JPH0323181B2 - - Google Patents

Description

[Detailed description of the invention]

I. BACKGROUND TECHNICAL FIELD OF THE INVENTION The present invention relates to a plasma separation device that separates plasma by passing blood through a membrane. Prior Art Conventionally, there are two types of hyperformed plasma separation apparatuses for continuous hyperseparation of blood using microporous membranes having pore diameters of about 0.1 to 1.0 microns: hollow fiber type and flat membrane type. The hollow fiber type is widely used because it can provide a large area, requires fewer members, and is easy to operate. However, in the hollow fiber type, the pore shape becomes slightly oval due to the fact that tension is applied in the longitudinal direction of the tube compared to a flat membrane during membrane formation, and because there is no support during membrane formation. Furthermore, it is difficult to maintain uniform tension during film formation, making it difficult to make the pore diameters uniform. For this reason, the pore distribution of the obtained hollow fiber membrane not only becomes wide-ranging, but also varies considerably depending on the membrane manufacturing lot compared to a flat membrane. Due to this fact, the maximum pore diameter must be selected to be small in order to prevent blood cells from leaking into the plasma during filtration, resulting in a low permeability of high-molecular plasma components. Furthermore, if the length of the upstream path of the structure is shortened, both ends of the hollow fiber membrane are covered with a potting agent, which increases the loss of effective membrane area and reduces the possibility of leakage and productivity. For this reason, the length of the pipe (flow path length) must be increased, resulting in a large pressure loss, and because the diameter of the pipe cannot be reduced due to membrane manufacturing technology, the excess efficiency per unit area of the membrane is reduced. For this reason, one good method is to reduce the film thickness and aim to increase the amount of excess per unit area of the film and the permeability of polymeric substances, but this reduces the strength and increases the risk of leakage. The variation in the pore size of the membrane becomes larger. On the other hand, the flat membrane laminated type has a wider selection of membranes and is stable in performance, so it is expected to be compact and high-performance, but the overengineering mechanism has not been sufficiently analyzed. and hematological problems that cannot be solved by calculation alone.
Unable to solve the problem of membrane shape and modular structure to uniformly form extremely fine thin layers,
It was considered difficult to make it concrete. As a flat membrane laminated type plasma separator, there is, for example, one shown in FIG. 1 in the past. This device has a side plate 3 having a blood inlet 1 and a blood outlet 2, and a side plate 5 having a plasma outlet 4, and a side plate 5 having a plasma outlet 4. The channel-forming plate 6, the membrane 7, and the plasma channel-forming plate 8 provided with a packing section 8b around the network-like plasma channel section 8a are superposed and fixed by pressure in a fluid-tight manner. . In this device, blood flowing in from the blood inlet 1 passes through the gap 6a and passes through the membrane 7, and blood cell components flow from the blood outlet 2 and from the plasma outlet 4 through the plasma flow part 8a. Each is discharged. However, this device had the following problems in terms of excessive characteristics. In other words, in this type of plasma separation device, it is known that the thinner the blood flow path is, the greater the membrane wall shear rate becomes, resulting in superior characteristics. In this case, by reducing the film thickness of the flow path forming plate 6, it is possible to reduce the thickness of the flow path of the gap 6a through which blood flows. however,
Since the membrane 7 is easily deformed, the blood flow path formed by the gap 6a cannot maintain a uniform flow path thickness set by the film thickness of the flow path forming plate 6, resulting in large variations. For example, even if the channel thickness is set to 300 microns, an error of about ±100 microns will occur. Therefore,
Even if the flow path forming plate 6 is formed extremely thin with this device, it is difficult to secure a desired excess amount, and the variation is significant. In order to overcome the drawbacks of such separation devices,
The membranes were abutted through rubber gaskets each having three parallel channels on both sides of an elongated manifold plate having a blood inlet at one end and a blood outlet at the other end, and these membranes were fitted with a plasma liquid inlet. A device made by pressing a gathering plate has been proposed [Trans.Am.Soc.Aritif.Intern.Organs,
, 21-26 (1978)]. However, in such a device, since the flow path is long compared to the flow path width, pressure loss is large and there is a problem in practical use. Further, at least one void-like filter is arranged, at least on one side bordering the filter material and below which a liquid discharge member is arranged, and having an inlet for the medium to be filtered and an outlet for the medium concentrated by the filter. An ultraviolet filtration device, particularly suitable for blood filtration, consisting of a chamber with an internal diameter of 2.5 mm or less and an opening of 0.1 to 0.5 mm.
