JP2013170990A - Separation collection chip and separation collection method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To reduce an amount of plasma uncollectable by a safety margin layer while preventing blood corpuscles from mixing in a flow path flowing plasma.SOLUTION: The plasma collection chip is provided with: a separation flow path 4 for separating a blood sample S into a plasma layer 21 on one side in the flow path width direction and a corpuscle layer 22 on the other side in the flow path width direction; and a collection flow path 6 which is provided on the downstream side of the separation flow path 4 and has a first flow path part 11 for flowing plasma in the plasma layer 21 and a second flow path part 12 for flowing blood corpuscles in the corpuscle layer 22. The collection flow path 6 has: a cross section change flow path part 9 which is expanded in the flow path width direction and reduced in the flow path thickness direction compared with the separation flow path 4; and a branching wall 17 which is provided on the side of plasma layer 21 away from a boundary surface 23 between the plasma layer 21 and the corpuscle layer 22 which flow in the cross section change flow path 9 branches the cross section change flow path part 9 into the first flow path part 11 and the second flow path part 12.

Description

  The present invention is a separation / recovery chip for separating and recovering a mixed solution containing a plurality of components for each component, and a method for separating and recovering each component, specifically, included in a blood sample The present invention relates to a separation and recovery chip that separates blood cells and plasma and collects plasma, and a method of separating blood cells and plasma and recovering plasma.

In recent years, technological development for performing blood tests on a chip has progressed. In particular, by reducing the size of this chip, the required blood sample can be reduced, and the cost of testing can be reduced by reducing the amount of reagents. Is expected.
By the way, since the main item of the blood test is based on the soluble portion in the blood sample, the blood cells that occupy almost half of the blood sample become unnecessary portions (intrusive portions) for the blood test. Therefore, it is necessary to extract only plasma from the blood sample prior to the examination.

Examples of a method for separating blood cells and plasma include a method using a filter, a method using a centrifuge, a method using gravity (see, for example, Patent Document 1), and the like. A microchip in which is formed inside is used.
In the microchip described in Patent Document 1, as shown in the longitudinal sectional view of the flow path in FIG. 8A, the separation flow path 99 and the separation flow path 99 are branched into the substrate body. The first and second flow paths 94 and 95 are formed, and the inlet of the first flow path 94 and the inlet of the second flow path 95 are provided vertically.
When the blood sample flows through the separation channel 99, blood cells settle, the blood cells flow downward on the downstream side of the channel 99, and the blood cell layer 91 formed by the blood cells flows into the second channel 95 on the lower side. To do. In contrast, most of the plasma, which is a component other than blood cells, flows on the upper side of the separation channel 99 and flows into the first channel 94 on the upper side.

International Publication No. 2007-136057 (see FIG. 1)

According to the flow channel structure described in Patent Document 1, blood cells flow in the lower flow channel 95, plasma flows in the upper flow channel 94, and the plasma can be separated from the blood cells and collected.
However, in order to prevent blood cells from entering the upper flow path 94 through which the plasma flows, the branch wall 93 serving as a branch portion of the flow paths 94 and 95 is provided with a boundary surface 92 between the plasma layer 90 and the blood cell layer 91. As shown in FIGS. 8A and 8B, the safety margin layer is provided between the boundary surface 92 and the branch wall 93 with a predetermined dimension ΔL from the boundary surface 92 on the plasma layer 90 side. It is necessary to provide M (portion indicated by a double hatch in FIG. 8B).

The safety margin layer M is a margin layer for preventing blood cells from entering the upper flow path 94 for collecting plasma. According to the safety margin layer M, for example, the boundary surface 92 has a plasma layer. Even if it fluctuates within the range of the safety margin layer M on the 90 side, blood cells can be prevented from entering the upper flow path 94.
However, since the safety margin layer M is included in the plasma layer 90, the plasma in the safety margin layer M does not flow to the upper flow path 94 but flows to the lower flow path 95 together with the blood cells. This plasma is wasted without being used for testing.

Therefore, in order to reduce the amount of plasma that cannot be collected by the safety margin layer M, the branch wall 93 may be set in the vicinity of the boundary surface 92. However, in this case, there is a high probability that blood cells will be mixed into the upper flow path 94 through which plasma flows. In particular, if the boundary surface 92 fluctuates at the start of inflow of the blood sample, the probability becomes even higher. End up.
Thus, there is a trade-off relationship between the reduction of the amount of plasma that cannot be collected by the safety margin layer M and the prevention of blood cell mixing into the flow path 94 through which the plasma flows.
In addition to such a blood sample containing blood cells and plasma, other mixed liquids (particle mixed liquids) containing a plurality of components also have the above-mentioned trade-off relationship with respect to separation / recovery.

  Accordingly, an object of the present invention is to reduce the amount of a predetermined component (plasma amount) that cannot be collected by a safety margin layer while preventing one component (blood cell) from being mixed into another component (plasma). An object of the present invention is to provide a separation / recovery chip and a separation / recovery method that can be reduced as compared with the above. In the case of a blood sample, a separation / recovery chip and a separation / recovery method capable of reducing the amount of plasma that cannot be collected by a safety margin layer compared to conventional methods while preventing blood cells from mixing into the flow path for plasma. Is to provide.

