Flow channel chip and separation system

Abstract

To provide a flow channel chip and a separation system capable of stabilizing the separation work of a specific kind of dielectric particles from a suspension.SOLUTION: A flow channel chip 10 includes: a substrate 10a having an inlet 21 into which a suspension L1 containing a plurality of kinds of dielectric particles P1, P2 including a specific kind of dielectric particles P1 is introduced and a flow channel 30 through which the suspension L1 introduced from the inlet 21 flows; a separation electrode 50 located in the flow channel 30 for generating a dielectrophoretic force for guiding the specific kind of dielectric particles P1 of the plurality of kinds of dielectric particles P1, P2 in a prescribed direction; and a sensor electrode 60 located in the flow channel 30 for measuring an electric resistance of the suspension L1.SELECTED DRAWING: Figure 1

Description

Technical Field

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[0001] The present disclosure relates to a flow channel chip and a separation system.

Background Art

[0002] As a particle control technology in a microspace such as a microfluidic device, dielectrophoresis is utilized. In the biological field, various research and developments have been carried out mainly on the characterization, 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 channel 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 channel 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 channel chip and a separation system capable of stabilizing the separation operation of specific types of dielectric particles from a suspension.

Means for Solving the Problems

[0006] A flow channel chip according to one aspect of the present disclosure comprises a substrate, a separation electrode, and a sensor electrode. The substrate has an inlet into which a suspension containing a plurality of types of dielectric particles, including a specific type of dielectric particle, is introduced, and a flow channel through which the plurality of types of dielectric particles of the suspension introduced from the inlet flow. The separation electrode is located in the flow channel to generate dielectrophoretic force to guide a specific type of dielectric particle among the plurality of types of dielectric particles in a predetermined direction. The sensor electrode is located in the flow channel to measure the electrical resistance of the suspension.

[0007] A separation system according to one aspect of the present disclosure comprises the above-mentioned flow channel chip and a measuring device for measuring the electrical resistance of a suspension based on the output from a sensor electrode. [Effects of the Invention]

[0008] According to the embodiments of this disclosure, the separation of specific types of dielectric particles from a suspension can be stabilized. [Brief explanation of the drawing]

[0009] [Figure 1] Block diagram of an example configuration of a separation system equipped with a flow channel chip according to Embodiment 1. [Figure 2] Schematic plan view of the flow channel chip in Figure 1. [Figure 3] A graph showing the time evolution of the resistance and reactance components of the impedance obtained from the sensor electrodes. [Figure 4] A log-log graph showing the change in impedance with respect to frequency due to differences in the area of ​​the sensor electrodes. [Figure 5] A semi-logarithmic graph showing the change in measurement efficiency with respect to frequency due to differences in the area of ​​the sensor electrodes. [Figure 6] A log-log graph showing the range of impedance change with respect to frequency when the sensor electrode area is small. [Figure 7] A log-log graph showing the range of impedance change with respect to frequency when the sensor electrode area is large. [Figure 8] Schematic plan view of an example of the flow channel chip configuration in Embodiment 2 [Figure 9]Schematic plan view of Example 1 of the flow path chip configuration in Embodiment 3 [Figure 10] Schematic plan view of example 2 of the flow path chip configuration in Embodiment 3 [Figure 11] Schematic plan view of Example 1 of the flow path chip configuration in Embodiment 4 [Figure 12] Schematic plan view of Example 2 of the flow path chip configuration in Embodiment 4 [Figure 13] Schematic plan view of example 3 of the flow path chip configuration in Embodiment 4 [Modes for carrying out the invention]

[0010] [1. Embodiments] [1.1 Embodiment 1] [1.1.1 Overview] Figure 1 is a block diagram of an example configuration of separation system 1 of Embodiment 1. Separation system 1 in Figure 1 enables the separation of a specific type of dielectric particle P1 from a suspension L1. Suspension L1 contains multiple types of dielectric particles, including the specific type of dielectric particle P1. Separation system 1 in Figure 1 uses the principle of dielectrophoresis to separate the specific type of dielectric particle P1 from the multiple types of dielectric particles contained in suspension L1. In this embodiment, suspension L1 is blood. The multiple types of dielectric particles are, for example, cells contained in blood. Examples of cells contained in blood include cancer cells and leukocytes. In this embodiment, for the sake of clarity, suspension L1 is assumed to contain two types of dielectric particles P1 and P2. The specific type of dielectric particle P1 is cancer cells, in particular circulating cancer cells (CTCs). Dielectric particle P2 is leukocytes. Separation system 1 in Figure 1 is used to separate circulating cancer cells (specific type of dielectric particle P1) from blood (suspension L1).

[0011] The separation system 1 in Figure 1 includes a channel tip 10 through which a suspension L1 flows. The channel tip 10 in Figure 1 includes a substrate 10a, a separation electrode 50, and a sensor electrode 60. The substrate 10a has an inlet 21 through which a suspension L1 containing multiple types of dielectric particles P1 and P2, including a specific type of dielectric particle P1, is introduced, and a channel 30 through which the multiple types of dielectric particles P1 and P2 of the suspension L1 introduced from the inlet 21 flow. The separation electrode 50 is located in the channel 30 to generate dielectrophoretic force that guides a specific type of dielectric particle P1 among the multiple types of dielectric particles P1 and P2 in a predetermined direction. The sensor electrode 60 is located in the channel 30 to measure the electrical resistance of the suspension L1.