An ultrafiltration device is known (UK Patent No. 1,555,389) in which a base layer of fabric of fiber mesh having a thickness of . However, since such devices are used for ultrafiltration, they are subject to large negative pressures, and there is a structural limit to reducing the channel thickness, so the wall shear rate of the membrane is low, and proteins and blood cells There was a drawback that clogging was likely to occur due to the adhesion of such substances to the membrane surface. This clogging caused blood to stagnate, causing problems such as hemolysis, coagulation, and other blood damage. ．． OBJECTS OF THE INVENTION It is therefore an object of the present invention to provide a novel plasma separation device. Another object of the invention is to
It is an object of the present invention to provide a plasma separation device which reduces damage to blood and decrease in separation ability over time, ensures a sufficient excess amount, and has a satisfactory and economical membrane shape and number of laminated layers. These objectives are therefore: (a) having a circular opening in the center with a diameter of 2 to 8 cm and a concentric outer diameter of 10 to 20 cm, the ratio of the opening diameter to the outer diameter being 1:2
A circular membrane having micropores with a ratio of ~1:5 and a pore size of 0.1 to 0.8 microns, and (b) a blood flow path formed on one side of the membrane with a gap of 50 to 150 microns. (c) a circular plasma flow path forming member provided on the other surface of the membrane to form a plasma flow path and having a central opening; and (d) a seal for avoiding mixing of blood and plasma. (e) The laminate thus formed is placed between the blood inlet and the ^excess membrane. (f) blood injected from the blood inlet passes through the blood flow path and plasma is separated by the membrane, and then flows into the excess residual liquid outlet; and a liquid path through which the plasma excessively separated by the membrane passes through the plasma flow path formed by the plasma flow path forming member and reaches the plasma outlet. This is accomplished by a separation device. ．． DETAILED DESCRIPTION OF THE INVENTION The present invention will be described below with reference to the drawings.
That is, as shown in FIGS. 2 and 3, there is a blood inlet 11 in the center of the bottom and an excess liquid outlet 1 in the side wall.
2, a cylindrical case 13 with a plasma outlet 1
4, 14 and the O-ring 1 as a liquid-tight means on the periphery.
The main body 17 consists of a lid 16 to which a membrane 5 is attached, and a membrane, a blood flow path regulating plate, and a plasma flow path forming member are housed within the main body 17. That is,
Opening 18 in the center and plasma passage hole 1 near the periphery
A circular plasma flow path forming member 20 made of a screen mesh with
a, 21b are narrowed together, and the periphery thereof and the periphery of the central opening are sealed by heat fusion, adhesion, etc., and a sealing material 26 is attached to the outer periphery of the plasma passage hole 19 to complete the membrane unit 22. Let it form. Here, the circular plasma flow path forming member 20 is not limited to the above-mentioned mesh as long as it can secure a flow path for plasma. A central opening 18 and a plasma passage hole 19 corresponding to the membrane units 22 are provided between the plurality of membrane units 22, and a large number of convex portions are provided on both sides (however, the outer periphery of the passage hole 19 is is flat.) A circular plasma flow path forming member 23 is provided. Moreover, above the top and below the bottom of the membrane unit 22, there are provided a central opening 18 and plasma passage holes 19 corresponding to the circular plasma flow path regulating plate 23 or the unit 22, and a large number of plasma passage holes 19 are provided on one side. A circular plasma flow path regulating plate 24 having a convex portion (however, the outer periphery of the passage hole 19 is flat) is brought into contact with the convex portion side. These membrane units 22 and blood flow path regulating plates 23, 24 are stacked in 1 to 30 sheets (2 to 60 membranes) and inserted into the case 13, covered with the lid 16 and pressed. The third
A blood filtration device as shown in the figure is obtained. Also,
Due to such pressure, the membrane unit 22 and the blood flow path regulating plates 23 and 24 are separated by the sealing material 26.