  (1) The present invention is a separation / recovery chip that includes a flow path in which a blood sample containing blood cells and plasma flows in a laminar flow, and separates the blood cells and plasma in the flow path to recover the plasma. A separation channel for separating the blood sample into a plasma layer on one side in the channel width direction and a blood cell layer on the other side in the channel width direction; provided on the downstream side of the separation channel; A recovery flow path having a first flow path section through which plasma in a layer flows in and a second flow path section through which blood cells in the blood cell layer flow in, the recovery flow path being compared with the flow path for separation. A cross-section change flow path portion that is expanded in the width direction and reduced in the flow path thickness direction, and is provided on the plasma layer side from the boundary surface between the plasma layer and the blood cell layer that flows through the cross-section change flow path portion. A branching portion for branching the cross-section changing flow path portion into the first flow path portion and the second flow path portion; The features.

  According to the present invention, in the cross-section changing flow path portion of the recovery flow path, the dimension in the flow path width direction and the dimension in the flow path thickness direction are reduced compared to the separation flow path. The plasma layer of the blood sample flowing through the cross-section changing flow path portion can be expanded in the flow path width direction and reduced in the flow path thickness direction. Therefore, even if a safety margin layer having the same width as the conventional one is provided on the plasma layer side with respect to the boundary surface between the plasma layer and the blood cell layer flowing through the cross-section change flow path portion, the safety margin can be provided. The cross section of the layer can be made smaller than before, and as a result, the amount of plasma that cannot be collected by the safety margin layer can be reduced compared to the conventional case. In addition, the first flow path for flowing plasma by providing a branching portion with a safety margin layer having the same width as the conventional one (width that can prevent blood cells from being mixed into the first flow path portion through which plasma flows). It is possible to prevent blood cells from entering the part. The flow channel thickness direction is a direction orthogonal to both the flow direction of the blood sample and the flow channel width direction.

(2) Moreover, it is preferable that the cross-sectional area of the said cross-section change flow-path part is the same as the cross-sectional area of the said flow path for isolation | separation.
In this case, the flow rate of the blood sample in the separation channel and the cross-section change channel part can be made the same, and the laminar flow state between the plasma layer and the blood cell layer formed in the separation channel is changed to the cross-section change flow. It is possible to maintain the passage portion, and the plasma in the plasma layer can be stably allowed to flow from the cross-section changing flow passage portion to the first flow passage portion.

(3) Further, the separation channel has a channel configuration in which an action direction of the inertial force is on the other side in the channel width direction in order to separate the plasma layer and the blood cell layer based on the inertial force. In the cross-section changing flow path portion, it is preferable that the amount of expansion toward the other side in the flow path width direction is larger than the amount of expansion toward the one side in the flow path width direction.
In this case, on the one side in the flow path width direction where the plasma layer is formed, the amount of expansion in the flow path width direction is small, and the plasma layer can be prevented from being disturbed due to the expansion of the flow path width. As a result, the plasma in the plasma layer can be stably allowed to flow from the cross-section changing flow path portion to the first flow path portion.

(4) Further, the separation / recovery chip is provided between the downstream flow path portion of the separation flow path and the cross-sectional change flow path portion of the recovery flow path, and the cross section from the downstream flow path portion. It is preferable to further include a transition channel that changes the channel cross section continuously or stepwise to the change channel part.
In this case, the plasma layer can be gradually expanded in the flow channel width direction, and can be gradually reduced in the flow channel thickness direction.

  (5) Further, the present invention is a separation and recovery method for recovering plasma by flowing a blood sample containing blood cells and plasma as a laminar flow and separating the blood cells and plasma in the blood sample. As the blood sample flows along the channel, the blood sample is separated into a plasma layer on one side in the channel width direction and a blood cell layer on the other side in the channel width direction, and the plasma layer is expanded in the channel width direction. In addition, the plasma layer is reduced in the thickness direction, and plasma in the plasma layer is caused to flow into a flow channel portion branched on the plasma layer side from the boundary surface between the plasma layer and the blood cell layer.

  According to the present invention, the plasma layer of the blood sample is enlarged in the flow channel width direction and reduced in the flow channel thickness direction, and is the same as the conventional one on the plasma layer side with respect to the boundary surface between the plasma layer and the blood cell layer. When plasma flows into a branched flow channel with a width safety margin layer, the safety margin layer can be made smaller in cross section than before, so it cannot be recovered by the safety margin layer. As a result, it is possible to reduce the amount of plasma compared to the conventional art. In addition, by having a safety margin layer of the same width as before (a width that can prevent blood cells from being mixed into the flow channel portion through which plasma flows in), the plasma flows into the branched flow channel portion, It is possible to prevent blood cells from being mixed into this flow path portion through which plasma flows.

  (6) Further, the present invention is a separation and recovery chip for providing a flow path in which a mixed liquid containing a plurality of components flows in a laminar flow, and separating and recovering the mixed liquid for each component in the flow path. A separation channel for separating the mixed liquid into layers for each component from one side to the other side in the channel width direction, and each layer provided and separated on the downstream side of the separation channel A recovery flow path having a plurality of flow path portions through which the components contained in each flow in, the recovery flow path being enlarged in the flow path width direction and in the flow path thickness direction as compared with the separation flow path And a branch that is provided in the channel width direction with respect to the boundary surface between the layers flowing through the cross-section change flow path section and branches the cross-section change flow path section into the plurality of flow path sections. It has the part.

