JPH0526873A - Blood-separating member - Google Patents

Abstract

PURPOSE:To obtain a blood-separating member which can be inserted into a blood-sampling tube so that it can be inserted or removed freely, has an improved operability when separating blood, and enables serum and clotted blood to be separated properly. CONSTITUTION:A title item consists of a cylindrical assembly 4 where three cylinders 2a, 2b, and 2c with different diameters are fixed in concentric shape, a main body 6 where an annular elastic body 5 is provided outside the cylindrical assembly 4, and a spherical body 7 which blocks an opening of innermost cylinder 2c.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a blood separating member used for separating a blood sample into serum and blood clot by centrifugation.

[0002]

2. Description of the Related Art Among clinical test items, a blood test is indispensable for diagnosing diseases and the like, and is regarded as very important clinically. Particularly in serological tests and the like, various test methods have been developed, and the number of test cases and test items have significantly increased. In this hematological test, the serum (plasma) mainly separated from whole blood is used for the test.Therefore, a blood sample collected in a blood collection tube such as Spitz as a pre-operation for the test is used as serum or plasma (hereinafter referred to as serum). It is necessary to separate into blood clots and blood cells (hereinafter referred to as blood clots).

Conventionally, in this blood separation operation, a whole blood sample collected is put in a blood collection tube such as Spitz and centrifuged to separate serum as a sample.

However, in this centrifugation operation, the separation state between serum and blood clot is very unstable, and the blood cells in the blood clot that have settled down are mixed with the serum even with a small impact, so that the blood after separation is separated. Considerable care is required when handling specimens.

Therefore, various means have been tried for improving the unstable separation state of the blood sample after centrifugation and for facilitating the test operation. As an example thereof, there is a method of using a blood separating agent having a thixotropic property, which has a specific gravity intermediate between serum and blood clot, and is widely used at present. There is also known a device called a serum separating member, which is designed to be positioned between the serum and the blood clot when the blood is centrifuged. Further, particles having a specific gravity between serum and blood clot (for example, polystyrene beads) are also known. In addition, there are some separation methods such as an example using a porous filter medium. The most widely used of these separation methods is a blood separating agent having a thixotropic property, and several kinds having different compositions are used for actual blood analysis. These blood separating agents have a good separation behavior during centrifugation, and have a great effect from the viewpoint of facilitating blood test operations.

[0006]

However, the above-mentioned blood separating agent has some drawbacks as described below. That is, the separating agent has a low molecular weight synthetic resin as a main component, is fluidized during centrifugation, and moves in the blood collection tube while being in contact with blood. Therefore, some physical or chemical change such as component transfer or chemical change between the separating agent and blood may occur, resulting in variation in blood test values.
Separation agents are subject to changes in physical properties (e.g., changes in viscosity) and chemical changes (e.g., oxidation) due to changes over time, and the expiration date is limited. The separating agent is directly filled into the inner wall of the blood collection tube, and it can be collected before or after using the blood collection tube.
Reusing (glass or plastic) is difficult. It is extremely troublesome to remove the separating agent from the blood collection tube and wash it. This is a major drawback in terms of waste treatment and resource saving. The separating agent is a means for effectively extracting serum, but the blood clot (blood cell) is in a state of being mixed with the separating agent, and it is impossible to take out pure blood clot (blood cell) for analysis.

[0007] In addition to this separating agent, various blood separating members have been proposed, but these conventional blood separating members have limited use methods, and pure serum cannot be separated and collected. There was a problem such as fear.

For example, the serum separating member described in Japanese Patent Publication No. 62-56461 has a problem in its usage. That is, the method of using this member is as follows. First, the blood collecting blood sample is left to stand for a certain period of time to be sufficiently coagulated, and then the separation member is faced downward and carefully inserted into the separation tube.
Centrifuge for about 10 minutes with a centrifugal force of about 0G. Although such an operation is possible, it is complicated to perform an operation of inserting a member into a blood collection tube in an actual site (such as a blood analysis room), and it is necessary to operate it very carefully.
Not realistic.

Further, this member has a drawback that it cannot be applied to plastic blood collection tubes which are currently used in large quantities. That is, a commonly used plastic blood collection tube has a tapered inner diameter due to manufacturing restrictions. For example, in a commercially available 10 ml blood collection tube, the inner diameter fluctuates by about 1 mm, but this member has a constant outer diameter. Therefore, it cannot absorb the variation of the inner diameter of the blood collection tube, and cannot be used for the blood collection tube of which inner diameter varies.

Further, in terms of performance, it is difficult to remove the separated serum by decantation because the separated blood cell liquid easily mixes through the gap between the inner wall of the tube and the end of the member. .

As another conventional example, Japanese Patent Publication No. 1-283
The barrier for blood centrifugation described in Japanese Patent Publication No. 46 uses a columnar elastic porous body having continuous pores with a porosity of 40% or more and a diameter of 50 to 400 μ, and blood is centrifuged to separate solid components such as serum and blood cells. The serum is collected only after separation into. The blood separation operation using this barrier is basically performed by an operation method similar to the above-mentioned serum separation member, and it is complicated to perform the above-mentioned insertion operation of the member at the actual site. And, it requires caution and is not realistic.

Further, although this barrier is made of a porous elastic body and can absorb the fluctuation of the inner diameter of the blood collection tube, during the separation operation, the barrier sediments the serum layer and solids such as serum and blood cells. In order to reach the boundaries of the components, when passing through the serum layer, the components to be analyzed are often excessively filtered by the porous elastic body, or there is a possibility that they will be adsorbed, which is preferable as a blood separation member. I can not say. As described above, the conventional blood separation member has some drawbacks.

The present invention has been made in view of the above circumstances, and is a blood separation member that is inserted into and taken out of a blood collection tube, has good operability during blood separation, and has excellent separation performance between serum and blood clot. The purpose is to provide.

[0014]

As a result of various studies, the present inventors have found that the following conditions are necessary to overcome the drawbacks of the conventional blood separation members.

In order to avoid affecting the analysis value of blood, a stable material having a high molecular weight is used instead of a substance having a low molecular weight such as the conventionally used blood separating agent.

