JP2010071857A - Plasma separation device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a plasma separation device capable of rapidly separating plasma from blood without causing hemolysis. <P>SOLUTION: In the plasma separation device 1, a first channel 11 is connected to a blood supply port 2; and a first end of a plurality of branch channels 13 is connected to the first channel 11; a second end of the plurality of branch channels 13 is connected to a second channel 12; and an aperture to which the first end of each branch channel 13 of the first channel 11 is connected, is configured to have an aperture area larger than the outer shape of blood cells, wherein the pressure loss ratio of the channel structure, consisting of the first channel 11 the plurality of branch channels 13 and the second channel 12, is set out such that the flow rate in the vicinity of the aperture along a direction of the first channel 11 is three or more times the flow rate in the direction of the branch channels. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a plasma separator used to extract plasma components from blood, for example, in blood tests and blood product pretreatment, and more specifically, it is possible to quickly and easily separate plasma from a small amount of blood. The present invention relates to a plasma separation apparatus.

  In recent years, microfluidic analysis chips that handle microfluids have attracted attention. In the microfluidic analysis chip, a sample made of a microfluid is transported and diluted, or a substance to be detected in the microfluidic sample is quantified.

  By the way, when the specimen is blood, depending on the analysis item, it is necessary to separate serum and plasma from the blood.

  The following Patent Document 1 discloses a method of rotating a blood analyzer chip including a U-shaped capillary at a rotation speed of 3000 to 5000 rpm for 30 minutes, thereby separating blood into blood cell components and plasma by centrifugation. ing.

On the other hand, Patent Document 2 below discloses an analysis chip on which a blood separation element having a diameter of 5 μm or less and having a length equal to or longer than the diameter is mounted. Here, it is described that the blood cell separation element is preferably glass fiber or filter paper made of glass fiber.
JP 2001-258868 A JP 2006-58280 A

  In the method described in Patent Document 1, the blood analyzer chip had to be rotated at a high speed such as 3000 to 5000 rpm for 30 minutes. For this reason, since the rotary drive device is bulky, it is difficult to reduce the size of the entire material necessary for analysis. Moreover, the centrifugation process occupied most of the total analysis time, and plasma separation took too much time. For this reason, all analyzes could not be performed quickly on site.

  In the method described in Patent Document 2, blood is physically filtered by a blood cell separation element, that is, blood is filtered using a filter material having a through hole or an opening smaller than the blood cell component. The blood cell component tended to be clogged. When the blood cell component was clogged, the pressure increased and there was a risk of hemolysis. In order to prevent hemolysis, the pressure difference before and after the filter may be reduced. However, in that case, the flow rate becomes very low and plasma separation takes a long time.

  An object of the present invention is to provide a plasma separation apparatus that can rapidly separate plasma from blood without causing hemolysis, and can further reduce the size of the entire analyzer, in view of the current state of the prior art described above. Is to provide.

  According to the present invention, there is provided a blood supply port through which blood is supplied, a first flow path connected to the blood supply port, through which blood flows, and first and second ends, A plurality of branch channels connected to the first channel at one end, and a second channel connected to a second end of the plurality of branch channels, In the first channel, the inner diameter of the opening to which the first end of each branch channel is connected is larger than the outer diameter of the blood cell, and the flow velocity in the direction along the first channel in the vicinity of the opening However, the pressure loss ratio in the flow path structure including the first flow path, the plurality of branch flow paths, and the second flow path is determined so that the flow velocity in the branch flow path direction is three times or more. A plasma separation device is provided.

  In a specific aspect of the plasma separation device according to the present invention, the direction in which the branch flow path branches from the first flow path is a direction inclined to the upstream side of the first flow path. . In this case, the blood cell component becomes more difficult to flow into the branch channel.

  In still another specific aspect of the plasma separator according to the present invention, a plurality of the branch flow channels are connected to the first flow channel on one side of the first flow channel. Thereby, many branch flow paths can be connected to the first flow path. Further, since the branch channel is connected only to one side of the first channel, the size can be reduced.

