Flow path chip, separation system, and separation method

Abstract

To provide a flow path chip capable of improving accuracy of separation of target dielectric particles from a suspension, a separation system, and a control method.SOLUTION: A flow path chip 10 comprises: a substrate 10a that has an inlet 21 through which a suspension L1 containing a plurality of types of dielectric particles P1, P2 including a specific type of dielectric particles P1 is introduced, and a flow path 30 through which the plurality of types of dielectric particles P1, P2 of the suspension L1 introduced from the inlet 21 flow; a first electrode 50 that guides the specific type of dielectric particles P1 among the plurality of types of dielectric particles P1, P2 to a first end 311 side in a width direction W1 of the flow path 30; and a second electrode 60 between the inlet 21 and the first electrode 50 that guides the plurality of types of dielectric particles P1, P2 to a second end 312 side in the width direction W1 of the flow path 30.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present disclosure relates to a flow path chip, a separation system, and a separation method.

Background Art

[0002] Dielectrophoresis is utilized as a particle control technique in a microspace such as a microfluidic device. In the biological field, various research and developments have been conducted mainly on the characterization analysis, separation, and concentration of cells and microorganisms. Although there are various forms, for example, Patent Document 1 can be cited.

[0003] The separation device disclosed in Patent Document 1 includes a flow path through which a sample solution (suspension) containing circulating cancer cells in blood (specific types of dielectric particles) flows in a predetermined direction (liquid flow direction), a replacement unit, an analysis unit, and a separation unit. The separation unit includes a pair of electrodes, a power supply unit, and a collection unit. The power supply unit generates an alternating voltage and supplies it between the pair of electrodes. As a result, a positive dielectrophoretic force (attractive force) acts on the cancer cells, and the cancer cells are attracted to the pair of electrodes and flow through the flow path along the extending direction of the pair of electrodes and are collected by the collection unit.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] The present disclosure provides a flow path chip, a separation system, and a control method capable of improving the separation accuracy of specific types of dielectric particles from a suspension.

Means for Solving the Problems

[0006] The flow channel chip according to one aspect of the present disclosure includes a substrate having an inlet into which a suspension containing a plurality of types of dielectric particles including a specific type of dielectric particles is introduced and a flow channel through which the plurality of types of dielectric particles of the suspension introduced from the inlet flow, a first electrode that guides the specific type of dielectric particles among the plurality of types of dielectric particles to a first end side in the width direction of the flow channel, and a second electrode that is between the inlet and the first electrode and guides the plurality of types of dielectric particles to a second end side in the width direction of the flow channel.

[0007] A separation system according to one aspect of the present disclosure includes the above-described flow channel chip and a voltage control device that controls the voltage of the second electrode so as to guide the plurality of types of dielectric particles including the specific type of dielectric particles contained in the suspension to the second end side in the width direction of the flow channel, and controls the voltage of the first electrode so as to guide the specific type of dielectric particles among the plurality of types of dielectric particles to the first end side in the width direction of the flow channel.

[0008] A separation method according to one aspect of the present disclosure is a separation method using the above-described flow channel chip, and controls the voltage of the second electrode so as to guide the plurality of types of dielectric particles including the specific type of dielectric particles contained in the suspension to the second end side in the width direction of the flow channel, and controls the voltage of the first electrode so as to guide the specific type of dielectric particles among the plurality of types of dielectric particles to the first end side in the width direction of the flow channel.

Advantages of the Invention

[0009] According to the aspect of the present disclosure, the accuracy of separating specific types of dielectric particles from a suspension can be improved.

Brief Description of the Drawings

[0010]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

[0011] [1. Embodiment] [1.1 Embodiment 1] [1.1.1 Outline] FIG. 1 is a block diagram of a configuration example of the separation system 1 of Embodiment 1. The separation system 1 of FIG. 1 enables the separation of a specific type of dielectric particle P1 from the suspension L1. The suspension L1 contains a plurality of types of dielectric particles including a specific type of dielectric particle P1. The separation system 1 of FIG. 1 separates a specific type of dielectric particle P1 from the plurality of types of dielectric particles contained in the suspension L1 by utilizing the principle of dielectrophoresis. In the present embodiment, the suspension L1 is blood. The plurality of types of dielectric particles are, for example, cells contained in blood. Examples of cells contained in blood include cancer cells and white blood cells. In the present embodiment, for ease of explanation, it is assumed that the suspension L1 contains two types of dielectric particles P1 and P2. The specific type of dielectric particle P1 is a cancer cell, particularly a circulating tumor cell (CTC) in the blood. The dielectric particle P2 is a white blood cell. The separation system 1 of FIG. 1 is used to separate circulating tumor cells (specific type of dielectric particles P1) from blood (suspension L1).

[0012] The separation system 1 in FIG. 1 includes a flow channel chip 10 through which a suspension L1 flows. The flow channel chip 10 in FIG. 1 includes a substrate 10a, a first electrode 50, and a second electrode 60. The substrate 10a has an inlet 21 into which a suspension L1 containing a plurality of types of dielectric particles P1, P2 including a specific type of dielectric particle P1 is introduced, and a flow channel 30 through which the plurality of types of dielectric particles P1, P2 of the suspension L1 introduced from the inlet 21 flow. The first electrode 50 guides a specific type of dielectric particle P1 among the plurality of types of dielectric particles P1, P2 to the first end 311 side in the width direction W1 of the flow channel 30. The second electrode 60 is located between the inlet 21 and the first electrode 50 and guides the plurality of types of dielectric particles P1, P2 to the second end 312 side in the width direction W1 of the flow channel 30.

[0013] In the flow channel chip 10 of FIG. 1, the second electrode 60 is disposed between the inlet 21 and the first electrode 50. The second electrode 60 can guide the plurality of types of dielectric particles P1, P2 to the second end 312 side in the width direction W1 of the flow channel 30. That is, before the first electrode 50 guides a specific type of dielectric particle P1 among the plurality of types of dielectric particles P1, P2 to the first end 311 side in the width direction W1 of the flow channel 30, the second electrode 60 can position the plurality of types of dielectric particles P1, P2 on the second end 312 side in the width direction W1 of the flow channel 30. Thereby, the probability that dielectric particles P2 other than the specific type of dielectric particle P1 among the plurality of types of dielectric particles P1, P2 exist on the first end 311 side in the width direction W1 of the flow channel 30 can be reduced. Therefore, according to the flow channel chip 10, the separation accuracy of the specific type of dielectric particle P1 from the suspension L1 can be improved.

[0014] [1.1.2 Details] Hereinafter, the flow channel chip 10 and the separation system 1 of Embodiment 1 will be further described. As shown in FIG. 1, the separation system 1 includes a flow channel chip 10, a voltage control device 11, and an analysis device 12.

[0015] [1.1.2.1 Flow Channel Chip] The flow path chip 10 constitutes a micro flow path for separating specific types of dielectric particles P1 from the suspension L1. In the separation system 1, the suspension L1 is flowed into the flow path chip 10, and specific types of dielectric particles P1 are separated from the suspension L1 within the flow path chip 10. In the separation system 1, the flow path chip 10 is configured to be disposable from the viewpoint of preventing contamination.

[0016] FIG. 2 is a schematic plan view of the flow path chip 10. The flow path chip 10 in FIG. 2 includes a substrate 10a, a first electrode 50, a second electrode 60, first electrode pads 71 and 72, and second electrode pads 81 and 82.

[0017] The substrate 10a has inlets 21 and 22, a flow path 30, and a plurality of collection parts 40-1 and 40-2 (hereinafter collectively referred to by the reference numeral 40). The substrate 10a is a part that defines the outer shape of the flow path chip 10. In the present embodiment, the substrate 10a is in the shape of a rectangular plate. The substrate 10a is formed using, for example, a substrate made of glass or silicone (for example, polydimethylsiloxane (PDMS)). As an example, the substrate 10a may be formed by attaching a second substrate (for example, a PDMS substrate) having spaces corresponding to the inlets 21 and 22, the flow path 30, and the plurality of collection parts 40-1 and 40-2 formed on the surface thereof to a first substrate (for example, a glass substrate) on which the first electrode 50, the second electrode 60, the first electrode pads 71 and 72, and the second electrode pads 81 and 82 are formed on the surface.

