Separating device

Abstract

A separation device (100) is provided with a main flow path (11), a plurality of sub flow paths (13), a control liquid flow path (21), a downstream-side converging section (23), and a common flow path (25). A sample liquid (L1) containing particles flows through the main flow channel (11). The plurality of sub-runners (13) branch from the main runner (11). The control liquid flow path (21) merges in a portion of the main flow path (11) downstream of the sub-flow path (13), and the control liquid (L3) flows in the control liquid flow path (21). The main flow path (11) and the control liquid flow path (21) merge at a downstream-side merging section (23). The common flow path (25) is connected to the downstream-side confluence section (23). The particles at least larger than the predetermined particle size and the control liquid (L3) flow in a common flow channel (25).

Description

Technical Field

[0001] The invention relates to a separation device. Background Art

[0002] A separation device for separating specific cells from blood is known in the past (for example, see Patent Document 1). Patent Document 1 describes a flow channel chip having a main flow channel and a plurality of branch flow channels branching from the main flow channel. The flow channel chip also has two inlet flow channels connected to one end of the main flow channel and an outlet flow channel connected to the other end of the main flow channel.

[0003] Blood as a sample liquid flows into an inlet flow channel. Buffer flows into another inlet flow channel. Thus, blood and buffer flow into one end of the main flow channel. And, cancer cells present in the blood reach the other end of the main flow channel and flow to the outlet flow channel. On the other hand, blood components other than cancer cells flow into a plurality of branch flow channels. In this way, cancer cells are separated from the blood. In addition, a portion of the buffer flows into a plurality of branch flow channels, and the remaining buffer reaches the other end of the main flow channel and flows to the outlet flow channel.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Publication No. 2020-99256 Summary of the invention

[0007] Problems to be solved by the invention

[0008] However, in the flow channel chip of Patent Document 1, for example, when the cross-sectional dimensions of each flow channel are formed to be larger or smaller than the set value by only 1 μm or less, the flow channel resistance of each portion may be smaller or larger than the set value by more than 10%. In this case, cancer cells may flow to the branch flow channel, while particles smaller than cancer cells or liquid components of blood may flow to the outlet flow channel. In other words, there is a problem that cancer cells may not be separated from blood.

[0009] The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide a separation device capable of separating particles of a predetermined particle diameter even when a flow channel dimension deviates from a set value.

[0010] Solutions to Solve Problems

[0011] A separation device according to one embodiment of the present invention comprises a main flow channel, a plurality of side flow channels, a control liquid flow channel, a first confluence portion, and a common flow channel. A sample liquid containing particles flows in the main flow channel. The plurality of side flow channels branch from the main flow channel. The control liquid flow channel merges in a portion of the main flow channel that is further downstream than the side flow channels. The control liquid flows in the control liquid flow channel. The main flow channel merges with the control liquid flow channel at the first confluence portion. The common flow channel is connected to the first confluence portion. The particles at least larger than a predetermined particle size flow in the common flow channel together with the control liquid.

[0012] In one aspect of the present invention, the separation device may further include a control liquid adjustment unit capable of adjusting the amount of the control liquid flowing through the control liquid flow path.

[0013] In one aspect of the present invention, the separation device may further include a sample liquid feeding unit configured to cause the sample liquid to flow in the main channel. The control liquid adjustment unit and the sample liquid feeding unit may be driven independently of each other.

[0014] In one embodiment of the present invention, the separation device may further include a sample liquid supply channel, a transport liquid supply channel, a second confluence portion, and a transport liquid feeding portion. The sample liquid may flow in the sample liquid supply channel. The transport liquid that transports the particles to the common channel may flow in the transport liquid supply channel. The sample liquid supply channel and the transport liquid supply channel may merge at the second confluence portion. The transport liquid feeding portion may allow the transport liquid to flow in the transport liquid supply channel. The transport liquid feeding portion and the control liquid adjustment portion may be driven independently of each other.

[0015] In one aspect of the present invention, the control liquid and the transport liquid may have the same composition.

[0016] In one aspect of the present invention, the width of the common flow channel may be greater than the sum of the width of the main flow channel and the width of the control liquid flow channel.

[0017] Effects of the Invention

[0018] According to the present invention, it is possible to provide a separation device capable of separating particles having a predetermined particle diameter even when the flow channel dimension deviates from a set value. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a plan view schematically showing the structure of a separation device according to one embodiment of the present invention.

[0020] Figure 2 It is a plan view schematically showing the structure around the upstream merging portion of the separation device.

[0021] Figure 3This is a schematic diagram used to explain the operating principle of HDF.

