JP2001299730A - Plasma collecting instrument - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an instrument by which a plasma sample can be prepared by simultaneously and easily performing drawing and filtering of blood with a simple structure. SOLUTION: The above described purpose can be achieved by providing a plasma collecting instrument consisting of a blood filtration tool consisting of a blood filtration material consisting of a glass fiber filter paper and a fine porous membrane and a holder for storing this tool and having an inlet for the blood and an outlet for the filtrate, a blood drawing needle connected with the inlet for the blood through a tube and a vacuum blood drawing tube or a syringe connected with the outlet for filtrate through a tube.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a device for preparing a plasma sample by simultaneously performing blood collection and hemofiltration.

[0002]

2. Description of the Related Art The type and concentration of constituents in blood such as metabolites, proteins, lipids, electrolytes, enzymes, antigens and antibodies are usually measured using plasma or serum obtained by centrifuging whole blood. Have been done. However, centrifugation takes time and effort. In particular, when a small number of samples are to be processed quickly or on site, the centrifugal method using electricity and requiring a centrifuge is not suitable. Thus, methods for separating plasma and serum from whole blood by filtration have been studied.

[0003] For this filtration method, several methods have been known in which a column is filled with glass fiber filter paper, whole blood is injected from one side of the column, and pressure or pressure is reduced to obtain plasma or serum from the other side. (Japanese Patent Publication No. 44-14673,
JP-A-2-208565, JP-A-4-20885
No. 6, Japanese Patent Publication No. 5-52463, etc.).

[0004] However, the method of obtaining the amount of plasma or serum necessary for measurement by automatic analysis or the like from whole blood by filtration is still in the trial stage except for some items such as blood sugar, and has been widely put into practical use. Has not been reached.

Therefore, the present inventors have previously developed a blood filtration unit capable of efficiently separating plasma and serum even with a small amount of blood by combining glass fiber filter paper with a microporous membrane as a filter medium, A blood filtration unit in which the opening area of the filtration material was narrowed by providing a seal member on the outlet side was completed (Japanese Patent Application Laid-Open No. 9-196911).

[0006] A blood collection needle was connected to the blood inlet, and a plasma receiving tank was provided at the plasma outlet side (JP-A-10-225448).

On the other hand, there is also a device for separating serum or plasma components from blood, comprising a vacuum blood collection tube having a serum separation column or filter inside and a connection needle for connecting the two, and an injection needle attached to the tip. It has been developed (JP-A-4-208856, JP-A-5-93721, JP-A-5-188053).

[0008]

The plasma collection tool developed earlier by the present inventors connects a suction adapter or a syringe to a blood filtration unit having a plasma receiving tank to perform blood collection and blood filtration. There was a problem in handling and it was still insufficient for practical use.

[0009] In addition, an instrument for joining a vacuum blood collection tube and a vacuum-separated serum collection tube with a joining needle requires four members to be connected and the insertion of three needles to be performed in order, and the operation is complicated.

An object of the present invention is to provide a device which can easily perform blood collection and blood filtration simultaneously with a simple structure to prepare a plasma sample.

[0011]

Means for Solving the Problems The present inventors have made intensive studies to solve the above problems, and as a result, removed the plasma receiving tank from the blood filtration unit developed earlier by the present inventors to replace the vacuum blood collection tube or syringe. It has been found that a plasma sample can be easily and reliably prepared by simultaneously performing blood collection and hemofiltration by using these as a blood suction source and using them as a plasma receiving tank.

The present invention has been made on the basis of such findings, and has been made of a blood filtering material comprising a glass fiber filter paper and a microporous membrane, and a blood filter comprising a holder containing the blood filtering material and having a blood inlet and a filtrate outlet. A blood collection needle connected to the blood inlet via a tube, and a vacuum blood collection tube or a syringe connected to the filtrate outlet via a tube.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION A blood filter contains a blood filtering material and has a blood inlet and a filtrate outlet.

Although the type of blood filtration material is not limited, the filtration material of the present invention is not a so-called surface filtration material that traps blood cells only on its surface, but initially penetrates in the thickness direction of glass fiber filter paper or the like. A so-called volume filtration material is used, which gradually entraps a large blood cell component and later a small blood cell component in a void structure, and retains and removes blood cells over the entire length in the thickness direction. Preferred are glass fiber filter paper and the like, and a combination of a glass fiber filter paper and a microporous membrane is particularly preferred.