They are integrally connected at the outer periphery of the plasma passage hole 19, and the passage holes 19 are formed in communication with each other. In addition, although the example in which the plasma outflow hole 14 is provided in the lid body 16 has been described above, the plasma outflow hole 14 does not necessarily need to be provided in the lid body 16, and the lid body 16 may not be provided with any outflow hole. Of course, the plasma outflow holes 14, 14 may be provided at the bottom of the case 13. Therefore, the membranes 21a and 21b phase-separate cellulose esters such as organic acid esters such as cellulose nitrate and cellulose acetate, and synthetic resin thin films (film thickness 50 to 200 microns, preferably 130 to 170 microns) such as polycarbonate. The membrane is formed by a method such as a method, an extraction method, a stretching method, a charged particle irradiation method, etc., and its pore size is 0.1 to 0.8 microns, preferably 0.2 to 0.6
Porosity in micron is 40-90%, preferably 60-90
%, and has a circular shape with a circular opening 18 in the center. Its central opening diameter ID is 2~8
cm, the outer diameter OD is 10-20cm, and its ratio ID:
OD=1:2 to 1:5, and the total number of layers is 2 to 60 (the membrane unit 22 is 1).
~30 pieces) are used. The pore size of the membranes 21a and 21b can be determined by (a) mercury intrusion method, (b) electron microscopy method, (c) permeation method using fine particles of known particle size (standard particles, microorganisms, etc.), (d) bubble point method ( ASTM-F316-70), etc., but the apparent pore size and effective pore size may differ depending on the surface condition, and in membrane forming methods based on phase separation, if the maximum pore size is indicated, the minimum pore diameter and the pore diameter are measured. The pore diameter is indicated by the maximum pore diameter using bubble points because the distribution etc. can be almost estimated and measurement is easy. Usually, in the case of a hydrophilic membrane, a hydrophilic agent is coated on the surface of the membrane or added to the resin that makes up the membrane, so the liquid used to measure the bubble point is extracted from these agents or added to the membrane. The measurement is carried out using a mineral oil (light oil, white kerosene, etc.) whose surface tension is known and does not dissolve the material, or the hydrophilizing agent is thoroughly washed and extracted with distilled water and then the measurement is carried out using water. Maximum pore size is 0.005~1.2
Plasma separation can be performed down to the micron size, but
Near the lower limit, the permeation of polymer substances becomes insufficient,
On the other hand, near the upper limit, blood cell components leak, so the above range is practically preferable. The porosity is calculated as follows: If the weight of the membrane unit area is W (g), the membrane thickness is t (cm), and the specific gravity of the membrane is S (g/cm ³ ), then the apparent specific gravity is W/t (g/cm ³ ). Therefore, it becomes as follows. Porosity = SW/t/S x 100 (%) However, in membrane formation by phase separation, the porosity is 40 to 90%.
is technically possible, but if it exceeds 90%, the mechanical strength of the membrane will be insufficient, while if it is less than 40%,
Too much is usually unsuitable in terms of membrane resistance, clogging, etc. A higher rate is advantageous in terms of practical plasma separation, but from a cost perspective 60-90% is preferable (
Overdose variation ±12.5%). Technically, it is possible to form a film with a thickness of 50 to 200 microns; if it is less than 50 microns, the mechanical strength is insufficient, and if it exceeds 200 microns, the pore distribution will become wider, so the maximum pore size should be selected smaller. As a result, material permeation efficiency decreases and product performance variations also increase. Also, ID of hypermembrane:
The OD ratio is 1:2 to 1:5, and the total membrane area is
The reason for setting the ratio to be 100 to 8000 cm ² is that if the ratio exceeds this value or the membrane area is less than this value, blood damage will be large and blood coagulation will occur more easily. On the other hand, if the ID:OD ratio is less than the above value, the economic loss caused by providing an opening in the center of the membrane becomes large.
