JP2010060417A - Blood testing microreaction vessel - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a blood testing microreaction vessel capable of preventing an inert particle and an antibody from being removed from a vessel, progressing the agitation of a sample with a reagent, and precisely testing blood. <P>SOLUTION: The blood testing microreaction vessel includes an opening, an injector in which a solution is injected from the opening, a storage with inert particles filled therein, a reaction tank arranged between the injector and the storage, and a plug with an inner diameter greater than that of the storage that is fixed in the opening in which the plug is pushed down to drop the reaction tank allows the reaction vessel to be opened. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a micro reaction container for blood test.

  In recent years, centrifugal agglutination methods using columns and microtubes have been used as means for performing biological tests such as blood tests. For example, in Patent Document 1, an inactive particle typified by 10 to 200 μm polymer particles or glass particles is filled in an elongated micro reaction vessel, and a reaction vessel capable of efficiently distinguishing erythrocyte aggregates and non-aggregates by centrifugation is provided. Disclosure. Patent Document 2 discloses a similar reaction vessel using glass beads. Each method has a shape in which a plurality of elongated microreaction containers filled with inert particles are embedded in a plate-like plastic plate, and is used in a state where the microreaction containers are set up in a vertical direction. Such a micro reaction container is sealed with an aluminum seal or the like, and is used by peeling off the seal at the time of use.

In the analysis, a liquid sample is injected from the top opening of a vertically arranged microreaction vessel and centrifuged. When an antibody for reaction is contained in the upper part of the inert particle layer and an aggregate is generated by the reaction, the aggregate is captured by the inert particle layer to form a positive image. If no aggregate is formed, the injected sample passes through the inert particle layer and moves to the bottom of the column to form a negative image. By capturing the aggregates with the inert particles in this way, it is possible to easily test without washing the red blood cells (B / F separation).
Japanese Patent Publication No.8-7215 European Patent No. 725276

  However, when vibration or impact is applied to the micro reaction container before use, inert particles and reaction antibodies may scatter and adhere to the sealing seal. In this case, there is a problem that the inert particles and antibodies attached to the seal are removed together with the seal, and the inert particles and antibodies in the container are reduced. If the inert particles and antibodies contained in the container are reduced from the specified amount, accurate test results cannot be obtained. Furthermore, there is a risk that scattered objects may get on the hand when the seal is peeled off.

  As another problem, when a reagent is added to a reaction container together with a liquid sample, it is necessary to perform centrifugation after sufficiently reacting them. Sometimes it is difficult to do enough. If stirring is not performed sufficiently, the antigen-antibody reaction becomes insufficient, and there is a problem that detection sensitivity is deteriorated.

  In view of the above-mentioned problems, the present invention prevents inactive particles and antibodies from being removed from the container, and can promote stirring of the sample solution and the reagent solution, thereby enabling a more accurate test. An object is to provide a micro reaction vessel.

  According to the present invention, the micro reaction container for blood test has an opening, an injection part into which a solution is injected from the opening, a storage part filled with inert particles, and the injection part. A reaction tank disposed between the container and a stopper fixed in the opening having an inner diameter larger than the inner diameter of the container, and the stopper is pushed down to drop into the reaction tank The reaction container characterized by being opened by this is provided.

  In one embodiment, the reaction vessel further includes a fixing member for holding the stopper on the inner wall of the opening. Moreover, in one aspect, the said stopper is a stirring body for stirring the solution inject | poured from the said injection | pouring part in the said reaction tank.

  In one embodiment, the stopper is made of a substance that floats in the solution injected from the injection part. In another aspect, the reaction vessel includes a holding body that holds a stopper dropped in the reaction vessel.

  In one embodiment, the plug has a spherical shape. In another aspect, the plug has a shape selected from the group consisting of a polyhedron, a cone, a frustum, and a polygonal column. In one embodiment, the injection part has an inner diameter larger than the inner diameter of the accommodating part, and the reaction tank has an inverted frustum shape. In one embodiment, the reaction container further contains an antibody on the inert particles filled in the storage unit.

  In a further aspect, there is provided the above micro reaction container for blood test, which is fixed to a carrier that can be subjected to centrifugation. In one embodiment, the micro reaction container for blood test described above is provided, which is formed integrally with the carrier. In one embodiment, the carrier has a flat card shape.

  From another aspect of the present invention, there is provided a blood test card comprising a plurality of the above micro test containers for blood test.