[0018] As shown in FIG. 1, the inlet 21 is a portion of the substrate 10a where the suspension L1 is introduced. The inlet 21 is connected to the supply source of the suspension L1 by a tube, for example, and the suspension L1 is supplied through the tube. As shown in FIG. 1, the inlet 22 is a portion of the substrate 10a where the replacement liquid L2 is introduced. The replacement liquid L2 is used, for example, to remove unnecessary components from the suspension L1 and transport a plurality of types of dielectric particles P1, P2 in the suspension L1. The unnecessary components are components unnecessary in the separation of a specific type of dielectric particle P1 from the suspension L1. Examples of the unnecessary components include small cells P3 such as red blood cells contained in the suspension L1 and the solution. The replacement liquid L2 may be selected so as to be capable of transporting a plurality of types of dielectric particles P1, P2 and not inhibiting the application of dielectrophoretic force to the plurality of types of dielectric particles P1, P2. In particular, a liquid having a lower conductivity than the solution of the suspension L1 is used as the replacement liquid L2 in order to facilitate the separation of a specific type of dielectric particle P1. However, this is not the case when the conductivity of the solution of the suspension L1 is low.

[0019] The flow path 30 is a portion where a plurality of types of dielectric particles P1, P2 of the suspension L1 introduced from the inlet 21 flow in the substrate 10a. As shown in FIG. 2, the flow path 30 includes a main flow path 31, a connecting flow path 32, a plurality (two in the illustrated example) of branch flow paths 33-1, 33-2 (hereinafter collectively referred to by reference numeral 33), connection paths 34, 35, and a filter 90. In the present embodiment, the surface of the substrate 10a on the first substrate side in the flow path 30 is the bottom surface, and the surface of the substrate 10a on the second substrate side in the flow path 30 is the top surface.

[0020] The main flow path 31 constitutes the main body of the flow path 30. The main flow path 31 is a part for separating specific types of dielectric particles P1 in the flow path 30. In the present embodiment, the main flow path 31 is rectangular in a plan view (when viewed from the thickness direction of the base 10a). The cross-sectional shape of the main flow path 31 in a plane orthogonal to the length direction of the main flow path 31 is rectangular. The width direction of the main flow path 31 corresponds to the width direction W1 of the flow path 30. The first end 311 and the second end 312 in the width direction W1 of the main flow path 31 correspond to the first end and the second end in the width direction W1 of the flow path 30. As shown in FIG. 2, a first electrode 50 is disposed in the main flow path 31. This will be described in detail later.

[0021] The connecting flow path 32 is a part between the main flow path 31 and the inlet 21 in the flow path 30. Therefore, the connecting flow path 32 is located upstream of the main flow path 31 (the left side in FIG. 2). In the present embodiment, the connecting flow path 32 is rectangular in a plan view (when viewed from the thickness direction of the base 10a). The cross-sectional shape of the connecting flow path 32 in a plane orthogonal to the length direction of the connecting flow path 32 is rectangular. The first end in the length direction of the connecting flow path 32 is connected to the inlet 21, and the second end in the length direction of the connecting flow path 32 is connected to the main flow path 31. The width direction of the connecting flow path 32 corresponds to the width direction W1 of the flow path 30. The first end 321 and the second end 322 in the width direction W1 of the connecting flow path 32 correspond to the first end and the second end in the width direction W1 of the flow path 30. In the present embodiment, the width of the connecting flow path 32 is narrower than the width of the main flow path. As shown in FIG. 2, a second electrode 60 is disposed in the connecting flow path 32. This will be described in detail later.

[0022] The plurality of branch channels 33-1 and 33-2 are parts in the channel 30 that convey the dielectric particles P1 and P2 so that the dielectric particles P1 and P2 separated from each other in the main channel 31 do not mix again. The plurality of branch channels 33-1 and 33-2 are on the side opposite to the connecting channel 32 in the main channel 31. Therefore, each branch channel 33 is located on the downstream side (the right side in FIG. 2) with respect to the main channel 31. The branch channel 33-1 is connected to the side of the first end 311 in the width direction W1 of the main channel 31. As shown in FIG. 1, the branch channel 33-1 is the part through which a specific type of dielectric particle P1 separated in the main channel 31 flows. The branch channel 33-2 is connected to the side of the second end 312 in the width direction W1 of the main channel 31. As shown in FIG. 2, the branch channel 33-1 is the part through which the remaining dielectric particles P2 from which a specific type of dielectric particle P1 has been separated from the plurality of types of dielectric particles P1 and P2 flow.

[0023] The connection path 34 is the part in the channel 30 that connects the inlet 21 and the connecting channel 32. The connection path 34 is located between the first end in the length direction of the connecting channel 32 and the inlet 21. The connection path 35 is the part in the channel 30 that connects the inlet 22 and the connecting channel 32. The connection path 35 is located between the first end 321 in the width direction W1 of the connecting channel 32 and the inlet 22 on the first end side in the length direction of the connecting channel 32.

[0024] Filter 90 is located between the inlet 21 and the second electrode 60 in the flow path 30. Filter 90 is connected to the second end side in the width direction W1 of the flow path 30. Filter 90 removes particles smaller in size than the plurality of types of dielectric particles P1, P2 from the suspension L1. Filter 90 separates particles by size. The particles smaller in size than the plurality of types of dielectric particles P1, P2 are particles smaller in size than the smallest-sized dielectric particle among the plurality of types of dielectric particles P1, P2. In the present embodiment, the particles smaller in size than the plurality of types of dielectric particles P1, P2 are small cells P3 such as red blood cells, which are the above-described unnecessary components of the suspension L1. The filter 90 in FIG. 2 separates the plurality of types of dielectric particles P1, P2 from the suspension L1 based on the principle of hydrodynamic filtration (HDF). Specifically, the filter 90 in FIG. 2 includes a collection unit 91, a plurality of discharge paths 92, and a connection path 93. The dimensions (length, width, and height) of the plurality of discharge paths 92 are smaller than the dimensions of the connection flow path 32 to which the plurality of discharge paths 92 are connected, but are set to allow particles smaller in size than the plurality of types of dielectric particles P1, P2 to pass through. The first end in the length direction of the plurality of discharge paths 92 is connected to the second end 322 in the width direction W1 of the connection flow path 32 on the first end side in the length direction of the connection flow path 32. The plurality of discharge paths 92 are located downstream of the connection path 35 in the flow path 30. As a result, the unnecessary components of the suspension L1 that have entered the connection flow path 32 via the inlet 21 and the connection path 34 are pushed out into the plurality of discharge paths 92 by the replacement liquid L2 that has entered the connection flow path 32 via the inlet 22 and the connection path 35. The plurality of types of dielectric particles P1, P2 flow through the connection flow path 32 while being biased toward the second end 322 side in the width direction W1 of the connection flow path 32 without being pushed out into the plurality of discharge paths 92. According to the filter 90, the plurality of types of dielectric particles P1, P2 can be guided to the second end side in the width direction W1 of the flow path 30. In this way, even by the filter 90, the orientation of the plurality of types of dielectric particles P1, P2 to the second end side in the width direction W1 of the flow path 30 is realized. However, depending on the shape of the flow path 30 (especially when the width of the flow path 30 is wide), as the plurality of types of dielectric particles P1, P2 travel through the flow path 30, the plurality of types of dielectric particles P1, P2 tend to disperse.Therefore, it is difficult to stably position only the filter 90 to position the plurality of types of dielectric particles P1 and P2 on the second end side in the width direction W1 of the flow path 30. The connecting path 93 connects the second ends in the length direction of the plurality of discharge paths 92 to the collecting portion 91. As a result, the unnecessary components removed from the suspension L1 are conveyed to the collecting portion 91. The collecting portion 91 includes, for example, a discharge port, whereby the solution S3 containing the unnecessary components removed from the suspension L1 is discharged from the flow path chip 10 to the outside. In the filter 90, only particles having a desired size or more can be introduced into the main flow path 31 mainly by changing the dimensions (length, width, and height) of the discharge path 92.