  In still another specific aspect of the plasma separation device according to the present invention, the branch passage has a cross-sectional shape having a longitudinal direction and a transverse direction, and the longitudinal direction of the cross-section of the branch passage is It is substantially orthogonal to the direction in which the first flow path extends. In this case, the branch channel can be easily formed. For example, when connecting a branch channel to the first channel by providing a through-hole in the plate-shaped member, the branch channel is formed by forming a through-hole in the plate-shaped member stacked on the first channel. Can be connected easily.

  According to still another specific aspect of the plasma separator according to the present invention, the branch channel has a shape in which a transverse section has a longitudinal direction and a transverse direction, and the longitudinal dimension of the transverse section is It is made smaller than one third of the width of the first flow path. In this case, the plurality of openings in which the plurality of branch channels are connected to the first channel can be arranged in various forms, for example, can be arranged in a staggered pattern. Therefore, the number of branch channels per unit area can be increased, and thereby the plasma separation efficiency can be further increased.

  In another specific aspect of the plasma separator according to the present invention, the flow path forming member includes a stacked plate in which a plurality of plates are stacked, and the first and second flow paths and the plurality of the plurality of plates are stacked in the stacked plate. A branch channel is formed, and the blood supply part opens on the outer surface of the laminated plate. In this case, the plasma separator according to the present invention can be easily manufactured by laminating a plurality of plates made of synthetic resin or the like.

  In still another specific aspect of the plasma separator according to the present invention, in the laminated plate, a height position where the branch flow path is provided and a height where the first and second flow paths are provided. The position is different. As described above, in the laminated plate, the branch flow path may be provided at a height different from that of the first and second flow paths, and the branch flow may be caused by the interface between the plates or the through portion provided in the plate. The path and the first and second flow paths can be formed as appropriate.

  According to still another specific aspect of the plasma separator according to the present invention, the plasma separator further includes a plurality of second branch channels having first and second ends, and a third channel, A first end of a plurality of second branch channels is connected to the second channel, and a second end of the second branch channel is connected to the third channel. ing. In this case, the multistage configuration can more reliably prevent blood cell components from being mixed into the plasma.

  According to still another specific aspect of the plasma separator according to the present invention, the downstream end of the first flow path and the upstream end of the second flow path are connected, and the first , One flow path is formed by the second flow path, and the downstream end of the second flow path is branched into at least two flow paths. The blood cell component is drawn in the direction opposite to the side where the branch flow paths merge, and the flow of plasma alone and the flow enriched with the blood cell component flow as if in a two-layer flow. By branching into at least two flow paths, these two laminar flows can actually be branched into two flows. Thereby, plasma can be more reliably separated from blood cell components.

  The single flow channel can have various forms, but it is desirable to have a spiral shape. As a result, the same effect can be obtained as when the number of stages in the multi-stage configuration is increased by the spiral flow path arranged in a small area.

  According to the plasma separator according to the present invention, since the flow velocity in the direction along the first and second flow paths in the vicinity of the opening is set to be three times or more than the flow speed in the branch flow path direction, Instead of flowing into the branch channel having the same size, the first channel goes straight, and only the plasma component flows into the branch channel. Therefore, plasma can be collected from the second flow path, and plasma can be reliably separated from blood. Moreover, since the inner diameter of the branch channel is larger than the outer diameter of the blood cell, even if the blood cell should flow into the branch channel, the branch channel is not clogged. Therefore, no hemolysis occurs. In addition, since a centrifuge device is not required for plasma separation, the entire analyzer can be miniaturized. In addition, plasma separation does not require a long operation.

  Therefore, according to the present invention, plasma can be separated from blood in a short time without causing hemolysis.

  Hereinafter, the present invention will be clarified by describing specific embodiments of the present invention with reference to the drawings.