[0012] In the channel chip 10 shown in Figure 1, the separation electrode 50 generates dielectrophoretic force, which allows the separation electrode 50 to guide a specific type of dielectric particle P1 from among multiple types of dielectric particles P1 and P2 in a predetermined direction, thereby enabling the separation of the specific type of dielectric particle P1 from the suspension L1. The magnitude of the dielectrophoretic force depends on the electric field strength generated in the suspension L1. The electric field strength generated in the suspension L1 is determined by the impedance (reactance and resistance) of the separation electrode 50 and the electrical resistance of the suspension L1. The influence of the electrical resistance of the suspension L1 is relatively large, and a change in the electrical resistance of the suspension L1 changes the electric field strength, which leads to a change in the magnitude of the dielectrophoretic force. If the magnitude of the dielectrophoretic force changes, the separation of the specific type of dielectric particle P1 from the suspension L1 may not be successful. To address this situation, the channel chip 10 shown in Figure 1 is equipped with a sensor electrode 60, which makes it possible to measure the electrical resistance of the suspension L1. Therefore, the flow channel chip 10 can take into account the electrical resistance of the suspension L1 and perform the separation of specific types of dielectric particles P1 from the suspension L1. For example, the voltage applied to the separation electrode 50 can be adjusted according to the measurement value of the electrical resistance of the suspension L1 by the sensor electrode 60, or the components of the suspension L1 supplied to the flow channel chip 10 can be adjusted. If the measurement value of the electrical resistance of the suspension L1 by the sensor electrode 60 is abnormal, the separation operation can be stopped. Thus, the flow channel chip 10 can stabilize the separation operation of specific types of dielectric particles P1 from the suspension L1.

[0013] [1.1.2 Details] Hereinafter, the flow path 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 path chip 10, a voltage control device 11, a measurement device 12, and an analysis device 13.

[0014] [1.1.2.1 Flow Path 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 in 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.

[0015] 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 separation electrode 50, a sensor electrode 60, separation electrode pads 71, 72, and sensor electrode pads 81, 82.

[0016] The substrate 10a has an inlet 21, a flow path 30, and a plurality of collection parts 40-1, 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, for example, using 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 inlet 21, the flow path 30, and the plurality of collection parts 40-1, 40-2 formed on the surface to a first substrate (for example, a glass substrate) on which the separation electrode 50, the sensor electrode 60, the separation electrode pads 71, 72, and the sensor electrode pads 81, 82 are formed on the surface.

[0017] The inlet 21 is, as shown in FIG. 1, a part where the suspension L1 is introduced into the substrate 10a. The inlet 21 is connected, for example, to a supply source of the suspension L1 by a tube, and the suspension L1 is supplied through the tube.

[0018] The flow path 30 is the portion in the substrate 10a through which multiple types of dielectric particles P1 and P2 of the suspension L1 introduced from the inlet 21 flow. As shown in Figure 2, the flow path 30 includes a main flow path 31 and multiple (two in the illustrated example) branched flow paths 32-1 and 32-2 (hereinafter collectively referred to as reference numeral 32).

[0019] The main channel 31 in Figure 2 constitutes the main body of the channel 30. The main channel 31 is the part of the channel 30 that separates specific types of dielectric particles P1. In this embodiment, the main channel 31 is rectangular in plan view. The first end (left end in Figure 2) of the main channel 31 in the longitudinal direction (left-right direction in Figure 2) is connected to the inlet 21. The second end (right end in Figure 2) of the main channel 31 in the longitudinal direction is connected to each branch channel 32.

[0020] The multiple branch channels 32-1 and 32-2 are sections in the channel 30 that transport dielectric particles P1 and P2 that have been separated from each other in the main channel 31, so as not to mix again. The multiple branch channels 32-1 and 32-2 are located on the opposite side of the main channel 31 from the inlet 21. Therefore, each branch channel 32 is located downstream of the main channel 31 (on the right side in Figure 2). Branch channel 32-1 is connected to the first end 311 in the width direction (up and down direction in Figure 2) of the main channel 31. As shown in Figure 1, branch channel 32-1 is the section through which specific types of dielectric particles P1 separated in the main channel 31 flow. Branch channel 32-2 is connected to the second end 312 in the width direction of the main channel 31. As shown in Figure 2, branch channel 32-1 is the section through which the remaining dielectric particles P2, after specific types of dielectric particles P1 have been separated from multiple types of dielectric particles P1 and P2, flow.

[0021] The multiple collection units 40 include a first collection unit 40-1 and a second collection unit 40-2. The first collection unit 40-1 is connected to the first end 311 in the width direction of the main flow channel 31 via a branched flow channel 32-1. The first collection unit 40-1 collects specific types of dielectric particles P1 flowing through the branched flow channel 32-1. The first collection unit 40-1 may, for example, be equipped with an outlet, thereby supplying a solution S1 containing the specific types of dielectric particles P1 from the flow channel tip 10 to the outside. The second collection unit 40-2 is connected to the second end 312 in the width direction W1 of the main flow channel 31 via a branched flow channel 32-2. The second collection unit 40-2 collects dielectric particles P2 flowing through the branched flow channel 32-2. The second collection unit 40-2 may, for example, be equipped with an outlet, thereby supplying a solution S2 containing the dielectric particles P2 from the flow channel tip 10 to the outside.