[0025] The plurality of collecting portions 40 include a first collecting portion 40-1 connected to the first end side in the width direction W1 of the flow path 30 and a second collecting portion 40-2 connected to the second end side in the width direction W1 of the flow path 30. The first collecting portion 40-1 is connected to the first end 311 side in the width direction W1 of the main flow path 31 via the branch flow path 33-1. The first collecting portion 40-1 collects a specific type of dielectric particle P1 flowing through the branch flow path 33-1. The first collecting portion 40-1 includes, for example, a discharge port, whereby the solution S1 containing the specific type of dielectric particle P1 may be supplied from the flow path chip 10 to the outside. The second collecting portion 40-2 is connected to the second end 312 side in the width direction W1 of the main flow path 31 via the branch flow path 33-2. The second collecting portion 40-2 collects the dielectric particle P2 flowing through the branch flow path 33-2. The second collecting portion 40-2 includes, for example, a discharge port, whereby the solution S2 containing the dielectric particle P2 may be supplied from the flow path chip 10 to the outside.

[0026] The first electrode 50 is used to guide a specific type of dielectric particle P1 among the plurality of types of dielectric particles P1 and P2 in the suspension L1 to the first end side in the width direction W1 of the flow path 30. In the present embodiment, as shown in FIG. 2, the first electrode 50 is disposed in the main flow path 31 of the flow path 30, and guides a specific type of dielectric particle P1 among the plurality of types of dielectric particles P1 and P2 in the suspension L1 to the first end 311 side in the width direction W1 of the main flow path 31. The first electrode 50 is configured to apply a dielectrophoretic force in a direction toward the first end (the first end 311 in the width direction W1 of the main flow path 31) in the width direction W1 of the flow path 30 to the specific type of dielectric particle P1. As an example, as shown in FIG. 2, the specific type of dielectric particle P1 receives a force F11 in the direction of flowing through the flow path 30 and moves within the flow path 30. The first electrode 50 applies a dielectrophoretic force F12 to the specific type of dielectric particle P1, thereby causing a force F13 in a direction toward the first end 311 side in the width direction W1 of the main flow path 31 to act on the specific type of dielectric particle P1.

[0027] The first electrode 50 is disposed on one surface of the flow path 30. In the present embodiment, the first electrode 50 is disposed on the bottom surface of the main flow path 31. The first electrode 50 may be formed of, for example, a relatively inexpensive planar electrode. As an example, the first electrode 50 may be configured to include an electrode layer formed on the first substrate of the base body 10a and a protective layer formed on the electrode layer. The material of the electrode layer is, for example, a metal such as Al. The protective layer is, for example, silicon oxide.

[0028] The first electrode 50 is a comb-shaped electrode having a plurality of tooth portions 511 and 521 arranged in a first predetermined direction D1. The first predetermined direction D1 is a direction from the first end (the upper end in FIG. 2) to the second end (the lower end in FIG. 2) of the width direction W1 of the flow path 30 along the direction in which the suspension L1 flows in the flow path 30 (the right direction in FIG. 2). The plurality of tooth portions 511 and 521 include a plurality of first tooth portions 511 and a plurality of second tooth portions 521. The first tooth portions 511 and the second tooth portions 521 are arranged alternately. The plurality of first tooth portions 511 extend from the first end to the second end in the width direction W1 of the flow path 30. That is, the plurality of first tooth portions 511 extend from the first end 311 to the second end 312 in the width direction W1 of the main flow path 31. The plurality of second tooth portions 521 extend from the second end to the first end in the width direction of the flow path 30. That is, the plurality of second tooth portions 521 extend from the second end 312 to the first end 311 in the width direction W1 of the main flow path 31.

[0029] The first electrode 50 in FIG. 2 includes a pair of electrode patterns 51 and 52. The electrode pattern 51 includes a plurality of first tooth portions 511 and a connecting portion 512 that is on the first end 311 side in the width direction W1 of the main flow path 31 and connects the base ends of the plurality of tooth portions 511. The connecting portion 512 is outside the flow path 30. The electrode pattern 52 includes a plurality of second tooth portions 521 and a connecting portion 522 that is on the second end 312 side in the width direction W1 of the main flow path 31 and connects the base ends of the plurality of second tooth portions 521. The connecting portion 522 is outside the flow path 30.

[0030] The second electrode 60 is located between the inlet 21 and the first electrode 50. The second electrode 60 is used to guide the plurality of types of dielectric particles P1, P2 in the suspension L1 to the second end 312 side in the width direction W1 of the flow path 30. FIG. 3 is an enlarged view of a portion around the second electrode 60 of the flow path chip 10. In FIG. 3, only the second electrode 60 is shown for simplicity of the drawing. As shown in FIG. 3, the second electrode 60 is disposed in the connecting flow path 32 of the flow path 30 and guides the plurality of types of dielectric particles P1, P2 in the suspension L1 to the second end 322 side in the width direction W1 of the connecting flow path 32. The second electrode 60 is configured to apply a dielectrophoretic force in a direction toward the second end (the second end 322 in the width direction W1 of the connecting flow path 32) in the width direction W1 of the flow path 30 to the plurality of types of dielectric particles P1, P2. As an example, as shown in FIG. 3, the plurality of types of dielectric particles P1, P2 receive a force F21 in the flowing direction of the flow path 30 and move within the flow path 30. The second electrode 60 applies a dielectrophoretic force F22 to the plurality of types of dielectric particles P1, P2, thereby applying a force F23 in a direction toward the second end 322 side in the width direction W1 of the connecting flow path 32 to the plurality of types of dielectric particles P1, P2.

[0031] The second electrode 60 is disposed on one surface of the flow path 30. In the present embodiment, the second electrode 60 is disposed on the bottom surface of the connecting flow path 32. The second electrode 60 may be formed of, for example, a relatively inexpensive planar electrode. As an example, the second electrode 60 may be configured to include an electrode layer formed on the first substrate of the base body 10a and a protective layer formed on the electrode layer. The material of the electrode layer is, for example, a metal such as Al. The protective layer is, for example, silicon oxide.

[0032] As shown in FIGS. 2 and 3, the second electrode 60 is a comb-shaped electrode having a plurality of tooth portions 611 and 621 arranged in a second predetermined direction D2. The second predetermined direction D2 is a direction toward the opposite side of the above-described first predetermined direction D1 in the width direction W1 of the flow path 30. More specifically, the second predetermined direction D2 is a direction from the second end (the lower end in FIG. 2) to the first end (the upper end in FIG. 2) of the width direction W1 of the flow path 30 along the direction in which the suspension L1 flows in the flow path 30 (the right direction in FIG. 2). The plurality of tooth portions 611 and 621 includes a plurality of first tooth portions 611 and a plurality of second tooth portions 621. The first tooth portions 611 and the second tooth portions 621 are arranged alternately. The plurality of first tooth portions 611 extends from the first end to the second end in the width direction W1 of the flow path 30. That is, the plurality of first tooth portions 611 extends from the first end 321 to the second end 322 in the width direction W1 of the connecting flow path 32. The plurality of second tooth portions 621 extends from the second end to the first end in the width direction of the flow path 30. That is, the plurality of second tooth portions 621 extends from the second end 322 to the first end 321 in the width direction W1 of the connecting flow path 32. As shown in FIG. 3, in the second electrode 60, the tips 611a of the first tooth portions 611 and the tips 621a of the second tooth portions 621 are outside the flow path 30, that is, outside the connecting flow path 32. In the second electrode 60 of FIG. 3, it is sufficient that the tips 611a of the first tooth portions 611 and the tips 621a of the second tooth portions 621 are outside the flow path 30, so that the alignment between the second electrode 60 and the flow path 30 becomes easy. In particular, as described above, when the base 10a is formed by bonding the first substrate and the second substrate, it is not necessary to align the second substrate having the recess corresponding to the flow path 30 with high precision with respect to the first substrate on which the second electrode 60 is formed, so that high alignment accuracy is not required. Therefore, the manufacturing of the flow path chip 10 can be facilitated.

[0033] The second electrode 60 in Fig. 2 includes a pair of electrode patterns 61 and 62. The electrode pattern 61 includes a plurality of first tooth portions 611 and a connecting portion 612 that is on the first end 321 side in the width direction W1 of the connecting channel 32 and connects the base ends of the plurality of tooth portions 611. The connecting portion 612 is outside the channel 30. The electrode pattern 62 includes a plurality of second tooth portions 621 and a connecting portion 622 that is on the second end 322 side in the width direction W1 of the connecting channel 32 and connects the base ends of the plurality of second tooth portions 621. The connecting portion 622 is outside the channel 30.