Furthermore, if the membrane area exceeds the above value, the shear rate will decrease, resulting in a decrease in separation ability and the need to use a large amount of membrane, which is not economically preferable. The plasma flow path forming member 20 is formed of a circular open screen mesh made of synthetic resin such as polyester, polypropylene, polyamide, etc. and having a central opening. The blood flow path regulating plates 23 and 24 include the membrane 21
a, 21b, and has a circular shape with a central opening and a large number of protrusions 25, as shown in FIGS. 4 and 5. This blood flow path regulating plate 23 may be hard or flexible and elastic. A material that is flexible and elastic has a Young's modulus of 1.0.
~ ¹⁰⁶ ~2.0× ¹⁰¹⁰ dyne/ ^cm2 , preferably 1.0× ¹⁰⁶
The material is ~1.0× ¹⁰⁹ dyne/ ^cm2 . The reason is that when the blood flow path is easily narrowed and relaxed by pressing the separation device, the flow path reversibly restores itself.
This is to make it easier to obtain a desired excess amount. Examples of materials having a Young's modulus within this range include low density polyethylene, silicone rubber, isoprene rubber, butyl rubber, styrene-butadiene rubber (SBR), and ethylene-vinyl acetate copolymer resin (EVA). Further, the surface hardness of the body fluid flow path regulating plate provided with the convex portions 25 is preferably a Shore A hardness of 10 to 100. The convex portions 25 of the blood flow path regulating plates 23 and 24 are connected to the membrane 21 here.
a, 21b to prevent deformation and ensure a blood flow path in the gap between the protrusions 25. The thickness of the channel formed between the convex portion 25 and the membrane surface is 50~
150 micron is preferred. The reason for this is that 50
It is difficult to adjust the channel thickness below microns, and
This is because if the thickness exceeds 150 microns, the deformation is large and errors are likely to occur, and the wall shear rate cannot be increased. Further, the interval between these convex portions 25 is preferably 100 to 2000 microns, particularly 400 to 2000 microns.
800 microns is preferred. Further, the ratio of the radius of the bottom of the convex portions, the length of a diagonal line or one side, and the distance between the convex portions is preferably 1:1 to 1:3. As mentioned above, the main body consists of the cylindrical case 13 and the lid 16, and is made of a hard plastic material such as polycarbonate, polyamide, polyacetal, ABS resin, or hard polyvinyl chloride. It is inserted into the case 13 in a liquid-tight manner. As the liquid-tight means, other than a method of fitting an O-ring around the peripheral edge of the lid 16, other known sealing means can also be used. FIG. 6 shows another embodiment of the present invention,
In a plasma separation device similar to the embodiment shown in FIGS. 2 and 3, the same cylindrical case 113 is equipped with an excess residual liquid outlet 112, and a lid body 116 is equipped with a blood inlet 111 and a plasma outlet 114. Both sides of a circular plasma flow path forming member 120 having an opening 118 in the center and a plasma passage hole 119 near the periphery are fitted into a main body 117 which is fitted through an O-ring 115 externally fitted to the peripheral edge as a liquid-tight means. A plurality of units (2 to 60 membranes) are stacked and housed around the opening 119 with a sealing material 126 interposed therebetween. In this case, the plasma flow path forming member 120
is similar to the blood flow path regulating plate in the apparatus shown in FIGS. 2 and 3, and although the blood flow path regulating plate is not used, the unevenness formed by the plasma flow path forming member 120 causes unevenness on the membrane surface. Therefore, a blood flow path is formed between the membrane surfaces, and the gap is 50 to 150 microns.
Preferably it is 70-100 microns. In this case, a flat plate with a smooth surface may be provided between each membrane unit as a plasma flow path forming member. FIG. 7 shows still another embodiment of the present invention, in which an excess residual liquid outlet 212, a blood inlet 211, and a plasma outlet A main body 21 is formed by fitting a cylindrical case 213 with a cylindrical case 214 and an O-ring 215 fitted to the peripheral edge as a liquid-tight means.