As a structure for absorbing fluctuations in the inner diameter of a blood collection tube, it is fixed at a fixed position in the blood collection tube by a repulsive elastic force under gravity, but under centrifugal force, centrifugal force acting on a separating member and separation in blood are performed. An elastic annular member or an annular elastic body having a structure that moves between blood clot and serum by the interaction of buoyancy and repulsive elastic force acting on the member is used.

In order to improve the operability of blood separation, a structure such as a cylinder assembly is formed by stacking cylinders or cylinders having different diameters with an appropriate gap. With such a configuration, the blood separation member can be mounted in the blood collection tube in advance, and the blood collected by using the syringe or the like can be injected into the blood collection tube through the central opening of the cylinder or the cylinder assembly, and the centrifugal separation can be performed. At times, blood escapes upward through the centers of the cylinders or the gaps between the cylinders.

In order to obtain a structure in which blood clots (blood cells) do not mix into the separated serum through the separating member,
a) By providing a ring-shaped elastic body that can expand and contract in the radial direction on the outside of the cylinder or cylinder assembly, the elastic force of the ring-shaped elastic body presses the inner wall of the blood collection tube to bring the separating member into close contact with the inner wall of the blood collection tube. Prevents blood cells from leaking inside. b) The gap between the cylinders of the cylinder assembly should be such that blood cells do not leak to the serum side through this gap. c) When the separating member is located between the blood clot (blood cell) and serum (plasma) under centrifugal force to close the central opening of the elastic annular member or the cylinder or the cylindrical assembly, it is almost equal to the diameter of the opening. Alternatively, the opening is closed with a sphere having a slightly smaller diameter.

Furthermore, the present inventors have completed the present invention as a result of earnest research on a blood separation member satisfying the above respective conditions.

That is, the blood separation member of the present invention comprises, as described in claim 1, an elastic annular member and a sphere fitted into the opening of this elastic annular member, and at the time of blood separation,
The elastic annular member inserted into the blood collection tube in a compressed state moves to the serum-clot boundary portion, and the sphere located below the elastic annular member closes the opening of the annular elastic body. It is configured to move.

Further, according to a second aspect of the present invention, there is provided a main body provided with an annular elastic body on the outside of one cylinder or a cylindrical assembly formed by concentrically fixing two or more cylinders having different diameters. The main body, which is inserted into the blood collection tube in a compressed state during blood separation, moves to the boundary between the serum and the blood clot.

According to a third aspect of the present invention, the main body comprises the main body and a sphere that closes the innermost cylindrical opening of the main body, and is inserted into the blood collection tube in a compressed state during blood separation. It is desirable that the sphere located below the main body moves so as to close the innermost cylindrical opening of the main body while moving to the serum-clot boundary.

[0023]

With the blood separating member of the present invention having the above-mentioned structure, the diameter of the blood separating member having the elastic annular member and the sphere fitted inside the elastic annular member is reduced in the blood collection tube. After mounting, inject blood (whole blood) into the tube from the center of the elastic annular member with a syringe, and centrifuge this blood collection tube to move the blood separating member between the separated serum and clot. The elastic ring member is fixed at that position by the elastic force, and the sphere located below the elastic ring member moves so as to close the opening of the elastic ring member.

Further, the blood separating member consisting of a cylinder or a cylindrical assembly having an annular elastic body on the outside is inserted into a blood collection tube in a compressed state at the time of blood separation, and the blood (the whole body is removed from the center of the annular elastic body by a syringe or the like). Blood) is injected into the tube, and the blood collection tube is centrifuged to move between the separated blood serum and the blood clot and the serum fixed at that position by the elastic force of the elastic annular member. And move to the clot border.

Further, a blood separating member including a main body of a cylinder or a cylindrical assembly having an annular elastic body on the outside, and a sphere inserted into the innermost cylinder of the main body is provided in a blood collection tube during blood separation. The main body inserted in the compressed state,
While moving to the boundary between the serum and the blood clot, the sphere is inserted into the innermost cylinder of the main body and closes the opening of the main body.

[0026]

EXAMPLES The present invention will be described in detail below with reference to examples. 1 to 3 show a first embodiment of a blood separating member of the present invention, in which reference numeral 1 is a blood separating member.

The blood separating member 1 is made of a plastic thin plate and has three cylinders 2a, 2b, each having a different diameter.
2c are arranged concentrically, and a thin plastic plate is bent into a cylindrical shape on the outside of the cylindrical assembly 4 which is fixed to each other by a supporting member 3, and a gap is provided between both ends of the cylindrical elastic body 4 to make it expandable and contractible in a radial dimension. A main body 6 formed by fixing the body 5, and the main body 6
And a sphere 7 having a diameter smaller than the inner diameter of the innermost cylinder 2c.

A pair of protrusions 9 for preventing upward passage of the sphere 7 are provided inside the upper part of the innermost cylinder 2c of the main body 6. Further, the sphere 7 has a main body 6 as shown in FIG. 3 when the blood separation member 1 is attached to the blood collection tube 8.
It is made to fall to the bottom of the blood collection tube 8 apart from.

The plastic material forming the cylindrical assembly 4 and the annular elastic body 5 has a specific gravity of serum (plasma).
Heavier, i.e. semi-rigid or hard plastic materials with a specific gravity of 1.03 or more are used. More preferably, a plastic having a specific gravity of 1.05 to 1.5, such as ABS resin, polyethylene terephthalate resin, polybutylene terephthalate resin, polycarbonate resin, polyamide resin,
Acrylic resin and the like are preferable.

Each of the cylinders of the cylindrical assembly 4 and the annular elastic body 5 are made of the above-mentioned plastic thin plate and have a plate thickness of 0.
4-2.0 mm, the difference between the inner diameter and the outer diameter is 0.6-4.0 m
m, and the height of the cylinder is preferably 3 to 10 mm. When the plate thickness is less than 0.4 mm, the strength of the cylinder is insufficient and it is difficult to manufacture the blood separation member. The plate thickness is 2.
If it exceeds 0 mm, it may be difficult to move when it is in the coagulated blood.

When the height (M) of the cylinder is less than 3 mm, the stability inside the blood collection tube 8 is deteriorated. On the other hand, if the height (M) exceeds 10 mm, the main body 6 has a problem in moving to the boundary between the blood clot and the serum during centrifugation. More preferably, the height (M) of this cylinder is 5 to 8 mm.