[0034] Figs. 4(a) to 4(c) are cross-sectional views of the flow channel chip 10 showing how a plurality of types of dielectric particles P1 and P2 move by the second electrode 60. Fig. 4(a) is a cross-sectional view of the flow channel chip 10 at the end on the inlet 21 side (the left end in Fig. 2) of the second electrode 60. Fig. 4(b) is a cross-sectional view of the flow channel chip 10 at the central portion of the second electrode 60. Fig. 4(c) is a cross-sectional view of the flow channel chip 10 at the end on the first electrode 50 side (the right end in Fig. 2) of the second electrode 60. As understood from Figs. 4(a) to 4(c), the dielectric particles P1 and P2 in the connecting channel 32 of the flow channel 30 are attracted to the second electrode 60. Thereby, the dielectric particles P1 and P2 are attracted to the bottom surface of the flow channel 30 where the second electrode 60 is provided. Further, the dielectric particles P1 and P2 are guided to the second end 322 side in the width direction W1 of the connecting channel 32.

[0035] In the present embodiment, a filter 90 is provided between the inlet 21 and the second electrode 60 in the flow channel 30, and the filter 90 also orients a plurality of types of dielectric particles P1 and P2 to the second end side in the width direction W1 of the flow channel 30. That is, in the flow channel chip 10, after the filter 90 orients a plurality of types of dielectric particles P1 and P2 to a certain extent to the second end side in the width direction W1 of the flow channel 30, the dielectrophoretic force by the second electrode 60 further stably positions the plurality of types of dielectric particles P1 and P2 to the second end side in the width direction W1 of the flow channel 30.

[0036] The first electrode pads 71 and 72 are used to apply a first predetermined voltage to the first electrode 50. The first electrode pads 71 and 72 are respectively connected to a pair of electrode patterns 51 and 52 of the first electrode 50 in order to apply the first predetermined voltage between the pair of electrode patterns 51 and 52 of the first electrode 50. The first electrode pads 71 and 72 are respectively connected to the pair of electrode patterns 51 and 52 of the first electrode 50 by, for example, wiring patterns or the like. The first electrode pads 71 and 72 are arranged to be located on the outer surface of the substrate 10a. By controlling the voltage between the first electrode pads 71 and 72, the voltage of the first electrode 50 can be controlled.

[0037] The second electrode pads 81 and 82 are provided separately from the first electrode pads 71 and 72. The second electrode pads 81 and 82 are used to apply a second predetermined voltage different from the first predetermined voltage to the second electrode 60. The second electrode pads 81 and 82 are respectively connected to a pair of electrode patterns 61 and 62 of the second electrode 60 in order to apply the second predetermined voltage between the pair of electrode patterns 61 and 62 of the second electrode 60. The second electrode pads 81 and 82 are respectively connected to the pair of electrode patterns 61 and 62 of the second electrode 60 by, for example, wiring patterns or the like. The second electrode pads 81 and 82 are arranged to be located on the outer surface of the substrate 10a. By controlling the voltage between the second electrode pads 81 and 82, the voltage of the second electrode 60 can be controlled.

[0038] As described above, in the flow channel chip 10, a second electrode 60, which is a position control electrode specialized for position control, is disposed upstream of a first electrode 50, which is a separation dielectrophoresis electrode specialized for separation. In the flow channel chip 10, before the separation of a specific type of dielectric particle P1 by the first electrode 50, a plurality of types of dielectric particles P1, P2 can be controlled to desired positions, so that the separation accuracy can be improved. Even if a lower voltage is applied to the first electrode 50, separation is possible. At the same voltage, the flow rate can be increased, and the separation speed can be improved. Further, since the second electrode 60 for position control is separately provided from the first electrode 50 for separation, the voltages of the first electrode 50 and the second electrode 60 can be set individually. For example, it is possible to apply a voltage having a frequency and amplitude suitable for the position control of a plurality of types of dielectric particles P1, P2 to the second electrode 60 while applying a voltage having a frequency and amplitude suitable for the separation of a specific type of dielectric particle P1 to the first electrode 50. Also by this, the separation accuracy and the separation speed can be improved.

[0039] [1.1.2.2 Voltage control device] The voltage control device 11 in FIG. 1 controls the voltage applied to the flow channel chip 10 to generate a dielectrophoretic force. In the present embodiment, the voltage control device 11 separates a specific type of dielectric particle P1 from a plurality of types of dielectric particles P1, P2 contained in the suspension L1 by controlling the voltage of the first electrode 50 and the voltage of the second electrode 60, respectively. The voltage control device 11 includes, for example, a function generator.

[0040] The voltage control device 11 in FIG. 1 is connected to the first electrode 50 via the first electrode pads 71, 72. The voltage control device 11 in FIG. 1 is connected to the second electrode 60 via the second electrode pads 81, 82.

[0041] The voltage control device 11 controls the voltage of the first electrode 50 so as to guide the specific type of dielectric particles P1 among the plurality of types of dielectric particles P1 and P2 to the first end side in the width direction W1 of the flow path 30. In the present embodiment, the voltage control device 11 applies a first predetermined voltage to the first electrode 50 via the first electrode pads 71 and 72. The first predetermined voltage is, for example, an alternating voltage. The frequency of the first predetermined voltage is set so that a positive dielectrophoretic force acts on the specific type of dielectric particles P1 by the first electrode 50. In this case, for the dielectric particles P2 other than the specific type of dielectric particles P1 among the plurality of types of dielectric particles P1 and P2, even if a dielectrophoretic force does not act, or even if a positive or negative dielectrophoretic force (attractive force or repulsive force) acts, the frequency is set so that the dielectrophoretic force becomes relatively small. The frequency of the first predetermined voltage is, for example, 600 kHz.

[0042] The voltage control device 11 controls the voltage of the second electrode 60 so as to guide the plurality of types of dielectric particles P1 and P2 including the specific type of dielectric particles P1 contained in the suspension L1 to the second end side in the width direction W1 of the flow path 30. In the present embodiment, the voltage control device 11 applies a second predetermined voltage to the second electrode 60 via the second electrode pads 81 and 82. The second predetermined voltage is different from the first predetermined voltage. The second predetermined voltage is, for example, an alternating voltage different from the first predetermined voltage. The frequency of the second predetermined voltage is set so that a positive dielectrophoretic force acts on the plurality of types of dielectric particles P1 and P2 including the specific type of dielectric particles P1 by the second electrode 60. The frequency of the second predetermined voltage is, for example, 1500 kHz.

[0043] The second predetermined voltage may be an alternating voltage with a fixed amplitude and frequency. When such a second predetermined voltage is continuously applied to the second electrode 60, as shown in FIG. 3, the dielectric particles P1 and P2 are attracted to the second electrode 60 (particularly the tooth portions 611 and 621) and accumulate near the tooth portions 611 and 621 on the second end 322 side in the width direction W1 of the connecting channel 32. When a certain amount of dielectric particles P1 and P2 accumulate, they flow into the main channel 31 from the connecting channel 32 in a form pushed out by the subsequent dielectric particles P1 and P2. When an alternating voltage with a fixed amplitude and frequency is continuously applied to the second electrode 60, the dielectric particles P1 and P2 accumulated on the second end 322 side in the width direction W1 of the connecting channel 32 are utilized to be pushed out by the subsequent dielectric particles P1 and P2. The dielectric particles P1 and P2 pushed out by the subsequent dielectric particles P1 and P2 will lift off from the second electrode 60 and move in the connecting channel 32 toward the main channel 31. When it is desired to stably position the dielectric particles P1 and P2 on the second end 322 side in the width direction W1 of the connecting channel 32, it is better not to utilize such pushing. Also, since the dielectric particles P1 and P2 remain in contact with the second electrode 60 until they are pushed out by the subsequent dielectric particles P1 and P2, the contact time with the second electrode 60 is relatively long. Therefore, considering the burden on the dielectric particles P1 and P2, the contact time should be shorter.