  According to the present invention, in the cross-section changing flow path portion of the recovery flow path, the dimension in the flow path width direction and the dimension in the flow path thickness direction are reduced compared to the separation flow path. Each layer of the mixed liquid flowing through the cross-section changing flow path portion can be enlarged in the flow path width direction and reduced in the flow path thickness direction. For this reason, the predetermined layer (first layer) is more than the boundary surface between the predetermined layer (first layer) flowing through the cross-section changing flow path portion and the adjacent layer (second layer) on the other side in the width direction. Even if a branch portion is provided with a safety margin layer having the same width as the conventional one on the layer) side, the cross section of the safety margin layer can be made smaller than the conventional one. This makes it possible to reduce the amount of the component of the predetermined layer (first layer) that cannot be recovered compared to the conventional case. In addition, by providing a branch portion so as to have a safety margin layer having the same width as the conventional one, another layer (second layer) is provided to the flow path portion through which the component of the predetermined layer (first layer) flows. ) Can be prevented from being mixed. In addition, although a liquid mixture is isolate | separated for every component, what may be collect | recovered may be one or more of several components.

  (7) Further, the present invention is a separation and recovery method in which a mixed liquid containing a plurality of components is flowed through a flow path as a laminar flow, and the mixed liquid is separated and recovered for each component. The mixed liquid is separated into layers for each component from one side to the other side in the flow path width direction as it flows along the flow path, and the mixed liquid separated for each layer is expanded in the flow path width direction and the flow path thickness. The component contained in the layer on the one side in the channel width direction is caused to flow into the channel part that is reduced in the vertical direction and branched on one side in the channel width direction from the boundary surface between the layers.

  According to the present invention, each layer of the mixed solution is enlarged in the flow channel width direction and reduced in the flow channel thickness direction, and this predetermined layer (first layer) and this are adjacent to the other side in the width direction. The predetermined layer (first layer) has a safety margin layer having the same width as that of the conventional layer at the boundary layer with the layer (second layer). When the component of (first layer) is introduced, the cross section of the safety margin layer can be made smaller than the conventional one, so that the predetermined layer (first layer) that cannot be recovered by the safety margin layer It is possible to reduce the amount of the component compared to the prior art. In addition, by having a component of the predetermined layer (first layer) flow into the branched flow path portion so as to have a safety margin layer having the same width as the conventional one, another layer is introduced into this flow path portion. It is possible to prevent the (second layer) component from being mixed.

  According to the present invention, it becomes possible to reduce the amount of plasma that cannot be collected by the safety margin layer (the amount of components in the predetermined layer) compared to the conventional case, and to have a safety margin layer having the same width as the conventional one. Thus, blood plasma (components of other layers) can be prevented from being mixed into the flow channel portion by allowing plasma (components of a predetermined layer) to flow into the branched flow channel portion.

It is a perspective view which shows schematic structure of the isolation | separation collection | recovery chip | tip of this invention. It is an enlarged explanatory view of the downstream part of the separation channel, the transition channel, and the upstream part of the recovery channel. FIG. 3 is a plan view of FIG. 2. (A) is sectional drawing of the NN arrow of FIG. 3, (B) is sectional drawing of a prior art example. It is explanatory drawing explaining the modification of the flow path which the separation-and-recovery chip | tip has. It is a perspective view showing other embodiments of a separation recovery chip. It is explanatory drawing explaining the modification of the flow path which the separation-and-recovery chip | tip has. It is sectional drawing of the flow path with which the conventional chip | tip is provided, (A) is a longitudinal cross-sectional view of a flow path, (B) is sectional drawing of the BB arrow of (A).

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 is a perspective view showing a schematic configuration of a separation and recovery chip of the present invention. This separation / recovery chip 1 (hereinafter also simply referred to as chip 1) is formed by forming a flow path 3 inside a substrate body 2. In this embodiment, the substrate body 2 has a circular shape in plan view and a thin plate shape. It is comprised from the member of. In FIG. 1, the substrate body 2 is cut and illustrated in order to explain the internal configuration (flow path 3). The flow path 3 includes a separation flow path 4, a transition flow path 5, and a recovery flow path 6. In this flow path 3, a mixed liquid containing a plurality of components flows in a laminar flow, and in this flow path 3, the mixed liquid is separated for each component, and one, a plurality, or all of the plurality of components are separated. In this embodiment, the mixed solution is a blood sample S containing blood cells and plasma, and the blood sample S flows through the flow path 3 as a laminar flow. A case will be described in which plasma is collected after separation.

  One end of the separation channel 4 is provided with an injection part 7 for injecting the blood sample S. The injected blood sample S passes from the separation channel 4 to the recovery channel 6 via the transition channel 5. And flow. As will be described later, the recovery flow path 6 has a first flow path section 11 and a second flow path section 12, and a first liquid reservoir section 13 is provided at the end of the first flow path section 11. A second liquid reservoir portion 14 is provided at the end of the two flow path portion 12. That is, in this flow path 3, the injection part 7 of the separation flow path 4 is on the upstream side, and the ends of the recovery flow path 6 (the first liquid reservoir part 13 and the second liquid reservoir part 14) are on the downstream side.

