Flow path chip

Abstract

A flow path chip (1) is provided with a plurality of filter layers (40), a first common supply path (5), a common flow path (7), and a dielectrophoresis layer (50). Each of the plurality of filter layers (40) has an HDF (3). The first common supply path (5) supplies the sample liquid (L1) to the HDFs (3) of the plurality of filter layers (40). The liquid passing through the plurality of HDFs (3) passes through the common flow path (7). The dielectrophoresis layer (50) has an electrode (51) and an electrode (53) for dielectrophoresis of dielectric particles contained in the liquid passing through the common flow path (7). The plurality of filter layers (40) and the dielectrophoresis layer (50) are laminated.

Description

Technical Field

[0001] The invention relates to a flow path chip. Background Art

[0002] At present, a flow chip for separating specific cells from blood as a sample liquid is known (for example, see Patent Document 1). Patent Document 1 describes a flow chip comprising: a displacement section for extracting cells larger than a predetermined size from blood; and a separation section for separating cancer cells from a plurality of cells that have passed through the displacement section by dielectrophoresis.

[0003] Prior art literature

[0004] Patent Literature

[0005] Patent Document 1: Japanese Patent Application Publication No. 2017-134020 Summary of the invention

[0006] Problems to be solved by the invention

[0007] However, in general, the processing capacity of a flow channel chip such as that described in Patent Document 1 is low, being several tens to several hundreds of μL / minute. Therefore, a flow channel chip capable of processing a larger amount of sample solution is desired.

[0008] The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide a flow channel chip capable of processing a larger amount of sample liquid.

[0009] Solutions to Solve Problems

[0010] A flow path chip of one embodiment of the present invention comprises a plurality of filter layers, a common supply path, a common flow path and a dielectrophoresis layer. The plurality of filter layers respectively have a fluid dynamic filter. The common supply path supplies a sample liquid to the fluid dynamic filters of the plurality of filter layers. The liquid that has passed through the plurality of fluid dynamic filters passes through the common flow path. The dielectrophoresis layer has an electrode for causing the dielectric particles contained in the liquid passing through the common flow path to dielectrophoretically. The plurality of filter layers and the dielectrophoresis layer are stacked.

[0011] In one embodiment of the present invention, the plurality of filtration layers may include: a first filtration layer stacked on the dielectrophoretic layer; and one or more second filtration layers stacked on the first filtration layer. The common flow path may also be disposed in the first filtration layer.

[0012] In one embodiment of the present invention, the plurality of filter layers may include a plurality of second filter layers. The flow path chip may also include a plurality of outlet-side connecting flow paths connecting the outlets of the fluid dynamic filters of the plurality of second filter layers to the common flow path. The plurality of outlet-side connecting flow paths may not merge with each other in the second filter layer, but extend to the first filter layer and connect to the common flow path.

[0013] In one embodiment of the present invention, the filter layers may each include a plurality of the fluid dynamic filters.

[0014] In one aspect of the present invention, the plurality of hydrodynamic filters of each of the filter layers may be arranged symmetrically with respect to the common flow path.

[0015] In one aspect of the present invention, each of the filter layers may include a plurality of inlet-side connecting flow paths connecting the common supply path and the inlets of the plurality of fluid dynamic filters. In each of the filter layers, the plurality of inlet-side connecting flow paths may have substantially the same flow path length.

[0016] In one embodiment of the present invention, the flow path chip may include a first recovery path and a pair of second recovery paths connected to the downstream portion of the common flow path. The pair of second recovery paths may be arranged in a manner of sandwiching the first recovery path. The dielectric particles separated from the liquid passing through the fluid dynamic filter may flow through the first recovery path.

[0017] Effects of the Invention

[0018] According to the present invention, a flow channel chip capable of processing more sample solutions can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a cross-sectional view schematically showing the structure of a separation device including a flow channel chip according to one embodiment of the present invention.

[0020] Figure 2 This is a perspective view schematically showing a structure in which a flow channel chip is decomposed into a plurality of filtration layers and dielectrophoretic layers.

[0021] Figure 3 It is a plan view schematically showing the structure of the first filter layer.

[0022] Figure 4 It is a plan view schematically showing the structure of the second filter layer.

[0023] Figure 5 It is a top view schematically showing the structure of a fluid dynamic filter.

[0024] Figure 6It is a plan view schematically showing the structure of the common flow path and its surroundings.

[0025] Figure 7 It is a plan view schematically showing the structure of the dielectrophoretic layer.

[0026] Figure 8 It is a plan view schematically showing the structure of a common flow channel and electrodes.

[0027] Fig. 9 It is a top view schematically showing the structure of the flow channel chip.

[0028] Fig.10 It is a plan view schematically showing the structure around the branching portion of the common flow path.

[0029] Fig.11 It is a block diagram showing the structure of the separation device.

[0030] Fig.12 It is a cross-sectional view schematically showing the structure of a separation device including a flow channel chip according to a first modified example of the present invention.

[0031] Fig.13 It is a plan view schematically showing the structure of the first filter layer of the flow channel chip according to the second modified example of the present invention. DETAILED DESCRIPTION

[0032] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In addition, in the drawings, the same reference numerals are used for the same or corresponding parts, and the description thereof will not be repeated.

[0033] Reference Figures 1 to 11 , a separation device 100 including a flow channel chip 1 according to an embodiment of the present invention will be described. Figure 1 It is a cross-sectional view schematically showing the structure of a separation device 100 including a flow channel chip 1 according to an embodiment of the present invention. Figure 2 It is a perspective view schematically showing a structure in which the flow channel chip 1 is decomposed into a plurality of filtration layers 40 and dielectrophoretic layers 50 .