[0044] Therefore, the second predetermined voltage may be set such that its amplitude changes with time. For example, the second predetermined voltage may be set such that a first period with an amplitude of a first value and a second period with an amplitude of a second value appear alternately. For example, the first period may be an on period where the first value is a specified value, and the second period may be an off period where the second value is 0. In this case, the second predetermined voltage is intermittently applied to the second electrode 60. That is, a duty ratio may be set for the second predetermined voltage. The duty ratio may be, for example, 50% or more or 90% or more, and may be 99% or less.

[0045] FIG. 5 is a partial plan view of the flow channel chip 10 showing the movement of the dielectric particles P1 and P2 when the amplitude of the voltage (second predetermined voltage) applied to the second electrode 60 changes with time. By changing the amplitude of the second predetermined voltage with time, the dielectrophoretic force acting on the dielectric particles P1 and P2 by the second electrode 60 can be changed with time. Therefore, while the dielectrophoretic force is relatively large, the dielectric particles P1 and P2 are attracted to the second electrode 60, and while the dielectrophoretic force is relatively small, the dielectric particles P1 and P2 are likely to move away from the second electrode 60. Therefore, the dielectric particles P1 and P2 are likely to flow into the main flow path 31 away from the second electrode 60 without being pushed by the subsequent dielectric particles P1 and P2. As a result, compared with the case of relying on the extrusion as described above, the alignment accuracy of the dielectric particles P1 and P2 by the second electrode 60 is improved. In addition, the time during which the dielectric particles P1 and P2 contact the second electrode 60 can be shortened, and the burden on the dielectric particles P1 and P2 can be reduced.

[0046] The second predetermined voltage may be set so that the frequency changes with time. The dielectrophoretic force acting on the dielectric particles by the second electrode 60 is affected by the frequency of the voltage applied to the second electrode 60. Therefore, by changing the frequency of the second predetermined voltage with time, it becomes possible to change the dielectrophoretic force acting on the dielectric particles P1 and P2 by the second electrode 60 with time.

[0047] Thus, at least one of the amplitude and the frequency of the second predetermined voltage may be changed with time. The time change of the amplitude of the second predetermined voltage may be performed by setting the duty ratio or amplitude modulation. The time change of the frequency of the second predetermined voltage may be performed by frequency modulation. By doing so, it becomes possible to temporally change the dielectrophoretic force acting on the dielectric particles P1 and P2 by the second electrode 60. Therefore, the dielectric particles P1 and P2 are attracted to the second electrode 60 while the dielectrophoretic force is relatively large, and the dielectric particles P1 and P2 are likely to move away from the second electrode 60 while the dielectrophoretic force is relatively small. As a result, compared with the case of relying on extrusion as described above, the accuracy of the orientation of the dielectric particles P1 and P2 by the second electrode 60 is improved. In addition, the time during which the dielectric particles P1 and P2 contact the second electrode 60 can be shortened, and the burden on the dielectric particles P1 and P2 can be reduced.

[0048] In the voltage control device 11 described above, the separation method using the flow channel chip 10 can be executed. In this separation method, the voltage of the second electrode 60 is controlled so as to guide a plurality of types of dielectric particles P1 and P2 including a specific type of dielectric particle P1 contained in the suspension L1 to the second end side in the width direction W1 of the flow channel 30, and the voltage of the first electrode 50 is controlled so as to guide the specific type of dielectric particle P1 among the plurality of types of dielectric particles P1 and P2 to the first end side in the width direction W1 of the flow channel 30. According to this separation method, the accuracy of separating the specific type of dielectric particle P1 from the suspension L1 can be improved.

[0049] [1.1.2.3 Analyzer] The analyzer 12 in FIG. 1 performs an analysis regarding the separation of a specific type of dielectric particle P1 from a plurality of types of dielectric particles P1 and P2 contained in the suspension L1. The analyzer 12 in FIG. 1 includes an imaging device 121, a processing device 122, and a display device 123.

[0050] The imaging device 121 acquires an image of the target site in the flow channel chip 10. The target site is, for example, the main flow channel 31. From the image of the main flow channel 31, the movement trajectories of the dielectric particles P1, P2 passing through the main flow channel 31 can be obtained. The imaging device 121 includes, for example, a camera having an imaging element such as a CCD image sensor or a CMOS image sensor, and an optical microscope module. The optical microscope module may be a phase contrast microscope or an epi-illumination microscope. Further, the optical microscope module may be configured to be switchable between a phase contrast microscope and an epi-illumination microscope, for example, by exchanging lenses. Also, when performing fluorescence observation, a fluorescence filter is used as appropriate. The operation of the imaging device 121 may be controlled by the processing device 122.

[0051] The display device 123 displays information from the processing device 122. The display device 123 is, for example, a liquid crystal display and an organic EL display.

[0052] The processing device 122 controls the operation of the analysis device 12. The processing device 122 can be realized, for example, by a computer system including one or more processors (microprocessors) and one or more memories. By executing a program (stored in one or more memories, etc.) by one or more processors, a predetermined function is realized. As an example, the processing device 122 performs image analysis on the image captured by the imaging device 121 and obtains the movement trajectories of the dielectric particles P1, P2 passing through the main flow channel 31. The processing device 122 may display the image captured by the imaging device 121 or the movement trajectory obtained by image analysis on the display device 123.

[0053] [1.1.3 Test] To confirm the effect of the separation system 1 including the above-described flow path chip 10, the separation rate of a specific type of dielectric particle P1 was measured. FIG. 6 is a graph showing the change over time of the separation rate in the separation system 1 of FIG. 1. In FIG. 6, the round dots indicate the separation rates measured at predetermined intervals (for example, 10 seconds), and the solid line indicates the average of the separation rates during the corresponding periods. The separation rate in FIG. 6 is the ratio of the dielectric particles P1 flowing through the branch flow path 33-1 to the total dielectric particles P1 flowing through the branch flow path 33-1 and the branch flow path 33-2. In FIG. 6, during the periods from time t1 to t2 and from time t3 to t4, no voltage (second predetermined voltage) is applied to the second electrode 60. During the periods from time t2 to t3 and from time t4 to t5, a voltage (second predetermined voltage) is applied to the second electrode 60. As understood from FIG. 6, the separation rate is higher during the periods when the voltage is applied to the second electrode 60 (the periods from time t2 to t3 and from time t4 to t5) than during the periods when no voltage is applied to the second electrode 60 (the periods from time t1 to t2 and from time t3 to t4).

[0054] [1.1.4 Effects, etc.] The flow path chip 10 described above includes a substrate 10a having an inlet 21 into which a suspension L1 containing a plurality of types of dielectric particles P1 and P2 including a specific type of dielectric particle P1 is introduced, and a flow path 30 through which the plurality of types of dielectric particles P1 and P2 of the suspension L1 introduced from the inlet 21 flow, a first electrode 50 that guides a specific type of dielectric particle P1 among the plurality of types of dielectric particles P1 and P2 to the first end side in the width direction W1 of the flow path 30, and a second electrode 60 that is between the inlet 21 and the first electrode 50 and guides the plurality of types of dielectric particles P1 and P2 to the second end side in the width direction W1 of the flow path 30. According to this configuration, the accuracy of separating a specific type of dielectric particle P1 from the suspension L1 can be improved.

[0055] In the flow channel chip 10, the first electrode 50 is a comb-shaped electrode having a plurality of tooth portions 511 and 521 arranged in the first predetermined direction D1. The second electrode 60 is a comb-shaped electrode having a plurality of tooth portions 611 and 621 arranged in the second predetermined direction D2. The first predetermined direction D1 and the second predetermined direction D2 are directions facing opposite sides in the width direction W1 of the flow channel 30. According to this configuration, the accuracy of separating specific types of dielectric particles P1 from the suspension L1 can be improved.

[0056] In the flow channel chip 10, each of the first electrode 50 and the second electrode 60 is on one surface of the flow channel 30. According to this configuration, each of the first electrode 50 and the second electrode 60 can be constituted by a planar electrode, and the manufacturing cost can be reduced.

[0057] In the flow channel chip 10, the first predetermined direction D1 is a direction from the second end to the first end of the width direction W1 of the flow channel 30 along the direction in which the suspension L1 flows in the flow channel 30. The second predetermined direction D2 is a direction from the first end to the second end of the width direction W1 of the flow channel 30 along the direction in which the suspension L1 flows in the flow channel 30. According to this configuration, the accuracy of separating specific types of dielectric particles P1 from the suspension L1 can be improved.