[0022] The separation electrode 50 is located in the channel 30 to generate dielectrophoretic force that guides a specific type of dielectric particle P1 from among multiple types of dielectric particles P1 and P2 in the suspension L1 in a predetermined direction. In Figure 2, only a part, not the entire, of the separation electrode 50 is located in the channel 30. In this embodiment, the predetermined direction is toward the first end 311 in the width direction of the main channel 31. In this embodiment, as shown in Figure 2, the separation electrode 50 is arranged in the main channel 31. The separation electrode 50 is located on the bottom surface of the main channel 31. The separation electrode 50 may be formed from, for example, a relatively inexpensive planar electrode. As an example, the separation electrode 50 may be configured to include an electrode layer formed on a 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.

[0023] The separation electrode 50 is a comb-shaped electrode having a plurality of teeth 511, 521 arranged in a predetermined direction D1 on the bottom surface of the main channel 31. The predetermined direction D1 corresponds to the direction of the dielectrophoretic force acting on the dielectric particles P1. The predetermined direction D1 is, for example, the direction from the first end 311 to the second end 312 in the width direction of the channel 30 (down-right direction in Figure 2), along the direction in which the suspension L1 flows in the channel 30 (right direction in Figure 2). The plurality of teeth 511, 521 include a plurality of first teeth 511 and a plurality of second teeth 521. The first teeth 511 and the second teeth 521 are arranged alternately. The plurality of first teeth 511 extend from the first end 311 to the second end 312 in the width direction of the main channel 31. The plurality of second teeth 521 extend from the second end 312 to the first end 311 in the width direction of the main channel 31.

[0024] The separation electrode 50 in Figure 2 includes a pair of electrode patterns 51 and 52. Electrode pattern 51 comprises a plurality of first teeth 511 and a connecting portion 512 located on the first end 311 side in the width direction of the main flow path 31, connecting the base ends of the plurality of teeth 511. The connecting portion 512 is outside the flow path 30. Electrode pattern 52 comprises a plurality of second teeth 521 and a connecting portion 522 located on the second end 312 side in the width direction of the main flow path 31, connecting the base ends of the plurality of second teeth 521. The connecting portion 522 is outside the flow path 30.

[0025] The sensor electrode 60 is a separate electrode from the separation electrode 50. The sensor electrode 60 is located on the opposite side of the channel 30 from the inlet 21 relative to the separation electrode 50. In this embodiment, the sensor electrode 60 is provided across multiple branched channels 32-1 and 32-2. The sensor electrode 60 is located within the channel 30 to measure the electrical resistance of the suspension L1. In Figure 2, only a portion, not the entire, of the sensor electrode 60 is located within the channel 30. In this embodiment, the electrical resistance of the suspension L1 is assumed to include impedance, or at least one of resistance and reactance.

[0026] The sensor electrode 60 is positioned at the bottom of the branched channel 32. The sensor electrode 60 may be formed from, for example, a relatively inexpensive planar electrode. As an example, the sensor electrode 60 may be configured to include an electrode layer formed on a 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.

[0027] As shown in Figure 2, the sensor electrode 60 is a comb-shaped electrode having a plurality of teeth 611, 621 arranged along the length of the flow path 30 on the bottom surface of the flow path 30. In this embodiment, the plurality of teeth 611, 621 are arranged along the length of each branch flow path 32 of the flow path 30. The plurality of teeth 611, 621 include a plurality of first teeth 611 and a plurality of second teeth 621. The first teeth 611 and the second teeth 621 are arranged alternately. In the first branch flow path 32-1, the plurality of first teeth 611 extend from the side opposite to the second branch flow path 32-2 in the first branch flow path 32-1 toward the side of the second branch flow path 32-2 in the first branch flow path 32-1. The plurality of second teeth 621 extend from the side of the second branch flow path 32-2 in the first branch flow path 32-1 toward the side opposite to the second branch flow path 32-2 in the first branch flow path 32-1. In the second branch channel 32-2, the multiple first teeth 611 extend from the side of the second branch channel 32-2 opposite to the first branch channel 32-1 toward the side of the first branch channel 32-1. The multiple second teeth 621 extend from the side of the first branch channel 32-1 toward the side of the second branch channel 32-2 opposite to the first branch channel 32-1.

[0028] The sensor electrode 60 in Figure 2 includes a first electrode pattern 61 and a second electrode pattern 62. The first electrode pattern 61 includes a plurality of first teeth 611 located in the first and second branched channels 32-1 and 32-2, respectively, a connecting portion 612 that connects the base ends of the plurality of first teeth 611 located in the first branched channel 32-1, a connecting portion 612 that connects the base ends of the plurality of first teeth 611 located in the second branched channel 32-2, and a connecting portion 613 that connects the connecting portions 612 to each other. Each connecting portion 612 is located outside the channel 30. The second electrode pattern 62 includes a plurality of second teeth 621 located in the first and second branched channels 32-1 and 32-2, respectively, and a connecting portion 622 that is located between the first and second branched channels 32-1 and 32-2 and connects the base ends of the plurality of second teeth 621.