The upper portion of the main body 6 may have a pointed structure as shown in FIG. With this configuration, even when the main body 6 is in the coagulated blood, it is easy to move during centrifugation.

In the cylindrical assembly 4, the difference between the outer diameter of the inner cylinder and the inner diameter of the outer cylinder is 0.6 to 1.2 m.
m, that is, the gap between the cylinders of the cylinder assembly 4 is 0.3 to
It is desirable to set it to 0.6 mm. If this gap is less than 0.3 mm, it becomes difficult to manufacture the cylindrical aggregate 4. On the other hand, when the gap exceeds 0.6 mm, the blood cell solution in the blood clot easily passes through the space, and blood cells and the like are easily mixed in the separated serum.

The numerical values of the difference between the inner diameter and the outer diameter of the cylinder, the height of the cylinder, and the gap between the cylinders of the cylinder assembly are preferably fixed values for one cylinder assembly. .

At present, there are two types of blood collection tubes 8 made of glass and plastic. The inner diameter variation of the glass blood collection tube in the length direction is extremely small, but the plastic blood collection tube has a taper due to its manufacturing method. As an example of the inner diameter fluctuation of this plastic blood collection tube,
In the ml blood collection tube, the inner diameter (actual effective diameter) varies from 14.0 mm to 13.0 mm. In order for the blood separation member to move and be fixed at an arbitrary position in the blood collection tube, a structure is required that absorbs fluctuations in the outer diameter of the body 6 and fluctuations in the inner diameter of the blood collection tube. As a method of absorbing this inner diameter fluctuation of the blood collection tube,
For example, it is possible to make the outer diameter variable by a spring body 10 formed by spirally winding a plastic plate as shown in FIG. 5, but such a spring body 10 is difficult to manufacture, and the spring body is Since a relatively large gap is likely to occur when 10 is inserted into the blood collection tube 8, it is not preferable as the elastic body of the blood separation member according to the present invention. Therefore, as an annular elastic body to be attached to the cylindrical assembly 4, as shown in FIGS. 1 and 2, a plastic plate is bent into a cylindrical shape, and both ends thereof are separated into notches 11 to form an annular elastic body 5.
Is desirable. When the annular elastic body 5 is pushed inward, the notch 11 approaches to reduce the diameter of the annular elastic body 5, and when the annular elastic body 5 is released, the notch 1 is formed by the elastic force of the plastic plate.
1 separates and the annular elastic body 5 swells. Therefore, the cylindrical assembly 4
By attaching this annular elastic body 5 to the outside of the, the diameter of the annular elastic body 5 is reduced and the main body 6 is inserted into the blood collection tube 8,
When mounted, the annular elastic body 5 swells and pushes the inner wall of the blood collection tube to support the main body 6, and under centrifugal force, the main body 6 slides in the blood collection tube and reaches the boundary between serum and blood clot. The specific gravity of this plastic is preferably 1.05 to 1.5.

At present, there are two types of blood collection tubes 8 made of glass and plastic. The inner diameter variation of the glass blood collection tube in the length direction is extremely small, but the plastic blood collection tube has a taper due to its manufacturing method. As an example of the inner diameter fluctuation of this plastic blood collection tube,
In the ml blood collection tube, the inner diameter (actual effective diameter) varies from 14.0 mm to 13.0 mm. In order for the blood separation member to move and be fixed at an arbitrary position in the blood collection tube, a structure is required that absorbs fluctuations in the outer diameter of the body 6 and fluctuations in the inner diameter of the blood collection tube. As a method of absorbing this inner diameter fluctuation of the blood collection tube,
For example, it is possible to make the outer diameter variable by a spring body 10 formed by spirally winding a plastic plate as shown in FIG. 5, but such a spring body 10 is difficult to manufacture, and the spring body is Since a relatively large gap is likely to occur when 10 is inserted into the blood collection tube 8, it is not preferable as the elastic body of the blood separation member according to the present invention. Therefore, as the elastic body to be attached to the cylindrical assembly 4, as shown in FIGS. 1 and 2, an annular elastic body 5 is preferable in which a plastic plate is bent into a cylindrical shape, and both ends thereof are separated to form notches 11. When the annular elastic body 5 is pushed inward, the notch 11 approaches to reduce the diameter of the annular elastic body 5, and when the annular elastic body 5 is released, the elastic force of the plastic plate separates the notch 11 and the annular elastic body 5 swells. Therefore, by attaching the annular elastic body 5 to the outside of the cylindrical assembly 4, the annular elastic body 5 is reduced in diameter and the main body 6 is inserted into the blood collection tube 8, and when the body 6 is attached, the annular elastic body 5 swells and the inside of the blood collection tube is expanded. The wall 6 is pushed to support the main body 6, and under centrifugal force, the main body 6 slides in the blood collection tube to reach the boundary between the serum and the blood clot.

In this example, the shape of the notch 11 of the annular elastic body 5 is stepwise as shown in FIG. 2, but the shape of the notch 11 is not limited to this, and may be, for example, multistep or curved. Other shapes such as a shape can also be used.

The sphere 7 has a specific gravity of blood (whole blood) (1.
It is made of a material smaller than 05 to 1.06), such as polystyrene, polyethylene, or polypropylene. The diameter of the spherical body 7 is set to be smaller than the inner diameter of the innermost cylinder 2c of the cylindrical aggregate 4 and larger than the dimension between the protrusions 9,9. The size of the sphere 7 can be theoretically considered to be about 1 mm in diameter, but from many experimental results, the sphere having a small diameter has poor stability in blood and may not enter the cylinder 2c of the main body 6. Therefore, it is desirable that the diameter of the sphere 7 is 35% or more, more preferably about 50 to 90% of the inner diameter of the blood collection tube.

The spherical body 7 is the innermost cylinder 2c of the main body 6.
As a structure that is easy to enter, as shown in FIG.
The heights of b and 2c may be smaller than the heights of the outer cylinder 2a and the annular elastic body 5.

The blood separating member 1 in which the main body 6 and the sphere 7 are combined is located at the boundary between the blood serum and the blood clot at the time of blood separation. This is due to the elastic force of the annular elastic body 5, the centrifugal force and the specific gravity of the blood. The position is determined by interactions such as the specific gravity of the main body 6 and buoyancy in blood, and the specific gravity of the separating member does not necessarily have to be an intermediate value between serum (plasma) and blood clot (blood cell). It is desirable to set the average specific gravity of the main body 6 and the sphere 7 to an intermediate value between serum and blood clot.