[0058] In the flow channel chip 10, the plurality of tooth portions 611 and 621 of the second electrode 60 include a first tooth portion 611 extending from the first end to the second end of the width direction W1 of the flow channel 30 and a second tooth portion 621 extending from the second end to the first end of the width direction W1 of the flow channel 30. The tip 611a of the first tooth portion 611 and the tip 621a of the second tooth portion 621 are outside the flow channel 30. According to this configuration, the alignment between the second electrode 60 and the flow channel 30 becomes easy, and the manufacturing of the flow channel chip 10 can be facilitated.

[0059] In the flow channel chip 10, the flow channel 30 includes a main flow channel 31 and a connecting flow channel 32 between the main flow channel 31 and the inlet 21. The first electrode 50 is in the main flow channel 31. The second electrode 60 is in the connecting flow channel 32. The width of the connecting flow channel 32 is narrower than the width of the main flow channel 31. According to this configuration, the manufacturing cost can be reduced.

[0060] Further, in the flow channel chip 10, the substrate 10a has a first collection part 40-1 connected to the first end side in the width direction W1 of the flow channel 30 and a second collection part 40-2 connected to the second end side in the width direction W1 of the flow channel 30. According to this configuration, the accuracy of separating specific types of dielectric particles P1 from the suspension L1 can be improved.

[0061] Further, in the flow channel chip 10, the flow channel 30 is provided with a filter 90 connected to the second end side in the width direction W1 of the flow channel 30 between the inlet 21 and the second electrode 60, and removing particles P3 smaller in size than a plurality of types of dielectric particles P1, P2 from the suspension L1. According to this configuration, the accuracy of separating specific types of dielectric particles P1 from the suspension L1 can be improved.

[0062] Further, in the flow channel chip 10, there are provided first electrode pads 71, 72 for applying a first predetermined voltage to the first electrode 50, and second electrode pads 81, 82 provided separately from the first electrode pads for applying a second predetermined voltage different from the first predetermined voltage to the second electrode 60. According to this configuration, the accuracy of separating specific types of dielectric particles P1 from the suspension L1 can be improved.

[0063] Further, in the flow channel chip 10, the second predetermined voltage is set such that at least one of the amplitude and the frequency changes with time. According to this configuration, the accuracy of the orientation of the dielectric particles P1, P2 by the second electrode 60 is improved. Also, the time for which the dielectric particles P1, P2 contact the second electrode 60 can be shortened, and the burden on the dielectric particles P1, P2 can be reduced.

[0064] The separation system 1 described above includes a flow channel chip 10 and a voltage control device 11 that controls the voltage of the second electrode 60 so as to guide a plurality of types of dielectric particles P1, P2 including specific types of dielectric particles P1 contained in the suspension L1 to the second end side in the width direction W1 of the flow channel 30, and controls the voltage of the first electrode 50 so as to guide specific types of dielectric particles P1 among the plurality of types of dielectric particles P1, P2 to the first end side in the width direction W1 of the flow channel 30. According to this configuration, the accuracy of separating specific types of dielectric particles P1 from the suspension L1 can be improved.

[0065] In the separation system 1, the flow channel chip 10 is disposable. According to this configuration, contamination can be prevented, and the usability of the separation system 1 can be further improved.

[0066] The separation method described above is a separation method using the flow channel chip 10. The voltage of the second electrode 60 is controlled so as to guide a plurality of types of dielectric particles P1, P2 including the specific type of dielectric particle P1 contained in the suspension L1 to the second end side in the width direction W1 of the flow channel 30, and the voltage of the first electrode 50 is controlled so as to guide the specific type of dielectric particle P1 among the plurality of types of dielectric particles P1, P2 to the first end side in the width direction W1 of the flow channel 30. According to this configuration, the separation accuracy of the specific type of dielectric particle P1 from the suspension L1 can be improved.

[0067] [1.2 Embodiment 2] FIG. 7 is an enlarged view of a portion around the second electrode 60 in a configuration example of the flow channel chip 10A according to Embodiment 2. In the flow channel chip 10A according to Embodiment 2, the position of the second electrode 60 with respect to the connecting flow channel 32 is different from that of the flow channel chip 10 according to Embodiment 1.

[0068] The second electrode 60 in FIG. 7 is disposed in the connecting flow channel 32 of the flow channel 30, and guides a plurality of types of dielectric particles P1, P2 in the suspension L1 to the second end 322 side in the width direction W1 of the connecting flow channel 32, similar to Embodiment 1. The second electrode 60 is configured to apply a dielectrophoretic force in the direction toward the second end (the second end 322 in the width direction W1 of the connecting flow channel 32) in the width direction W1 of the flow channel 30 to the plurality of types of dielectric particles P1, P2. As an example, as shown in FIG. 7, the plurality of types of dielectric particles P1, P2 receive a force F21 in the flowing direction of the flow channel 30 and move in the flow channel 30. The second electrode 60 applies a dielectrophoretic force F22 to the plurality of types of dielectric particles P1, P2, thereby applying a force F23 in the direction toward the second end 322 side in the width direction W1 of the connecting flow channel 32 to the plurality of types of dielectric particles P1, P2.

[0069] As shown in FIG. 7, the second electrode 60 is a comb-shaped electrode having a plurality of tooth portions 611 and 621 arranged in a second predetermined direction D2 on the bottom surface of the flow path 30, similar to the first embodiment. The plurality of tooth portions 611 and 621 include a plurality of first tooth portions 611 and a plurality of second tooth portions 621. The first tooth portions 611 and the second tooth portions 621 are arranged alternately. The plurality of first tooth portions 611 extend from the first end to the second end in the width direction W1 of the flow path 30. That is, the plurality of first tooth portions 611 extend from the first end 321 to the second end 322 in the width direction W1 of the connecting flow path 32. The plurality of second tooth portions 621 extend from the second end to the first end in the width direction of the flow path 30. That is, the plurality of second tooth portions 621 extend from the second end 322 to the first end 321 in the width direction W1 of the connecting flow path 32. In the second electrode 60 of FIG. 7, the tip 611a of the first tooth portion 611 is not outside the connecting flow path 32, but is inside the connecting flow path 32 at a predetermined distance from the second end 322 in the width direction W1 of the connecting flow path 32. That is, the tip 611a of the first tooth portion 611 is inside the flow path 30 at a predetermined distance from the second end in the width direction W1 of the flow path 30. On the other hand, the tip 621a of the second tooth portion 621 is outside the connecting flow path 32, that is, outside the flow path 30.

[0070] In the second electrode 60 of FIG. 7, since the tip 611a of the first tooth portion 611 is not outside the connecting channel 32 but inside the connecting channel 32 at a predetermined distance from the second end 322 in the width direction W1 of the connecting channel 32, a passage for the dielectric particles P1 and P2 is likely to be formed between the second end 322 in the width direction W1 of the connecting channel 32 and the tip 611a of the first tooth portion 611. That is, as indicated by the arrow A in FIG. 7, the dielectric particles P1 and P2 guided to the second end 322 side in the width direction W1 of the connecting channel 32 by the second electrode 60 easily pass between the tip 611a of the first tooth portion 611 of the second electrode 60 and the second end 322 in the width direction W1 of the connecting channel 32 and tend to move from the second electrode 60 toward the first electrode 50. Therefore, even without the subsequent extrusion by the dielectric particles P1 and P2 described in the first embodiment, they naturally move away from the second electrode 60 and toward the main channel 31. Therefore, the accuracy of the orientation of the dielectric particles P1 and P2 by the second electrode 60 is improved. In addition, the time during which the dielectric particles P1 and P2 contact the second electrode 60 can be shortened, and the burden on the dielectric particles P1 and P2 can be reduced. The predetermined distance is not particularly limited and can be appropriately set so that the dielectric particles P1 and P2 can be moved from the second electrode 60 to the first electrode 50.