  According to the micro-reaction container for blood test of the present invention, inert particles and antibodies are prevented from being removed from the container, and stirring of the sample solution and the reagent solution is promoted, and a more accurate test can be easily performed. Is possible.

  The micro reaction container for blood test of the present invention may be of any shape as long as it is elongated in the vertical direction and can be subjected to centrifugation to observe an agglutination reaction image. The size can also be selected depending on the specimen. Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the following description, components having substantially the same function and configuration are denoted by the same reference numerals, and redundant description will be given only when necessary.

(First embodiment)
FIG. 1 is a perspective view of a micro reaction container 1 for blood test according to the first embodiment of the present invention. The micro reaction container in the present embodiment has an elongated cylindrical shape with different inner diameters depending on the part. That is, the container has a circular cross section. The reaction vessel 1 has an opening 8, an injection part 5 into which a solution is injected from the opening 8, a storage part 3 filled with inert particles 2, and a space between the injection part 5 and the storage part 3. And a stopper 7 having a larger inner diameter than the inner diameter of the container 3 and fixed in the opening 8.

  The solution injected from the opening 8 is a specimen solution containing red blood cells or antibodies to be examined, and a reagent solution is also injected if necessary. The injection unit 5 provides a space for injecting the sample solution and the reagent solution into the reaction container.

  The reaction tank 4 is disposed below the injection unit 5 and provides a space for mixing the solution injected from the injection unit 5. In this embodiment, the injection | pouring part 5 has an internal diameter larger than the internal diameter of the accommodating part 3, and, thereby, the reaction tank 4 becomes a reverse frustum shape where a lower part narrows from upper part.

  The accommodating part 3 is arrange | positioned under the reaction tank 4, and is filled with the inert particle 2 for forming an agglutination reaction image.

  The stopper 7 in this embodiment has a spherical shape and is made of a substance that floats in the injected solution. Examples of the substance that floats in the solution include, but are not limited to, polystyrene foam. As will be described later, the stopper 7 functions as a stirring body for stirring the injected solution after dropping into the reaction vessel 4.

  The reaction vessel of the present invention is sealed until use. In the present embodiment, the opening 8 is sealed by the stopper 7. The reaction vessel can be opened by dropping the stopper 7 and dropping it. Since the stopper 7 has an inner diameter larger than the inner diameter of the container 3 as described above, it stops at the reaction tank 4 and does not move to the container 3.

  The micro reaction container 1 for blood test according to the present embodiment further includes a fixing member 6 for holding the stopper 7 on the inner wall of the opening 8. The fixing member 6 in the present embodiment has a band shape, is disposed along the inner periphery of the opening 8, and is fixed to the reaction vessel using an adhesive.

  The fixing member 6 fixed to the reaction vessel is fixed by sandwiching a stopper 7 in the central hole portion. The thickness and width of the fixing member 6 depends on the size of the stopper 7 and is selected so that it can drop when the stopper 7 is pushed down from above. In addition, the position of the fixing member 6 is preferably adjusted so that the upper part of the stopper 7 is substantially contained in the reaction vessel.

  The fixing member 6 may be a packing formed from a polymer compound such as rubber having elasticity, for example. Preferably, a material capable of sealing the reaction vessel with the fixing member 6 and the stopper 7 is used.

  The inert particles 2 filled in the container 3 are particles that can capture an agglutination reaction image by supplementing an agglutination product of red blood cells or antibodies. Preferably, it is selected from, but not limited to, polymers, gels such as Sephadex gel, polyacrylamide gel, glass beads, silica, dextran, gelatin particles and the like.

(Function)
Next, the procedure for using the blood reaction microreaction container 1 according to this embodiment will be described.

  First, the stopper 7 is pushed and dropped, and the reaction container is opened. The stopper 7 may be pushed in by hand or may be pushed in by a machine. The dropped stopper 7 remains in the reaction tank 4. Next, the sample solution and, if necessary, the reagent solution are injected. Since these solutions are in a very small amount, they remain in the reaction tank 4 and do not move to the container 3 as they are.

  Next, the reaction vessel 1 is shaken in the horizontal direction, the stopper 7 is rolled in the reaction tank 4, and the injected solution is stirred. This procedure is not necessary when the injected solution is only the sample solution, but when the reagent solution is injected together with the sample solution, it may be difficult to mix each solution as it is as a water droplet. Therefore, mixing of the solution is promoted by using the stopper 7 (stirring body). In addition, the method of shaking the reaction vessel 1 to move the stopper 7 may be performed manually or by a machine.