The body 6 and the sphere 7 are made of plastic, respectively, and have good blood releasability. However, when these are buried in the coagulated blood, there is a possibility that the coagulated blood may not be removed by centrifugation. Therefore, in order to improve the releasability of the coagulated blood, it is desirable to attach a blood adhesion preventing agent or a blood coagulation inhibiting agent to the surfaces of the main body 6 and the sphere 7.

As the blood adhesion preventing agent, for example, a silicone material such as silicone oil or a coating material such as a fluororesin material is preferably used. Heparin is preferably used as the blood coagulation inhibitor. These blood adhesion preventives and blood coagulation inhibitors can be easily adhered to the surfaces of the main body 6 and the sphere 7 by a method such as coating, spraying or dipping.

After blood separation, cell components such as erythrocytes consume sugar in serum and the blood sugar level cannot be displayed correctly. Therefore, in order to obtain a correct blood glucose level, serum obtained by removing blood clots after blood separation is used as an analysis sample. However, when the blood separation member of the present invention is used, the blood clot and the serum can be completely isolated, and therefore the blood glucose level in the serum rarely changes even if the blood separation member is stored as it is after centrifugation. Further, in order to obtain a more accurate blood glucose level, a blood separation member (including spheres) may be coated with a glycolytic inhibitor in advance. In addition, sodium fluoride, sodium monoiodoacetate or the like is used as the glycolysis inhibitor.

Further, a small amount of sealing agent is further present in the gap between the cylindrical aggregate and the annular elastic body on the outer side thereof to further ensure that the constituents in the blood clot do not enter the serum after blood separation. The method is also a peripheral technology of the present invention. The sealant is
It is effective to make it exist in the cutout portion, and it is more effective to fill the groove-shaped gap of the cutout portion.

Since the above-mentioned sealing agent has an extremely small amount, it has no special limitation except that it does not affect blood analysis and does not affect the movement of the annular elastic body during centrifugation. Specifically, a water-insoluble silicone gel or a silicone gel in which a glycolytic inhibitor is kneaded is preferable.

Next, a blood separating operation using the blood separating member 1 will be described with reference to FIG.

This blood separating member can be mounted in the blood collection tube 8 in advance. When collecting blood, the lid of the blood collection tube 8 is removed as shown in FIG. 6A, the needle 12 of the syringe is inserted through the opening in the center of the main body 6, and the blood 13 is injected into the blood collection tube 8. The body 6 of the blood separation member 1 is located above the blood collection tube 8, preferably just below the cap,
Further, the sphere 7 separates from the main body 6 and is suspended in the blood 13.

Then, as shown in FIG. 6B, the blood collection tube 8
After injecting a predetermined amount of blood 13 therein, the blood collection tube 8 is covered with the cap 14 and left as needed to coagulate the blood 13.

Next, the blood collection tube 8 is centrifuged at about 1200 G. By this centrifugation, the blood 13 becomes (c) in FIG.
As shown in (3), serum (plasma) 15 and blood clot (blood cell) 16 are separated. At this time, the main body 6 slides downward in the blood collection tube by centrifugal force, passes through the separated serum 15 and
5 and the clot 16 are reached and stop at the boundary. In addition, the sphere 7 floats above the blood clot 16, and the serum 15 and the blood clot 16
When it enters the innermost cylinder 2c of the main body 6 that has moved to the boundary of (2) and comes into contact with the protrusion 9 of the cylinder 2c, the upward movement is suppressed and the body 6 is stabilized in the inserted state.

When the centrifugal separation shown in FIG. 6 (c) is completed, the blood separating member 1 is located at the boundary between the separated serum 15 and blood clot 16 and covers the upper part of the blood clot 16. The lid is closed to prevent the blood clot 16 from mixing into the serum 15. The separated serum 15 is
It can be fractionated by an automatic serum fractionator or decantation. The separated blood clot (blood cell)
It is also possible to collect the blood clot (blood cell) component in the blood collection tube 8 by pulling up the blood separating member after collecting and removing the serum without excess materials such as a blood separating agent mixed therein. It is possible.

In this embodiment, the cylindrical assembly 4 is composed of three cylinders 2a, 2b and 2c.
The number of cylinders forming the cylindrical aggregate 4 is not limited to three, and may be two cylinders or four or more cylinders.

10 and 11 show a second embodiment of the present invention, in which reference numeral 1A is a blood separating member.

The difference between the first embodiment and this embodiment is that the former uses a cylindrical assembly 4 in which three cylinders 2a, 2b, 2c are concentrically fixed, whereas the latter has one. The annular elastic body 5 is fixed to the cylinder 2a to constitute the main body 6.

In the present embodiment, the protrusion 9 is provided in order to suppress the movement of the sphere 7 that has moved to the opening of the cylinder 2a of the main body 6 when the blood is separated.
However, the mechanism for preventing the upward movement of the sphere 7 is not limited to this, and as shown in FIG. 12, the inside of the cylinder 2a of the main body 6 is provided with a mouth portion below the cylinder 2a. The taper may be formed such that the diameter is larger than the diameter of the spherical body 7 and the diameter of the upper mouth portion is smaller than the diameter of the spherical body 7.

The blood separation member 1A of this embodiment is the same as the first
Similar to the blood separation member of the above example, it exhibits excellent blood separation ability during blood separation by centrifugation.

FIG. 14 shows a third embodiment of the present invention, in which reference numeral 1B is a blood separating member. The blood separating member 1B according to the present embodiment is characterized in that the flange 1 is provided at the upper and lower ports.
A taper is provided on the inner surface of the thread-wound cylinder 18 provided with 7, 17 such that the lower opening of the cylinder 18 is larger than the diameter of the sphere 7 and the upper opening is smaller than the diameter of the sphere 7. The flange 1 of the cylinder 18 that has been formed and is wound
The configuration is such that the annular elastic body 5 is fitted between 7 and 17.