[0029] To measure the electrical resistance of the suspension L1 using the sensor electrode 60, a measurement voltage is applied between the first and second electrode patterns 61 and 62 of the sensor electrode 60, and the current flowing through the suspension L1 between the first and second electrode patterns 61 and 62 of the sensor electrode 60 is measured. The measurement voltage is, for example, an AC voltage of a predetermined frequency. This makes it possible to measure the impedance between the first and second electrode patterns 61 and 62 of the sensor electrode 60. The impedance between the first and second electrode patterns 61 and 62 of the sensor electrode 60 includes a reactance component (imaginary part) and a resistance component (real part). The reactance component is mainly determined by the sensor electrode 60, and the resistance component is mainly determined by the electrical resistance of the suspension L1. More specifically, the resistance component includes the electrical resistance of the sensor electrode 60. Therefore, it is possible to determine the electrical resistance of the suspension L1 from the impedance between the first and second electrode patterns 61 and 62 of the sensor electrode 60 with respect to the measurement voltage. The predetermined frequency of the measurement voltage may be a specific frequency or a frequency band with a certain range. If the predetermined frequency of the measurement voltage is a frequency band with a certain range, measurements may be performed using sawtooth waves, triangular waves, etc.

[0030] Figure 3 is a graph showing the time evolution of the resistance and reactance components of the impedance (impedance between the first and second electrode patterns 61 and 62 of the sensor electrode 60) determined by the sensor electrode 60. Figure 3 shows the results of impedance measurements over a predetermined period of time. The predetermined period is, for example, 2 hours. In Figure 3, X represents the reactance component and R represents the resistance component. As is clear from Figure 3, the reactance component X hardly changes, but the resistance component R changes over time. In particular, in Figure 3, the resistance component R decreases over time.

[0031] The isolation electrode pads 71 ​​and 72 are used to apply a predetermined voltage to the isolation electrode 50. The isolation electrode pads 71 ​​and 72 are connected to the pair of electrode patterns 51 and 52 of the isolation electrode 50, respectively, in order to apply a predetermined voltage between them. The isolation electrode pads 71 ​​and 72 are connected to the pair of electrode patterns 51 and 52 of the isolation electrode 50, respectively, by, for example, a wiring pattern. The isolation electrode pads 71 ​​and 72 are positioned on the outer surface of the substrate 10a. The voltage of the isolation electrode 50 can be controlled by controlling the voltage between the isolation electrode pads 71 ​​and 72.

[0032] The sensor electrode pads 81 and 82 are provided separately from the isolation electrode pads 71 ​​and 72. The sensor electrode pads 81 and 82 are used to apply a measurement voltage to the sensor electrode 60. The sensor electrode pads 81 and 82 are connected to the first and second electrode patterns 61 and 62 of the sensor electrode 60, respectively, in order to apply a measurement voltage between the first and second electrode patterns 61 and 62 of the sensor electrode 60. The sensor electrode pads 81 and 82 are connected to the pair of electrode patterns 61 and 62 of the sensor electrode 60, respectively, by, for example, a wiring pattern. The sensor electrode pads 81 and 82 are arranged so as to be located on the outer surface of the base body 10a. The voltage of the sensor electrode 60 can be controlled by controlling the voltage between the sensor electrode pads 81 and 82.

[0033] As shown in Figures 1 and 2, the flow channel chip 10 is equipped with a sensor electrode 60 for measuring the electrical resistance of the suspension L1. In the flow channel chip 10, the separation electrode 50 and the sensor electrode 60 are separate electrodes. Therefore, it is possible to design the separation electrode 50 and the sensor electrode 60 under conditions suitable for their respective purposes. For example, when the separation electrode 50 is used as the sensor electrode 60, its configuration is limited by the conditions required of the separation electrode 50, which is to apply dielectrophoretic force to a specific type of dielectric particle P1. However, in this embodiment, since the sensor electrode 60 is an electrode independent of the separation electrode 50, the configuration of the sensor electrode 60 is not limited by the conditions required of the separation electrode 50. Therefore, since the sensor electrode 60 does not depend on the structure of the separation electrode 50, the detection sensitivity of the sensor electrode 60 can be adjusted with a high degree of design freedom. As a result, the separation of a specific type of dielectric particle P1 from the suspension L1 can be stabilized.

[0034] The configuration of the sensor electrode 60 will be further described below. In this embodiment, the area of ​​the portion of the sensor electrode 60 located within the flow path 30 is larger than the area of ​​the portion of the separation electrode 50 located within the flow path 30. In this embodiment, the area of ​​the portion of the sensor electrode 60 located within the flow path 30 is the sum of the areas of the portions of the multiple teeth 611, 621 of the sensor electrode 60 located within the flow path 30. The area of ​​the portion of the sensor electrode 60 located within the flow path 30 can be changed, for example, by the dimensions (mainly width) of the teeth 611, 621, the spacing between the teeth 611, 621, and the number of teeth 611, 621. When adjusting the area of ​​the portion of the sensor electrode 60 located within the flow path 30, it is preferable to change the number of teeth 611, 621. In this embodiment, the area of ​​the portion of the separation electrode 50 located within the flow path 30 is the sum of the areas of the multiple teeth 511, 521 of the separation electrode 50 located within the flow path 30. The area of ​​the portion of the separation electrode 50 located within the flow path 30 can be changed, for example, by the dimensions (mainly width) of the teeth 511, 521, the spacing between the teeth 511, 521, and the number of teeth 511, 521. When adjusting the area of ​​the portion of the separation electrode 50 located within the flow path 30, it is preferable to change the number of teeth 511, 521.