[0022] Figure 4 This is a conceptual diagram for explaining the flow channel resistance acting on the sample liquid and the transport liquid in the main flow channel, the sub-flow channel, and the common flow channel.

[0023] Figure 5 This is a schematic diagram for explaining the relationship between the supply amount of the control liquid and the amount of the transfer liquid flowing through the common flow channel.

[0024] Figure 6 This is a schematic diagram for explaining the relationship between the supply amount of the control liquid and the amount of the transfer liquid flowing through the common flow channel.

[0025] Figure 7 It is a plan view schematically showing the structure of a separation device according to a modified example of the present invention. DETAILED DESCRIPTION

[0026] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In addition, the same reference numerals are given to the same or corresponding parts in the drawings, and repeated descriptions are omitted.

[0027] Reference Figures 1 to 6 , a separation device 100 according to an embodiment of the present invention is described. Figure 1 It is a plan view schematically showing the structure of a separation device 100 according to one embodiment of the present invention.

[0028] like Figure 1 As shown, the separation device 100 of this embodiment includes a HDF (Hydrodynamic filtration) chip 1. The HDF chip 1 has a function as a hydrodynamic filter. For example, the HDF chip 1 is a microchannel chip for the purpose of separation and concentration of microparticles. In addition, for example, the HDF chip 1 is composed of a transparent substrate or the like.

[0029] The HDF chip 1 includes a main channel 11, a plurality of sub-channels 13, a sample liquid supply channel 15, a transport liquid supply channel 17, an upstream confluence portion 19, a control liquid channel 21, a downstream confluence portion 23, and a common channel 25. The main channel 11, the plurality of sub-channels 13, the sample liquid supply channel 15, the transport liquid supply channel 17, the upstream confluence portion 19, the control liquid channel 21, the downstream confluence portion 23, and the common channel 25 are formed, for example, by a resin layer disposed on a transparent substrate. In addition, the upstream confluence portion 19 is the "second confluence portion" of the present invention. In addition, the downstream confluence portion 23 is an example of the "first confluence portion" of the present invention.

[0030] The main channel 11 extends in a straight line, for example, in a predetermined direction. The sample liquid L1 flows in the main channel 11. In the present embodiment, the sample liquid L1 and the transport liquid L2 flow in the main channel 11. The sample liquid L1 is a liquid containing microparticles. The sample liquid L1 is not particularly limited, and is, for example, blood. The transport liquid L2 is, for example, a liquid not containing microparticles. The transport liquid L2 is not particularly limited, and is, for example, a liquid culture medium.

[0031] A plurality of secondary flow channels 13 are branched from the main flow channel 11. Specifically, the plurality of secondary flow channels 13 are arranged at approximately equal intervals, for example, along the extension direction of the main flow channel 11. The plurality of secondary flow channels 13 have, for example, the same length. The plurality of secondary flow channels 13 extend in a direction intersecting the main flow channel 11. In the present embodiment, the plurality of secondary flow channels 13 extend in a direction orthogonal to the main flow channel 11.

[0032] In addition, a plurality of secondary flow channels 13 are formed so that the flow channel resistance gradually decreases from the upstream side of the main flow channel 11 to the downstream side. Specifically, in the present embodiment, the portion of the base end side (the side close to the main flow channel 11) of each secondary flow channel 13 is formed to have a first width. On the other hand, the portion of the terminal side (the side away from the main flow channel 11) of each secondary flow channel 13 is formed to have a second width greater than the first width. Moreover, the closer the secondary flow channel 13 is to the downstream confluence portion 23, the closer the position where the first width changes to the second width is to the base end side. The first width is not particularly limited, and is, for example, about 10 μm to several 10 μm. The second width is not particularly limited, and is, for example, about 10 μm to 100 μm. Furthermore, all secondary flow channels 13 may also be formed to have the same constant width. In this case, for example, the closer the secondary flow channel 13 is to the downstream confluence portion 23, the shorter it may be formed.

[0033] HDF2 is composed of a main channel 11 and a plurality of sub-channels 13. Specifically, a portion of the liquid flowing through the main channel 11 flows into the plurality of sub-channels 13. In addition, a portion of the particles contained in the liquid flowing through the main channel 11 flows into the plurality of sub-channels 13. The reason for whether the particles flow into the plurality of sub-channels 13 is, for example, the particle size. The smaller the particle size, the easier it is for the particles to flow into the sub-channels 13, while the larger the particle size, the more difficult it is for the particles to flow into the sub-channels 13. For example, when blood is used as the sample liquid L1, blood plasma (also called plasma) and red blood cells and platelets, which are liquid components of the blood, can be made to flow into the sub-channels 13, and cancer cells and white blood cells contained in the blood are not made to flow into the sub-channels 13. That is, particles with larger particle sizes, such as cancer cells and white blood cells, can be separated from the blood. In addition, the operating principle of HDF2 will be described in detail later.