  1 (a) and 1 (b) are a schematic plan view showing the upper part of the plasma separator of the present invention and a schematic partially cut-away enlarged plan sectional view for explaining the principle of plasma separation. ) Is a schematic perspective view showing the appearance of the plasma separation device of the present embodiment, and (b) and (c) are an enlarged cross-sectional view and a branch of a portion along line AA in FIG. 1 (a), respectively. It is sectional drawing which shows the cross section of a flow path.

  As shown in FIG. 2 (a), the plasma separator 1 is configured using a rectangular laminated plate. The rectangular laminated plate is sized so that it can be easily handled at a clinical site or the like. Although the size is not particularly limited, for example, the length is about 20 to 100 mm, the width is about 20 to 100 mm, and the thickness is about 1 to 10 mm. In that case, the laminated plate can be easily carried.

  In this laminated plate, the flow channel structure shown in FIG. 1A is formed. This flow channel structure has a first flow channel 11 connected to the blood supply port 2. A discharge port 3 is connected to the downstream side of the first flow path 11.

  The blood supply port 2 and the discharge port 3 are opened on the upper surface of the laminated plate as shown in FIG.

  The first flow path 11 is formed in the laminated plate. The first flow path 11 has a cross-sectional shape shown in FIG. That is, the cross-sectional shape of the first flow path 11 has a substantially rectangular shape having a longitudinal direction and a short direction. Although the depth of the 1st flow path 11 is not specifically limited, It is about 10-100 micrometers, More preferably, it is about 10-30 micrometers. If the depth is too shallow, blood cell components may be clogged and the first flow path 11 may be blocked. If the depth is too large, the flow rate may not be controlled with high accuracy. A deeper channel may be formed on the upstream side and / or downstream side of the first channel 11.

  A plurality of branch channels 13 are connected to one side in the extending direction of the first channel 11. The branch flow path 13 has a first end and a second end, and the first end is connected to the first flow path 11. A second end of the branch channel 13 is connected to the second channel 12.

  The inner diameter of the opening, which is the portion where the first end of the branch channel 13 is connected to the first channel 11, is larger than the outer diameter of the blood cell. In the present embodiment, the inner diameter of the branch channel 13 is made larger than the outer diameter of the blood cell over the entire length of the branch channel 13 as well as the opening.

  Therefore, even if blood cells accidentally flow into the branch flow path 13 side, the branch flow path 13 is hardly clogged.

  On the other hand, the depth of the second channel 12 is not particularly limited, but is about 10 to 100 μm, more preferably about 10 to 30 μm, like the first channel 11. If the depth is too shallow, the second flow path 12 may be blocked if a blood cell component enters by mistake. If the depth is too large, it may be difficult to control the flow rate with high accuracy.

  In the second flow path 12, deeper flow paths may be connected on the upstream side and the downstream side of the portion where the branch flow path 13 is connected.

  A plasma recovery port 4 is connected to the downstream end of the second flow path 12. As shown in FIG. 2A, the plasma collection port 4 is opened on the upper surface of the laminated plate.

  Therefore, in the plasma separator 1 shown in FIG. 2A, when blood is supplied from the blood supply port 2 using a syringe or the like and blood is poured into the first flow path 11, the plasma is separated as will be described later. The separated plasma is recovered from the plasma recovery port 4. For collection, a tube, syringe, or the like may be connected to the plasma collection port 4.

  In the plasma separation device 1 of the present embodiment, the flow velocity in the first flow channel direction in the vicinity of the opening to which the branch flow channel 13 in the first flow channel is connected is three times or more than the flow velocity in the branch flow channel direction. Thus, the pressure loss ratio in the flow channel structure is defined as described above, whereby plasma can be promptly separated without causing hemolysis. This will be described in detail below.

  In addition, in this specification, plasma shall mean the thing which removed formed components, such as erythrocytes and leukocytes, from blood. In addition, serum shall mean the thing remove | eliminating coagulation components, such as a fibrin, from plasma. Mammalian erythrocytes do not contain cell nuclei. Enucleated erythrocytes usually have a disk shape with a hollow center. The size or outer diameter of erythrocytes is about 8 μm for human erythrocytes and about 6 μm for rats. The size of leukocytes is about 6-14 μm. The size of the plasma plate is 2-3 μm.