  Subsequently, the reaction vessel 1 is subjected to centrifugation. As a result, the solution in the reaction vessel 4 moves to the container 3, and further passes through the inert particles 2 and settles to form a reaction image. Since the stopper 7 used in this embodiment floats in the solution, it does not hinder the movement of the solution by closing the upper portion of the container 3 when being subjected to centrifugation.

  The agglutination reaction image thus formed is observed to determine the inspection result.

  Next, inspection modes that differ depending on the inspection target will be described.

(1) When testing red blood cells in a sample In this test mode, an antibody (or antiserum) is contained above the inert particles 2 and a sample solution containing red blood cells is injected into a reaction container. For example, in the case of a blood type test, anti-A, anti-B and anti-D antibodies are added in advance to separate reaction containers. Since the specimen is erythrocytes, this antibody reacts with erythrocytes and, if positive, forms an aggregate. If the reaction is negative, no aggregates are formed.

  After injecting the solution containing the sample, the reaction vessel is subjected to centrifugation, so that the sample solution moves onto the inert particles and reacts with the antibody. Aggregates or non-aggregates after the reaction settle through the filled inert particles. If the reaction is positive, the aggregate remains in the upper layer of the inert particles and forms a positive image. If the reaction is negative, the sample solution settles at the bottom of the reaction vessel and forms a negative image. The reaction result can be discriminated visually, but can also be discriminated using an automatic reading device.

(2) When testing red blood cells in a specimen In this test mode, no antibody is contained on the inactive particles 2. Therefore, a reagent solution containing an antibody, such as an antiserum reagent solution, is injected together with a sample solution containing red blood cells. Next, the sample solution and the reagent solution are mixed and reacted by stirring in the reaction vessel as described above. Aggregates are formed when the reaction is positive, and no aggregates are formed when the reaction is negative. Next, in the same manner as in the above embodiment, the aggregate or non-aggregate is settled by centrifugation to form an aggregated image.

(3) When examining antibodies in a sample In this test mode, a reagent solution containing red blood cells is injected into a reaction container together with a sample solution containing antibodies. Next, the sample solution and the reagent solution are mixed and reacted by stirring in the reaction vessel as described above. Aggregates are formed when the reaction is positive, and no aggregates are formed when the reaction is negative. Next, in the same manner as in the above embodiment, the aggregate or non-aggregate is settled by centrifugation to form an aggregated image.

  In any of the above-described inspection modes, additional antibody reagents or other reagents may be used, which are injected into the reaction container together with the sample solution, previously injected into the reaction container, or stored in the container. It may be contained on filled inert particles.

Next, the modification of the reaction container 1 which concerns on the said embodiment is shown in FIG.
The reaction container 100 illustrated in FIG. 2 is a diagram illustrating another installation method of the fixing member 6. The reaction vessel 100 has a groove 11 below the opening 8, and a fixing member (not shown), for example, a packing, can be fitted into the groove 11 and fixed. The groove 11 may be formed at the same time when the reaction vessel 100 is formed, and the fixing member can be fixed easily and stably without using an adhesive.

  In the above embodiment, the reaction vessel is sealed by the stopper 7. However, the present invention is not limited to this, and the reaction vessel may be sealed by sealing a peelable seal. At the time of use, the seal 9 is peeled off, and the specimen is added by pushing down the stopper. An aluminum seal is preferably used as the seal, but is not limited thereto.

  The reaction vessel with the seal need not be sealed by the stopper 7. In this case, as shown in FIG. 3, the injection portion 5 may be provided with a support 13, and the stopper 7 may be placed on the support 13. The support 13 has, for example, a shape in which a plurality of substantially semicircular protrusions protrude toward the inside of the injection portion 5. The shape and the number of protrusions are not limited to the example in FIG. 3, and may be, for example, a triangular shape. These protrusions and the like may be fixed to the reaction vessel with an adhesive or the like, but can be easily formed by forming them integrally with the reaction vessel.

  Even when the reaction vessel is sealed with the stopper 7, it is preferable to cover the opening with a seal or the like in order to prevent impurities from adhering to the stopper 7.