[0034] like Figure 1 and Figure 2 As shown, the separation device 100 of this embodiment includes a flow channel chip 1. The flow channel chip 1 includes a plurality of filtration layers 40 and a dielectrophoretic layer 50. Each of the plurality of filtration layers 40 includes a hydrodynamic filter 3 (Hydrodynamic filtration: HDF) (hereinafter referred to as HDF3). Figure 1 In order to simplify the drawing, the HDF 3 is depicted by a rectangular dotted line. For example, the flow channel chip 1 is a micro flow channel chip for separating and concentrating microparticles. For example, the flow channel chip 1 can separate specific cells from blood as described later.

[0035] In this embodiment, a plurality of filter layers 40 and dielectrophoretic layers 50 are stacked. Therefore, a plurality of HDF3 are configured for one flow path chip 1, so that more sample liquid L1 described below can be processed. In addition, there is no need to provide a dielectrophoretic layer 50 for each of the plurality of HDF3. That is, there is no need to provide the same number of dielectrophoretic layers 50 as the number of HDF3. Therefore, it is possible to suppress the enlargement of the flow path chip 1 or the enlargement of the separation device 100.

[0036] HDF3 is obtained from the sample liquid L1 (refer to Figure 5 ) to separate particles larger than a predetermined particle size. In addition, the detailed structure of HDF3 will be described later.

[0037] The dielectrophoretic layer 50 includes an electrode 51 and an electrode 53. The electrode 51 and the electrode 53 are electrodes for causing dielectric particles contained in a liquid passing through a common flow path 7 described later to undergo dielectrophoresis (DEP). The detailed structure of the dielectrophoretic layer 50 will be described later.

[0038] In addition, the plurality of filter layers 40 include a first filter layer 41 stacked on the dielectrophoretic layer 50 and one or more second filter layers 42 stacked on the first filter layer 41. In addition, in the present embodiment, the common flow path 7 described later is arranged on the first filter layer 41. Therefore, the dielectrophoretic layer 50 can be arranged near the common flow path 7, so that the dielectrophoretic force can be easily applied to the dielectric particles contained in the liquid passing through the common flow path 7. In addition, compared with the case where the first filter layer 41 is arranged on one side of the dielectrophoretic layer 50 and the second filter layer 42 is arranged on the other side of the dielectrophoretic layer 50, the second filter layer 42 can be easily stacked. In other words, compared with the case where the plurality of filter layers 40 are arranged in a manner of sandwiching the dielectrophoretic layer 50, the flow path chip 1 can be easily manufactured.

[0039] The flow path chip 1 further includes a first common supply path 5 and a common flow path 7. In addition, the first common supply path 5 is an example of the "common supply path" of the present invention. The first common supply path 5 extends along the stacking direction of the filter layer 40 and the dielectrophoretic layer 50. The first common supply path 5 supplies the sample liquid L1 to the HDF3 of the plurality of filter layers 40. In addition, Figure 1 In the figure, two first common supply paths 5 are depicted for easy understanding, but it is also possible to Figure 2 As shown, only one first common supply path 5 is provided. Hereinafter, an example in which only one first common supply path 5 is provided will be described. In addition, the outlets 3b of the HDF3 of the plurality of filter layers 40 are connected to the common flow path 7. The liquid after passing through the plurality of HDF3 flows into the common flow path 7.

[0040] In this embodiment, each filter layer 40 includes a plurality of (two in this case) HDFs 3. Therefore, more sample liquids L1 can be processed by one flow channel chip 1 compared to a case where each filter layer 40 includes one HDF 3.

[0041] The plurality of HDF3 of each filter layer 40 is arranged symmetrically with respect to the common flow path 7. Therefore, the design of each filter layer 40 can be simplified. In addition, the dimensions (length, width, and depth) of the flow paths (main flow path 31 and secondary flow path 33 described later) constituting the HDF3 are formed to be the same size as each other between the plurality of HDF3 of each filter layer 40. In the present embodiment, the dimensions of the flow paths constituting the HDF3 are formed to be the same size as each other in all the filter layers 40.

[0042] Figure 3 It is a plan view schematically showing the structure of the first filter layer 41 . Figure 4 4 is a top view schematically showing the structure of the second filter layer 42. Figure 3 and Figure 4 As shown, the flow channel chip 1 further includes a first connecting flow channel 9 and a second connecting flow channel 11. In addition, the first connecting flow channel 9 is an example of the "inlet side connecting flow channel" of the present invention. In addition, the second connecting flow channel 11 is an example of the "outlet side connecting flow channel" of the present invention.

[0043] The first connecting flow path 9 connects the first common supply path 5 and the inlet 3a of the HDF3. Specifically, the flow path chip 1 has a plurality of first connecting flow paths 9 in each filter layer 40. In each filter layer 40, the flow path lengths from the first common supply path 5 to the inlets 3a of the plurality of HDF3 are substantially the same. That is, in each filter layer 40, the flow path lengths of the plurality of (here two) first connecting flow paths 9 are substantially the same. Therefore, when the sample liquid L1 is supplied to the first common supply path 5, in each filter layer 40, the sample liquid L1 flows through the plurality of HDF3 substantially simultaneously. Therefore, the sample liquid L1 flows through the plurality of HDF3 under substantially the same conditions, thereby being able to suppress uneven separation performance of the HDF3.

[0044] In addition, in order to make the flow path lengths of a plurality of first connecting flow paths 9 roughly the same, at least one first connecting flow path 9 has a circuitous portion 9a, but in order to simplify the drawing, the circuitous portion 9a is depicted with three points. In addition, in each filter layer 40, the cross-sectional dimensions such as the width and depth of a plurality of first connecting flow paths 9 are roughly the same. In addition, between a plurality of filter layers 40, the flow path length and cross-sectional dimensions of the first connecting flow path 9 can be roughly the same, or can be different considering the flow path resistance, etc.