  The separation channel 4 is a channel for separating the blood sample S into two layers of a plasma layer 21 and a blood cell layer 22, and in this embodiment, the separation channel 4 has an arc shape (spiral shape). Is formed. In the separation channel 4, the radial direction of the arc (separation channel 4) is the channel width direction, and the direction perpendicular to the channel width direction and the flow direction of the blood sample S is the thickness direction. . The channel width direction at the downstream end of the separation channel 4 and the channel width direction at the transition channel 5 and the recovery channel 6 are the same direction, and the thickness direction at the downstream end of the separation channel 4 And the thickness direction in the transition flow path 5 and the recovery flow path 6 is the same direction.

Blood cells in the blood sample S injected from the injection part 7 and flowing through the separation channel 4 move radially outward by centrifugal force. For this reason, in the downstream portion (downstream channel portion 8) of the separation channel 4, the blood cell layer 22 is formed on the radially outer side, and the plasma layer 21 is formed on the radially inner side.
That is, according to the separation channel 4, as the blood sample S flows through the separation channel 4, the plasma layer 21 on one side in the channel width direction (inside in the radial direction) and the other in the channel width direction. It can be separated into two layers with the blood cell layer 22 on the side (radially outer side).
Thus, in the separation channel 4, the blood sample S is separated into layers for each component from one side to the other side in the channel width direction. In the present embodiment, as described above, the case where the mixed solution is the blood sample S and is separated into two layers of the plasma layer 21 and the blood cell layer 22 will be described. However, depending on the type of the mixed solution, three or more layers are used. They may be separated and recovered (see FIG. 7).

The shape of the channel cross section of the separation channel 4 is set to a shape optimized for separation into two layers of a plasma layer 21 and a blood cell layer 22. The flow channel cross section of the separation flow channel 4 according to the present embodiment is rectangular, and the flow channel cross section is constant along the longitudinal direction of the flow channel 4 (the flow direction of the blood sample S) and does not change. .
FIG. 2 is an enlarged explanatory view of the downstream part (downstream channel part 8) of the separation channel 4, the upstream part of the transition channel 5 and the recovery channel 6. FIG. 3 is a plan view thereof. In FIG. 2, when the width direction (flow channel width direction) of the downstream end of the downstream flow channel portion 8 is the X direction and the flow direction of the blood sample S is the Y direction, the Z direction orthogonal to the X direction and the Y direction is shown. The direction is the thickness direction (flow channel thickness direction).
Various values can be adopted for the ratio (h1 / W1) of the dimension w1 in the width direction and the dimension h1 in the thickness direction of the separation channel 4, and the blood sample S flowing in the channel 3 can be used. Based on the flow rate, the dimension h1 is determined, and the dimension w1 is changed as a parameter. In addition to the fluid condition, the manufacturing condition of the chip 1 is also considered as a constraint condition for the determination / change. As a specific example, the dimension h1 can be several tens of μm (for example, 20 μm, 30 μm, 50 μm, etc.), and the dimension w1 can be several hundred μm. Alternatively, the dimension h1 and the dimension w1 can each be about 1 mm.

1, 2, and 3, the recovery channel 6 is provided on the downstream side of the separation channel 4, and is a channel compared to the separation channel 4 (downstream channel unit 8). Each of the components has a plurality of cross-section changing flow path portions 9 whose cross sections change and flow path portions into which components contained in the respective layers separated in the separation flow path 4 are allowed to flow. That is, the recovery flow path 6 includes a cross-section change flow path section 9, a first flow path section 11 that allows plasma in the plasma layer 21 to flow in, and a second flow path section 12 that flows in blood cells in the blood cell layer 22. Yes.
In this embodiment, the first flow path portion 11 and the second flow path portion 12 are provided as flow path portions for each component. However, when there are three components to be separated and recovered, for example, It has the one flow path part 11, the 2nd flow path part 12, and the 3rd flow path part 15 (refer FIG. 7).

The cross section of the cross section changing flow path section 9 is rectangular, and extends linearly along the flow direction of the blood sample S. The cross-section changing flow path portion 9 is an upstream portion of the recovery flow path 6, and the downstream portion of the recovery flow path 6 is a first flow path portion 11 and a second flow path portion 12.
The transition flow path 5 is provided between the downstream flow path section 8 of the separation flow path 4 and the cross-section change flow path section 9 of the recovery flow path 6, and the cross-section change flow path section 9 extends from the downstream flow path section 8. It consists of an inclined channel that continuously changes the channel cross-section. The transition channel 5 has a rectangular channel cross section.

  In the cross-section changing flow path section 9, the dimension in the flow path width direction (X direction) is expanded and the flow path thickness direction (Z direction) as compared with the downstream flow path section 8 of the separation flow path 4. The dimensions have been reduced. That is, the dimension w2 in the flow path width direction of the cross-section change flow path section 9 is larger than the dimension w1 in the flow path width direction at the downstream end of the separation flow path 4 (w2> w1), and the cross-section change flow path section. The dimension h2 in the channel thickness direction 9 is smaller than the dimension h1 in the channel thickness direction at the downstream end of the separation channel 4 (h2 <h1). In the present embodiment, the cross-section of the cross-section change flow path section 9 is constant without changing along the flow direction, and the cross-sectional area (w2 × h2) of the cross-section change flow path section 9 is for separation. This is the same as the cross-sectional area (w1 × h1) at the downstream end of the downstream-side channel portion 8 of the channel 4.