[0034] Figure 2 1 is a top view schematically showing the structure of the vicinity of the upstream confluence portion 19 of the separation device 100. Figure 2As shown, the sample liquid L1 flows in the sample liquid supply flow channel 15. The sample liquid supply flow channel 15 is a flow channel for supplying the sample liquid L1 to the main flow channel 11. In addition, in the present embodiment, the sample liquid supply flow channel 15 is inclined relative to the main flow channel 11, but the present invention is not limited thereto. For example, the sample liquid supply flow channel 15 may be parallel to the main flow channel 11 or may be perpendicular to the main flow channel 11.

[0035] The transport liquid L2 flows in the transport liquid supply flow channel 17. The transport liquid supply flow channel 17 is a flow channel for supplying the transport liquid L2 to the main flow channel 11. The transport liquid L2 is, for example, a liquid for transporting particles larger than a predetermined particle size to the common flow channel 25. In other words, the transport liquid L2 is a liquid for transporting particles that have not flowed into the secondary flow channel 13 to the common flow channel 25. In addition, in the present embodiment, the transport liquid supply flow channel 17 is inclined relative to the main flow channel 11, but the present invention is not limited thereto. For example, the transport liquid supply flow channel 17 may be parallel to the main flow channel 11 or may be perpendicular to the main flow channel 11.

[0036] In addition, the sample liquid supply flow channel 15 is configured so that the sample liquid L1 flows through the portion of the main channel 11 on the side of the secondary flow channel 13. On the other hand, the transport liquid supply flow channel 17 is configured so that the transport liquid L2 flows through the portion of the main channel 11 on the opposite side of the secondary flow channel 13. In the present embodiment, the sample liquid supply flow channel 15 is connected to the inner wall 11a on the side of the secondary flow channel 13 of the inner wall of the main channel 11. On the other hand, the transport liquid supply flow channel 17 is connected to the inner wall 11b on the opposite side of the secondary flow channel 13 of the inner wall of the main channel 11.

[0037] The sample liquid supply flow channel 15 and the transport liquid supply flow channel 17 merge at the upstream merging portion 19. The upstream merging portion 19 is disposed at the upstream end of the main channel 11. Therefore, the sample liquid L1 passing through the sample liquid supply flow channel 15 and the transport liquid L2 passing through the transport liquid supply flow channel 17 merge at the upstream merging portion 19 and flow through the main channel 11.

[0038] like Figure 1 As shown, the control liquid flow channel 21 merges at a portion of the main channel 11 that is more downstream than the secondary flow channel 13. In the present embodiment, the control liquid flow channel 21 merges at the downstream end of the main channel 11. The control liquid L3 flows in the control liquid flow channel 21. The control liquid flow channel 21 is a flow channel for supplying the control liquid L3 to the common flow channel 25. The control liquid L3 is, for example, a liquid that does not contain microparticles. The control liquid L3 is not particularly limited, and for example, it is the same component as the transport liquid L2. For example, the liquid component of the control liquid L3 is the same as the liquid component of the transport liquid L2. In addition, for example, the conductivity of the control liquid L3 is the same as the conductivity of the transport liquid L2.

[0039] Here, by adjusting the amount of the control liquid L3 flowing in the control liquid flow channel 21, the particle size of the particles flowing from the main channel 11 into the plurality of sub-channels 13 can be controlled. In other words, by adjusting the amount of the control liquid L3 flowing in the control liquid flow channel 21, the particle size of the separated particles can be controlled. In addition, in the present embodiment, the control liquid flow channel 21 is perpendicular to the main channel 11, but the present invention is not limited thereto. For example, the control liquid flow channel 21 may be parallel to the main channel 11, or may be inclined relative to the main channel 11. In addition, the method for controlling the particle size of the separated particles by the control liquid flow channel 21 will be described in detail later.

[0040] The main flow channel 11 and the control liquid flow channel 21 merge at a downstream merging portion 23. The downstream merging portion 23 is disposed at the downstream end of the main flow channel 11.

[0041] The common flow channel 25 is connected to the downstream confluence portion 23. Therefore, the liquid passing through the main flow channel 11 and the control liquid L3 passing through the control liquid flow channel 21 merge at the downstream confluence portion 23 and flow in the common flow channel 25. At least particles larger than a predetermined particle size contained in the sample liquid L1 and the control liquid L3 flow in the common flow channel 25. In the present embodiment, particles larger than a predetermined particle size, the control liquid L3, and the transport liquid L2 flow.