7, a circular plasma flow path forming member 220 made of a relatively coarse open screen mesh with an opening 218 in the center and plasma passage holes 219 near the periphery is attached to two upper and lower circular membranes 221a, 221.
b are sandwiched, and the periphery thereof and the periphery of the central opening are sealed by heat fusion, adhesion, etc., and a sealing material 226 is attached to the outer periphery of the plasma passage hole 219 to form a membrane unit 222. 1 to 30 pieces of this membrane unit 222 (2 to 30 pieces as a membrane)
(60 sheets) A plasma separator can be obtained by storing the plasma separator in the main body 217. In this case, a blood flow path regulating plate is not used, but by using a coarse open screen mesh as a plasma flow path forming plate, unevenness corresponding to the unevenness of the mesh is created on the membrane surface, and the opposing membrane surface A blood flow path with a gap of 50 to 150 microns is formed between them. Next, the operation of the plasma separator according to the present invention will be described. That is, as shown in FIG. 8, blood removed from a human body or a blood container (not shown) is introduced from a circuit inlet 31 by a blood pump 32, passes through a chamber 33, and enters the plasma separation device 1.
7 into the blood inlet 11. The device 17
As shown in FIG.
While flowing through the blood flow path formed between a and 21b, the plasma passes through the membrane, flows between the plasma flow path forming members 20, passes through the plasma passage hole 19, flows out from the plasma outlet 14, and becomes plasma. It is collected in a collection container 34. On the other hand, the blood cells are discharged from the excess residual liquid outlet 12 together with the excess residual liquid, and are returned to the human body or the blood container through the circuit outlet 36 through the chamber 35. In addition, in the figure, 37 and 38 are pressure gauges. Examples 1 to 12 and Comparative Examples 1 to 17 Using the apparatus shown in FIGS. 2 and 3, blood was passed under the experimental conditions shown in Table 1, and the excess amount was measured. The results are shown in Table 1. Note that cellulose acetate with an average pore diameter of 0.3 to 0.5 microns was used as the membrane material.

【table】

[Table] Judge.
In Table 1, the width of the blood flow path in the overflow device is a, the thickness of the blood flow path is b, the length of the blood flow path is the overflow condition, the blood flow rate is Q, the blood viscosity is _μ , the gravity unit conversion coefficient is _g , and the overflow condition is as follows. If the pressure drop is PD, then PD=12Q _B μ/ab ³ g _c () If the shear rate is j, then j=6Q _B /ab ² () If the overflow rate is Q _F , then Q _F = α. j)〓・S () (where α and β are membrane coefficients,
Further, S is the membrane area a. Note that the channel width a indicates the average channel width, and in the case of a circular membrane, it is determined by the following equation. a=a ₂ −a ₁ / _o (a ₂ /a ₁ )×N a ₁ : Length of the circumference of the circular opening of the membrane a ₂ : Length of the outer circumference of the membrane N: Number of laminated layers of the membrane In addition, the present invention The channel thickness b in is a calculated value obtained from measured values of pressure loss, etc., and is obtained by transforming equation (). The blood flow path length is the length along the blood flow direction, and in this case, it is the outer diameter of the membrane minus the diameter of the circular opening divided by 2, and is the length measured along the radial direction of the membrane. Refers to the length from the inner circumference to the outer circumference. The blood flow rate Q _B represents the amount of blood flowing through the blood flow path per unit time. In the case of the same membrane area and the same blood flow rate, it is theoretically better to make the blood flow channel shape as large as possible, with the channel width a as large as possible, and the channel length and channel thickness b as small as possible in balance with the channel width a. . In other words, it is desirable to increase the shear rate j in order to further reduce the pressure loss that causes hemolysis and to increase the excess amount Q _F. Therefore, it is ideal to make the channel thickness b as small as possible, and in theory, 0<b≦150 microns.
In practice, dimensional errors, deformation, and distortion of the membrane and support should be taken into account, and on the other hand, the wider the channel thickness b, the more uneven blood flow (channelling) will occur.