  As described above, in the cross-section changing flow path section 9, the dimension in the flow path width direction is enlarged and the dimension in the flow path thickness direction is reduced compared to the downstream end of the separation flow path 4. The plasma layer 21 of the blood sample S flowing through the cross-section changing flow path section 9 can be expanded in the flow path width direction and reduced in the flow path thickness direction. That is, at the downstream end of the separation channel 4, the dimension in the channel width direction of the plasma layer 21 is L1, whereas in the cross-section change channel unit 9, the dimension in the channel width direction of the plasma layer 21 is L2 (L2> L1). And, at the downstream end of the separation channel 4, the dimension of the plasma layer 21 in the channel thickness direction is the same h1 as the dimension of the downstream end in the channel thickness direction, whereas the cross-section change channel In the part 9, the dimension of the plasma layer 21 in the channel thickness direction is h2 (h2 <h1), which is the same as the dimension of the cross-sectional change channel part 9 in the channel thickness direction.

Further, the recovery flow path 6 has a branch wall 17 as a branch section that branches the cross-section changing flow path section 9 into the first flow path section 11 and the second flow path section 12. A downstream portion of the flow path 6 is partitioned into a first flow path section 11 and a second flow path section 12. The first flow path portion 11 allows the plasma of the plasma layer 21 flowing through the cross-section change flow path portion 9 to flow in, and the second flow path portion 12 allows the blood cell layer 22 flowing through the cross-section change flow path portion 9 to flow in. .
The upstream end of the branch wall 17, that is, the branch point K is provided on the plasma layer 21 side with respect to the boundary surface 23 between the plasma layer 21 and the blood cell layer 22 flowing through the cross-section changing flow path portion 9. The dimension in the flow path width direction from the boundary surface 23 to the branch point K is ΔL.

  This region ΔL is a safety margin layer M formed between the boundary surface 23 and the branch wall 17, and this safety margin layer M does not mix blood cells into the first flow path portion 11 for collecting plasma. It is a margin layer (margin allowance) for doing so. According to the safety margin layer M, even if the boundary surface 23 fluctuates toward the plasma layer 21 within the range of the safety margin layer M (within the range of ΔL), blood cells are prevented from entering the first flow path portion 11. can do. However, the plasma in the safety margin layer M does not flow to the first flow path portion 11 but flows to the second flow path portion 12 together with blood cells, and the plasma that has flowed to the second flow path portion 12 is used for the test. Absent.

  4A is a cross-sectional view taken along line NN in FIG. 3, and FIG. 4B is a cross-sectional view of a conventional example. In the conventional example shown in FIG. 4B, the recovery channel 6 does not have the cross-sectional change channel part 9 as in this embodiment, and the channel cross section of the recovery channel 106 in the conventional example is the upstream side. This is the same as the channel cross section of the separation channel 4 on the side. The separation channel 4 is the same as the conventional example and the present embodiment. FIG. 4B is a cross-sectional view of a portion corresponding to the NN arrow in FIG. 3 in the conventional channel structure.

First, the conventional example of FIG. 4B will be described. The dimensions of the recovery channel 106 in the channel width direction and the channel thickness direction are the same w1 and h1 as the separation channel 4 on the upstream side.
Therefore, the dimension in the flow path width direction of the plasma layer 121 in the recovery flow path 106 is the same L1 as the dimension in the flow path width direction of the plasma layer 121 in the separation flow path 4, and the plasma layer 121 in the recovery flow path 106. The dimension in the channel thickness direction is h1 which is the same as the dimension in the channel thickness direction of the plasma layer 121 in the separation channel 4. The position of the dimension L <b> 1 from the wall surface 106 a of the recovery channel 106 becomes the boundary surface 123 between the plasma layer 121 and the blood cell layer 122.
A branch wall 117 is provided on the plasma layer 121 side from the boundary surface 123. A safety margin layer M is formed between the branch wall 117 and the boundary surface 123, and the dimension of the safety margin layer M in the flow path width direction is ΔL. For this reason, in the case of FIG. 4B, the plasma passing through the cross section of the flow path with the cross hatch cannot flow to the first flow path section 111 by the safety margin layer M, and the second flow path section 112. It will flow to.

Next, this embodiment of FIG. 4A will be described. The dimension w2 in the flow path width direction of the cross-sectional change flow path portion 9 included in the recovery flow path 6 is larger than the dimension w1 in the flow path width direction of the separation flow path 4 (W2> W1). The dimension h2 in the thickness direction 9 is smaller than the dimension h1 in the channel thickness direction of the separation channel 4 (h2 <h1).
For this reason, the dimension L2 in the flow path width direction of the plasma layer 21 in the cross section changing flow path section 9 is larger than the dimension L1 in the flow path width direction of the plasma layer 21 in the separation flow path 4 (L2> L1). The dimension h2 in the flow path thickness direction of the plasma layer 21 in the change flow path section 9 is smaller than the dimension h2 in the flow path thickness direction of the plasma layer 21 in the separation flow path 4 (h2 <h1). The position of the dimension L2 from the wall surface 9a of the cross-section changing flow path portion 9 becomes the boundary surface 23 between the plasma layer 21 and the blood cell layer 22.
A branch wall 17 is provided on the plasma layer 21 side from the boundary surface 23. Between the branch wall 17 and the boundary surface 23 is a safety margin layer M, and the dimension of the safety margin layer M in the flow path width direction is ΔL, which is the same as that in the conventional example of FIG. The dimension ΔL of the safety margin layer M in the flow path width direction is a width that can prevent blood cells from being mixed into the first flow path portions 11 and 111 through which plasma flows in both the present embodiment and the conventional example. It is.
For this reason, in the case of FIG. 4A, the plasma passing through the cross-section of the flow path with the cross hatch cannot flow to the first flow path section 11 by the safety margin layer M, and the second flow path section 12 It will flow to.