[0045] The second connecting flow path 11 connects the outlet 3b of HDF3 and the common flow path 7. Specifically, the second connecting flow path 11 connecting the outlet 3b of HDF3 of the first filter layer 41 and the common flow path 7 is composed of a first portion 11a extending from the outlet 3b of HDF3 in the surface direction (a direction orthogonal to the stacking direction). The second connecting flow path 11 connecting the outlet 3b of HDF3 of the second filter layer 42 and the common flow path 7 is composed of a first portion 11a extending from the outlet 3b of HDF3 in the surface direction, a second portion 11b extending from the first portion 11a in the stacking direction, and a third portion 11c extending from the second portion 11b in the surface direction and connected to the common flow path 7. In addition, Figure 1 In order to simplify the drawing, in the first filter layer 41, the first portion 11a and the third portion 11c are depicted as a common portion.

[0046] The flow channel chip 1 further includes a second common supply path 13 and a third connecting flow channel 15. Figure 1 In order to simplify the drawing, the second common supply path 13 and the third connecting flow path 15 are omitted. Figure 2 to Figure 4 As shown, the second common supply path 13 extends along the stacking direction of the filter layer 40 and the dielectrophoretic layer 50 .

[0047] The second common supply path 13 supplies the transport liquid L2 (see Figure 5 ) is supplied to HDF3 of multiple filter layers 40.

[0048] The third connecting flow path 15 connects the second common supply path 13 and the inlet 3 a of the HDF 3 .

[0049] In each filter layer 40, the flow path length from the second common supply path 13 to the inlet 3a of multiple HDF3 is roughly the same. That is, in each filter layer 40, the flow path length of multiple (two here) third connecting flow paths 15 is roughly the same. In addition, in order to make the flow path length of multiple third connecting flow paths 15 roughly the same, at least one third connecting flow path 15 has a circuitous portion 15a, but in order to simplify the drawing, the circuitous portion 15a is described with three points. In addition, in each filter layer 40, the cross-sectional dimensions such as the width and depth of multiple third connecting flow paths 15 are roughly the same. In addition, between multiple filter layers 40, the flow path length and cross-sectional dimensions of the third connecting flow path 15 can be roughly the same, and can also be different considering flow path resistance, etc.

[0050] The flow channel chip 1 further includes a recovery liquid supply path 17 and a fourth connecting flow channel 19. Figure 1 In order to simplify the drawing, the recovery liquid supply path 17 and the fourth connecting flow path 19 are omitted. The recovery liquid supply path 17 supplies the recovery liquid L3 (see Fig.10) is supplied to the common flow path 7. The recovery liquid L3 is not particularly limited, and for example, it is the same component as the transport liquid L2. In addition, the recovery liquid L3 may also be a component different from the transport liquid L2. The fourth connecting flow path 19 is arranged on the first filter layer 41. The fourth connecting flow path 19 connects the recovery liquid supply path 17 and the common flow path 7.

[0051] Next, refer to Figure 1 , the cross-sectional structure of the flow channel chip 1 is described. Figure 1 As shown, the dielectrophoretic layer 50 includes a substrate 55 and an insulating protective film 57 in addition to the electrodes 51 and 53. The substrate 55 is not particularly limited, and is made of glass, for example. In this embodiment, the substrate 55 is made of quartz glass. In addition, the substrate 55 is, for example, a substantially rectangular flat plate.

[0052] The electrodes 51 and 53 are disposed on one surface of the substrate 55. The electrodes 51 and 53 are made of metal such as aluminum or copper. The electrodes 51 and 53 are formed into a predetermined shape by vacuum deposition, photolithography, and etching.

[0053] The insulating protective film 57 covers the electrodes 51, 53 and the substrate 55. The insulating protective film 57 is not particularly limited, and may be, for example, an oxide film such as a silicon oxide film or a silicon nitride film. The insulating protective film 57 suppresses, for example, the time-dependent degradation of the electrodes 51 and 53 due to moisture.

[0054] The filter layer 40 also has an insulating layer 45. The insulating layer 45 is made of, for example, resin. In the present embodiment, the insulating layer 45 is transparent. The insulating layer 45 is formed of, for example, PDMS (dimethylpolysiloxane). HDF3 and various flow paths are formed in the insulating layer 45. The plurality of filter layers 40 are formed, for example, by sequentially stacking the plurality of insulating layers 45 formed with HDF3 and various flow paths on the dielectrophoretic layer 50. In addition, the filter layer 40 can also be formed, for example, by stacking an uncured resin on the dielectrophoretic layer 50 and curing it.

[0055] Next, refer to Figure 5 , the structure of HDF3 is explained in detail. Figure 5 FIG. 1 is a top view schematically showing the structure of HDF3. Figure 5 As shown, the HDF 3 has a main flow path 31 and a plurality of sub-flow paths 33 .

[0056] The main flow path 31 extends in a straight line, for example, in a predetermined direction. The sample liquid L1 flows in the main flow path 31. In the present embodiment, the sample liquid L1 and the transport liquid L2 flow in the main flow path 31. 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 that does not contain microparticles. The transport liquid L2 is not particularly limited, and is, for example, a liquid culture medium.

[0057] A plurality of secondary flow paths 33 are branched from the main flow path 31. Specifically, the plurality of secondary flow paths 33 are arranged at approximately equal intervals, for example, along the direction in which the main flow path 31 extends. The plurality of secondary flow paths 33 have, for example, the same length. The plurality of secondary flow paths 33 extend in a direction intersecting the main flow path 31. In the present embodiment, the plurality of secondary flow paths 33 extend in a direction orthogonal to the main flow path 31.