The glass fiber filter paper has a density of 0.02-0.5.
g / cm ³ , preferably about 0.03-0.2 g / c
m ³ degrees, particularly preferably 0.05 to 0.13 g / cm ³
And the retained particle diameter is about 0.6 to 9 μm, especially 1 to 5 μm.
It is preferably about μm. By treating the surface of the glass fiber with a hydrophilic polymer by a method as described in JP-A-2-208565 and JP-A-4-208856, filtration can be performed more quickly and smoothly. Further, the surface of the glass fiber can be treated with lectin.

A microporous membrane having a hydrophilic surface and capable of separating blood cells specifically separates blood cells and plasma from whole blood without substantially hemolyzing to affect the analytical value. Things. This microporous membrane has a pore size smaller than the retained particle size of the glass fiber filter paper and 0.2 μm or more, preferably about 0.3 to 5 μm, more preferably 0.5 to 3 μm.
m is appropriate. Further, the porosity is preferably high, and specifically, the porosity is about 40% to about 95%.
%, Preferably from about 50% to about 95%, more preferably from about 70% to about 95%. Examples of the microporous membrane include a polysulfone membrane and a fluorine-containing polymer membrane.

Preferred microporous membranes are polysulfone membranes and cellulose acetate membranes, and particularly preferred are polysulfone membranes. In the blood filtration material of the present invention, the glass fiber filter is disposed on the lower side, and the microporous membrane is disposed on the upper side. The most preferable material is a laminate in which a glass fiber filter paper and a polysulfone membrane are laminated in this order from the bottom.

The filtration material used in the present invention is disclosed in
According to the methods disclosed in JP-A-138756-8, JP-A-2-105043, JP-A-3-16651, etc., each layer can be integrated by bonding with a partially arranged adhesive.

The thickness of the glass fiber filter layer is determined by the amount of plasma or serum to be collected and the density (porosity) and area of the glass fiber filter paper. When performing multiple analysis using a dry analytical element, the required amount of plasma or serum is 100 to 500 μm.
It is practical that the glass fiber filter paper has a density of about 0.02 to 0.2 and an area of about 1 to 5 cm ² . In this case, the thickness of the glass fiber filter layer is about 1 to 10 mm, preferably about 2 to 8 mm. This glass fiber filter paper can be laminated to a plurality of sheets, for example, about 2 to 10 sheets, preferably about 3 to 8 sheets, to have the above thickness.

The thickness of the microporous membrane is 0.05 to 0.5 mm
The thickness may be about 0.1 to 0.3 mm, and usually one microporous membrane may be used. However, a plurality of sheets can be used if necessary.

The hemofiltration material is placed in a holder. This holder is provided with a blood inlet and a filtrate outlet, and is generally manufactured in a mode in which a main body containing a blood filtering material and a lid are separated. Usually, each has at least one opening, one used as a blood inlet and the other used as a filtrate outlet.

The volume of the blood filtering material storage section must be larger than the dry state of the filtering material to be stored and the total volume when the sample (whole blood) is absorbed and swollen. If the volume of the storage part is small with respect to the total volume of the filtration material, filtration does not proceed efficiently or hemolysis occurs. Although the ratio of the volume of the storage portion to the total volume of the filter material when dried is dependent on the degree of swelling of the filter material, it is usually 101% to 400%, preferably 110% to 150%, and more preferably 120% to 1%.
40%. Specifically, it is determined depending on the required amount of plasma or serum, but is about 0.5 to 2.5 ml, usually 0.6 to 2.
It is about 2 ml.

It is preferable to provide a member for preventing the blood filtration material, usually a microporous membrane, from adhering between the inner surface of the holder on the filtrate outlet side and the surface of the blood filtration material opposed thereto. This member separates the blood filtration material from the opposing surface of the holder so that the filtration is performed over the entire surface of the blood filtration material.
^{About 2} to 20 projections, usually about 3 to 10 projections per ² are provided, or a plurality of projections converging toward the filtrate outlet are provided.

The shape of the projection can be any shape such as a column, a prism, a cone, a pyramid, a truncated cone, a truncated pyramid, a mushroom, and an irregular shape. The tip of the projection is preferably flat or circular. The number of ridges is about 2 to 20, preferably about 3 to 10. The ridge may be linear or curved. The tips of the protrusions and the ridges have a contact area of all protrusions with the blood filtration material at the time of suction of about 1 to 50% of the surface area of the blood filtration material, preferably 2 to
It is good to make it about 10%. Since the amount of blood filtered by the hemofilter of the present invention is small, the volume of the space between the blood filtration material and the opposite surface of the holder is 50 to 500.
It is good to make it about μl, preferably about 100-200 μl.