The practical limit is preferably 50 microns or more. The overefficiency E (%) indicates how much the amount of plasma contained in the supplied blood has been overseparated, and is expressed by the following formula. In addition, in the formula, P
is the amount of plasma contained in a unit blood volume. E=Q _F /P×100 The pressure drop that causes hemolysis is as shown in the critical pressure drop curve at a hemoglobin concentration of 50 mg/d shown by curve A in Table 1 and FIG. 9 based on the relationship with the shear rate. The permissible limit for free hemoglobin concentration in the blood due to hemolysis is 100 mg/d or less from a medical perspective, but it is desirable to keep it 50 mg/d or less as a practical safe range, and 0≦PD≦0.2Kg/cm ² TMP≦ By setting 0.1Kg/cm ² (TMP: diaphragm pressure), the blood free hemoglobin concentration will not exceed the critical TMP value that causes hemolysis.
It is possible to keep it to almost mg/d. Further, below the curve A in FIG. 9, the blood free hemoglobin concentration can be suppressed to 50 mg/d, and it is preferable to keep the pressure loss within this range. In addition, the pressure loss was measured with a pressure gauge, the excess was measured with a graduated cylinder and a stopwatch, the shear rate was calculated as j = 6Q _B /ab ² , and the hemoglobin concentration was calculated as 2,2',4,4'-tetra It was measured by a conventional method using methylbenzidine. Also,
Pressure drop change △PD was measured with a mercury manometer.
Plasma separation efficiency E and membrane efficiency Q _S are calculated according to the following formulas. E=Q _F /Q _B (1-Hct/100) x 100% (Hct: hematocrit value) Q _S = Q _F / (OD/2) ² x π x N x 1000 (ml/ ^m2 ) Hemoglobin concentration Changes of 50.0 mg/d or more, plasma separation efficiency of 50% or less, membrane efficiency of 10.0 ml/m ² or less, and pressure drop changes of 100 mmHg or less were considered unfavorable changes for practical use. As is clear from the data in the comparative examples, blood damage such as hemolysis and blood coagulation is particularly noticeable in products that deviate from the structure of the present invention, and even in products with little blood damage, sufficient overdose may not be obtained. It is unfavorable in clinical practice, as it is inferior in terms of plasma separation efficiency. ．． Specific Effects of the Invention Since the plasma separator according to the present invention has the above configuration, (a) drifting is less likely to occur than when the membrane is rectangular, (b) blood damage and accompanying (c) Plasma separation can be performed using an economical membrane area within a range where hemolysis and blood coagulation do not occur; (c) Economical performance changes are small and a sufficient excess amount can be obtained. (d) It has advantages such as good separation ability. Furthermore, by forming the main body of the device into a cylindrical case and a lid that is fitted into the case in a liquid-tight manner, and by using an O-ring as the liquid-tight means, it becomes easy to maintain the cylindrical case and the lid in a liquid-tight manner. By pressing the cylindrical case and the lid, they can be slid against each other, and the thickness of the blood flow path can be adjusted to a predetermined value.

[Brief explanation of the drawing]

FIG. 1 is an exploded perspective view of a conventional plasma separation device, FIG. 2 is an exploded perspective view of an embodiment of the plasma separation device according to the present invention, and FIG. 3 is a sectional view of the device shown in FIG. 2 in an assembled state. , FIG. 4 and FIG. 5 are cross-sectional views of the flow path regulating plate, FIG. 6 is a cross-sectional view showing another embodiment of the device of the present invention, and FIG. 7 is a cross-sectional view showing still another embodiment of the device of the present invention. 8 are system circuit diagrams showing an example of how the device is used, and FIG. 9 is a graph showing the relationship between shear rate and critical pressure loss for hemolysis. 11,111,211...Blood inlet, 12,
112, 212... Excess residual liquid outlet, 13, 11
3,213...Cylindrical case, 14,114,2
14...Plasma outflow port, 15,115,215...
O-ring, 16, 116, 216...Lid, 1
7,117,217...Main body, 18,118,2
18... Central opening, 19, 119, 219...