(Second Embodiment)
Next, a second embodiment of the present invention will be described. In the present embodiment, the stoppers 7 having different shapes are used in the blood reaction microreaction container 1 of the first embodiment. The plug 7 is not limited to a substance that floats in the solution, and may be composed of any substance including resin, glass, plastic, metal, and the like. When the stopper 7 is made of metal, the stopper 7 may be rotated by a magnetic force without shaking the reaction vessel when stirring the solution.

  The plug 7 has a shape other than a sphere. For example, a pyramid, a pyramid obtained by cutting a pyramid at a height in the middle and a plane parallel to the bottom surface, a prism, a polyhedron including a regular polyhedron and a semi-polyhedron, and other irregularities. It may be a shape selected from regular shapes.

  4 is an example of a pyramid, FIG. 4 (a) is a quadrangular pyramid, and FIG. 4 (b) is a regular hexagonal pyramid. In addition, a triangular pyramid or another polygonal pyramid may be used.

  FIG. 5 is an example of a frustum. FIG. 6 (a) is a quadrangular frustum, and FIG. 6 (b) is a regular hexagonal frustum. In addition, a triangular frustum or other polygonal frustums may be used.

  FIG. 6 shows an example of a prism, FIG. 6 (a) is a quadrangular prism, and FIG. 6 (b) is a regular hexagonal prism. In addition, a triangular prism or another polygonal column may be used.

  FIG. 7 shows an example of a regular polyhedron, in which FIG. 7 (a) is a regular tetrahedron, FIG. 7 (b) is a cube, and FIG. 7 (c) is a regular dodecahedron. In addition, various regular polyhedrons and polyhedrons may be used.

  As another irregular shape, for example, a shape in which a part of a polyhedron is circular may be used.

  In the present embodiment, the shape of the fixing member 6 is appropriately selected according to the stopper to be used. For example, when the stopper 7 has a cubic shape, the outer side of the fixing member 6 has a circular shape along the inner wall of the container, and the inner side has a rectangular shape in which the cube can be accommodated.

  As described above, in the present embodiment, since the stopper 7 has the shape as described above, the solution can be smoothly moved without blocking the inlet of the cylindrical housing 3.

  Even if the reaction vessel is not cylindrical, the plug 7 having a shape different from the cross-sectional shape of the housing portion 3 may be used, and the present invention is not limited to the cylindrical reaction vessel.

(Third embodiment)
Next, a third embodiment of the present invention will be described. FIG. 8 is a schematic view of a micro reaction container 300 for blood test according to the present embodiment. In addition to the reaction container in the first embodiment, the reaction container 300 according to the present embodiment includes a holding body 15 that holds the dropped stopper 7 in the reaction tank 4.

  The holding body 15 is disposed above the boundary between the reaction tank 4 and the storage unit 3, and is preferably disposed as low as possible in the reaction tank 4. The holding body 15 in FIG. 8 has a shape in which a plurality of substantially semicircular protrusions protrude toward the inside of the reaction vessel 4. The shape and the number of protrusions are not limited to the example in FIG. 8, and may be, for example, a triangular shape. These protrusions and the like may be fixed to the reaction vessel with an adhesive or the like, but can be easily formed by forming them integrally with the reaction vessel.

  The holding body 15 may be formed of an arbitrary substance, and is preferably designed to have a strength capable of continuing to hold the stopper 7 even when the reaction vessel is subjected to centrifugation.

  In the present embodiment, since the stopper 7 dropped from the opening 8 is held by the holding body 15, the stopper 7 can be configured from an arbitrary material into an arbitrary shape. A spherical stopper is preferably used.

  The blood test reaction container according to each embodiment described above may be used alone, or may be used by being fixed to a carrier that can be subjected to centrifugation. In one embodiment, a plurality of reaction vessels are immobilized on the carrier. For example, a reaction container may be attached to the cartridge for use. When mounted on a cartridge, the reaction containers are preferably arranged in a row for the convenience of reading the reaction image, and a cartridge arranged in a linear or cylindrical shape is preferably used. By fixing the reaction vessel to the carrier, it can be handled easily and a plurality of reaction vessels can be operated simultaneously.

  Moreover, in one embodiment, the said support | carrier and reaction container are integrally formed. In a preferred embodiment, the carrier is formed in a flat card shape and can be provided as a blood test card. When the carrier has a flat card shape, the card body can be copied by a copying machine after the test, and the determination result can be stored for a long time.