[0042] Continue to refer to Figure 1 , further describing the separation device 100 and the HDF chip 1. The separation device 100 further includes a sample liquid feeding unit 31, a transport liquid feeding unit 33, and a control liquid adjustment unit 35. The separation device 100 may also include a control unit that drives the sample liquid feeding unit 31, the transport liquid feeding unit 33, and the control liquid adjustment unit 35. The sample liquid feeding unit 31, the transport liquid feeding unit 33, and the control liquid adjustment unit 35 are not particularly limited, and are, for example, micro pumps. The micro pump may be a mechanical pump or a non-mechanical pump.

[0043] The sample liquid feeding section 31 is connected to the sample liquid supply flow channel 15, and allows the sample liquid L1 to flow into the sample liquid supply flow channel 15. Specifically, the sample liquid supply flow channel 15 has a sample liquid inlet 15a. The sample liquid inlet 15a is arranged at the upstream end of the sample liquid supply flow channel 15. The sample liquid feeding section 31 is connected to the sample liquid inlet 15a. The sample liquid feeding section 31 supplies the sample liquid L1 to the sample liquid inlet 15a, thereby the sample liquid L1 flows in the sample liquid supply flow channel 15 and the main flow channel 11.

[0044] The transport liquid feeding section 33 is connected to the transport liquid supply channel 17, so that the transport liquid L2 flows to the transport liquid supply channel 17. Specifically, the transport liquid supply channel 17 has a transport liquid inlet 17a. The transport liquid inlet 17a is arranged at the upstream end of the transport liquid supply channel 17. The transport liquid feeding section 33 is connected to the transport liquid inlet 17a. The transport liquid feeding section 33 supplies the transport liquid L2 to the transport liquid inlet 17a, thereby the transport liquid L2 flows in the transport liquid supply channel 17 and the main channel 11.

[0045] The control liquid adjusting section 35 is connected to the control liquid flow channel 21, and allows the control liquid L3 to flow to the control liquid flow channel 21. Specifically, the control liquid flow channel 21 has a control liquid inlet 21a. The control liquid inlet 21a is arranged at the upstream end of the control liquid flow channel 21. The control liquid adjusting section 35 is connected to the control liquid inlet 21a. The control liquid adjusting section 35 supplies the control liquid L3 to the control liquid inlet 21a, thereby allowing the control liquid L3 to flow in the control liquid flow channel 21 and the common flow channel 25.

[0046] In the present embodiment, the sample liquid feeding section 31 supplies the sample liquid L1 in such a way that the sample liquid L1 becomes a laminar flow. The transport liquid feeding section 33 supplies the transport liquid L2 in such a way that the transport liquid L2 becomes a laminar flow. The control liquid adjustment section 35 supplies the control liquid L3 in such a way that the control liquid L3 becomes a laminar flow. Therefore, in the present embodiment, in the HDF chip 1, each liquid becomes a laminar flow. In addition, the control liquid adjustment section 35 can also supply the control liquid L3 in such a way that the control liquid L3 does not become a laminar flow.

[0047] In addition, in the present embodiment, the control liquid adjustment unit 35 is capable of adjusting the amount of the control liquid L3 flowing through the control liquid flow channel 21. That is, the control liquid adjustment unit 35 is capable of adjusting the amount of the control liquid L3 supplied to the control liquid flow channel 21. In addition, the sample liquid feeding unit 31 may be capable of adjusting the amount of the sample liquid L1 flowing through the sample liquid supply flow channel 15, or it may be unable to adjust the amount of the sample liquid L1 flowing through the sample liquid supply flow channel 15. In addition, the transport liquid feeding unit 33 may be capable of adjusting the amount of the transport liquid L2 flowing through the transport liquid supply flow channel 17, or it may be unable to adjust the amount of the transport liquid L2 flowing through the transport liquid supply flow channel 17.

[0048] In addition, in the present embodiment, the control liquid adjustment unit 35 and the sample liquid feeding unit 31 are driven independently of each other. Therefore, for example, regardless of the supply amount of the sample liquid L1, the supply amount of the control liquid L3 can be changed. In addition, the transport liquid feeding unit 33 and the control liquid adjustment unit 35 are driven independently of each other. Therefore, for example, regardless of the supply amount of the transport liquid L2, the supply amount of the control liquid L3 can be changed. In addition, the sample liquid feeding unit 31 and the transport liquid feeding unit 33 can be driven independently of each other, or they can not be driven independently. In addition, the sample liquid feeding unit 31 and the transport liquid feeding unit 33 can also be the same pump.