[0071] As described above, in the flow channel chip 10A, the plurality of tooth portions 611 and 621 of the second electrode 60 include a first tooth portion 611 extending from the first end to the second end in the width direction W1 of the flow channel 30 and a second tooth portion 621 extending from the second end to the first end in the width direction W1 of the flow channel 30. The tip 611a of the first tooth portion 611 is inside the flow channel 30 at a predetermined distance from the second end in the width direction W1 of the flow channel 30. The tip 621a of the second tooth portion 621 is outside the flow channel 30. According to this configuration, the dielectric particles P1 and P2 guided to the second end side in the width direction W1 of the flow channel 30 easily pass between the tip 611a of the first tooth portion 611 of the second electrode 60 and the second end in the width direction W1 of the flow channel 30 and tend to move from the second electrode 60 toward the first electrode 50. Therefore, the accuracy of the orientation of the dielectric particles P1 and P2 by the second electrode 60 is improved. In addition, the time during which the dielectric particles P1 and P2 contact the second electrode 60 can be shortened, and the burden on the dielectric particles P1 and P2 can be reduced.

[0072] [2. Modification Example] Embodiments of the present disclosure are not limited to the above embodiments. If the above embodiments can achieve the problems of the present disclosure, various modifications are possible according to design and the like. Hereinafter, modification examples of the above embodiments will be listed. The modification examples described below can be applied in appropriate combinations.

[0073] In one modification example, the separation system 1 does not necessarily have to include the analysis device 12. The separation system 1 only needs to include at least the flow channel chip 10 and the voltage control device 11.

[0074] In one modification example, the suspension L1 is not limited to blood. The suspension L1 is not particularly limited as long as it contains dielectric particles to be separated. The dielectric particles are not limited to the above cells. The dielectric particles may be, for example, membrane vesicles, microorganisms, fungi, spores, viruses, exosomes, nucleic acids such as DNA and RNA.

[0075] In one modification example, the shape of the flow channel chip 10 can be changed. In particular, the shape of the substrate 10a is not limited to the above embodiments. The shape of the substrate 10a may be appropriately set according to the flow channel 30. The flow channel 30 may not be linear as in the above embodiments, but may be curved. The flow channel 30 does not necessarily have to be clearly divided into a main flow channel 31, a connecting flow channel 32, a branching flow channel 33, and connecting paths 34, 35. The widths of the main flow channel 31 and the connecting flow channel 32 may be the same, or the connecting flow channel 32 may be bent with respect to the main flow channel 31.

[0076] In one modification example, the inlet 22 is not essential. That is, the replacement of the components of the suspension L1 with the replacement liquid L2 is not essential. Also, depending on the shape of the flow channel 30, the collection unit 40 is not essential either.

[0077] In one modification example, the number and shape of the first electrodes 50 can be changed. The first electrodes 50 only need to be able to guide specific types of dielectric particles from a plurality of types of dielectric particles to the first end side in the width direction W1 of the flow channel 30. Depending on the shape of the first electrodes 50, the first electrode pads 71, 72 can be omitted.

[0078] In a modified example, the shape of the second electrode 60 can be changed. The second electrode 60 only needs to be able to guide a plurality of types of dielectric particles to the second end side in the width direction W1 of the flow path 30. The flow path chip 10 may include a plurality of second electrodes 60. The plurality of second electrodes 60 may cooperate with each other to guide a plurality of types of dielectric particles to the second end side in the width direction W1 of the flow path 30. For example, when the first to fourth dielectric particles are guided to the second end side in the width direction W1 of the flow path 30 by the plurality of second electrodes 60, the first second electrode 60 may guide the first and second dielectric particles to the second end side in the width direction W1 of the flow path 30, and the second second electrode 60 may guide the third and fourth dielectric particles to the second end side in the width direction W1 of the flow path 30. Further, depending on the shape of the second electrode 60, the second electrode pads 81 and 82 may be omitted.

[0079] In a modified example, the number and shape of the filter 90 can be changed. The filter 90 is not limited to a configuration using HDF (hydrodynamic filtration). The filter 90 may be, for example, a configuration using DLD (Deterministic lateral displacement). Further, the filter 90 is not essential.

[0080] [3. Aspect] As is clear from the above embodiments and modified examples, the present disclosure includes the following aspects. Hereinafter, reference numerals are attached in parentheses only for the purpose of clarifying the correspondence with the embodiments.

[0081] The first aspect is a flow channel chip (10; 10A), which includes a substrate (10a) having an inlet (21) into which a suspension (L1) containing a plurality of types of dielectric particles (P1, P2) including a specific type of dielectric particles (P1) is introduced, and a flow channel (30) through which the plurality of types of dielectric particles (P1, P2) of the suspension (L1) introduced from the inlet (21) flow. The flow channel chip further includes a first electrode (50) that guides the specific type of dielectric particles (P1) among the plurality of types of dielectric particles (P1, P2) to the first end side in the width direction (W1) of the flow channel (30), and a second electrode (60) that is between the inlet (21) and the first electrode (50) and guides the plurality of types of dielectric particles (P1, P2) to the second end side in the width direction (W1) of the flow channel (30). According to this aspect, the accuracy of separating the specific type of dielectric particles (P1) from the suspension (L1) can be improved.

[0082] The second aspect is a flow channel chip (10; 10A) based on the first aspect. In the second aspect, each of the first electrode (50) and the second electrode (60) is on one surface of the flow channel (30). According to this aspect, each of the first electrode (50) and the second electrode (60) can be constituted by a planar electrode, and the manufacturing cost can be reduced.

[0083] The third aspect is a flow channel chip (10; 10A) based on the first or second aspect. In the third aspect, the first electrode (50) is a comb-shaped electrode having a plurality of tooth portions (511, 521) arranged in a first predetermined direction (D1) on the bottom surface of the flow channel (30). The second electrode (60) is a comb-shaped electrode having a plurality of tooth portions (611, 621) arranged in a second predetermined direction (D2) on the bottom surface of the flow channel (30). The first predetermined direction (D1) and the second predetermined direction (D2) are directions facing opposite sides in the width direction (W1) of the flow channel (30). According to this aspect, the accuracy of separating the specific type of dielectric particles (P1) from the suspension (L1) can be improved.

[0084] The fourth aspect is the flow channel chip (10; 10A) based on the third aspect. In the fourth aspect, the first predetermined direction (D1) is a direction from the second end to the first end in the width direction (W1) of the flow channel (30) along the direction in which the suspension (L1) flows in the flow channel (30). The second predetermined direction (D2) is a direction from the first end to the second end in the width direction (W1) of the flow channel (30) along the direction in which the suspension (L1) flows in the flow channel (30). According to this aspect, the accuracy of separation of a specific type of dielectric particles (P1) from the suspension (L1) can be improved.

[0085] The fifth aspect is the flow channel chip (10) based on any one of the second to fourth aspects. In the fifth aspect, the plurality of tooth portions (611, 621) of the second electrode (60) include a first tooth portion (611) extending from the first end to the second end in the width direction (W1) of the flow channel (30), and a second tooth portion (621) extending from the second end to the first end in the width direction (W1) of the flow channel (30). The tip (611a) of the first tooth portion (611) and the tip (621a) of the second tooth portion (621) are outside the flow channel (30). According to this aspect, the alignment between the second electrode (60) and the flow channel (30) becomes easy, and the facilitation of manufacturing the flow channel chip (10) can be achieved.

[0086] The sixth aspect is a flow channel chip (10A) based on any one of the second to fourth aspects. In the sixth aspect, the plurality of tooth portions (611, 621) of the second electrode (60) include a first tooth portion (611) extending from a first end to a second end in the width direction (W1) of the flow channel (30), and a second tooth portion (621) extending from the second end to the first end in the width direction (W1) of the flow channel (30). The tip (611a) of the first tooth portion (611) is inside the flow channel (30) at a predetermined distance from the second end in the width direction (W1) of the flow channel (30). The tip (621a) of the second tooth portion (621) is outside the flow channel (30). According to this aspect, the dielectric particles (P1, P2) guided to the second end side in the width direction (W1) of the flow channel (30) can easily pass between the tip (611a) of the first tooth portion (611) of the second electrode (60) and the second end in the width direction (W1) of the flow channel (30) and move from the second electrode (60) toward the first electrode (50). Therefore, the accuracy of the orientation of the dielectric particles (P1, P2) by the second electrode (60) is improved. In addition, the time during which the dielectric particles (P1, P2) contact the second electrode (60) can be shortened, and the burden on the dielectric particles (P1, P2) can be reduced.