When the thread-wound cylinder 18 shown in FIG. 14 is used, the thread-wound cylinder 1 is used.
The annular elastic body provided between the flanges 17, 17 of 8 is
The annular elastic body 5 is not limited to the annular elastic body 5 described above, and may be, for example, an annular elastic body 5A obtained by molding a material made of a shrinkable sponge-like foam into a cylindrical shape.

Fibers (metals such as stainless fibers, minerals such as glass fibers, plant fibers such as cellulose, animal fibers such as silk, and mixtures thereof) are molded into an annular ring having elasticity in the annular elastic body 5A. The above may be used, or the elastic body may be formed by winding a flat plate or a thread. If a substance such as SiO2 powder that promotes blood coagulation is mixed into these elastic bodies, the separation of the separated blood from each other after centrifugation will be more complete.

The blood separation member 1B of this embodiment is the same as the first
Similar to the blood separation member of the above example, it exhibits excellent blood separation ability during blood separation by centrifugation.

FIG. 16 shows a fourth embodiment of the present invention, in which reference numeral 1C is a blood separating member. The blood separating member 1C according to the present embodiment is characterized in that an inner surface of a thread-wound cylinder 18 having flanges 17 and 17 at upper and lower mouths has a lower mouth than the diameter of the sphere 7 and an upper mouth. The diameter of the mouth of the taper is smaller than the diameter of the sphere 7, and the flange 1 of the thread-wound cylinder 18 is formed.
A rubber-like elastic material is formed between 7 and 17 in the form of a hollow ring tube, and an annular elastic body 5B formed by filling a gas body such as air in this ring tubular member is movably provided without being fixed. It has just been configured. Also, this annular elastic body 5B
As the rubber-like elastic material used for preparing the above, a material that does not biochemically affect blood as a sample is preferable, and for example, silicon rubber or the like is preferable. The annular elastic body 5B may be doubled as shown in FIG.

The blood separating member 1C of this embodiment is the same as the first embodiment.
Similar to the blood separation member of the above example, it exhibits excellent blood separation ability during blood separation by centrifugation.

FIG. 18 shows a fifth embodiment of the present invention, in which reference numeral 1D is a blood separating member. The blood separating member 1D according to the present embodiment is characterized in that a groove 19 is provided on an outer surface of a cylinder 18A, and an annular elastic body 5B similar to that used in the fourth embodiment is fitted in the groove 19. The annular elastic body 5B is provided so as not to move.

The blood separating member 1C of the present embodiment is the first
Similar to the blood separation member of the above example, it exhibits excellent blood separation ability during blood separation by centrifugation.

FIG. 13 shows a sixth embodiment according to the present invention, in which reference numeral 21 is a blood separating member.

The blood separating member 21 is made of the same plastic material as in the first embodiment, and has five cylinders 22a, 22b, 22c, 22d and 22 having different diameters.
e are arranged concentrically, and a thin plastic plate is bent into a cylindrical shape on the outside of the cylindrical assembly 24 fixed to each other with a support member 23, and a gap is provided on both end sides thereof so that the diameter dimension can shrink. It is composed of the same annular elastic body 5 as that used in the first embodiment.

The point of difference of the present embodiment from the first embodiment is that the spherical body fitted inside the cylinder located at the innermost side of the cylindrical assembly used in the previous example is not used, but instead of the cylindrical assembly. We have just added the number of cylinders.

In the blood separation member 21 of this embodiment,
With the above configuration, when the blood separating member 21 inserted into the blood collection tube in a compressed state at the time of blood separation moves to the boundary between the serum and the blood clot, the space between the five cylinders is sufficient. Since it is small, blood cells do not leak into the separated serum without using the spheres used in the previous examples.

FIG. 19 shows a seventh embodiment according to the present invention, in which reference numeral 31 is a blood separating member.

The blood separating member 31 is composed of a cylindrical elastic annular member 32 and a sphere 7 fitted inside the elastic annular member.

The elastic annular member 32 is a cylindrical member made of a plastic material and having a notch 33 on its side. When the elastic annular member 32 is pushed inward, the notch 33 approaches to reduce the diameter of the elastic annular member 32, and when the elastic annular member 32 is released, the notch 33 is separated by the elastic force of the plastic plate so that the elastic annular member 32 is separated. Swell. Therefore, when the elastic annular member 32 is reduced in diameter and inserted into the blood collection tube 8 and mounted, the elastic annular member 32 swells and pushes the inner wall of the blood collection tube, and the elastic annular member 32 is supported, and under the centrifugal force, the elastic annular member 32 is supported. The member 32 slides in the blood collection tube and reaches the boundary between the serum and the blood clot. The specific gravity of this plastic is preferably 1.05 to 1.5. The sphere 7 is the same as the sphere used in the first embodiment.

In the blood separation member 31 of this embodiment,
While the elastic annular member 32 inserted into the blood collection tube in a compressed state at the time of blood separation moves to the serum-clot boundary,
Blood can be separated into serum and blood clot by moving the spherical body 7 located below the elastic annular member 32 so as to close the inside of the annular elastic member 32.

The blood separating member 31 in which the elastic annular member 32 and the sphere 7 are combined is located at the boundary between the blood serum and the blood clot at the time of blood separation. This is due to the specific gravity of the elastic annular member 32 and the elastic force and centrifugal force. The position is determined by the interaction between the specific gravity of blood and the specific gravity of blood, and the specific gravity of the separating member does not necessarily have to be an intermediate value between serum (plasma) and blood clot (blood cell).
It is desirable to set the average specific gravity of the elastic annular member 32 and the sphere 7 to an intermediate value between serum and blood clot.

In the present embodiment, the cylindrical elastic annular member 32 having the notch 33 on the side is used as the elastic annular member, but the elastic annular member is not limited to the above. For example, as shown in FIG. 20, on the inner surface of the cylindrical elastic annular member 34, the lower opening of the elastic annular member 34 is larger than the diameter of the sphere 7, and the upper opening is smaller than the diameter of the sphere 7. Elastic flanges 35 that form such a taper and project outward in the radial direction at the two mouths,
It may be wound with a thread 35. The elastic annular member 34 absorbs the variation of the inner diameter of the blood collection tube by the elasticity of the elastic flanges 35, 35, and exhibits the same effect as the elastic annular member 32 described above.

21 and 22 show an eighth embodiment according to the present invention, in which reference numeral 36 is a blood separating member.