[0049] The HDF chip 1 also has a first outlet 27 and a second outlet 29. The first outlet 27 is connected to the plurality of secondary flow channels 13. The liquid passing through the plurality of secondary flow channels 13 is recovered to a first recovery section not shown in the figure via the first outlet 27. The first recovery section includes, for example, a recovery container. The second outlet 29 is connected to the downstream end of the common flow channel 25. The particles, the transport liquid L2, and the control liquid L3 passing through the common flow channel 25 are recovered to a second recovery section not shown in the figure via the second outlet 29. The second recovery section includes, for example, a recovery container.

[0050] Secondly, refer to Figure 3 , which explains the operating principle of HDF2. Figure 3 is a diagram used to illustrate the operating principle of HDF2. Figure 3 As shown, when the sample liquid supply unit 31 supplies the sample liquid L1 and the transport liquid supply unit 33 supplies the transport liquid L2, the sample liquid L1 and the transport liquid L2 flow in the main channel 11. The sample liquid L1 flows along the inner wall 11a on the side of the secondary channel 13, and the transport liquid L2 flows along the inner wall 11b on the opposite side of the secondary channel 13. At this time, the center of each particle passes through a position separated from the inner wall 11a of the main channel 11 by more than the particle radius.

[0051] Here, the flow velocity varies depending on the position in the width direction of the main channel 11. Specifically, the flow velocity decreases near the inner wall 11a and the inner wall 11b in the main channel 11. On the other hand, the flow velocity is maximum at a position away from the inner wall 11a and the inner wall 11b in the main channel 11 (the center in the width direction of the main channel 11).

[0052] Therefore, small-sized particles passing near the inner wall 11a tend to flow into the secondary flow channel 13 due to their low flow velocity. On the other hand, large-sized particles passing through a position away from the inner wall 11a tend to flow straight through the main flow channel 11 instead of flowing into the secondary flow channel 13 due to their high flow velocity. That is, under predetermined conditions such as constant supply amounts of the sample liquid L1 and the transport liquid L2, particles larger than a predetermined size will not be discharged from the main flow channel 11, while particles smaller than a predetermined size will be discharged from the main flow channel 11. Since the discharge from the main flow channel 11 to the secondary flow channel 13 is repeated through a plurality of secondary flow channels 13, particles smaller than a predetermined size will not reach the downstream end (downstream confluence portion 23) of the main flow channel 11. In addition, plasma, which is a liquid component, will not reach the downstream end of the main flow channel 11. Therefore, by means of the HDF chip 1, large-sized particles such as cancer cells and white blood cells can be separated from the blood, for example.

[0053] Secondly, refer to Figures 4 to 6 , a method for controlling the particle size of separated particles using the control liquid flow channel 21 is described. Figure 4This is a conceptual diagram for explaining the flow channel resistance acting on the sample liquid L1 and the transport liquid L2 in the main flow channel 11 , the sub-flow channel 13 , and the common flow channel 25 . Figure 5 and Figure 6 This is a schematic diagram for explaining the relationship between the supply amount of the control liquid L3 and the amount of the transfer liquid L2 flowing through the common flow channel 25 .

[0054] like Figure 4 As shown, the flow resistances of the plurality of secondary flow passages 13 are set to r1, r3, r5, ... rn-2 in order from the upstream side. The total flow resistance of the downstream confluence portion 23 and the common flow passage 25 is set to rn. Wherein n is a positive odd number. In addition, the flow resistances of the main flow passages 11 between the secondary flow passages 13 are set to r2, r4, r6, ... in order from the upstream side. In addition, the flow resistance between the most downstream secondary flow passage 13 and the downstream confluence portion 23 is set to rn-1.

[0055] At the branching portion P1 between the most upstream secondary flow channel 13 and the main flow channel 11, the ease of flowing to the secondary flow channel 13 is determined by the ratio of the flow channel resistance r1 to the combined resistance from the flow channel resistance r2 to the flow channel resistance rn. Similarly, at the branching portion P2 between the second secondary flow channel 13 from the upstream side and the main flow channel 11, the ease of flowing to the secondary flow channel 13 is determined by the ratio of the flow channel resistance r3 to the combined resistance from the flow channel resistance r4 to the flow channel resistance rn. The same is true thereafter.