  FIG. 9 is a diagram showing an embodiment of the blood test card 20. In the card 20, each reaction vessel 1 is sealed with a stopper 7, and a seal 17 is further sealed on the upper surface of the card 20. At the time of use, the seal 17 is peeled off, the stopper 7 is pushed down to open it, and a sample solution or the like is added to each reaction container 1.

  As described above, according to the micro reaction container for blood test according to the present invention, by providing a stopper, it adheres to the stopper even when internal inert particles or antibodies are scattered when an impact is applied to the reaction container. To do. Since the stopper enters the reaction container when opened, the amount of inert particles and antibodies contained in the reaction container does not decrease. Thereby, it is possible to carry out an accurate inspection.

  Moreover, the stopper dropped into the reaction tank by opening functions as an agitator, and by stirring the solution in the reaction tank, reaction abnormality due to insufficient stirring can be reduced, and more accurate test results can be obtained. .

[Appendix]
1. A micro reaction container for blood test for testing red blood cells in a sample, wherein the solution injected into the injection part is a sample solution containing red blood cells, on the inactive particles filled in the storage part A reaction container containing an antibody.

2. A blood reaction micro reaction container for examining red blood cells in a sample, wherein the solution injected into the injection part is a sample solution containing red blood cells and a reagent solution containing an antibody. container.

3. A reaction container for testing an antibody in a specimen, wherein the solution to be injected into the injection part is a specimen solution containing an antibody and a red blood cell reagent solution.

The perspective view of the micro reaction container for blood tests concerning a 1st embodiment. The fragmentary perspective view which shows the modification of the micro reaction container for blood tests which concerns on 1st Embodiment. The fragmentary perspective view which shows the modification of the micro reaction container for blood tests which concerns on 1st Embodiment. An example of the stopper in the second embodiment. The other Example of the stopper in 2nd Embodiment. The other Example of the stopper in 2nd Embodiment. The other Example of the stopper in 2nd Embodiment. The perspective view of the micro reaction container for blood tests which concerns on 3rd Embodiment. The front view which shows one Embodiment of the card | curd for blood tests.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Micro reaction container, 2 ... Inactive particle, 3 ... Accommodating part, 4 ... Reaction tank, 5 ... Injection | pouring part, 6 ... Fixing member, 7 ... Stopper, 8 ... Opening part, 9 ... Antibody solution, 11 ... Groove, DESCRIPTION OF SYMBOLS 13 ... Support body, 15 ... Holding body, 17 ... Seal, 20 ... Card for blood test.

Claims (13)

A micro reaction vessel for blood testing,
An injection portion having an opening, into which a solution is injected from the opening;
A container filled with inert particles;
A reaction vessel disposed between the injection part and the accommodating part;
A stopper fixed in the opening having an inner diameter larger than the inner diameter of the housing portion;
A reaction vessel which is opened by depressing the stopper and dropping it into the reaction vessel.   The reaction container according to claim 1, further comprising a fixing member for holding the stopper on an inner wall of the opening.   The reaction vessel according to claim 1 or 2, wherein the stopper is a stirring body for stirring the solution injected from the injection section in the reaction tank.   The reaction vessel according to any one of claims 1 to 3, wherein the stopper is made of a substance floating in the solution injected from the injection part.   The reaction vessel according to any one of claims 1 to 3, wherein the reaction vessel is provided with a holding body that holds a stopper dropped in the reaction vessel.   The reaction vessel according to any one of claims 1 to 5, wherein the stopper has a spherical shape.   The reaction vessel according to any one of claims 1 to 5, wherein the stopper has a shape selected from the group consisting of a polyhedron, a cone, a frustum, and a polygonal column.   The reaction container according to claim 1, wherein the injection part has an inner diameter larger than an inner diameter of the storage part, and the reaction tank has an inverted frustum shape.   The reaction container according to any one of claims 1 to 8, wherein the reaction container contains an antibody on the inert particles filled in the storage unit.   The reaction container according to claim 1, wherein the reaction container is fixed to a carrier that can be subjected to centrifugation.   The reaction container according to claim 10, wherein the reaction container is formed integrally with the carrier.   The reaction container according to claim 10 or 11, wherein the carrier has a flat card shape.   A card for blood test comprising a plurality of micro reaction containers for blood test according to any one of claims 1 to 9.

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