[0058] In addition, a plurality of secondary flow paths 33 are formed in such a manner that the flow path resistance gradually decreases from the upstream side toward the downstream side of the main flow path 31. Specifically, in the present embodiment, the portion of the base end side (the side close to the main flow path 31) of each secondary flow path 33 is formed as a first width. On the other hand, the portion of the terminal side (the side away from the main flow path 31) of each secondary flow path 33 is formed as a second width larger than the first width. Moreover, the closer the secondary flow path 33 is to the downstream side, the closer the position at which the change from the first width to the second width is configured 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. In addition, all the secondary flow paths 33 may also be formed to the same constant width. In this case, for example, the closer the secondary flow path 33 is to the downstream side, the shorter it is formed.

[0059] A portion of the liquid flowing in the main flow path 31 flows into the plurality of side flow paths 33. In addition, a portion of the particles contained in the liquid flowing in the main flow path 31 flows into the plurality of side flow paths 33. Whether the particles flow into the plurality of side flow paths 33 depends, for example, on the particle size. The smaller the particle size, the easier it is for the particles to flow into the side flow paths 33, and the larger the particle size, the more difficult it is for the particles to flow into the side flow paths 33. For example, when blood is used as the sample liquid L1, plasma (also called serum) and red blood cells and platelets, which are liquid components of the blood, can be made to flow into the side flow paths 33, and cancer cells and white blood cells contained in the blood can be made not to flow into the side flow paths 33. That is, particles with larger particle sizes, such as cancer cells and white blood cells, can be separated from the blood.

[0060] Next, refer to Figure 3 to Figure 5 , the operating principle of HDF3 is explained. Figure 3 and Figure 4 As shown, when the sample liquid L1 is supplied to the first common supply path 5 and the transport liquid L2 is supplied to the second common supply path 13, the sample liquid L1 and the transport liquid L2 flow to the main flow path 31 via the first connecting flow path 9 and the third connecting flow path 15, respectively. Figure 5 As shown, the sample liquid L1 flows along the inner wall 31a on the side of the secondary flow channel 33, and the transport liquid L2 flows along the inner wall 31b on the opposite side of the secondary flow channel 33. At this time, the center of each particle passes through a position of the main flow channel 31 that is larger than the radius of the particle separation from the inner wall 31a.

[0061] Here, the flow velocity varies depending on the position in the width direction of the main channel 31. Specifically, the flow velocity decreases near the inner wall 31a and the inner wall 31b in the main channel 31. On the other hand, the flow velocity is maximum at a position away from the inner wall 31a and the inner wall 31b in the main channel 31 (the center in the width direction of the main channel 31).

[0062] Therefore, particles having a small particle size and passing near the inner wall 31a are easy to flow into the secondary flow path 33 due to the low flow velocity. On the other hand, particles having a large particle size and passing at a position far from the inner wall 31a do not flow into the secondary flow path 33 due to the high flow velocity, but move straight in the main flow path 31. That is, particles larger than a predetermined size will not be discharged from the main flow path 31 to the secondary flow path 33, and on the other hand, particles below a predetermined size are discharged from the main flow path 31 to the secondary flow path 33. The discharge from the main flow path 31 to the secondary flow path 33 is repeated through a plurality of secondary flow paths 33, so particles below a predetermined size will not reach the downstream end of the main flow path 31 (the outlet 3b of the HDF3). In addition, plasma, which is a liquid component, will not reach the downstream end of the main flow path 31. Therefore, by using the flow path chip 1, particles having a large particle size, such as cancer cells and white blood cells, can be separated from the blood.

[0063] Next, refer to Figure 6 , the first filter layer 41 is further described. Figure 6 2 is a top view schematically showing the structure of the common flow path 7 and its surroundings. Figure 6 As shown, a common flow path 7 is arranged in the first filter layer 41. The common flow path 7 extends in a straight line toward a predetermined direction. The common flow path 7 has a confluence portion 7a and a branch portion 7b. The confluence portion 7a is arranged at the upstream end of the common flow path 7. The branch portion 7b is arranged at the downstream end of the common flow path 7.

[0064] The second connecting flow path 11 is connected to the upstream end of the common flow path 7. In the present embodiment, four second connecting flow paths 11 are connected to the upstream end of the common flow path 7. In addition, the fourth connecting flow path 19 is connected to the upstream end of the common flow path 7. In the present embodiment, the fourth connecting flow path 19 is arranged between two second connecting flow paths 11 and two second connecting flow paths 11. In addition, the four second connecting flow paths 11 are arranged symmetrically with respect to the fourth connecting flow path 19. The second connecting flow paths 11 and the fourth connecting flow path 19 merge at the confluence portion 7a of the common flow path 7.

[0065] The flow path chip 1 also includes a first recovery path 21 and a second recovery path 23 connected to the downstream portion of the common flow path 7. In the present embodiment, the flow path chip 1 includes a first recovery path 21 and a pair of second recovery paths 23 connected to the downstream portion of the common flow path 7. The first recovery path 21 and a pair of second recovery paths 23 are connected to the downstream end of the common flow path 7. The common flow path 7 branches into the first recovery path 21 and a pair of second recovery paths 23 at the branching portion 7b. The pair of second recovery paths 23 are configured in a manner that separates the first recovery path 21. Therefore, as described later, in the case of recovering the target recyclate (here, cancer cells) from the first recovery path 21, the target recyclate can be recovered from one first recovery path 21. Therefore, compared with the case where a pair of first recovery paths 21 are provided, the target recyclate can be recovered more easily.