[0056] Here, if Figure 5 and Figure 6 As shown in FIG. 1 , when the control liquid L3 flows to the control liquid flow channel 21, the amount of the delivery liquid L2 flowing from the main channel 11 to the common flow channel 25 is limited. Specifically, if the control liquid L3 flowing to the control liquid flow channel 21 decreases, the flow channel area of ​​the delivery liquid L2 flowing in the common flow channel 25 becomes larger (refer to FIG. 1 ). Figure 5 ). On the other hand, if the amount of control liquid L3 flowing into the control liquid flow channel 21 increases, the flow channel area of ​​the delivery liquid L2 flowing in the common flow channel 25 becomes smaller. In this way, by changing the amount of control liquid L3 flowing into the control liquid flow channel 21, the flow channel area of ​​the delivery liquid L2 flowing in the common flow channel 25 changes. In other words, by changing the amount of control liquid L3 flowing into the control liquid flow channel 21, the flow channel resistance rn acting on the delivery liquid L2 changes.

[0057] In addition, if the channel resistance rn changes, the combined resistance from the channel resistance r2 to the channel resistance rn will change. Therefore, the ratio of the channel resistance r1 to the combined resistance from the channel resistance r2 to the channel resistance rn will change, and thus the ease of flowing to the secondary channel 13 at the branch portion P1 will change. Similarly, the ratio of the channel resistance r3 to the combined resistance from the channel resistance r4 to the channel resistance rn will change, and thus the ease of flowing to the secondary channel 13 at the branch portion P2 will change. The same is true for the branches P3, P4...P(n-1) / 2. In addition, for example, if the amount of control liquid L3 flowing into the control liquid flow channel 21 increases, the channel resistance rn increases. Therefore, for example, the combined resistance from the channel resistance r2 to the channel resistance rn increases, and thus the liquid easily flows from the branch portion P1 to the secondary channel 13. That is, for example, if the amount of the control liquid L3 flowing into the control liquid flow channel 21 increases, the sample liquid L1 is more likely to flow from the main flow channel 11 to the plurality of sub-flow channels 13 .

[0058] As mentioned above Figures 1 to 6 As described above, the separation device 100 includes a control liquid flow channel 21 that merges with a portion of the main channel 11 that is on the downstream side of the secondary flow channel 13 and through which the control liquid L3 flows. Therefore, by changing the amount of the control liquid L3 flowing into the control liquid flow channel 21, the ease of flowing to the secondary flow channel 13 in each branch portion P1 ... changes. Thus, for example, even when the dimensions such as the width and depth of the flow channel at each position of the HDF chip 1 deviate from the set value due to manufacturing deviation, it is possible to suppress particles larger than a predetermined particle size (for example, cancer cells, white blood cells) from flowing into the secondary flow channel 13, or to suppress particles smaller than a predetermined particle size (for example, red blood cells, platelets) from flowing through the main channel 11 and into the common flow channel 25. Thus, even when the flow channel dimensions deviate from the set value, it is possible to separate particles of a predetermined particle size.

[0059] In addition, as described above, the separation device 100 includes the control liquid adjustment unit 35 capable of adjusting the amount of the control liquid L3 flowing in the control liquid flow path 21. Therefore, the amount of the control liquid L3 flowing into the control liquid flow path 21 can be easily changed. Thus, it is easy to suppress particles larger than a predetermined particle size from flowing into the secondary flow path 13, or to suppress particles smaller than a predetermined particle size from flowing into the common flow path 25.

[0060] In addition, as described above, the control liquid adjustment unit 35 and the sample liquid feeding unit 31 are driven independently of each other. Therefore, the supply amount of the sample liquid L1 can be kept constant, for example, while the supply amount of the control liquid L3 can be changed. Thus, unlike the case where the supply amount of the sample liquid L1 and the supply amount of the control liquid L3 are linked, the particle size of the particles flowing into the secondary flow channel 13 and the particle size of the particles flowing into the common flow channel 25 can be easily adjusted.

[0061] In addition, as described above, the transport liquid delivery unit 33 and the control liquid adjustment unit 35 are driven independently of each other. Therefore, the supply amount of the transport liquid L2 can be kept constant, for example, while the supply amount of the control liquid L3 can be changed. Thus, unlike the case where the supply amount of the transport liquid L2 and the supply amount of the control liquid L3 are linked, the particle size of the particles flowing into the secondary flow channel 13 and the particle size of the particles flowing into the common flow channel 25 can be easily adjusted.

[0062] In addition, as described above, the control liquid L3 and the transport liquid L2 have the same components. Therefore, it is possible to suppress the liquid component of the liquid recovered at the second outlet 29 from changing due to the supply amount of the control liquid L3.

[0063] Secondly, refer to Figure 7 , a separation device 100a according to a modified example of the present invention will be described. Figure 7 It is a plan view schematically showing the structure of a separation device 100a according to a modified example of the present invention.