The blood separating member 36 is composed of a main body 39 composed of a cylinder 37 and an annular elastic body 38, and a sphere 40 fitted inside the cylinder 37.

The cylinder 37 is provided with a flange 41 projecting outward in the radial direction on the peripheral edge of the lower opening. Further, the annular elastic body 38 is similar to the annular elastic body 5 used in the first embodiment described above, and the annular elastic body is formed by bending a plastic plate into a cylindrical shape and separating both ends thereof into notches 42. Further, the annular elastic body 38 and the cylinder 37 are fixed and integrated with the support member 43, respectively.

When the annular elastic body 38 is pushed inward, the notch 42 approaches to reduce the diameter of the annular elastic body 38. When the annular elastic body 38 is released, the elastic force of the plastic plate separates the notch 42 from the annular elastic body 38. Swells. Therefore, by attaching the annular elastic body 38 to the outside of the cylinder 37, the annular elastic body 38 is reduced in diameter and the main body 39 is inserted into the blood collection tube. When the body 39 is attached, the annular elastic body 38 expands and pushes the inner wall of the blood collection tube, The main body 39 is supported, and the main body 3 is supported under centrifugal force.
9 slides in the blood collection tube and reaches the boundary between serum and blood clot. After the centrifugation, the sphere 40 floating from the blood clot enters the opening of the cylinder 37 of the main body 39 that reaches the boundary between the serum and the blood clot, and abuts the protrusion 44 of the cylinder 37 to suppress the upward movement. It is stable in the state that it is inserted into the main body 39.

FIG. 23 shows a ninth embodiment according to the present invention, in which reference numeral 50 is a blood separating member.

The blood separating member 50 is composed of a cylindrical elastic annular member 51 and the same spherical body 7 used in the first embodiment.

The elastic annular member 51 is a cylindrical member made of a material having rubber-like elasticity (elastomer), and is made of a material such as polyvinyl chloride (PVC) elastomer or urethane elastomer. Also,
A plurality of ridges 52 for facilitating the movement of the elastic annular member 51 in the blood collection tube are vertically projected on the outer peripheral surface thereof,
Moreover, they are formed at equal intervals in the circumferential direction.

Further, in the vicinity of the upper opening of the inner peripheral surface of the elastic annular member 51, three locking claws 53 for preventing the spherical body 7 from passing upward are respectively directed inward in the circumferential direction. It is formed to project.

The blood separating member 50, which is a combination of the elastic annular member 51 and the sphere 7, is located at the boundary between serum and blood clot during blood separation. This is due to the specific gravity of the elastic annular member 51 and the elastic force and centrifugal force. The position is determined by the interaction between the specific gravity of blood and the specific gravity of blood, and the specific gravity of the separating member does not necessarily have to be an intermediate value between serum (plasma) and blood clot (blood cell).
It is desirable to set the average specific gravity of the elastic annular member 51 and the sphere 7 to an intermediate value between serum and blood clot.

In order to perform a blood separation operation using the blood separation member 50 of the present embodiment, first, the sphere 7 is put into the blood collection tube containing the collected blood, and the compressed elastic annular member 51 is placed. Insert (the sphere 7 may be put in the blood collection tube first, and the blood may be put after inserting the elastic annular member 51). At this time, the outer peripheral surface of the elastic annular member 51 inserted into the blood collection tube is in a state of being pressed against the inner wall of the blood collection tube by the elastic force of the elastic annular member 51 in the outward direction. Due to the plurality of ridges 52 formed on the surface, the contact portion between the both surfaces is reduced, frictional resistance is reduced, and smooth movement of the elastic annular member 51 in the blood collection tube is secured.

Next, the elastic annular member 51 is inserted,
The blood collection tube containing the sample blood is centrifuged, and the elastic annular member 51 located above the blood collection tube is slid to move to the serum-clot boundary portion, and at the same time, the sphere located below the elastic annular member 51. 7 moves so as to close the inside of the annular elastic member 51 to separate blood into serum and clot.

In this embodiment, in order to prevent the spherical body 7 from passing through the central opening of the elastic annular member 51, the elastic annular member 51 is provided with three holes near the upper opening of the inner peripheral surface thereof.
Although one locking claw 53 is provided, the method of preventing passage of the central opening of the spherical body 7 is not limited to the above, and for example, as shown in FIG.
In the vicinity of the upper opening of the inner peripheral surface of the above, a protrusion 54 may be provided which projects inward of the central opening and projects over the entire circumference in the circumferential direction. In addition, the elastic annular member 3 of FIG.
As shown in FIG. 4, by forming a taper such that the lower opening is larger than the diameter of the spherical body 7 and the upper opening is smaller than the diameter of the spherical body 7, the central opening of the spherical body 7 is prevented. You may do it.

The blood separating agent of this embodiment is composed of the elastic annular member 5
Since the shape of 1 is a simple single cylinder, it is easy to manufacture.

Further, since a plurality of ridges 52 are vertically projected on the outer peripheral surface of the elastic annular member 51 and are formed at equal intervals in the circumferential direction, when the annular elastic member 51 is inserted into the blood collection tube, The contact portion between the elastic member and the inner wall surface of the blood collection tube is reduced, and the frictional resistance between both surfaces is reduced. Therefore, during centrifugation, the elastic annular member 51 located above the blood collection tube can smoothly slide in the blood collection tube and move to the serum-clot boundary. It goes without saying that the annular elastic member can be easily taken in and out of the blood collection tube.

The blood separating member according to the embodiment of the present invention described above can be applied without problem to a vacuum blood collection tube which has been often used these days. In the case of a vacuum blood collection tube, the blood collection needle is passed through the cap of the vacuum blood collection tube, and blood is injected without removing the cap. At this time, since the blood separating member of the present invention is installed right under the cap, the needle does not collide with the blood separating member when the blood collecting needle is passed through the cap. In particular, if the blood separation member has a wide opening as shown in FIGS. 10, 14, 15, 16, 17, 18, 19, 20, 20, 21, 22 and 23, it can be said that there is no concern.

Hereinafter, the effects of the present invention will be clarified by experimental examples.