Thus, in this embodiment of FIG. 4 (A), the plasma layer 21 side is closer to the plasma layer 21 than the boundary surface 23 so as to have the safety margin layer M having the same width ΔL as the conventional example of FIG. 4 (B). Even if the wall 17 is provided, the cross section of the safety margin layer M can be made smaller than in the conventional example. As a result, the amount of plasma that cannot be collected by the safety margin layer M can be reduced as compared with the conventional example.
For example, the dimension W2 in the channel width direction of the channel cross section in the cross section changing flow path portion 9 is twice that (w1) of the separation flow path 4, and the flow of the cross section in the cross section changing flow path portion 9 is When the dimension h2 in the path thickness direction is 1/2 times that of the separation channel 4 (h1), ΔL is the same between the conventional example and the present embodiment. In comparison with the cross section, in this embodiment, it can be ½ of the conventional example. For this reason, the amount of plasma that cannot be collected by the safety margin layer M can be reduced by half compared to the conventional case.

  The width ΔL is set as a width that can prevent blood cells from being mixed into the first flow path portion 11 through which plasma flows, and therefore, in the present embodiment, the width ΔL has a safety margin layer M having the width ΔL. Thus, since the branch wall 17 is provided, it is possible to prevent blood cells from being mixed into the first flow path portion 11 through which plasma flows.

A separation and recovery method that can be performed using the chip 1 of the present embodiment is such that the blood sample S flows into the plasma on one side in the channel width direction as the blood sample S flows along the separation channel 4. The layer 21 and the blood cell layer 22 on the other side in the channel width direction are separated into two layers, and the separated plasma layer 21 is expanded in the channel width direction and reduced in the channel thickness direction by the cross-section changing channel unit 9. Let Then, the plasma of the plasma layer 21 reduced in the channel thickness direction is caused to flow into the first channel portion 11 branched from the boundary surface 23 between the plasma layer 21 and the blood cell layer 22 on the plasma layer 21 side. Is done.
And the plasma which does not contain the blood cell which flowed through the 1st flow path part 11 is stored in the 1st liquid reservoir part 13 (refer FIG. 1), and the plasma which contains the blood cell which flowed through the 2nd flow path part 12 is the 2nd liquid It is stored in the reservoir 14.

  As described above, conventionally, there has been a trade-off relationship between the reduction of the amount of plasma that cannot be collected by the safety margin layer M and the prevention of blood cells from being mixed into the flow path portion through which the plasma flows, but the chip 1 of the present embodiment. According to the separation and recovery method, the amount of plasma that cannot be recovered by the safety margin layer M can be reduced as compared to the conventional method, and the plasma margin is divided so as to have the safety margin layer M having a width ΔL. By allowing plasma to flow into the first flow path portion 11, it is possible to prevent blood cells from entering the first flow path portion 11.

  In this embodiment, in FIG. 2, the cross-sectional area (w2 × h2) of the cross-section changing flow path portion 9 is the same as the cross-sectional area (w1 × h1) of the separation flow path 4. And the flow velocity of the blood sample S in the cross-section changing flow path portion 9 are the same. For this reason, the laminar flow state of the plasma layer 21 and the blood cell layer 22 formed in the separation channel 4 can be maintained also in the cross-section change flow path portion 9, and the cross-section change flow path portion 9 to the first flow path. It becomes possible to stably flow the plasma in the plasma layer 21 into the part 11.

  Since the transition channel 5 continuously changes the channel cross-section from the downstream channel 8 of the separation channel 4 to the cross-section changing channel 9 of the recovery channel 6, plasma The layer 21 can be smoothly expanded in the channel width direction, and can be smoothly reduced in the channel thickness direction. In the present embodiment, the case where the inner wall surface of the transition channel 5 is configured by a plane and the channel cross section is continuously changed has been described. However, the change in the channel cross section is not continuous but stepwise. May be. That is, the inner wall surface of the transition channel 5 may be configured in a staircase shape.

  Furthermore, in the present embodiment, the separation flow path 4 is separated into the plasma layer 21 and the blood cell layer 22 based on the centrifugal force (inertial force). The flow path configuration is such that the blood cell layer 22 is formed on the other side in the flow path width direction, with the direction from the side toward the radially outer side being the other in the flow path width direction. Then, in the cross section changing flow path section 9 provided on the downstream side of the separation flow path 4, as shown in FIGS. 2 and 3, the flow path cross section is the other side in the flow path width direction (blood cell layer). 22 side), but does not expand to one side (plasma layer 21 side) in the channel width direction. Thus, in this embodiment, in the cross-section changing flow path section 9, the amount of expansion to the other side in the flow path width direction is set to be larger than the amount of expansion to the one side in the flow path width direction.

  In this case, on one side in the flow path width direction where the plasma layer 21 is formed, the change (enlargement amount) in the flow path width direction is small, and the plasma flow is reduced between the separation flow path 4 and the cross-section change flow path section 9. The change in the channel width direction of the streamline of the layer 21 can be reduced. As a result, the disturbance of the plasma layer 21 due to the expansion of the flow path can be prevented, and the plasma in the plasma layer 21 can be stably allowed to flow from the cross-section changing flow path portion 9 to the first flow path portion 11. .

