conventional immunological analysis methods, or a water-miscible organic solvent that can be diluted with such a solvent to directly carry out an antigen-antibody reaction. Solvents used in conventional immunological analysis methods include, for example, water, physiological saline, or a buffer solution. The recovery solution can also be functionalized with a buffering agent, a surfactant, or other additives, as needed. The recovery solution is preferably a buffer solution, and more preferably PBS (Phosphate Buffered Salts). A portion of the sample solution may also be used as the recovery solution. The recovery solution may contain a preservative, such as Proclin 950 (trade name, manufactured by Sigma-Aldrich Japan Partnership).

[0084] 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. As the salt contained in the recovery liquid, sodium chloride and magnesium chloride are preferred because they have smaller variations in the recovery amount of the concentrated liquid. Of sodium chloride and magnesium chloride, magnesium chloride is more preferred because magnesium chloride has even smaller variations in the recovery amount of the concentrated liquid.

[0085] The salt content of the recovery liquid is preferably 25 mg / mL (milliliter) or more. When the salt content of the recovery liquid is 25 mg / mL or more, absorption of the recovery liquid by the water-absorbent polymer can be suppressed, thereby reducing variation in the recovery amount of the concentrated liquid. It has been confirmed that when the salt content of the recovery liquid is 25 mg / mL or more, the water absorption rate of the water-absorbent polymer becomes constant. When the salt content of the recovery liquid is 25 mg / mL or more, depending on the type of salt, the detection sensitivity may change when the concentrated liquid is used in an immunochromatography kit. For this reason, the upper limit of the salt content of the recovery liquid is preferably 100 mg / mL or less. The salt content of the recovery liquid is the mass of the salt as a solute relative to the amount of solvent in the recovery liquid. The salt content of the recovery liquid is the value obtained by converting the mass of the salt in the recovery liquid into mass per milliliter.

[0086] The amount of recovery liquid is smaller than the amount of liquid sample injected into the container from the viewpoint of concentrating 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)) may be less than 100% by volume, preferably 30% or less, more preferably 20% or less, and even more preferably 0.01% to 10%.

[0087] Salts contained in the recovery solution are required not to inhibit the antigen-antibody reaction in immunochromatography. The effect of salts contained in the recovery solution on the antigen-antibody reaction of an immunochromatography kit was investigated. Four types of recovery solutions containing sodium chloride, calcium chloride, magnesium chloride, or citric acid were used as additives. To evaluate the effect on the antigen-antibody reaction, an immunochromatography kit for detecting Mycobacterium tuberculosis antigens was used as the test substance described in WO 2020 / 045625. The immunochromatography 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 at a concentration of 1 mg / mL and BSA (Bovine Serum Albumin). The LAM concentration was diluted to a value equivalent to 200 pg / mL. In addition, to examine the effect of the recovery liquid, the recovery liquid was added to the sample liquid.

[0088] 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 and antigen to react. The sample was then applied to the immunochromatography kit to evaluate its effect on the antigen-antibody reaction. The evaluation results of the effect on the antigen-antibody reaction are shown in Table 1 below. The effect on the antigen-antibody reaction was evaluated by evaluating the effect on the surface condition, sensitivity, and false positives. The effect on the surface condition was visually confirmed by observing the surface condition observed through the observation window of the immunochromatography kit. The effect on sensitivity and false positives was evaluated by increasing the content of the additive, and visually confirming the color of the test line appearing on the surface observed through the observation window of the immunochromatography kit and the color of the line indicating a positive result. The easier it is for the test line and the line indicating a positive result to be visible, 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 lower the S / N ratio, the lower the sensitivity, and the higher the possibility of a false positive. Note that calcium chloride and citric acid were not examined for their effects on sensitivity and false positives because they gave poor evaluation results for their effects on surface condition, as described below. For this reason, a "-" is entered in the "Effect on sensitivity and false positives" column in Table 1 below.

[0089] When calcium chloride and citric acid were used as additives in 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 were used as additives in the recovery solution, sodium chloride and magnesium chloride were preferred because they had little effect on the surface observed through the observation window of the immunochromatography kit. It was discovered that magnesium chloride is even more preferred because it has little effect on sensitivity and false positives. From the perspective of the effect on the surface observed through the observation window and the effect on sensitivity and false positives, sodium chloride and magnesium chloride are preferred as salts contained in the recovery solution, with magnesium chloride being even more preferred. Note that the surface refers to the immunochromatographic reaction area (components holding various lines) visible through the observation window. Regarding the effect on the surface, a small effect on the surface means little discoloration, such as blackening, and little effect on the positive or negative determination due to discoloration. A small effect on the surface and a small effect on the surface are synonymous.