[0066] like Figure 2 As shown, the first recovery path 21 and the second recovery path 23 extend in the stacking direction after being led out from the common flow path 7 in the surface direction. In addition, the first recovery path 21 and the second recovery path 23 have an outlet 21a and an outlet 23a, respectively. The outlet 21a and the outlet 23a are arranged in the second filter layer 42. The liquid after passing through the first recovery path 21 is recovered to the first recovery part not shown in the figure via the outlet 21a. The first recovery part, for example, includes a recovery container. The liquid after passing through the second recovery path 23 is recovered to the second recovery part not shown in the figure via the outlet 23a. The second recovery part, for example, includes a recovery container. In addition, in the present embodiment, as described later, the dielectric particles (here, cancer cells) separated from the liquid after passing through HDF3 flow into the first recovery path 21.

[0067] Next, refer to Figure 7 to Figure 10 , separation based on the dielectrophoretic layer 50 and dielectrophoresis will be described. Figure 7 is a top view schematically showing the structure of the dielectrophoretic layer 50. Figure 7 As shown, the dielectrophoretic layer 50 has a lead wiring 52 and a lead wiring 54 in addition to the electrode 51 and the electrode 53. One end of the lead wiring 52 is connected to the electrode 51. The lead wiring 52 has a terminal portion 52a. The terminal portion 52a is arranged at the other end of the lead wiring 52. The separation device 100 includes an AC power supply 110, and the terminal portion 52a of the lead wiring 52 is electrically connected to the AC power supply 110. One end of the lead wiring 54 is connected to the electrode 53. The lead wiring 54 has a terminal portion 54a. The terminal portion 54a is arranged at the other end of the lead wiring 54. The terminal portion 54a of the lead wiring 54 is electrically connected to the AC power supply 110. An AC voltage is applied between the terminal portion 52a and the terminal portion 54a through the AC power supply 110.

[0068] Figure 8 It is a plan view schematically showing the structures of the common flow channel 7 , the electrode 51 , and the electrode 53 . Fig. 91 is a top view schematically showing the structure of the flow channel chip 1. Fig. 9 In the figure, for ease of understanding, the first filter layer 41 and the second filter layer 42 are indicated by solid lines, and the dielectrophoretic layer 50 is indicated by dotted lines. The dielectrophoretic layer 50 can further separate particles flowing in the common flow path 7 by dielectrophoresis. Specifically, Figure 8 and Fig. 9 As shown, the electrode 51 and the electrode 53 are arranged in a manner overlapping with the common flow path 7. That is, the electrode 51 and the electrode 53 are opposite to the common flow path 7 in the stacking direction. The electrode 51 and the electrode 53 are comb-tooth-shaped electrodes facing each other. The teeth of the electrode 51 and the electrode 53 are inclined relative to the common flow path 7, for example, by more than 10° and less than 60°. In the present embodiment, the teeth of the electrode 51 and the electrode 53 are arranged symmetrically in the width direction of the common flow path 7. Specifically, the teeth of the electrode 51 and the electrode 53 extend from the upstream side toward the downstream side and from the width direction outer side of the common flow path 7 toward the width direction center.

[0069] By applying an AC voltage between the electrodes 51 and 53 using the AC power supply 110, the particles passing through the common flow path 7 can be subjected to dielectrophoresis. Furthermore, by adjusting the frequency of the applied AC voltage, desired particles can be separated and recovered from the plurality of particles passing through the common flow path 7 by dielectrophoresis.

[0070] Specifically, when the plurality of particles passing through the common flow path 7 include dielectric particles, specific dielectric particles can be separated from the plurality of particles by dielectrophoresis. For example, cancer cells and leukocytes are dielectric particles. When the plurality of particles passing through the common flow path 7 include cancer cells and particles other than cancer cells (leukocytes, etc.) larger than a predetermined size, for example, an AC voltage of a specific frequency is applied between the electrode 51 and the electrode 53 in such a manner that the dielectrophoretic force easily acts on the cancer cells. Thus, as shown in FIG. Figure 8 As shown, cancer cells can be moved along electrodes 51 and 53, so that only cancer cells can be guided to the first recovery path 21 by dielectrophoresis. Therefore, cancer cells and other particles (white blood cells, etc.) can be separated. Figure 8 In the figure, arrow A represents the flow of cancer cells, and arrow B represents the flow of other particles.

[0071] Fig.10 7 is a top view schematically showing the structure around the branch portion 7b of the common flow path 7. More specifically, Fig.10As shown, the transport liquid L2 does not flow in the first recovery path 21, but only the recovery liquid L3 flows. In this embodiment, the transport liquid L2 flows in the second recovery path 23, but does not flow in the first recovery path 21. The recovery liquid L3 flows in the first recovery path 21 and the second recovery path 23. Therefore, when the dielectrophoretic force is not exerted, the particles will not flow in the first recovery path 21. On the other hand, in this embodiment, by exerting the dielectrophoretic force, for example, cancer cells can be moved from the outside in the width direction of the common flow path 7 to the inside in the width direction. Therefore, only cancer cells among the multiple particles can be guided to the first recovery path 21.

[0072] Next, refer to Figure 4 , further illustrating the separation device 100. Figure 4 As shown, the separation device 100 also includes a sample liquid feeding section 61, a transport liquid feeding section 63, and a recovery liquid feeding section 65. The separation device 100 may also include a control section, which drives the sample liquid feeding section 61, the transport liquid feeding section 63, and the recovery liquid feeding section 65. In this embodiment, the control section 131 described later drives the sample liquid feeding section 61, the transport liquid feeding section 63, and the recovery liquid feeding section 65. The sample liquid feeding section 61, the transport liquid feeding section 63, and the recovery liquid feeding section 65 are not particularly limited, and are, for example, micro pumps. The micro pump may be a mechanical pump or a non-mechanical pump.