[0087] The seventh aspect is a flow channel chip (10; 10A) based on any one of the first to sixth aspects. In the seventh aspect, the flow channel (30) includes a main flow channel (31) and a connecting flow channel (32) between the main flow channel (31) and the inlet (21). The width of the connecting flow channel (32) is narrower than the width of the main flow channel (31). According to this aspect, the manufacturing cost can be reduced.

[0088] The eighth aspect is a flow channel chip (10; 10A) based on any one of the first to seventh aspects. In the eighth aspect, the substrate (10a) has a first collection portion (40-1) connected to the first end side in the width direction (W1) of the flow channel (30) and a second collection portion (40-2) connected to the second end side in the width direction (W1) of the flow channel (30). According to this aspect, the accuracy of separating a specific type of dielectric particle (P1) from the suspension (L1) can be improved.

[0089] A ninth aspect is a flow channel chip (10; 10A) according to any one of the first to eighth aspects. In the ninth aspect, the flow channel (30) is connected to the second end side in the width direction of the flow channel (30) between the inlet (21) and the second electrode (60), and removes particles (P3) smaller in size than the plurality of types of dielectric particles (P1, P2) from the suspension (L1). A filter (90) is provided. According to this aspect, the accuracy of separating a specific type of dielectric particle (P1) from the suspension (L1) can be improved.

[0090] A tenth aspect is a flow channel chip (10; 10A) according to any one of the first to ninth aspects. In the tenth aspect, a first electrode pad (71, 72) for applying a first predetermined voltage to the first electrode (50), and a second electrode pad (81, 82) provided separately from the first electrode pad for applying a second predetermined voltage different from the first predetermined voltage to the second electrode (60) are provided. According to this aspect, the accuracy of separating a specific type of dielectric particle (P1) from the suspension (L1) can be improved.

[0091] An eleventh aspect is a flow channel chip (10; 10A) according to the tenth aspect. In the eleventh aspect, the second predetermined voltage is set such that at least one of the amplitude and the frequency changes with time. According to this aspect, the accuracy of the orientation of the dielectric particles (P1, P2) by the second electrode (60) is improved. Also, the time during which the dielectric particles (P1, P2) contact the second electrode (60) can be shortened, and the burden on the dielectric particles (P1, P2) can be reduced.

[0092] Aspect 12 is a separation system (1), comprising a flow channel chip (10; 10A) according to any one of Aspects 1 to 11, and a voltage control device (11) that controls the voltage of the second electrode (60) to guide the plurality of types of dielectric particles (P1, P2) including the specific type of dielectric particles (P1) contained in the suspension (L1) to the second end side in the width direction (W1) of the flow channel (30), and controls the voltage of the first electrode (50) to guide the specific type of dielectric particles (P1) among the plurality of types of dielectric particles (P1, P2) to the first end side in the width direction (W1) of the flow channel (30). According to this aspect, the accuracy of separating the specific type of dielectric particles (P1) from the suspension (L1) can be improved.

[0093] Aspect 13 is a separation system (1) based on Aspect 12. In Aspect 13, the flow channel chip (10; 10A) is disposable. According to this aspect, contamination can be prevented, and the usability of the separation system (1) is further improved.

[0094] Aspect 14 is a separation method using the flow channel chip (10; 10A) according to any one of Aspects 1 to 11, which controls the voltage of the second electrode (60) to guide the plurality of types of dielectric particles (P1, P2) including the specific type of dielectric particles (P1) contained in the suspension (L1) to the second end side in the width direction (W1) of the flow channel (30), and controls the voltage of the first electrode (50) to guide the specific type of dielectric particles (P1) among the plurality of types of dielectric particles (P1, P2) to the first end side in the width direction (W1) of the flow channel (30). According to this aspect, the accuracy of separating the specific type of dielectric particles (P1) from the suspension (L1) can be improved.

Industrial Applicability

[0095] The present disclosure is applicable to a flow channel chip, a separation system, and a separation method. Specifically, the present disclosure is applicable to a flow channel chip, a separation system, and a separation method for separating a specific type of dielectric particles from a plurality of types of dielectric particles contained in a suspension.

Explanation of Reference Numerals

[0096] 1 Separation system 10, 10A Flow path chip 10a Substrate 11 Voltage control device 21 Inlet 30 Flow path 31 Main flow path 32 Connecting flow path 40-1 First collection part 40-2 Second collection part 50 First electrode 511 First tooth part (tooth part) 521 Second tooth part (tooth part) 60 Second electrode 611 First tooth part (tooth part) 611a Tip 621 Second tooth part (tooth part) 621a Tip 71, 72 First electrode pads 81, 82 Second electrode pads 90 Filter L1 Suspension P1, P2 Dielectric particles P3 Particle W1 Width direction D1 First predetermined direction D2 Second predetermined direction

Claims

1. A substrate having an inlet into which a suspension containing a plurality of types of dielectric particles including a specific type of dielectric particles is introduced, and a flow path through which the plurality of types of dielectric particles of the suspension introduced from the inlet flow, A first electrode that guides the specific type of dielectric particles among the plurality of types of dielectric particles to the first end side in the width direction of the flow path, A second electrode that is provided between the inlet and the first electrode and guides the plurality of types of dielectric particles to the second end side in the width direction of the flow path, Comprising: Each of the first electrode and the second electrode is on one surface of the flow path, The plurality of tooth portions of the second electrode are A first tooth portion extending from the first end to the second end in the width direction of the flow path, A second tooth portion extending from the second end to the first end in the width direction of the flow path, Including: The tip of the first tooth portion is inside the flow path at a predetermined distance from the second end in the width direction of the flow path, The tip of the second tooth portion is outside the flow path, Flow path chip.

2. The first electrode is a comb-shaped electrode having a plurality of tooth portions arranged along a first predetermined direction, The second electrode is a comb-shaped electrode having a plurality of tooth portions arranged along a second predetermined direction, The first predetermined direction and the second predetermined direction are directions facing opposite sides in the width direction of the flow path, The flow path chip according to claim 1.

3. The first predetermined direction is a direction from the second end to the first end in the width direction of the flow path along the direction in which the suspension flows in the flow path, The second predetermined direction is a direction from the first end to the second end in the width direction of the flow path along the direction in which the suspension flows in the flow path, The flow path chip according to claim 2.

4. The plurality of tooth portions of the second electrode are A first tooth portion extending from the first end to the second end in the width direction of the flow path, A second tooth portion extending from the second end to the first end in the width direction of the flow path, Including: The tip of the first tooth portion and the tip of the second tooth portion are outside the flow path, The flow path chip according to any one of claims 1 to 3.

5. The substrate is A first collection portion connected to the first end side in the width direction of the flow path, A second collection portion connected to the second end side in the width direction of the flow path, Having: The flow path chip according to any one of claims 1 to 4.

6. A first electrode pad for applying a first predetermined voltage to the first electrode, A second electrode pad provided separately from the first electrode pad for applying a second predetermined voltage different from the first predetermined voltage to the second electrode, Comprising: The flow channel chip according to any one of claims 1 to 5.

7. The second predetermined voltage is set such that at least one of the amplitude and the frequency changes with time. The flow channel chip according to claim 6.

8. The flow channel chip according to any one of claims 1 to 7, and a voltage control device that controls the voltage of the second electrode so as to guide the plurality of types of dielectric particles including the specific type of dielectric particles contained in the suspension to the second end side in the width direction of the flow channel, and controls the voltage of the first electrode so as to guide the specific type of dielectric particles among the plurality of types of dielectric particles to the first end side in the width direction of the flow channel; comprising a separation system.

9. The flow channel chip is disposable. The separation system according to claim 8.

10. A separation method using the flow channel chip according to any one of claims 1 to 7, wherein the voltage of the second electrode is controlled so as to guide the plurality of types of dielectric particles including the specific type of dielectric particles contained in the suspension to the second end side in the width direction of the flow channel, and the voltage of the first electrode is controlled so as to guide the specific type of dielectric particles among the plurality of types of dielectric particles to the first end side in the width direction of the flow channel. A separation method.

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