It is preferable to provide a space on the blood inlet side of the holder so that the filtration is performed over the entire surface of the blood filtration material. As a result, air is first sucked from the entire surface of the blood filtration material, and as a result, blood spreads over the entire surface and is filtered by suction. At the blood supply port side of the holder, when filtering, the blood filtering material acts in a direction away from the inner wall of the holder, so a spacer for holding the edge of the blood filtering material on the side wall of the holder and opening the gap with the holder, for example, a ring shape Protrusions or several protrusions may be formed. The peripheral portion of the lid may be protruded toward the blood filtration material, and may function as a spacer. The volume of the space between the blood filtration material and the opposing surface of the holder (at the time of blood filtration) is 100 to 500 μl.
The amount is preferably about 100 to 200 μl.

Further, a glass fiber filter paper storage chamber for storing glass fiber filter paper and a microporous membrane storage chamber for storing a microporous membrane are formed in the holder body, and the microporous membrane storage chamber is made of glass fiber. It is better to make it larger than the filter paper storage chamber. Thereby, even if there is whole blood flowing through the side wall surface of the storage chamber in the glass fiber filter paper storage chamber, it is possible to prevent the ball from leaking.

The size of the microporous membrane is preferably at least about 0.01 mm, more preferably at least about 0.2 mm, larger than the glass fiber filter paper storage chamber. Further, the microporous membrane has a peripheral portion mounted on the microporous membrane accommodating chamber, and the length (radial direction) of the peripheral portion in contact with the microporous membrane accommodating chamber. Is 0.05mm
And more preferably about 0.1 mm or more.

When the lid is attached to the main body, the entire filter unit has a sealed structure except for the blood inlet and the filtrate outlet which is also used as a suction port.

The material of the holder is preferably plastic. For example, a transparent or opaque resin such as polymethacrylate, polyethylene, polypropylene, polyester, nylon, and polycarbonate is used.

The main body and the lid may be attached by any means such as joining using an adhesive and fusion. In this case, the peripheral edge of either the main body or the lid may be located inside, or may be in an abutting state. Also,
The main body and the lid may be structured so that they can be assembled and disassembled by means such as screws.

Although there is no particular limitation on the shape of the blood filtration material,
A circular shape is desirable for ease of manufacture. At this time, the diameter of the circle is made slightly larger than the inner diameter of the holder main body, so that the plasma can be prevented from leaking from the side surface of the filtration material. On the other hand, it is preferable to use a square shape, since cutting loss of the produced blood filtration material is eliminated.

The blood collection needle is connected to the blood inlet via a tube. The blood collection needle can be used as it is or after processing the injection needle. The blood inlet may be connected in advance or may be connected at the time of use. The connection means may be any means such as adhesion, fusion, screwing, fitting and the like.

In the plasma collection device of the present invention, reduced pressure for blood filtration is performed by a vacuum blood collection tube or a syringe. A commercially available product can be used for the vacuum blood collection tube. The connection to the vacuum blood collection tube is preferably made by processing a syringe needle to make a connection device. The syringe may be connected to the filtrate outlet after removing the injection needle if necessary.

In the plasma collection device of the present invention, a blood collection needle connected to a blood filter is inserted into a blood vessel, and a vacuum blood collection tube or a syringe is connected to a filtrate outlet of the blood filter to collect a required amount of plasma. do it.

[0035]

FIG. 1 shows a plasma collection tool according to an embodiment of the present invention.

This blood plasma collection tool comprises a blood filter 1 and a blood collection needle 2
And a vacuum blood collection tube 3.

This blood filtration unit has a holder as shown in FIG.
0 and a lid 20 closely adhered and fixed to the upper portion.

The holder body 10 is made of a high-impact polystyrene resin. The holder body 10 has a glass fiber filter paper storage chamber 11 for storing a glass fiber filter paper 31 constituting a blood filtration material. Above the upper part 11, a microporous membrane storage chamber 12 for storing a polysulfone porous membrane 32 as a microporous membrane constituting a blood filtration material is formed. The microporous membrane storage chamber 12 has a glass fiber filter paper storage chamber 11 at the lower end.
A step 19 having a larger diameter is formed.
9, the polysulfone porous membrane 32 is accommodated in a mounted state. Further, an inclined portion 13 that rises obliquely upward from the outer peripheral edge of the step portion 19 is formed.
A flange 14 is formed outwardly from the upper edge of 3.