[0035] In the separation electrode 50, a shorter contact time between the dielectric particles P1 and the separation electrode 50 is preferable to reduce the burden on the dielectric particles P1. Therefore, the area of ​​the portion of the separation electrode 50 located within the flow path 30 tends to be set to be small. On the other hand, in the sensor electrode 60, a larger area of ​​the portion located within the flow path 30 is sometimes preferable.

[0036] Figure 4 is a log-log graph showing the change in measured impedance values ​​with respect to frequency of the measurement voltage due to differences in the area of ​​the sensor electrode 60. In Figure 4, G11 corresponds to the case where the area of ​​the sensor electrode is small, and G12 corresponds to the case where the area of ​​the sensor electrode is large. In G12, the area of ​​the portion of the sensor electrode 60 located within the flow path 30 is larger than in G11. As can be seen from Figure 4, the change in measured impedance values ​​with respect to frequency of the measurement voltage differs depending on the area of ​​the sensor electrode 60.

[0037] Figure 5 is a semi-logarithmic graph showing the change in measurement efficiency with respect to frequency of the measurement voltage due to differences in the area of ​​the sensor electrode 60. Measurement efficiency is the percentage of the electrical resistance of the suspension L1 with respect to the measured impedance. In Figure 5, G21 corresponds to the case where the area of ​​the sensor electrode is small, and G22 corresponds to the case where the area of ​​the sensor electrode is large. As shown in Figure 5, the maximum measurement efficiency of G21 is about 40%, while the maximum measurement efficiency of G22 exceeds 90%. High measurement efficiency means that the influence of the impedance of the sensor electrode 60 on the measured impedance is small, and the influence of variations in the performance of the sensor electrode 60 can be reduced, thereby reducing variations in the performance of the flow channel chip 10. Therefore, higher measurement efficiency is desirable.

[0038] The electrical resistance of suspension L1 may change over time. The extent to which the change in the electrical resistance of suspension L1 can be tolerated is determined by the impedance (mainly reactance) of the sensor electrode 60. Figure 6 is a log-log graph showing the range of change in measured impedance with respect to frequency when the area of ​​the sensor electrode 60 is small. Figure 7 is a log-log graph showing the range of change in measured impedance with respect to frequency when the area of ​​the sensor electrode 60 is large. A change in the electrical resistance of suspension L1 causes a change in the measured impedance with respect to frequency. This is shown as an up and down movement of the graph in Figures 6 and 7. The extent to which the graph can change is determined by the impedance of the sensor electrode 60. In Figures 6 and 7, the region between the dotted lines G31 and G32 is the range in which the graph of measured impedance with respect to frequency can change, and the dotted lines G31 and G32 are determined by the impedance of the sensor electrode 60. The dotted lines G31 and G32 are not affected by changes in the electrical resistance of suspension L1. The wider the range of change in measured impedance between the dotted lines G31 and G32 in the frequency direction, the more efficient the measurement of the electrical resistance of the suspension L1 becomes, and the wider the frequency band available for measurement. As is clear from Figures 6 and 7, when the area of ​​the sensor electrode 60 is large, the frequency band available for measurement is wide, and in some cases it is possible to read fluctuations in the electrical resistance of the suspension L1 of more than an order of magnitude at a single frequency. On the other hand, when the area of ​​the sensor electrode 60 is small, the measurable frequency band is narrow, and the measurement performance by the sensor electrode 60 is inferior to that when the area of ​​the sensor electrode 60 is large.

[0039] Thus, it is preferable that the area of ​​the portion of the sensor electrode 60 located within the flow path 30 is large. Therefore, in this embodiment, the area of ​​the portion of the sensor electrode 60 located within the flow path 30 is set to be larger than the area of ​​the portion of the separation electrode 50 located within the flow path 30. This makes it possible to improve the measurement performance of the sensor electrode 60 while reducing the burden on the dielectric particles P1 by the separation electrode 50.

[0040] As described above, a higher measurement efficiency (the percentage of the electrical resistance of the suspension L1 relative to the measured impedance) is preferable. Therefore, the reactance of the sensor electrode 60 should be set to obtain a measurement efficiency of a specified value or higher. In this embodiment, the reactance of the sensor electrode 60 is smaller than the lower limit of the measurement range for the electrical resistance of the suspension L1. For example, the reactance of the sensor electrode 60 may be 1 / 5 or less of the lower limit of the measurement range for the electrical resistance of the suspension L1. The reactance of the sensor electrode 60 is a value with respect to the frequency of the measurement voltage. The measurement range for the electrical resistance of the suspension L1 is appropriately set based on the properties of the suspension L1 supplied to the flow channel chip 10. For example, if the measurement range for the electrical resistance of the suspension L1 is about 700Ω to 1000Ω, the reactance of the sensor electrode 60 is set to about 100Ω.