  Further, the separation / recovery chip 1 of the present invention is not limited to the form shown in the drawings, and may be of other forms within the scope of the present invention. For example, the transition flow path 5 may be omitted.

Moreover, as shown in FIG. 5, the transition flow path 5 and the cross-section change flow path section 9 may have a symmetrical shape on both sides in the flow path width direction with respect to the center line of the flow path that goes in the flow direction.
As for the separation channel 4, if the blood sample can be separated into a plasma layer and a blood cell layer using a hydrodynamic effect, the separation channel 4 has a linear shape as shown in FIG. May be.

  In the embodiment (see FIG. 1), the case where the plasma layer 21 and the blood cell layer 22 are separated based on the centrifugal force has been described. However, the separation method may be other methods, It may be based on a method. That is, the blood sample S flows through the separation channel 4, so that blood cells flow through the bottom of the channel 4 while precipitating. The blood cell layer 22 is formed at the lower part on the downstream side of the separation channel 4, and the plasma is formed at the upper part. It may be a flow channel structure in which the layer 21 is formed. That is, in FIG. 3, the flow channel structure may be such that “the other side in the channel width direction” is on the bottom and “one side in the channel width direction” is on the top.

  Further, as shown in FIG. 4, the width ΔL of the safety margin layer M is not the same as the conventional one, but may be set larger than the conventional one. However, in this case, the width ΔL is preferably set to a width that provides the same channel cross section as that of the conventional safety margin layer M. That is, as shown in FIG. 4A, in the case of the cross-section changing flow path portion 9 in which the dimension in the flow path width direction is doubled and the dimension in the flow path thickness direction is halved, the safety margin layer The width of M can be doubled by ΔL. In this case, while the amount of plasma that cannot be collected by the safety margin layer M is the same as the conventional amount, the width (2 × ΔL) of the safety margin layer M is larger than the conventional amount, so the probability that blood cells are mixed into the plasma is significantly reduced. It becomes possible.

  In addition to the blood sample S, the chip 1 of the present invention can also be applied to a mixed solution for performing chemical reaction evaluation for drug discovery or component analysis. That is, in the above-described embodiment, the case where the liquid mixture flowing in the flow path 3 is the blood sample S and separated into two layers of the plasma layer 21 and the blood cell layer 22 has been described. The number of separations can be changed according to the type of the mixed solution. For example, when the mixed solution includes three types of components A, B, and C, as shown in FIG. 7, in the separation channel 4, as a layer for each component from one side to the other side in the channel width direction, The first layer 31, the second layer 32, and the third layer 33 are separated. And the recovery flow path 6 is provided in the downstream of this separation flow path 4, and the recovery flow path 6 is a flow path part into which the components A, B, and C contained in the separated layers are respectively introduced. The first flow path part 11, the second flow path part 12, and the third flow path part 15 are provided.

  Further, the recovery flow path 6 has a cross-sectional change flow path section 9 similar to that in the above embodiment (FIG. 3). The channel width direction dimension L2-1 of the first layer 31 in the cross-section changing channel unit 9 is larger than the channel width direction dimension L1-1 of the first layer 31 in the separation channel 4 ( L2-1> L1-1), the channel width direction dimension L2-2 of the second layer 32 in the cross-section changing channel unit 9 is the channel width direction dimension L1 of the second layer 32 in the separation channel 4. −2 (L2-2> L1-2), and the flow path width direction dimension L2-3 of the third layer 33 in the cross-section changing flow path section 9 is equal to that of the third layer 33 in the separation flow path 4. It becomes larger than the dimension L1-3 of the flow path width direction (L2-3> L1-3). In addition, the dimension of each layer 31, 32, 33 in the channel thickness direction is smaller than that of the separation channel 4 in the cross-section changing channel unit 9.

  Moreover, the collection | recovery flow path 6 has the 1st branch wall 17 as a 1st branch part, and the 2nd branch wall 18 as a 2nd branch part. Of the three layers 31, 32, and 33 that flow through the cross-section changing flow path section 9, the dimension ΔL <b> 1 on the one side in the flow path width direction from the boundary surface 34 between the first layer 31 and the second layer 32, The first branch wall 17 is provided, and the second branch wall 18 is provided on the other side in the flow path width direction with respect to the dimension ΔL2 with respect to the boundary surface 35 between the second layer 32 and the third layer 33. ing. Or although not shown in figure, about the 2nd branch part 18, you may be provided in the flow path width direction one side rather than the boundary surface 35. FIG. Moreover, in FIG. 7, although the 1st branch wall 17 and the 2nd branch wall 18 exist in the same position regarding a flow direction, any one may be located downstream in the flow direction rather than the other.