[0064] like Figure 7 As shown in the figure, in the separation device 100a of the modified example of the present invention, the HDF chip 1a includes a main channel 11, a control liquid channel 21b, a downstream confluence portion 23a, a common channel 25a, a first recovery path 51, and a second recovery path 53. In addition, the downstream confluence portion 23a is an example of the "first confluence portion" of the present invention. In addition, similar to the HDF chip 1, the HDF chip 1a includes a plurality of secondary channels 13, a sample liquid supply channel 15, a transport liquid supply channel 17, and an upstream confluence portion 19.

[0065] The main channel 11 and the control liquid flow channel 21b are arranged in parallel, for example. The main channel 11 and the control liquid flow channel 21b merge at the downstream confluence portion 23a. The width of the downstream confluence portion 23a is greater than the sum of the width of the main channel 11 and the width of the control liquid flow channel 21b. The width of the common flow channel 25a is greater than the sum of the width of the main channel 11 and the width of the control liquid flow channel 21b. The width of the common flow channel 25a is the same as the width of the downstream confluence portion 23a. In addition, the depth of the main channel 11, the depth of the control liquid flow channel 21b, the depth of the downstream confluence portion 23a, and the depth of the common flow channel 25a are approximately equal. Therefore, the cross-sectional area of ​​the downstream confluence portion 23a is greater than the sum of the cross-sectional area of ​​the main channel 11 and the cross-sectional area of ​​the control liquid flow channel 21b. In addition, the cross-sectional area of ​​the common flow channel 25a is greater than the sum of the cross-sectional area of ​​the main channel 11 and the cross-sectional area of ​​the control liquid flow channel 21b.

[0066] By making the width of the common channel 25a larger than the sum of the width of the main channel 11 and the width of the control liquid channel 21b, the flow rate of the liquid flowing in the common channel 25a can be reduced. This facilitates the separation of particles by dielectrophoresis described later.

[0067] The first recovery path 51 and the second recovery path 53 are connected to the downstream end of the common flow path 25a. That is, the common flow path 25a is branched into the first recovery path 51 and the second recovery path 53.

[0068] In the HDF chip 1 a , the second outlet 29 includes a second outlet 29 a and a second outlet 29 b . The second outlet 29 a is connected to the downstream end of the first recovery path 51 , and the second outlet 29 b is connected to the downstream end of the second recovery path 53 .

[0069] Here, the HDF chip 1a can further separate the particles flowing in the common flow channel 25a by dielectrophoresis (DEP). Specifically, the HDF chip 1a also includes electrodes 55 and 57 arranged in a manner overlapping with the common flow channel 25a. The electrodes 55 and 57 are comb-shaped electrodes facing each other. The electrode 55 is connected to an AC power supply 61, for example. The electrode 57 is grounded, for example. In this modification, the separation device 100a includes an AC power supply 61. In addition, the separation device 100a may not include the AC power supply 61.

[0070] The teeth of the electrode 55 and the electrode 57 are inclined, for example, by 10° or more and 60° or less relative to the common flow channel 25a. Dielectrophoresis can be generated by applying an AC voltage between the electrode 55 and the electrode 57 using the AC power supply 61. Furthermore, by adjusting the frequency of the applied AC voltage, desired particles can be separated and recovered from several types of particles passing through the common flow channel 25a.

[0071] Specifically, in the case where several particles passing through the common flow channel 25a include dielectric particles, specific dielectric particles can be separated from the several particles by DEP. For example, cancer cells and white blood cells are dielectric particles. In the case where several particles passing through the common flow channel 25a include cancer cells and particles (white blood cells, etc.) larger than a predetermined size other than cancer cells, for example, an AC voltage of a specific frequency is applied between the electrode 55 and the electrode 57 so that the dielectrophoretic force can easily act on the cancer cells. Thus, the cancer cells can be moved along the electrode 55 and the electrode 57, and therefore, only the cancer cells can be guided to the second outlet 29a by dielectrophoresis. Thus, the cancer cells can be separated from other particles (white blood cells, etc.).

[0072] The other structures of the separation device 100a, HDF chip 1a, control liquid flow channel 21b, downstream confluence portion 23a and common flow channel 25a of the modified example of the present invention are the same as the separation device 100, HDF chip 1, control liquid flow channel 21, downstream confluence portion 23 and common flow channel 25 of the above-mentioned embodiment. In addition, other effects of the modified example of the present invention are the same as those of the above-mentioned embodiment.