[0041] [1.1.2.2 Voltage Control Devices] The voltage control device 11 in Figure 1 controls the voltage applied to the flow channel chip 10 to generate dielectrophoretic force. In this embodiment, the voltage control device 11 separates a specific type of dielectric particle P1 from multiple types of dielectric particles P1 and P2 contained in the suspension L1 by controlling the voltage of the separation electrode 50. The voltage control device 11 includes, for example, a function generator. The voltage control device 11 in Figure 1 is connected to the separation electrode 50 via separation electrode pads 71 ​​and 72. The voltage control device 11 controls the voltage of the separation electrode 50 to generate dielectrophoretic force that guides a specific type of dielectric particle P1 from multiple types of dielectric particles P1 and P2 in a predetermined direction. In this embodiment, the voltage control device 11 applies a predetermined voltage to the separation electrode 50 via the separation electrode pads 71 ​​and 72. The predetermined voltage is, for example, an AC voltage. The frequency of the predetermined voltage is set so that a positive dielectrophoretic force acts on the specific type of dielectric particle P1 by the separation electrode 50. In this case, the frequency is set such that, for dielectric particles P2 other than a specific type of dielectric particle P1 among multiple types of dielectric particles P1 and P2, no dielectrophoretic force acts, or if positive or negative dielectrophoretic force (attraction or repulsion) acts, the dielectrophoretic force is relatively small. The frequency of the predetermined voltage is, for example, 600 kHz.

[0042] [1.1.2.3 Measuring device] The measuring device 12 in Figure 1 measures the electrical resistance of the suspension L1 based on the output from the sensor electrode 60. In this embodiment, the measuring device 12 measures the electrical resistance of the suspension L1 by controlling the voltage of the sensor electrode 60. The measuring device 12 includes, for example, a combination of a signal generator such as a function generator and a measuring instrument such as an oscilloscope, or a source / measure unit. The measuring device 12 in Figure 1 is connected to the sensor electrode 60 via sensor electrode pads 81 and 82. With a measuring voltage applied between the first and second electrode patterns 61 and 62 of the sensor electrode 60 via the sensor electrode pads 81 and 82, the measuring device 12 measures the current flowing between the first and second electrode patterns 61 and 62 of the sensor electrode 60 as the output from the sensor electrode 60. From the measuring voltage and the output from the sensor electrode 60, the impedance between the first and second electrode patterns 61 and 62 of the sensor electrode 60 is determined. The impedance between the first and second electrode patterns 61 and 62 of the sensor electrode 60 includes a reactance component determined by the sensor electrode 60 and a resistance component determined by the electrical resistance of the suspension L1. Therefore, the measuring device 12 can determine the electrical resistance of the suspension L1 from the impedance between the first and second electrode patterns 61 and 62 of the sensor electrode 60 with respect to the measurement voltage.

[0043] [1.1.2.4 Analysis device] The analysis apparatus 13 in Figure 1 performs an analysis on the separation of a specific type of dielectric particle P1 from multiple types of dielectric particles P1 and P2 contained in the suspension L1. The analysis apparatus 13 in Figure 1 comprises an imaging device 131, a processing device 132, and a display device 133.

[0044] The imaging device 131 acquires an image of a target area in the flow channel chip 10. The target area is, for example, the main flow channel 31. From the image of the main flow channel 31, the movement trajectories of dielectric particles P1 and P2 passing through the flow channel 30 can be obtained. The imaging device 131 comprises, for example, a camera having an image sensor 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-optical microscope. The optical microscope module may also be configured to be switchable between a phase-contrast microscope and an epi-optical microscope, for example by changing lenses. When performing fluorescence observation, a fluorescence filter may be used as appropriate. The operation of the imaging device 131 may be controlled by the processing device 132.

[0045] The display device 133 displays information from the processing device 132. The display device 133 is, for example, a liquid crystal display or an organic EL display.

[0046] The processing unit 132 controls the operation of the analysis device 13. The processing unit 132 can be implemented, for example, by a computer system including one or more processors (microprocessors) and one or more memories. One or more processors execute programs (stored in one or more memories, etc.) to realize predetermined functions. As an example, the processing unit 132 performs image analysis on the image captured by the imaging device 131 to determine the movement trajectories of dielectric particles P1 and P2 passing through the main channel 31. The processing unit 132 may display the image captured by the imaging device 131, or the movement trajectories determined by image analysis, on the display device 133.

[0047] [1.1.3 Effects, etc.] As described above, the flow channel chip 10 comprises a substrate 10a having an inlet 21 into which a suspension L1 containing multiple types of dielectric particles P1 and P2, including a specific type of dielectric particle P1, is introduced, and a flow channel 30 through which the multiple types of dielectric particles P1 and P2 of the suspension L1 introduced from the inlet 21 flow; a separation electrode 50 located in the flow channel 30 to generate dielectrophoretic force to guide the specific type of dielectric particle P1 among the multiple types of dielectric particles P1 and P2 in a predetermined direction; and a sensor electrode 60 located in the flow channel 30 to measure the electrical resistance of the suspension L1. With this configuration, the separation of the specific type of dielectric particle P1 from the suspension L1 can be stabilized.

[0048] Furthermore, in the flow channel chip 10, the separation electrode 50 and the sensor electrode 60 are separate electrodes. With this configuration, the separation electrode 50 and the sensor electrode 60 can be designed under conditions suitable for their respective purposes, thereby stabilizing the separation of specific types of dielectric particles P1.

[0049] Furthermore, in the flow channel chip 10, the area of ​​the portion of the sensor electrode 60 located within the flow channel 30 is larger than the area of ​​the portion of the separation electrode 50 located within the flow channel 30. This configuration reduces performance variations in the flow channel chip 10 and further improves the measurement performance of the sensor electrode 60.

[0050] Furthermore, in the flow channel chip 10, the reactance of the sensor electrode 60 is smaller than the lower limit of the measurement range for the electrical resistance of the suspension L1. This configuration reduces performance variations in the flow channel chip 10.