  In addition, the fact that the inner diameter of the opening of the first channel to which the branch channel is connected is larger than the outer diameter of the blood cell means that the diameter of the circumscribed sphere surrounding the blood cell is d and the opening of the branch channel is short. When the length of the side or the shortest diameter is w, it means that w / d> 1. w / d is preferably in the range of 1.1 to 3, more preferably 1.2 to 1.5. When w / d is 1 or less, blood cells may be clogged in the opening to which the branch flow path is connected.

  By setting w / d to 1.1 or more, clogging of blood cells can be prevented more reliably. If w / d is too large, separation of blood cells may be difficult in principle.

As shown in FIG. 1 (b), the opening 11a near the branch passage 13 is connected at a first flow path 11, the flow direction of the flow rate of the first channel 11 and V _0. Let V ₁ be the flow velocity in the direction of the branch flow path in the vicinity of the opening. In this case, the pressure loss ratio in the flow channel structure having the first flow channel 11 and the branch flow channel 13 is determined so that V ₀ is larger than 3V ₁ . Therefore, even if the opening has a cross section larger than the outer shape of the blood cell, the blood cell component does not flow into the branch channel 13 having the same size, as indicated by an arrow A in FIG. Go straight through the first flow path. Therefore, only the plasma component flows into the branch flow path 13. The reason for this will be described in detail below.

  When the flow is an ideal laminar flow, there is a streamline D that is a boundary between the branch flow B and the main flow C indicated by multi-point hatching in FIG. Are separated by streamline D. When the center of the particle E such as a blood cell is located on the main flow C side with respect to the stream line D, the particle E does not flow into the branch flow path 13. Therefore, even if the width w of the opening is 1.5 times that of the particle E, the ratio of the flow rate in the flow direction of the first flow channel 11 to the flow rate in the flow direction of the branch flow channel 13 is 3 pairs. If it is 1 or more, the particles do not flow into the branch flow path 13.

Even when the flow is not an ideal laminar flow, the particle E does not flow into the branch flow path 13 in the same manner. That is, when considering the extreme state shown in FIG.
V ₀ / V ₁ > {w− (1 / √2) (d / 2)} / {(1-1 / √2) (d / 2)}
> {(2 w / d) -1 / √2} / (1-1 / √2)
The relationship is obtained. Therefore, even if the width w of the opening is 1.2 times the diameter of the particle E, the ratio of the flow rate in the flow direction of the first flow channel 11 to the flow rate in the direction of the branch flow channel 13 is 3: 1. If it is above, the said conditions are satisfy | filled and particles, such as a blood cell, do not flow into a branch flow path.

  Therefore, as in the present embodiment, the blood cell is branched by setting the ratio of the flow rate in the flow direction of the first flow channel 11 in the vicinity of the opening to the flow rate in the direction of the branch flow channel to 3: 1 or more. Only plasma that does not flow into the channel 13 and does not contain blood cells flows into the branch channel 13. Therefore, plasma can be collected from the plasma collection port 4. That is, the plasma is distributed to the second flow path 12, and the flow rate of the distributed plasma can be obtained based on the Hagen-Poiseuille equation based on the relationship between the flow channel diameter and the pressure loss and its derivative equation. That is, the pressure loss in the flow channel structure can be handled as an analogy of electric resistance in the electric circuit, and the flow velocity at each point can be obtained based on the distribution of the flow rate.

  As described above, the opening 11a has an inner diameter larger than the outer diameter of the blood cell, but in this embodiment, the width of the channel is made larger than the outer diameter of the blood cell over the entire length of the branch channel 13. Yes. If the width in the cross section of the branch channel 13 is smaller than the outer diameter of the blood cell, the blood cell may be clogged in the branch channel 13. However, if the channel width is too large, it is difficult for particles such as blood cells to be clogged, but there is an increase in the chance of erroneously entering the branch channel, resulting in poor separation. Since the purpose is to remove erythrocytes and leukocytes, the channel width of the branch channel 13 is preferably about 10 to 20 μm.