[0073] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the above-mentioned embodiments and can be implemented in various ways without departing from the main purpose thereof. In addition, various inventions can be formed by appropriately combining the multiple constituent elements disclosed in the above-mentioned embodiments. For example, several constituent elements can be deleted from all the constituent elements shown in the embodiments. In addition, the constituent elements in different embodiments can also be appropriately combined. For ease of understanding, the accompanying drawings are schematically represented with the respective constituent elements as the main body. In order to facilitate the preparation of the drawings, the thickness, length, number, spacing, etc. of the constituent elements illustrated in the drawings are sometimes different from the actual ones. In addition, the material, shape, size, etc. of the constituent elements shown in the above-mentioned embodiments are only examples and are not particularly limited. Various changes can be made within the scope that does not substantially depart from the effect of the present invention.

[0074] For example, in the above embodiment, blood is used as the sample liquid L1 and a liquid culture medium is used as the transport liquid L2, but the present invention is not limited thereto. For example, a liquid other than blood may be used as the sample liquid L1 and a liquid other than a culture medium may be used as the transport liquid L2.

[0075] In the above embodiment, particles (e.g., cancer cells and white blood cells) recovered from the second outlet 29 are cited as examples of target recovery products, but the present invention is not limited thereto. For example, particles or liquid components recovered from the first outlet 27 may also be used as target recovery products.

[0076] In the above modification, an example in which target particles (for example, cancer cells) are collected from the second outlet 29a is described, but the present invention is not limited thereto. For example, target particles may be collected from the second outlet 29b.

[0077] In addition, in the above embodiment, an example in which the transport liquid L2 and the control liquid L3 do not contain particles is described, but the present invention is not limited thereto. The transport liquid L2 and the control liquid L3 may also contain particles. However, in this case, it is preferable to set the transport liquid L2 and the control liquid L3 as shown in the reference Figure 7 The structure described above separates the particles contained in the transfer liquid L2 and the control liquid L3 from the particles contained in the sample liquid L1 .

[0078] In addition, in the above-mentioned embodiment, an example of using the transport liquid L2 is described. That is, an example of making the transport liquid L2 flow in the main channel 11 in addition to the sample liquid L1 is described. However, the present invention is not limited to this. For example, only the sample liquid L1 may flow in the main channel 11. For example, seawater containing particles may be used as the sample liquid L1, and the particles may be separated from the seawater.

[0079] In addition, in the above embodiment, an example is described in which the control liquid adjustment unit 35 can adjust the amount of the control liquid L3 flowing in the control liquid flow path 21, but the present invention is not limited thereto. For example, a plurality of control liquid adjustment units 35 may be prepared in advance, and particles may be separated from the sample liquid L1 using the control liquid adjustment unit 35 to which an appropriate amount of the control liquid L3 is supplied.

[0080] (Industrial Applicability)

[0081] The present invention can be used in the field of separation devices.

[0082] Explanation of symbols

[0083] 11—main flow channel, 13—secondary flow channel, 15—sample liquid supply flow channel, 17—transport liquid supply flow channel, 19—upstream side confluence section (second confluence section), 21, 21b—control liquid flow channel, 23, 23a—downstream side confluence section (first confluence section), 25, 25a—common flow channel, 31—sample liquid delivery section, 33—transport liquid delivery section, 35—control liquid adjustment section, 100, 100a—separation device, L1—sample liquid, L2—transport liquid, L3—control liquid.

Claims

1. A separation device, characterized in that: have: The main flow channel where the sample solution containing particles flows; A plurality of secondary flow channels branching from the primary flow channel; a control liquid flow channel in which the control liquid flows through a portion of the main flow channel which merges with the secondary flow channel at a downstream side; a first confluence portion where the main flow channel and the control liquid flow channel merge; and a common flow channel connected to the first confluence portion, The particles having at least a particle size larger than a predetermined particle size and the control liquid flow in the common flow channel.

2. The separation device according to claim 1, characterized in that: The invention further includes a control liquid adjusting unit capable of adjusting the amount of the control liquid flowing through the control liquid flow path.

3. The separation device according to claim 2, characterized in that: further comprising a sample liquid feeding section for causing the sample liquid to flow in the main flow channel, The control liquid adjustment unit and the sample liquid feeding unit are driven independently of each other.

4. The separation device according to claim 2 or 3, characterized in that: Also available: a sample liquid supply flow channel through which the sample liquid flows; a transport liquid supply flow channel through which a transport liquid for transporting the particles to the common flow channel flows; a second merging portion where the sample liquid supply channel merges with the transport liquid supply channel; and a transport liquid supplying section for causing the transport liquid to flow in the transport liquid supply flow channel, The transfer liquid delivery unit and the control liquid adjustment unit are driven independently of each other.

5. The separation device according to claim 4, characterized in that: The control liquid and the transport liquid have the same composition.

6. The separation device according to any one of claims 1 to 5, characterized in that: The width of the common flow channel is greater than the sum of the width of the main flow channel and the width of the control liquid flow channel.

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