On the other hand, at the bottom of the holder body 10, a glass fiber filter paper mounting portion 15 is provided slightly inside from the peripheral edge, from which a shallow funnel-shaped disc portion 16 is connected. A nozzle-like blood inlet 17 extends downward from the nozzle. A vacuum blood collection tube 3 or a syringe is attached to the nozzle-shaped blood inlet 17 during blood filtration. The glass fiber filter paper mounting portion 15 also functions as a spacer that forms a space 18 by separating the lower surface of the glass fiber filter paper 31 from the funnel-shaped disk portion 16 of the holder body 10.

The lid 20 has a disk shape, and its peripheral edge rises upward in the drawing to form a wall 21, and its upper end is bent outward to form a flange 22.
The wall portion 21 is formed in a tapered shape that spreads outward as going upward. The inclination angle of the wall portion 21 is the same as the inclination angle of the inclined portion 13, and the outer diameter of the It is the same as the inside diameter. That is, the wall portion 21 is fitted to the inclined portion 13 in a close contact state. The flange 22 is ultrasonically bonded to the flange 14 of the holder body 10. Before bonding, the bottom surface of the flange 22 (the surface to be bonded to the flange 14)
The ribs are formed so that the ultrasonic energy is collected there during the bonding and the bonding can be performed in a state where the liquid tightness is sufficiently ensured (the bonding is melted and disappeared after the bonding).

The bottom surface of the lid 20 has twelve projections 2
The protrusions 26 prevent the polysulfone porous membrane 32 from sticking to each other.

The lid 20 has a wall 2 corresponding to its bottom shape.
It rises slightly from the center slightly from the base of 1,
A nozzle-shaped filtrate outlet 23 projects upward from the center.

In the above blood filter,
The diameter of the glass fiber filter paper storage chamber 11 is 20.1 mm, the depth is 5.9 mm, the diameter at the lower end of the microporous membrane storage chamber 12 is 23.0 mm, the diameter at the upper end is 22.5 mm, the depth is 2.10 mm, 20. diameter of the lower end of the outer peripheral surface of wall 21
98 mm, height 2 mm from the lower surface to the flange 24,
20.0 mm in diameter and 0.9 in thickness of glass fiber filter paper 31
Six 1 mm-thick porous polysulfone membranes 32 have a diameter of 20.9 mm and a thickness of 150 μm.

FIG. 3 shows a connecting jig 4 for connecting to the vacuum blood collection tube 3. The connection jig 4 is provided with a filtrate passage 42 projecting upward and downward from the center of a cap 41 fitted on the vacuum blood collection tube 3, and a tube 43 connected to the filtrate outlet 23 is fitted into the upper projecting portion. The insertion needle 44 is provided at the lower protruding portion.
Is inserted. At the time of use, if the connection jig 4 is fitted into the vacuum blood collection tube 3, the insertion needle 44 pierces the insertion portion of the vacuum blood collection tube 3 to perform connection.

It should be noted that even if a syringe without an injection needle is connected in place of the vacuum blood collection tube, blood filtration can be performed in the same manner to collect plasma.

According to the present invention, a required amount of plasma can be obtained by easily performing blood collection and blood filtration by using the plasma collection device of the present invention.

[Brief description of the drawings]

FIG. 1 is a perspective view showing a configuration of an example of a plasma collection tool of the present invention.

FIG. 2 is a longitudinal sectional view of the blood filter.

FIG. 3 is a longitudinal sectional view of a jig for connecting to a vacuum blood collection tube.

[Explanation of symbols]

 1. Blood filter 2. Blood collection needle 3. Vacuum blood collection tube

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61B 5/14 300B 300E 300F

Claims (1)

[Claims] 1. A blood filter material comprising a glass fiber filter paper and a microporous membrane, a blood filter comprising a holder containing the blood filter material and having a blood inlet and a filtrate outlet, and connected to the blood inlet via a tube. A blood collection needle comprising a blood collection needle and a vacuum blood collection tube or syringe connected to the filtrate outlet via a tube