[0090]

[0091] [Piston] As described above, the piston has a plurality of holes at its tip that are smaller than the particle diameter of the absorbent polymer after absorbing water. The diameter of the holes 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 absorbent polymer after absorbing water. The diameter of the holes at the tip is preferably smaller than the particle diameter of the absorbent polymer before absorbing water. The diameter of the holes at the tip is preferably 0.01 to 5 mm, more preferably 0.1 to 2 mm. The number of holes at the tip is not particularly limited, but is preferably 10 to 100, more preferably 20 to 50. The ratio of the total area of ​​the holes at 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 Figures 1 and 2 can be used.

[0092] 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 using various known methods. The concentrated concentrate can be concentrated to a high concentration ratio, can be reliably extracted, and the recovery amount varies little from one collection to the next. This results in high detection sensitivity and high repeatability of the detection.

[0093] The method for detecting polymers 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, and the like. In particular, the treatment kit and treatment method can be suitably used to concentrate a liquid sample (analyte solution) for performing immunochromatography. Specific methods for detecting polymers in a concentrated solution and the configuration of a test kit for detecting polymers in a sample solution (concentrate) containing a polymer are described, for example, in JP 2009-150869 A and WO 2021 / 065300 A.

[0094] The present invention is basically configured as described above. While the processing kit and processing method of the present invention have been described in detail above, the present invention is not limited to the above-described embodiments, and various improvements and modifications may be made without departing from the spirit and scope of the present invention.

[0095] 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 these examples, the containers of Examples 1 to 12 and Comparative Examples 1 to 4 were used to evaluate the variation in recovery amount. The variation in recovery amount will be explained below.

[0096] (Variation in Recovery Amount) To evaluate the variation in the recovery amount, the concentrated solution was recovered 30 times. For each recovery, the amount of concentrated solution that could be extracted without being absorbed by the superabsorbent polymer was weighed. The standard deviation (σ) and average value were calculated from the recovery amounts of the concentrated solution from the 30 runs to determine the coefficient of variation. The coefficient of variation was calculated as follows: (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 less than 5%; B: Coefficient of variation 5% or more but less than 10%; C: Coefficient of variation 10% or more but less than 15%; D: Coefficient of variation 15% or more but less than 20%; E: Coefficient of variation greater than 20%. A rating of A indicates excellent repeatability of the recovered amount of concentrated solution, with very little variation in the recovered amount. A rating of B indicates excellent repeatability of the recovered amount of concentrated solution, with little variation in the recovered amount. If the evaluation is C, the variation in the recovered amount of the concentrated liquid is kept low and is practically acceptable. If the evaluation is D, the variation in the recovered amount of the concentrated liquid cannot be kept low and is practically unacceptable. If the evaluation is E, the variation in the recovered amount of the concentrated liquid is large and is practically unacceptable.

[0097] Examples 1 to 12 and Comparative Examples 1 to 4 are described below. (Example 1) Example 1 used a rigid container, such as the container 12 shown in FIG. 1. The container body 20 was cylindrical, with an inner diameter of 12 mm and a height of 60 mm, and had a male thread on the top. The piston 22 had a tip 22a with holes 22b smaller than the particle size of the superabsorbent polymer after absorption. The holes 22b had a diameter of 1 mm and 24 holes in total. A lid 24 (with a female thread) was prepared, equipped with a nozzle 24b having a recovery port 24c. The container 12 was completed by connecting it to the container body 20. 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. After that, 3 mL (milliliters) of recovery liquid was added, and the concentrated liquid was recovered. The mass of the recovered concentrated liquid was measured. This recovery operation was performed 30 times, and the mass of the recovered concentrated liquid was measured each time, for a total of 30 times. The mass of the recovered concentrated liquid from the 30 times was used to evaluate the variation in the recovered amount as described above. The superabsorbent polymer used was a superabsorbent polymer particle (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 liquid was an aqueous solution of pure water and salt. NaCl (sodium chloride) was used as the salt. The salt content of the recovery liquid was 20 mg / mL. Proclin 950 (trade name, manufactured by Sigma-Aldrich Japan Partnership) was added to the recovery liquid as a preservative.

[0098] (Example 2) Example 2 differs from Example 1 in that the salt content of the recovery solution was 28 mg / mL. Other than that, Example 2 was the same as Example 1. (Example 3) Example 3 differs from Example 1 in that the salt contained MgCl ２Example 4 differs from Example 3 in that the salt content of the recovery solution was set to 28 mg / mL. Other than that, Example 4 was the same as Example 3.

[0099] Example 5 Example 5 differs from Example 1 in that a flexible container was used, and the container 42 shown in Figures 8 and 9 was used. Other aspects were the same as Example 1. 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 tapered 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, as in Example 1, 3.0 g of superabsorbent polymer was placed inside the container body. 20 mL of artificial urine, which served as 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 water. After that, 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 performed 30 times, and the mass of the recovered concentrated liquid was measured each time. The mass of the collected concentrated solution from 30 runs was used to evaluate the variation in the collected amount as described above.