(Experimental Example 1) Using ABS resin (manufactured by Denki Kagaku Kogyo, transparent grade CL, specific gravity 1.10), the cylindrical assembly 4 and the annular elastic body 5 shown in FIGS. 1 and 2 were produced. The dimensions A to N in the figure are the outer diameter (A) of the cylindrical assembly.
Is 11.7 mm, the same inner diameter (B) is 7.3 mm, the sphere diameter (C) is 6.86 mm, the cylinder thickness (D) is 0.4 mm, the cylinder gap (E) is 0.5 mm, and the annular elastic body thickness is Sa (F) is 0.
4 mm, protrusion length (G) 1 mm, support material width (H) 1 mm, annular elastic body outer diameter (I) 14.0 mm (no load), deviation (J) 0.25 mm, annular Each part of the elastic body has K = 3.5 mm, L = 2.7 mm, M = 5 mm,
N = 2.5 mm, O = 2.5 mm, P = 3.5 mm, Q =
It was set to 2.3 mm. The weight of the main body composed of this cylindrical aggregate and the annular elastic body was about 0.323 g. As the spheres, polystyrene balls impregnated with butadiene (weight 0.172 g, specific gravity 1.02) were used. The average density of the main body and the sphere was 1.069 g / ml.

As the blood collection tube, a commercially available polypropylene Spitz tube (FIG. 7) having a volume of 10 ml was used. Reference numeral R shown in FIG.
Each dimension of ~ S has a length (R) of 97mm and 8m from the upper end.
The inner diameter (S) at the position below m is 14.0 mm, 40 from the top
The inner diameter (T) at the position below mm is 13.5 mm, 6 from the upper end.
The inner diameter (U) at a position 5 mm below was 13.0 mm.
When blood is collected by this Spitz tube, it is considered that the boundary surface between the blood clot (blood cell) and the serum (plasma) after centrifugation is actually located between the points S and U. It is extremely rare that the boundary is below the U point. So in this Spitz tube,
In effect, the inner diameter will vary from 14 mm to 13 mm.

In the main body of the blood separating member, the gap between the annular elastic body and the outermost cylinder 2a is set to 0.5 mm on the upper side in FIG. 1 and 1.0 mm on the lower side. However, the gap is 1.0m
A stepped notch shown in FIG. 2 is provided in the portion of the annular elastic body corresponding to the position of m, and the annular elastic body is reduced in diameter by being tightened from the outside, and the outer diameter of the annular elastic body is 14 mm to
Variable up to 13 mm.

The inner diameter (B) of the cylindrical aggregate was 7.3 mm, and the structure was such that polystyrene spheres having a diameter of 6.86 mm could easily enter. Further, a pair of protrusions 9 is provided on the upper part of the inner surface of the innermost cylinder 2c to prevent the spherical body from passing upward.

Three cylinders (2a, 2b, 2c) of a cylinder assembly
Are fixed at four points by a support made of the same quality plastic. The cylindrical aggregate and the annular elastic body are fixed at one place. Silicone grease was thinly applied to the upper surface of the main body and the surface of the sphere.

A blood separation operation was carried out using this blood separation member. First, the sphere was dropped into the Spitz tube, and then the main body was inserted into the Spitz tube while pressing the annular elastic body so as to reduce the diameter with the side having the protrusions facing upward. Next, 8 ml of blood was injected into the Spitz tube from the opening in the center of the body using a syringe.
Injected. After allowing it to stand for 5 hours to coagulate blood, the Spitz tube was transferred to a centrifuge, and 3000 rpm (about 1200
G) Centrifuged under the condition of 10 minutes (holding at 20 ° C.).

After centrifugation, the Spitz tube was taken out and observed. As a result, the main body of the blood separation member was located between the separated serum and blood clot, and the sphere was completely housed in the innermost cylinder. It was No blood clots were attached to the upper surface of the body and the sphere.

The lid of the Spitz tube was removed, and the spitz tube was tilted to allow the serum to flow out gently, but no blood clot was mixed in the serum.

(Experimental Example 2) The outermost cylinder 2a of the cylindrical aggregate and the height (M) of the annular elastic body are each 7 mm, and the heights of the two inner cylinders 2b and 2c are 5 mm. As shown, the two inner cylinders 2b and 2c are configured to be low, and further, among the dimensions of each part of the cutout, L = 4 mm,
O = 3.2 mm, N = 3.8, Q = 3 mm, K, P = 3.5
A blood separating member was produced using the same main body and spheres as in Experimental Example 1 except that the thickness was set to mm, and the same blood separating operation as in Experimental Example 1 was performed using this.

The weight of the main body was 0.39 g, and the average density of the main body and the sphere was 1.076 g / ml.

As a result of centrifugation, excellent blood separation performance similar to that of Experimental Example 1 was exhibited.

(Experimental Example 3) Of the cylindrical assembly used in Experimental Example 2, the inner two cylinders 2b and 2c are omitted, only the outermost cylinder 2a is used, and the annular elastic body is fixed to the outer side of this cylinder. Then, the main body shown in FIGS. 10 and 11 was produced. In this body, spheres made of polystyrene impregnated with butadiene (diameter 10.2 mm, weight 0.571 g, density 1.029 g / m
1) was combined to form a blood separation member. The weight of the main body was 0.24 g, and the average density of the main body and the sphere was 1.049 g / ml. Further, two protrusions having a length of 1 mm were formed on the inner side of the upper surface of the cylinder 2a to prevent passage of a sphere.

Using this blood separation member, the same blood separation operation as in Experimental Example 1 was performed. As a result, the same excellent blood separation performance as in Experimental Example 1 was exhibited.

(Experimental Example 4) In Experimental Example 4, an example is shown in which a glass blood collection tube is used as a blood collection tube.

FIG. 8 shows an outline of a commercially available glass collection tube of commonly called 10 ml. When measuring each dimension of this glass blood collection tube, the length (V) was 99 mm, and the inner diameter (W) at the upper end of the tube was
13.5 mm, the inner diameter (X) of other parts is 13.8 to 14.
It was 0 mm.

The blood separating member for a glass blood collection tube has substantially the same structure as that of the blood separating member used in Experimental Example 3, and the dimensions of the respective cutouts are indicated by K to K shown in FIG.
Q is L = 4mm, O = 3.2mm, N = 3.8mm, Q
= 3 mm, K, P = 2 mm, M = 7 mm to prepare a main body, and the same sphere as in Experiment Example 3 was used. The weight of the main body was 0.24 g, and the average density of the main body and the sphere was 1.049 g / mm.