  Since the minor axis dimension in the cross section of the branch channel 13 is larger than the outer diameter of the blood cell, it is not necessarily required to be formed with high accuracy. Accordingly, since it is not necessary to control the dimensions of the branch flow path 13 with high accuracy when the plasma separator 1 is manufactured, the yield in a manufacturing process such as molding can be increased.

  As described above, the distribution to the flow rate to the first flow path 11 and the branch flow path 13 is determined by the pressure loss ratio, and the flow rate of flowing blood is not particularly limited. However, preferably, the flow rate in the first flow path 11 is 1 to 1000 mm / second, more preferably about 10 to 100 mm / second. If the flow rate is too high, high pressure is required and hemolysis may occur. If the flow rate is too low, the plasma separation time may be long.

  In the plasma separation device 1 of the present embodiment, plasma is separated using the branch channel 13. That is, this embodiment is not an apparatus that physically separates blood by using a sieve or mesh to separate plasma. Therefore, clogging of blood cells is difficult to occur. In addition, since a large centrifuge device or the like is not required, the entire analyzer can be reduced in size, and a long-time centrifuge operation is not required.

  When the plasma separator 1 is manufactured, the laminated plate shown in FIG. 2 (a) may be formed. In this case, a laminated plate can be easily obtained by laminating a plurality of plate materials via an adhesive or the like. Further, a laminated plate may be obtained by diffusion bonding or pressure bonding with a holding jig. The material constituting the plurality of plates is not particularly limited, and various synthetic resins, glass, ceramics, silicon, or other metals can be used. Examples of the synthetic resin include polydimethylsiloxane (PDMS), acrylic resin, and silicone resin. Moreover, as a metal, the stainless steel etc. which were excellent in rust prevention property can be used suitably. Further, it is desirable that the plate constituting the plasma separation device 1 is transparent so that the plasma separation state, clogging of blood cells, and the like can be visually recognized. In particular, it is desirable that these portions are transparent so that the flow channel structure including the first flow channel 11, the branch flow channel 13, and the second flow channel 12 can be visually observed from the outside.

  When the laminated plate is molded from a synthetic resin, each plate may be molded using various molding methods. Such a molding method is not particularly limited, and examples thereof include a solution cast method, an injection molding method, an imprint method, and a laser ablation method.

  Prior to use, the plasma separation device 1 is preferably filled with physiological saline or phosphate buffer in the flow path.

  If necessary, the recovery rate of plasma can be increased by filling the used plasma separation apparatus 1 with physiological saline or phosphate buffer in the flow path. In some cases, a flush operation with a different pressure medium such as air may be performed.

  In the laminated plate, the first flow path 11, the second flow path 12, and the plurality of branch flow paths 13 are formed by laminating a plurality of plates. These are the same in the laminated plate. It is not necessarily required to be formed at the height position. For example, by stacking the three plates 21 to 23 shown in FIGS. 5A to 5C, the portion where the first and second flow paths 11 and 12 and the branch flow path 13 are formed is configured. May be. Here, in the first plate 21, through holes for forming the first and second flow paths 11 and 12 are formed. A connection port 22 a that penetrates the second plate 22 is formed on the second plate 22. A through hole for forming the branch channel 13 is formed in the third plate 23.

  By laminating the plates 21 to 23 and laminating the plates in which the through holes are not formed in the upper and lower sides, between the first flow path 11 and the second flow path 12, via the connection ports 22a and 22b. The branch flow path 13 is connected. In such a structure, the branch flow path 13 and the first and second flow paths 11 and 12 are formed at different height positions.

  Moreover, you may form the 1st flow path 11 and the 2nd flow path 12 in a different height position. For example, if the through hole forming the second flow path is formed so as to be connected to the through hole forming the branch flow path of FIG. 5C, and the connection port 22b is removed, the branch flow path 13 and The second flow path 12 can be formed at the same height position.