In the embodiment of FIG. 7, in the cross-section changing flow path section 9, the dimension in the flow path width direction and the dimension in the flow path thickness direction are reduced as compared with the separation flow path 4. Each of the layers 31, 32, and 33 flowing through the cross-section changing flow path portion 9 can be expanded in the flow path width direction and reduced in the flow path thickness direction.
For this reason, it is the same as the conventional one on the first layer 31 side rather than the boundary surface 34 between the first layer 31 flowing through the cross-section changing flow path portion 9 and the second layer 32 adjacent to the first layer 31 on the other side in the width direction. When the branch wall 17 is provided so as to have the safety margin layer M1 having the width, the cross section of the safety margin layer M1 can be made smaller than the conventional one, and as a result, the safety margin layer M1 collects the safety margin layer M1. It becomes possible to reduce the amount of the component A of the first layer 31 that is impossible. Further, by providing the branch wall 17 so as to have the safety margin layer M1 having the same width as the conventional one, the component B of the second layer 32 is passed to the first flow path portion 11 through which the component A of the first layer 31 flows. Can be prevented from being mixed.
Further, a predetermined safety margin is provided on the third layer 33 side from the boundary surface 35 between the second layer 32 flowing through the cross-section changing flow path portion 9 and the third layer 33 adjacent to the second layer 32 on the other side in the width direction. Since the branch wall 18 is provided so as to have the layer M2, the cross section of the safety margin layer M2 can be reduced. As a result, the third layer 33 that cannot be recovered by the safety margin layer M2 is obtained. It is possible to reduce the amount of component C. Further, by providing the branch wall 18 so as to have the safety margin layer M2 having a predetermined width, the component B of the second layer 32 is supplied to the third flow path portion 15 through which the component C of the third layer 33 flows. Can be prevented from being mixed. And the component B of the 2nd layer 32 can flow through the 2nd flow path 12, and can be collect | recovered. In addition, although a liquid mixture is isolate | separated for every component, what may be collect | recovered may be one or more of several components.

  1: Separation and recovery chip 3: Channel 4: Separation channel 5: Transition channel 6: Recovery channel 8: Downstream channel 9: Cross-section change channel 11: First channel 12: Second channel Road part 17: Branch wall (branch part) 21: Plasma layer 22: Blood cell layer 23: Interface M: Safety margin layer S: Blood sample

Claims (7)

A separation / recovery chip for collecting a blood sample containing blood cells and plasma in a laminar flow and separating the blood cells and plasma in the flow channel and collecting the plasma,
A separation channel for separating the blood sample into a plasma layer on one side in the channel width direction and a blood cell layer on the other side in the channel width direction;
A recovery channel provided on the downstream side of the separation channel, and having a first channel part for introducing plasma of the plasma layer and a second channel part for introducing blood cells of the blood cell layer,
The recovery channel is
A cross-section changing flow path portion that is enlarged in the flow path width direction and reduced in the flow path thickness direction as compared with the separation flow path;
A branching portion that is provided closer to the plasma layer than the boundary surface between the blood plasma layer and the blood cell layer that flows through the cross-section change flow path section, and branches the cross-section change flow path section into the first flow path section and the second flow path section. When,
A separation / recovery chip characterized by comprising:   The separation / recovery chip according to claim 1, wherein a cross-sectional area of the cross-sectional change flow path portion is the same as a cross-sectional area of the separation flow path. The separation channel has a channel configuration in which the direction of action of the inertial force is on the other side in the channel width direction in order to separate the plasma layer and the blood cell layer based on the inertial force,
The separation / recovery chip according to claim 1, wherein in the cross-section changing flow path portion, an enlargement amount toward the other side in the flow path width direction is larger than an enlargement amount toward the one side in the flow path width direction.   Provided between the downstream flow path portion of the separation flow path and the cross-sectional change flow path portion of the recovery flow path, and the flow path cross section is continuous from the downstream flow path portion to the cross-section change flow path portion The separation / recovery chip according to any one of claims 1 to 3, further comprising a transition channel that is changed in a stepwise or stepwise manner. A separation and recovery method for recovering plasma by flowing a blood sample containing blood cells and plasma as a laminar flow through a flow path, separating blood cells and plasma in the blood sample,
As the blood sample flows along the flow path, the blood sample is separated into a plasma layer on one side in the flow path width direction and a blood cell layer on the other side in the flow path width direction,
Expanding the plasma layer in the channel width direction and reducing in the channel thickness direction;
A separation and recovery method, characterized in that the plasma in the plasma layer is caused to flow into a flow path portion branched off from the boundary surface between the plasma layer and the blood cell layer on the plasma layer side. A separation / recovery chip for separating and recovering the mixed liquid for each component in the flow path including a flow path in which a mixed liquid containing a plurality of components flows in a laminar flow,
A separation channel for separating the mixture into layers for each component from one side to the other side in the channel width direction;
A recovery channel that is provided on the downstream side of the separation channel and has a plurality of channel units for allowing the components contained in the separated layers to flow in, respectively.
The recovery channel is
A cross-section changing flow path portion that is enlarged in the flow path width direction and reduced in the flow path thickness direction as compared with the separation flow path;
A branching section that is provided in the flow path width direction from the boundary surface between the layers flowing through the cross-section change flow path section and branches the cross-section change flow path section into the plurality of flow path sections;
A separation / recovery chip characterized by comprising: A separation and recovery method in which a mixed liquid containing a plurality of components flows through a flow path as a laminar flow, and the mixed liquid is separated and recovered for each component,
As the mixed liquid flows along the flow path, the mixed liquid is separated into layers for each component from one side to the other side in the width direction of the flow path,
The mixed liquid separated for each layer is enlarged in the flow channel width direction and reduced in the flow channel thickness direction,
A separation and recovery method, wherein a component contained in a layer on one side in the channel width direction is caused to flow into a channel part branched on one side in the channel width direction from the boundary surface between layers.

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