[0073] The sample liquid feeding unit 61 is connected to the first common supply path 5 to allow the sample liquid L1 to flow into the first common supply path 5. The sample liquid L1 is supplied to the first common supply path 5 by the sample liquid feeding unit 61, and thus flows to the first connecting flow paths 9 of each filter layer 40 and the HDF3.

[0074] The liquid feeder 63 is connected to the second common supply path 13 to allow the liquid L2 to flow into the second common supply path 13. The liquid feeder 63 supplies the liquid L2 to the second common supply path 13, so that the liquid L2 flows to the third connection flow path 15 of each filter layer 40 and the HDF3.

[0075] The recovery liquid feeding unit 65 is connected to the recovery liquid supply path 17 to allow the recovery liquid L3 to flow into the recovery liquid supply path 17. The recovery liquid L3 is supplied to the recovery liquid supply path 17 by the recovery liquid feeding unit 65, so that the recovery liquid L3 flows in the fourth connecting flow path 19 and the common flow path 7.

[0076] In this embodiment, the sample liquid feeding section 61 supplies the sample liquid L1 in a laminar flow. The transport liquid feeding section 63 supplies the transport liquid L2 in a laminar flow. The recovery liquid feeding section 65 supplies the recovery liquid L3 in a laminar flow. Therefore, in this embodiment, in the flow path chip 1, each liquid is in a laminar flow.

[0077] Next, refer to Fig.11 , further illustrating the separation device 100. Fig.11 is a block diagram showing the structure of the separation device 100. Fig.11 As shown, the separation device 100 also includes a photographing unit 120 and a control device 130. The photographing unit 120 obtains an image of a predetermined area of ​​the flow path chip 1. The photographing unit 120 sends the photographed image data to the control unit 131 described later of the control device 130. The photographing unit 120, for example, includes a camera having a photographing element such as a CCD image sensor or a CMOS image sensor and an optical microscope module. The photographing unit 120 may also include other cameras and other microscopes. In addition, the separation device 100 may also include a display unit, which displays the image photographed by the photographing unit 120.

[0078] The imaging unit 120 is used to confirm the operation of the flow channel chip 1. For example, in this embodiment, the imaging unit 120 is used to confirm whether particles larger than a predetermined particle size and particles smaller than a predetermined particle size are separated by HDF 3. In addition, in this embodiment, the imaging unit 120 is used to confirm whether cancer cells and other particles are separated by dielectrophoresis.

[0079] Here, in this embodiment, if Fig.10 As shown, the first recovery path 21 and the pair of second recovery paths 23 are arranged in the shooting area R120 of the shooting unit 120. Specifically, the entire width direction area of ​​the first recovery path 21 and the entire width direction area of ​​the pair of second recovery paths 23 are arranged in the shooting area R120. Therefore, the shooting unit 120 can shoot all particles passing through the first recovery path 21 and all particles passing through the pair of second recovery paths 23. Therefore, compared with the case where one shooting unit 120 is provided for each recovery path (the first recovery path 21, the pair of second recovery paths 23), the structure of the separation device 100 can be simplified.

[0080] The control device 130 includes a control unit 131 and a storage unit 132. The control unit 131 includes a processor. The control unit 131 includes, for example, a central processing unit (CPU).

[0081] The storage unit 132 stores data and computer programs. The storage unit 132 includes a main storage device and an auxiliary storage device. The main storage device is, for example, a semiconductor memory. The auxiliary storage device is, for example, a semiconductor memory and / or a hard disk drive. The storage unit 132 may also include a removable medium.

[0082] The control unit 131 executes the computer program stored in the storage unit 132 to perform the operation of the separation device 100 . The control unit 131 receives the image data from the imaging unit 120 .

[0083] For example, the control unit 131 determines whether particles with a predetermined particle size or less pass through the first recovery path 21 or the second recovery path 23 based on the image data from the imaging unit 120. When particles with a predetermined particle size or less pass through the first recovery path 21 or the second recovery path 23, there is a high possibility that separation based on HDF3 is not performed normally. Therefore, when the control unit 131 determines that particles with a predetermined particle size or less pass through the first recovery path 21 or the second recovery path 23, the driving of the sample liquid feeding unit 61, the transport liquid feeding unit 63, and the recovery liquid feeding unit 65 is stopped.

[0084] In addition, the control unit 131 determines whether the particle passes through the second recovery path 23 based on the image data from the imaging unit 120. In the case where the particle does not pass through the second recovery path 23, there is a high possibility that the separation based on HDF3 or the separation based on dielectrophoresis is not performed normally. Therefore, when the control unit 131 determines that the particle does not pass through the second recovery path 23, the drive of the sample liquid feeding unit 61, the transport liquid feeding unit 63, and the recovery liquid feeding unit 65 is stopped. In addition, the control unit 131 may also determine whether the particle passes through the first recovery path 21 based on the image data from the imaging unit 120. Moreover, the control unit 131 may also stop the drive of the sample liquid feeding unit 61, the transport liquid feeding unit 63, and the recovery liquid feeding unit 65 when it is determined that the particle does not pass through the first recovery path 21.

[0085] Next, refer to Fig.12 , a separation device 100 according to a first variation of the present invention will be described. Fig.12 1 is a cross-sectional view schematically showing the structure of a separation device 100 having a flow channel chip 1 according to a first variation of the present invention. Figures 1 to 11 Different from the above-described embodiment, an example in which the plurality of filter layers 40 include two or more second filter layers 42 will be described.