  Thus, the 1st flow path 11, the 2nd flow path 12, and the branch flow path 13 can be formed in various height positions in a lamination | stacking plate.

  FIG. 4 is a schematic plan view for explaining the plasma separator according to the second embodiment of the present invention. As shown in FIG. 4, the branch channel 14 is provided to be inclined with respect to the channel direction of the first channel 11. More specifically, the branch flow path 14 extends from the first end connected to the first flow path 11 toward the second end, but the second end side is located on the upstream side. In other words, the branch flow path 13 is inclined from the portion connected to the first flow path 11 to the upstream side in the first flow path. In this case, it is possible to more reliably prevent blood cell components from erroneously flowing into the branch flow path 14.

  In the first embodiment, the plurality of branch channels 13 are extended in the direction orthogonal to the channel direction of the first channel 11, but as in the second embodiment, a plurality of branch channels are provided. The direction in which 14 extends is not necessarily perpendicular to the flow path direction of the first flow path 11.

  FIG. 6 is a schematic plan view for explaining the third embodiment. In the present embodiment, the first ends of the plurality of second branch channels 15 are connected to the downstream side of the side of the second channel 12 to which the plurality of branch channels 13 are connected. Furthermore, a third flow path 16 is connected to the second end of the second branch flow path 15. In this case, the second branch channel 15 is formed in the same manner as the first branch channel 13. Accordingly, plasma of the blood supplied from the first flow path 11 is supplied to the second flow path 12 via the branch flow path 13, and further from the second flow path 12 to the second branch flow path 15. The plasma is collected from the third flow path 16. Therefore, since it has a multistage configuration, it is possible to more reliably prevent blood cells from being mixed.

  According to the experiment by the present inventor, in the case of the multi-stage configuration shown in FIG. 6, even if the flow path width of the branch flow path 13 is increased to 15 μL, which is twice the size of blood cells, plasma separation is not possible. It was confirmed that it was possible. In this case, since the width of the branch flow path 13 can be increased, the yield in manufacturing can be increased.

  FIG. 7 is a schematic plan view for explaining a plasma separator according to a fourth embodiment of the present invention. In the present embodiment, the downstream end of the first flow path 11 is connected to the upstream end of the second flow path 12 to form a single flow path 17. And it is branched into two flow paths 18A and 18B at the downstream end of the second flow path 12 or at the branching section 19.

  In the branch portion 19, the flow path 18 </ b> A is positioned on the side where the branch flow path 14 is connected to the second flow path 12, and the flow path 18 </ b> B is branched from the second flow path 12. It is located on the side opposite to the side to which the path 14 is connected.

  The flow that does not contain the blood cell component from the branch flow channel 14 presses the blood cell component on the opposite side of the portion that joins the second flow channel 12. That is, the blood cell component concentration is increased by plasma flowing into the branch channel 14 while passing through the first channel 11. In the portion where the blood cell component concentration is increased but the concentrated blood flows into the second flow path 12 and the branch flow path 14 and the second flow path 12 are merged, the branch flow path 14 is It is brought to the opposite side to the connected part. Therefore, in the flow in the second flow path 12, the plasma flowing from the branch flow path 14 and the flow containing a lot of blood cells flow as if in a two-layer flow. Therefore, in the branching portion 19, the plasma flows through the flow path 18 </ b> A disposed closer to the side to which the branch flow path 14 is connected, and is disposed on the side opposite to the side to which the branch flow path 14 is connected. A liquid containing blood cells flows through the flow path 18B.

  Therefore, plasma can be taken out from the plasma collection port 4 connected to the flow path 18A. And the liquid containing a blood cell component can be discharged | emitted from the discharge port 3 connected to the downstream edge part of the flow path 18B.