[0051] Furthermore, in the flow channel chip 10, the reactance of the sensor electrode 60 is less than or equal to 1 / 5 of the lower limit of the measurement range for the electrical resistance of the suspension L1. This configuration reduces performance variations in the flow channel chip 10 and further improves the measurement performance by the sensor electrode 60.

[0052] Furthermore, in the flow channel chip 10, the sensor electrode 60 is a comb-shaped electrode having multiple teeth 611, 621 arranged along the length of the flow channel 30 on the bottom surface of the flow channel 30. This configuration stabilizes the separation of specific types of dielectric particles P1 from the suspension L1.

[0053] Furthermore, in the flow channel chip 10, the sensor electrode 60 is located in the flow channel 30 on the opposite side of the inlet 21 from the separation electrode 50. This configuration allows for the stabilization of the separation of specific types of dielectric particles P1 from the suspension L1.

[0054] Furthermore, in the flow channel chip 10, the flow channel 30 includes multiple branched flow channels 32 connected to multiple collection units 40. The sensor electrode 60 is provided across the multiple branched flow channels 32. With this configuration, the electrical resistance of all the suspension L1 passing through the flow channel 30 can be measured. For example, if there is a distribution of electrical resistance of the suspension L1 in the width direction of the flow channel 30, the suspension L1 flowing into the multiple collection units 40 may have different electrical resistances. In the above configuration, since the electrical resistance of all the suspension L1 passing through the flow channel 30 is measured, the influence of such distributions of electrical resistance of the suspension L1 can be reduced, enabling more accurate measurement of the electrical resistance of the suspension L1. In addition, appropriate feedback can be provided to external devices such as the voltage control device 11, measuring device 12, and analysis device 13.

[0055] The separation system 1 described above comprises a flow channel chip 10 and a measuring device 12 that measures the electrical resistance of the suspension L1 based on the output from the sensor electrode 60. This configuration allows for the stabilization of the separation of specific types of dielectric particles P1 from the suspension L1.

[0056] Furthermore, in separation system 1, the flow channel tip 10 is disposable. This configuration prevents contamination and improves the usability of separation system 1.

[0057] [1.2 Embodiment 2] Figure 8 is a schematic plan view of an example configuration of a flow channel chip according to Embodiment 2. Hereinafter, the flow channel chip in Figure 8 will be denoted by reference numeral 10A. The flow channel chip 10A in Figure 8 is equipped with a plurality of sensor electrodes 60A-1, 60A-2 (hereinafter collectively referred to as reference numeral 60A). The plurality of sensor electrodes 60A-1, 60A-2 are provided in each of the plurality of branched flow channels 32-1, 32-2.

[0058] As shown in Figure 8, the sensor electrode 60A-1 is a comb-shaped electrode having a plurality of teeth 611, 621 arranged along the length of the flow path 30 on the bottom surface of the flow path 30. In this embodiment, the plurality of teeth 611, 621 of the sensor electrode 60A-1 are arranged along the length of the first branch flow path 32-1 of the flow path 30. The sensor electrode 60A-1 includes a first electrode pattern 61A-1 and a second electrode pattern 62A-1. The first electrode pattern 61A-1 includes a plurality of first teeth 611 located in the first branch flow path 32-1 and a connecting portion 612 located outside the first branch flow path 32-1 that connects the base ends of the plurality of first teeth 611. The second electrode pattern 62A-2 includes a plurality of second teeth 621 located in the second branch flow path 32-2 and a connecting portion 622 located outside the first branch flow path 32-1 that connects the base ends of the plurality of second teeth 621.

[0059] As shown in Figure 8, the sensor electrode 60A-2 is a comb-shaped electrode having a plurality of teeth 611, 621 arranged along the length of the flow path 30 on the bottom surface of the flow path 30. In this embodiment, the plurality of teeth 611, 621 of the sensor electrode 60A-2 are arranged along the length of the second branch flow path 32-2 of the flow path 30. The sensor electrode 60A-2 includes a first electrode pattern 61A-2 and a second electrode pattern 62A-2. The first electrode pattern 61A-2 includes a plurality of first teeth 611 located in the second branch flow path 32-2 and a connecting portion 612 located outside the second branch flow path 32-2 that connects the base ends of the plurality of first teeth 611. The second electrode pattern 62A-2 includes a plurality of second teeth 621 located in the second branch flow path 32-2 and a connecting portion 622 located outside the second branch flow path 32-2 that connects the base ends of the plurality of second teeth 621.

[0060] The flow channel chip 10A in Figure 8 includes sensor electrode pads 81-1 and 82-1 connected to sensor electrode 60A-1, and sensor electrode pads 81-2 and 82-2 connected to sensor electrode 60A-2. Voltage can be applied to each of the multiple sensor electrodes 60A individually.