[0086] like Fig.12 As shown, in the separation device 100 of the first variant of the present invention, the plurality of filter layers 40 include a first filter layer 41 and two or more second filter layers 42 stacked on the first filter layer 41. In the first variant, the plurality of filter layers 40 include a first filter layer 41 and three second filter layers 42. Figures 1 to 11Compared with the flow channel chip 1 of the above-described embodiment, the flow channel chip 1 of the first modified example can process a larger amount of sample liquid L1. In addition, the plurality of filter layers 40 may include two second filter layers 42 or four or more second filter layers 42.

[0087] In addition, the flow path chip 1 has a plurality of second connecting flow paths 11 that connect the outlets 3b of the HDF3 of the plurality of (here three) second filter layers 42 and the common flow path 7. In the first variant, the plurality of second connecting flow paths 11 do not merge with each other in the second filter layer 42, but extend to the first filter layer 41 and are connected to the common flow path 7. Here, in the case where the second connecting flow paths 11 are merged with each other in the second filter layer 42, a higher positioning accuracy is required when stacking the second filter layer 42. However, in the first variant, the second connecting flow paths 11 are not merged with each other in the second filter layer 42, so that the need for higher positioning accuracy when stacking the second filter layer 42 can be suppressed. That is, the manufacturing of the flow path chip 1 can be suppressed from becoming complicated. In addition, the plurality of second connecting flow paths 11 can also be connected to the common flow path 7 in the first filter layer 41 after merging with each other in the second filter layer 42.

[0088] The other structures and effects of the first modified example are the same as those of the above-mentioned embodiment.

[0089] Next, refer to Fig.13 , a separation device 100 according to a second variation of the present invention will be described. Fig.13 1 is a top view schematically showing the structure of the first filter layer 41 of the flow channel chip 1 according to the second modified example of the present invention. Figures 1 to 11 Different from the above-described embodiment, an example in which the first connecting flow path 9 and the third connecting flow path 15 are connected to the HDF 3 after merging will be described.

[0090] like Fig.13 As shown, in the flow path chip 1 of the second modified example of the present invention, the first connecting flow path 9 and the third connecting flow path 15 are connected to the inlet 3a of the HDF 3 after merging with each other. Therefore, the path through which the first connecting flow path 9 and the third connecting flow path 15 pass can be simplified, so the design of the flow path chip 1 can be simplified.

[0091] In addition, in the flow path chip 1 of the second variant, the second connecting flow path 11 is connected in a cross manner relative to the common flow path 7. Specifically, the second connecting flow path 11 is connected approximately perpendicularly to the common flow path 7. In the case where the second connecting flow path 11 is connected approximately perpendicularly to the common flow path 7 and in the case where it is connected in an inclined manner relative to the common flow path 7, as in the above-mentioned embodiment, specific particles can be separated by dielectrophoresis. In addition, although not shown in the figure, multiple second connecting flow paths 11 can also be connected to the common flow path 7 after merging with each other, similar to the first connecting flow path 9 and the third connecting flow path 15.

[0092] The other structures and effects of the second modified example are the same as those of the above-mentioned embodiment.

[0093] 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 various modes can be implemented within the scope without departing from its main purpose. 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 also be deleted from all the constituent elements shown in the embodiments. Moreover, the constituent elements of different embodiments can also be appropriately combined. For ease of understanding, the drawings are schematically shown with each constituent element as the main body, and for the convenience of drawing, the thickness, length, number, interval, etc. of each constituent element shown in the drawings are sometimes different from the actual ones. In addition, the material, shape, size, etc. of each constituent element shown in the above-mentioned embodiments are examples, and are not particularly limited. Various changes can be made within the scope of the effect of the present invention.

[0094] For example, in the above-mentioned embodiment, an example is described in which the plurality of filter layers 40 include a first filter layer 41 disposed on one side of the dielectrophoretic layer 50 and a second filter layer 42 disposed on the first filter layer 41, but the present invention is not limited thereto. For example, the plurality of filter layers 40 may also include a filter layer 40 disposed on one side of the dielectrophoretic layer 50 and a filter layer 40 disposed on the other side of the dielectrophoretic layer 50.

[0095] In addition, in the above embodiment, the example in which the common flow path 7 is arranged in the first filter layer 41 arranged on one surface of the dielectrophoretic layer 50 among the plurality of filter layers 40 is described, but the present invention is not limited thereto. For example, the common flow path 7 may be arranged in any one of the one or more second filter layers 42 stacked on the first filter layer 41.

[0096] In the above embodiment, the common flow path 7 is arranged in the filter layer 40 having HDF 3, but the present invention is not limited thereto. For example, a layer not having HDF 3 may be separately provided and the common flow path 7 may be arranged in the layer not having HDF 3.

[0097] In addition, in the above embodiment, each filter layer 40 has an example in which a plurality of HDFs 3 are provided, but the present invention is not limited thereto. For example, each filter layer 40 may have only one HDF 3 .

[0098] In addition, in the above embodiment, the example in which the HDF 3 is arranged symmetrically with respect to the common flow path 7 in each filter layer 40 is described, but the present invention is not limited thereto. For example, the HDF 3 may be arranged asymmetrically in each filter layer 40 .

[0099] In addition, in the above embodiment, for example, in each filter layer 40, the flow path lengths of the plurality of first connecting flow paths 9 are substantially the same, and the flow path lengths of the plurality of third connecting flow paths 15 are substantially the same, but the present invention is not limited thereto. For example, in each filter layer 40, the flow path lengths of the plurality of first connecting flow paths 9 may be different. In addition, in each filter layer 40, the flow path lengths of the plurality of third connecting flow paths 15 may be different.