  Thus, even when the downstream end of the first flow path and the second flow path upstream end are connected to form a single flow path, the flow paths 18A and 18B are connected to the first flow path. By connecting to the downstream end of the second flow path via the branch part 19, plasma can be quickly separated. In this embodiment, the branch channel 14 of the second embodiment is used, but the branch channel 13 of the first embodiment may be used.

  FIG. 8 is a schematic plan view for explaining the flow channel structure of the plasma separator according to the fifth embodiment of the present invention.

  In the present embodiment, unlike FIG. 7, one flow path 17A has a spiral shape, that is, a spiral shape. Although one flow path 17A has a spiral shape, the portion to which the first ends of the plurality of branch flow paths 14 are connected corresponds to the first flow path. The portion to which the second end is connected corresponds to the second flow path. However, since it has a spiral shape having a plurality of ends, for example, the flow path portion indicated by the arrow F corresponds to the first flow path and also corresponds to the second flow path. Therefore, the present embodiment corresponds to a structure having the characteristics of the configuration including a plurality of stages illustrated in FIG. 6 and the embodiment in which the first flow path and the second flow path illustrated in FIG. 7 are connected.

  As described above, in the present invention, in the case of a structure in which the first and second flow paths are connected to form one flow path, the planar shape may be a spiral shape. A channel structure having the first and second channels and the branch channel can be formed at a high density in a small area. Therefore, the plasma separator can be downsized.

  Instead of arranging a spiral channel on the plane as in the embodiment of FIG. 8, a spiral channel may be arranged on the outer right side of the cylinder.

  Furthermore, as in the modification shown in FIG. 9, the branch flow path 13A does not necessarily need to have a constant width over the entire length. That is, the first end side needs to have a size larger than that of the blood cell, but a channel portion 13a narrower than the blood cell may be formed in the downstream portion of the branch channel 13A. If blood cells accidentally flow into the branch flow path 13A, the narrow flow path portion 13a may be clogged, but there is no possibility that blood cells flow into the second flow path 12.

  Next, specific experimental examples will be described.

Example 1
A plasma separation apparatus according to the first embodiment shown in FIGS. 1 to 3 was produced. The channel widths of the first channel and the second channels 11 and 12 were 100 μm, the channel width of the branch channel 13 was 10 μm, and the length of the branch channel 13 was 10 μm. The depths of the first and second flow paths 11 and 12 and the branch flow path 13 were all 10 μm. The laminated plate was produced by laminating a plurality of resin plates made of polymethyl methacrylate and a photoresist film.

  After filling the flow path structure of the plasma separation device with physiological saline, dilute blood obtained by diluting whole blood 10-fold using a syringe pump from the blood supply port 2 so as not to contain air bubbles. 1 mL was introduced at a flow rate of minutes. 82 μL of plasma could be recovered from the plasma recovery port 4. When plasma collected with an optical microscope was observed, no contamination of blood cell components was observed. Further, no clogging occurred in the branch flow path 13.

(Example 2)
According to the second embodiment, a branch channel 14 extending in a direction inclined 10 ° upstream is formed with respect to the first channel 11, and a plasma separation apparatus is manufactured in the same manner as in Example 1. ,evaluated. When the blood supply rate was increased to 10 μL / min and plasma separation was attempted, 87 μL of plasma could be recovered. Therefore, it was possible to reliably collect plasma even when the blood supply rate was increased.

  In addition, although this invention is a plasma separator, it can be widely used for the use which isolate | separates only normal liquid from the liquid in which microparticles | fine-particles of a specific magnitude | size were disperse | distributed. Examples of such fine particles include polymer fine particles, metal fine particles, ceramic fine particles, cells, organelles, microorganisms, and pollen. In addition to liquids such as water, chemical substance-containing aqueous solutions and organic solvents, gases such as air may be handled. That is, the fluid in which the fine particles are dispersed is not limited to a liquid. Furthermore, the present invention can also be applied to applications that distinguish actively moving particle-like objects from those that are dull or non-moving. For example, the separation device of the present invention can also be used for sorting based on the sperm motility.