[0100] (Example 6) Example 6 differs from Example 5 in that the salt content of the recovery liquid was set to 28 mg / mL. Other than that, Example 6 was the same as Example 5. (Example 7) Example 7 differs from Example 5 in that the salt content of the recovery liquid was set to 100 mg / mL. Other than that, Example 7 was the same as Example 5.

[0101] Example 8: In Example 8, compared to Example 5, MgCl was used as salt. ２Example 9 differs from Example 8 in that the salt content of the recovery liquid is 28 mg / mL. Otherwise, it is the same as Example 8. Example 10 differs from Example 8 in that the salt content of the recovery liquid is 36 mg / mL. Otherwise, it is the same as Example 8. Example 11 differs from Example 8 in that the salt content of the recovery liquid is 100 mg / mL. Otherwise, it is the same as Example 8. Example 12 differs from Example 8 in that the salt is NaCl (sodium chloride) and MgCl ２ In Example 12, the content of NaCl (sodium chloride) was 125 mg / mL, and MgCl ２ The magnesium chloride content was 60 mg / mL.

[0102] Comparative Example 1 Comparative Example 1 differs from Example 1 in that no recovery liquid was used. Otherwise, the example was the same as Example 1. For Comparative Example 1, "-" is entered in the "Presence or Absence of Salt," "Type of Salt," and "Salt Content" columns in Table 2. Comparative Example 2 Comparative Example 2 differs from Example 1 in that the recovery liquid did not contain salt, and only pure water was used as the recovery liquid. Otherwise, the example was the same as Example 1. For Comparative Example 2, "-" is entered in the "Type of Salt" and "Salt Content" columns in Table 2. Comparative Example 3 Comparative Example 3 differs from Example 5 in that no recovery liquid was used. Otherwise, the example was the same as Example 5. For Comparative Example 3, "-" is entered in the "Presence or Absence of Salt," "Type of Salt," and "Salt Content" columns in Table 2. Comparative Example 4 Comparative Example 4 differs from Example 5 in that the recovery liquid did not contain salt, and pure water was used. Otherwise, the example was the same as Example 1. For Comparative Example 4, "-" is entered in the "Type of salt" and "Content of salt" columns of Table 2.

[0103]

[0104] As shown in Table 2, Examples 1 to 12 had smaller variations in recovery amount than Comparative Examples 1 to 4. From Examples 1 to 12, it can be seen that when the salt content is 25 mg / mL or more, the variations in recovery amount are smaller. Furthermore, when comparing the types of salt, sodium chloride and magnesium chloride, magnesium chloride has smaller variations in recovery amount.

[0105] In Examples 1 to 12, an immunochromatographic kit for detecting Mycobacterium tuberculosis antigens was used as the test substance described in WO 2020 / 045625 to detect lipoarabinomannan antigen. The immunochromatographic kit was configured as shown in Figures 1 to 3 of WO 2020 / 045625. For the liquid sample (analyte solution), artificial urine (JIS T3214) containing LAM (lipoarabinomannan) antigen and BSA (Bovine Serum Albumin) at a concentration of 1 mg / mL was used. The LAM concentration was diluted to a value equivalent to 200 pg / mL. The above-mentioned concentrated solution was obtained in the same manner as in Examples 1 to 12, except that this liquid sample was used. 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.

[0106] 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

1. A processing kit comprising: a water-absorbing polymer that absorbs water from a liquid sample containing a test substance and water; a container for accommodating the water-absorbing polymer; and a recovery liquid container for accommodating a recovery liquid containing salt, wherein the recovery liquid is added after the liquid sample is placed in the container.

2. The processing kit according to claim 1, wherein the salt contained in the recovery solution is at least one of sodium chloride and magnesium chloride.

3. The processing kit of claim 1, wherein the salt contained in the recovery solution is magnesium chloride.

4. A processing kit according to any one of claims 1 to 3, wherein the salt content of the recovery solution is 25 mg / mL or more.

5. The treatment kit according to any one of claims 1 to 3, wherein the liquid sample comprises a biological fluid.

6. A processing method comprising the steps of: placing a liquid sample containing a test substance and water into a container containing a water-absorbent polymer; concentrating the liquid sample in the container by allowing the water contained in the liquid sample to be absorbed by the water-absorbent polymer; placing a recovery liquid containing salt into the container; and removing the concentrated liquid of the liquid sample obtained by concentration in the container from the container.

7. The treatment method according to claim 6, wherein the salt contained in the recovered liquid is at least one of sodium chloride and magnesium chloride.

8. The treatment method according to claim 6, wherein the salt contained in the recovered solution is magnesium chloride.

9. The processing method according to any one of claims 6 to 8, wherein the salt content of the recovery liquid is 25 mg / mL or more.

10. The processing method according to any one of claims 6 to 8, wherein the liquid sample includes a biological fluid.

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