[0100] In addition, although not described in the above embodiment, the recovery liquid feeding section 65 can adjust the amount of the recovery liquid L3 supplied to the recovery liquid supply path 17. That is, the recovery liquid feeding section 65 can adjust the amount of the recovery liquid L3 flowing through the common flow path 7. In this case, by changing the amount of the recovery liquid L3 flowing through the common flow path 7, the amounts of the sample liquid L1 and the transport liquid L2 flowing through the common flow path 7 are changed. That is, the ease of flow of the sample liquid L1 and the transport liquid L2 relative to the common flow path 7 is changed. Therefore, in the HDF3 connected to the common flow path 7, the ease of flow from the main flow path 31 to the secondary flow path 33 is changed. Therefore, for example, even when the dimensions such as the width and depth of the flow path at each position of the HDF 3 deviate from the set values ​​due to manufacturing variations, it is possible to suppress particles larger than a predetermined particle size (such as cancer cells and white blood cells) from flowing into the secondary flow path 33, or particles smaller than a predetermined particle size (such as red blood cells and platelets) from flowing into the common flow path 7 through the main flow path 31 by adjusting the amount of the recovery liquid L3 flowing through the recovery liquid supply path 17. Therefore, even when the dimensions of the flow path deviate from the set values, particles of a predetermined particle size can be separated.

[0101] In addition, in the above-mentioned embodiment, the control unit 131 stops driving the sample liquid feeding unit 61, the transport liquid feeding unit 63, and the recovery liquid feeding unit 65 when it is determined that particles with a predetermined particle size or less have passed through the first recovery path 21 or the second recovery path 23, when it is determined that particles have not passed through the second recovery path 23, or when it is determined that particles have not passed through the first recovery path 21. However, the present invention is not limited to this.

[0102] For example, the control unit 131 may also adjust the amount of the recovery liquid L3 flowing through the common flow path 7 so that the particles with a predetermined particle size or less do not pass through the first recovery path 21 or the second recovery path 23 when it is determined that the particles have a predetermined particle size or less. For example, the control unit 131 may also adjust the amount of the recovery liquid L3 flowing through the common flow path 7 so that the particles pass through the second recovery path 23 when it is determined that the particles have not passed through the second recovery path 23. For example, the control unit 131 may also adjust the amount of the recovery liquid L3 flowing through the common flow path 7 so that the particles pass through the first recovery path 21 when it is determined that the particles have not passed through the first recovery path 21.

[0103] 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.

[0104] In the above embodiment, particles (such as cancer cells) recovered from the outlet 21a are cited as target recovery objects, but the present invention is not limited thereto. For example, particles or liquid components recovered from the outlet 23a may be used as target recovery objects.

[0105] In addition, in the above embodiment, an example in which the transport liquid L2 and the recovery liquid L3 do not contain particles is described, but the present invention is not limited to this. The transport liquid L2 and the recovery liquid L3 may also contain particles. However, it is preferred to separate the particles contained in the transport liquid L2 and the recovery liquid L3 from the particles contained in the sample liquid L1 by dielectrophoresis.

[0106] In addition, in the above embodiment, an example of using the transport liquid L2 is described. That is, an example of making the transport liquid L2 flow into the HDF3 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 into the HDF3. For example, seawater containing particles may be used as the sample liquid L1 to separate the particles from the seawater.

[0107] Availability in production

[0108] The present invention can be used in the field of flow path chips.

[0109] Explanation of symbols

[0110] 1—flow path chip, 3—HDF (hydrodynamic filter), 3a—inlet, 3b—outlet, 5—first common supply path (common supply path), 7—common flow path, 9—first connecting flow path (inlet side connecting flow path), 11—second connecting flow path (outlet side connecting flow path), 21—first recovery path, 23—second recovery path, 40—filtration layer, 41—first filtration layer, 42—second filtration layer, 50—dielectrophoresis layer, 51, 53—electrodes, L1—sample liquid.

Claims

1. A flow channel chip, characterized in that: have: a plurality of filter layers, each having a hydrodynamic filter; a common supply path for supplying a sample liquid to the hydrodynamic filters of the plurality of filter layers; a common flow path through which the liquid that has passed through the plurality of fluid dynamic filters passes; and a dielectrophoretic layer having electrodes for causing dielectric particles contained in the liquid passing through the common flow path to dielectrophoretically conduct, The plurality of filter layers and the dielectrophoretic layer are stacked.

2. The flow path chip according to claim 1, characterized in that: The above-mentioned multiple filtering layers include: A first filter layer stacked on the dielectrophoretic layer; and One or more second filter layers stacked on the first filter layer, The common flow path is disposed in the first filter layer.

3. The flow path chip according to claim 2, characterized in that: The plurality of filter layers include a plurality of the second filter layers. The flow channel chip includes a plurality of outlet-side connecting flow channels that connect the outlets of the plurality of fluid dynamic filters of the second filter layer to the common flow channel. The plurality of outlet-side connecting flow paths do not merge with each other in the second filter layer, but extend to the first filter layer and are connected to the common flow path.

4. The flow channel chip according to any one of claims 1 to 3, characterized in that: The filter layers each have a plurality of the fluid dynamic filters.

5. The flow path chip according to claim 4, characterized in that: The plurality of hydrodynamic filters of each of the filter layers are arranged symmetrically with respect to the common flow path.

6. The flow channel chip according to claim 4 or 5, characterized in that: Each of the filter layers is provided with a plurality of inlet-side connecting flow paths connecting the common supply path and the inlets of the plurality of fluid dynamic filters. In each of the filter layers, the plurality of inlet-side connecting flow paths have substantially the same flow path length.

7. The flow channel chip according to any one of claims 4 to 6, characterized in that: A first recovery path and a pair of second recovery paths connected to the downstream portion of the common flow path are provided, The pair of second recovery paths are arranged so as to sandwich the first recovery path. The dielectric particles separated from the liquid that has passed through the hydrodynamic filter flow through the first recovery path.

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