(A) is a typical top view which shows the flow-path structure of the plasma separation apparatus of the 1st Embodiment of this invention, (b) is a partial notch expansion plane sectional view for demonstrating the principle. (A) is a perspective view which shows the external appearance of the plasma separator of 1st Embodiment, (b) is sectional drawing of the part in alignment with the AA in FIG. 1 (a), (c) is It is sectional drawing which shows the cross-sectional shape of a branch flow path. In the plasma separation apparatus of 1st Embodiment, it is a typical plane sectional view for explaining the principle that a blood cell does not enter a branch channel. It is a typical top view which shows the flow-path structure of the plasma separation apparatus of the 2nd Embodiment of this invention. (A)-(c) is each top view of the 1st-3rd plate used the structure where the 1st, 2nd flow path and the branch flow path are formed in a different height position. It is a typical top view which shows the flow-path structure of the plasma separator which concerns on the 3rd Embodiment of this invention. It is a typical top view which shows the flow-path structure of the plasma separator which concerns on the 4th Embodiment of this invention. It is a typical top view which shows the flow-path structure of the plasma separator which concerns on the 5th Embodiment of this invention. It is a partial notch top view for demonstrating the modification of a branch flow path.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Plasma separator 2 ... Blood supply port 3 ... Discharge port 4 ... Plasma collection port 10 ... Channel width 11 ... 1st channel 11a ... Opening part 12 ... 2nd channel 13 ... Branch channel 13A ... Branch Channel 13a ... Channel portion 14 ... Branch channel 15 ... Second branch channel 16 ... Third channel 17, 17A ... Channel 18A, 18B ... Channel 19 ... Branch portions 21-23 ... First Third plate 22a, 22b ... connection port

Claims (10)

A blood supply port through which blood is supplied;
A first flow path connected to the blood supply port for flowing blood;
A plurality of branch flow paths having first and second ends and connected to the first flow path at the first end;
A second flow path connected to a second end of the plurality of branch flow paths,
In the first channel, the inner diameter of the opening to which the first end of each branch channel is connected is larger than the outer diameter of the blood cell, and the direction along the first channel in the vicinity of the opening The pressure loss ratio in the flow path structure including the first flow path, the plurality of branch flow paths, and the second flow path is determined so that the flow speed is three times or more the flow speed in the branch flow path direction. , Plasma separator.   The plasma separation device according to claim 1, wherein a direction in which the branch channel branches from the first channel is a direction inclined to the upstream side of the first channel.   The plasma separator according to claim 1 or 2, wherein a plurality of the branch flow paths are connected to one side of the first flow path.   The cross section of the branch channel has a shape having a longitudinal direction and a short side direction, and the longitudinal direction of the cross section of the branch channel is substantially orthogonal to the direction in which the first channel extends. Item 4. The plasma separator according to any one of Items 1 to 3.   The cross section of the branch channel has a shape having a longitudinal direction and a short direction, and the longitudinal dimension of the cross section is smaller than one third of the width of the first channel. The plasma separator according to any one of 1 to 4.   A plurality of second branch flow paths having first and second ends, and a third flow path, wherein the first ends of the plurality of second branch flow paths are the second The plasma separation device according to any one of claims 1 to 5, wherein the plasma separation device is connected to a flow path, and a second end of the second branch flow path is connected to the third flow path. .   The downstream end of the first flow path and the upstream end of the second flow path are connected to form a single flow path by the first and second flow paths; and The plasma separator according to any one of claims 1 to 5, wherein a downstream end portion of the second channel is branched into at least two channels.   The plasma separation apparatus according to claim 7, wherein the one channel has a spiral shape.   It has a laminated plate in which a plurality of plates are laminated, the first and second flow paths and the plurality of branch flow paths are formed in the laminated plate, and the blood supply port opens on the outer surface of the laminated plate The plasma separator according to any one of claims 1 to 8. The plasma separation according to claim 9, wherein, in the laminated plate, a height position where the branch flow path is provided is different from a height position where the first and second flow paths are provided. apparatus.

Images