Using this blood separation member, the same blood separation operation as in Experimental Example 1 was performed. As a result, the same excellent blood separation performance as in Experimental Example 1 was exhibited.

In the above-mentioned Experimental Examples 3 and 4, the annular elastic body 5 is fixed to the cylinder 2a by the support member 3, but a part of the cylindrical 2a and a part of the annular elastic body 5 are formed. Alternatively, the supporting member 3 may be omitted by fixing the supporting member 3 by being integrated. With this configuration, the cylinder and the annular elastic body can be integrally molded, and the manufacturing process of the main body can be simplified.

[0108]

As described above, the blood separation member of the present invention comprises the elastic annular member and the spherical body fitted in the opening of the elastic annular member, and is compressed into the blood collection tube during blood separation. Since the elastic annular member inserted in the state moves to the boundary part of the serum-clot, the sphere located below the elastic annular member moves so as to close the opening of the annular elastic body, Serum and clot can be completely separated. Separated serum is separated without contact with extra materials such as blood separating agent or porous material, so that highly reliable sample can be obtained without fluctuation of serum components during separation. .

The blood separating member has a ring-shaped elastic body which is expandable and contractible in the radial direction on the outside of the cylinder or the cylinder assembly, so that the ring-shaped elastic body is contracted even when the inner diameter of the blood collection tube changes. Since it can be bulged or swollen to absorb the variation in the inner diameter, it can be sufficiently used even in a plastic blood collection tube having a variation in the inner diameter.

Further, since the sphere is inserted into the innermost cylinder of the main body, the sphere is inserted into the opening of the main body at the time of blood separation, and by closing the opening, the sphere is separated into the separated serum. Blood cells and the like can be prevented from mixing, and serum can be easily taken out. It is also possible to take out the separated blood clot (blood cell) and analyze it.

Since this blood separation member can be pre-installed in the blood collection tube and sample blood can be injected from the opening in the center of the main body, the complicated operation of mounting the separation member on the blood collection tube at the time of blood collection can be omitted. You can Furthermore, this blood separation member can be applied to a vacuum blood collection tube.

Since this blood separating member can be freely taken in and out of the blood collection tube, the blood collecting tube can be reused and the blood separation member can be reused, contributing to resource saving and also preventing environmental pollution. Be useful.

[Brief description of drawings]

FIG. 1 is a plan view of a blood separation member showing a first embodiment of the present invention.

FIG. 2 is a side view of the blood separation member shown in FIG.

FIG. 3 is a side view showing a state in which the blood separation member shown in FIG. 1 is mounted inside a blood collection tube.

FIG. 4 is a side sectional view showing a first modification of the main body of the blood separation member indicated by reference numeral 6 in FIG.

5 is a plan view showing an example of an unsuitable annular elastic body shown by reference numeral 5 in FIG. 1. FIG.

FIG. 6 is a side view for explaining a blood separation operation using the blood separation member shown in FIG. 1 in order of steps.

FIG. 7 is a side view showing an example of a blood collection tube used in each example of the present invention.

FIG. 8 is a side view showing another example of a blood collection tube.

9 is a side sectional view showing a second modified example of the main body of the blood separation member indicated by reference numeral 6 in FIG.

FIG. 10 is a plan view of a blood separation member showing a second embodiment of the present invention.

11 is a side view of the blood separation member body indicated by reference numeral 6 in FIG.

12 is a side view showing a modified example of the main body of the blood separation member shown in FIG.

FIG. 13 is a plan view of a blood separation member showing a sixth embodiment of the present invention.

FIG. 14 is a side view of a blood separation member showing a third embodiment of the present invention.

FIG. 15 is a side view showing a modified example of the blood separation member shown in FIG.

FIG. 16 is a side view of a blood separation member showing a fourth embodiment of the present invention.

FIG. 17 is a side view showing a modified example of the blood separation member shown in FIG.

FIG. 18 is a side view of a blood separation member showing a fifth embodiment of the present invention.

FIG. 19 is a side view of a blood separation member showing a seventh embodiment of the present invention.

20 is a side view showing a modified example of the blood separation member shown in FIG.

FIG. 21 is a plan view of a blood separation member showing an eighth embodiment of the present invention.

22 is a side view of the blood separation member shown in FIG. 21. FIG.

FIG. 23 is a vertical sectional view (a) and a plan view (b) of a blood separating member according to a ninth embodiment of the present invention.

24 is a vertical sectional view (a) and a plan view (b) of a modified example of the blood separation member shown in FIG. 23.

[Explanation of symbols]

1, 1A, 1B, 1C, 1D, 21, 31, 36, 50 ... Blood separation members 2a, 2b, 2c, 18, 18A, 22a, 22b, 22c, 2
2d, 22e, 37 ... Cylinder 3 ... Support material 4, 24 ... Cylindrical aggregate 5, 5A, 5B, 38 ... Annular elastic body 6 ... Main body 7, 40 ... Sphere 8 ... Blood collection tube 9 ... Protrusion 11, 42 ... Notch 13 ... blood 15 ... serum 16 ... blood clot 23,43 ... support materials 32,34,51 ... elastic annular member 33 ... notch 39 ... main body

Claims (3)

[Claims] 1. A blood serum-blood clot comprising an elastic annular member and a sphere fitted into an opening of the elastic annular member, wherein the elastic annular member is inserted into a blood collection tube in a compressed state during blood separation. Blood separating member, wherein the sphere located below the elastic annular member moves so as to close the opening of the annular elastic member. 2. A body is provided with an annular elastic body on the outer side of a cylinder assembly formed by concentrically fixing one cylinder or two or more cylinders each having a different diameter, and collecting blood at the time of blood separation. A blood separation member, wherein the main body inserted in a tube in a compressed state moves to a boundary portion between serum and blood clot. 3. A serum-clot boundary portion comprising the main body and a sphere that closes the innermost cylindrical opening of the main body, and the main body inserted in a blood collection tube in a compressed state during blood separation. Blood separating member, wherein the sphere located below the main body moves so as to close the innermost cylindrical opening of the main body.