Plasma passage hole, 20, 120, 220...Plasma flow path forming member, 21a, 21b, 121, 221a,
221b...Circular membrane, 22, 222...Membrane unit, 23, 24...Blood flow path regulating plate, 2
5...Convex portion, 26, 126, 226...Sealing material.

Claims (1)

[Claims] 1 (a) A circular opening with a diameter of 2 to 8 cm at the center, concentric circles with an outer diameter of 10 to 20 cm, and the ratio of the opening diameter to the outer diameter is 1:2. A circular membrane having micropores with a ratio of ~1:5 and a pore size of 0.1 to 0.8 microns, and (b) a blood flow path formed on one side of the membrane with a gap of 50 to 150 microns. , (c) a circular plasma flow path forming member provided on the other surface of the membrane to form a plasma flow path and having a central opening; and (d) a seal for avoiding mixing of blood and plasma. (e) The laminate thus formed is placed between the blood inlet and the ^excess membrane. (f) blood injected from the blood inlet passes through the blood flow path and plasma is separated by the membrane, and then flows into the excess residual liquid outlet; and a liquid path through which the plasma excessively separated by the membrane passes through the plasma flow path formed by the plasma flow path forming member and reaches the plasma outlet. Separation device. 2. The device according to claim 1, wherein the main body includes a cylindrical case and a lid attached to the case in a liquid-tight manner. 3. The device according to claim 2, wherein the lid has liquid-tight means. 4. The device according to claim 3, wherein the liquid-tight means is an O-ring fitted around the peripheral edge of the lid. 5. The device according to any one of claims 1 to 4, wherein the plasma flow path forming member is enclosed within a membrane whose inner and outer edges are sealed. 6 (a) It has a circular opening with a diameter of 2 to 8 cm in the center, concentric circles with an outer diameter of 10 to 20 cm, and the ratio of the opening diameter to the outer diameter is 1:2 to 1:5. , and (b) a circular membrane having fine pores with a pore size of 0.1 to 0.8 microns, and (b) a circular membrane with a gap of 50 to 150 microns between the membrane and the membrane. (c) a circular blood flow path regulating plate that forms a blood flow path, has a large number of protrusions at regular intervals on its surface, and has a central opening; A circular plasma flow path forming member that forms a flow path and has a central opening, and (d) 2 to 60 membranes are integrated via a sealing material to avoid mixing of blood and plasma. (e) The laminate thus formed is housed in a main body having a blood inlet, an ^excess residual liquid outlet, and a plasma outlet. and (f) a liquid path in which blood injected from the blood inlet passes through the blood flow path, plasma is separated by the membrane, and then reaches the excess residual liquid outlet, and the plasma excessively separated by the membrane is separated. A plasma separation device characterized in that a liquid path is formed through a plasma flow path formed by a plasma flow path forming member to a plasma outflow port. 7. The device according to claim 6, wherein the blood flow path regulating plate is hard. 8. The device according to claim 6, wherein the blood flow path regulating plate is flexible and elastic. 9 Blood flow path regulation plate is 1.0×10 ⁶ to 2.0×10 ¹⁰ dyne/
9. A device according to claim 8, having a Young's modulus of cm ² . 10. The device according to any one of claims 6 to 9, wherein the convex portion is provided on one side of the blood flow path regulating plate. 11. The device according to any one of claims 6 to 9, wherein the convex portions are provided on both sides of the blood flow path regulating plate. 12 The distance between the convex parts of the blood flow path regulating plate is 100~
12. A device according to any one of claims 6 to 11, which is 2000 microns. 13. The device according to any one of claims 6 to 12, wherein the main body includes a cylindrical case and a lid attached to the case in a liquid-tight manner. 14. The device according to claim 13, wherein the lid has liquid-tight means. 15. The device according to claim 14, wherein the liquid-tight means is an O-ring fitted around the peripheral edge of the lid. 16. The device according to any one of claims 6 to 15, wherein the plasma flow path forming member is enclosed within a membrane whose inner and outer edges are sealed.