[0061] As described above, in the flow channel chip 10A, the flow channel 30 includes multiple branched flow channels 32 connected to multiple collection units 40. Sensor electrodes 60A are provided in each of the multiple branched flow channels 32. With this configuration, the electrical resistance of the suspension L1 passing through each of the multiple branched flow channels 32 can be measured. For example, if there is a distribution of electrical resistance of the suspension L1 in the width direction of the flow channel 30, the suspension L1 flowing into the multiple collection units 40 may have different electrical resistances. In the above configuration, since the resistance of the suspension L1 passing through each branched flow channel 32 is measured, the influence of such a distribution of electrical resistance of the suspension L1 can be reduced, and more accurate measurement of the electrical resistance of the suspension L1 becomes possible. In addition, appropriate feedback to external devices such as the voltage control device 11, measuring device 12, and analysis device 13 becomes possible. Since the flow channel chip 10A is equipped with multiple sensor electrodes 60A, the outputs from multiple sensor electrodes 60A can be utilized. For example, it is possible to determine the electrical resistance of the suspension L1 by using the average value of the outputs from multiple sensor electrodes 60A. In this case, the influence of variations in the sensor electrodes 60A can be reduced. Furthermore, even if some of the multiple sensor electrodes 60A are disconnected or otherwise damaged, it is still possible to determine the electrical resistance of the suspension L1.

[0062] [1.3 Embodiment 3] Figure 9 is a schematic plan view of Example 1 of the configuration of the flow channel chip of Embodiment 3. Hereinafter, the flow channel chip in Figure 9 will be denoted by reference numeral 10B1. The flow channel chip 10B1 in Figure 9 has a flow channel 30B that is different from the flow channel 30 of the flow channel chip 10 of Embodiment 1. The flow channel 30B in Figure 9 does not have a branch flow channel 32 like in Embodiment 1, and is composed of a main flow channel 31. The first end (left end in Figure 9) of the main flow channel 31 in the longitudinal direction (left-right direction in Figure 9) is connected to the inlet 21. The second end (right end in Figure 9) of the main flow channel 31 in the longitudinal direction is connected to the collection unit 40.

[0063] The flow channel chip 10B1 in Figure 9 is equipped with a sensor electrode 60B that is different from the sensor electrode 60 of the flow channel chip 10 in Embodiment 1. The sensor electrode 60B in Figure 9 is located on the opposite side of the inlet 21 from the separation electrode 50. More specifically, the sensor electrode 60B is located in the main flow channel 31 between the separation electrode 50 and the collection unit 40. As shown in Figure 9, the sensor electrode 60B is a comb-shaped electrode having a plurality of teeth 611, 621 arranged along the length of the main flow channel 31 on the bottom surface of the main flow channel 31. The sensor electrode 60B includes a first electrode pattern 61B and a second electrode pattern 62B. The first electrode pattern 61B includes a plurality of first teeth 611 located in the main flow channel 31 and a connecting portion 612 located outside the main flow channel 31 that connects the base ends of the plurality of first teeth 611. The second electrode pattern 62B includes a plurality of second teeth 621 located in the main channel 31 and a connecting portion 622 located outside the main channel 31 that connects the base ends of the plurality of second teeth 621.

[0064] In the flow channel chip 10B1 shown in Figure 9, the sensor electrode pads 81 and 82 are connected to the first electrode pattern 61B and the second electrode pattern 62B of the sensor electrode 60B, respectively.

[0065] In addition, in the flow channel chip 10B1, the separation electrode 50 may be configured to capture a specific type of dielectric particle P1. That is, the separation electrode 50 is located in the flow channel 30B to generate dielectrophoretic force that guides a specific type of dielectric particle P1 from among multiple types of dielectric particles P1 and P2 in a predetermined direction, and the predetermined direction may be a direction that approaches the separation electrode 50.

[0066] Figure 10 is a schematic plan view of example 2 of the flow channel chip configuration of Embodiment 3. Hereinafter, the flow channel chip in Figure 10 will be denoted by reference numeral 10B2. The flow channel chip 10B2 in Figure 10 differs from the flow channel chip 10B1 in Figure 9 in the positional relationship between the separation electrode 50 and the sensor electrode 60B. In Figure 10, the sensor electrode 60B is located between the inlet 21 and the separation electrode 50 in the flow channel 30B, rather than on the opposite side of the inlet 21 from the separation electrode 50.

[0067] In the flow channel chip of Embodiment 3, the sensor electrode 60B may be located both between the inlet 21 of the flow channel 30B and the separation electrode 50, and on the side of the separation electrode 50 opposite the inlet 21. When multiple sensor electrodes 60B are provided in this manner, for example, the electrical resistance of the suspension L1 can be determined by using the average value of the outputs from the multiple sensor electrodes 60B. In this case, the influence of variations in the sensor electrodes 60B can be reduced. Furthermore, even if some of the multiple sensor electrodes 60B are disconnected or otherwise broken, the electrical resistance of the suspension L1 can still be determined.

[0068] As described above, the sensor electrode 60B only needs to be located between the inlet 21 and the separation electrode 50, and on the side opposite the inlet 21 relative to the separation electrode 50. This configuration stabilizes the separation of specific types of dielectric particles P1 from the suspension L1. This is also true for Embodiment 1 described above and Embodiment 4 described below.

[0069] [1.4 Embodiment 4] Figure 11 is a schematic plan view of Example 1 of the configuration of a flow channel chip according to Embodiment 4. Hereinafter, the flow channel chip in Figure 11 will be denoted by reference numeral 10C1. The flow channel chip 10C1 in Figure 11 has a flow channel 30C that is different from the flow channel 30 of the flow channel chip 10 in Embodiment 1. The flow channel 30C in Figure 11 has a connecting passage 33 that connects the main flow channel 31 and the inlet 22. The inlet 22 is formed in the substrate 10a. The inlet 22 is the part in the substrate 10a into which the replacement liquid is introduced. The replacement liquid is used, for example, to remove unwanted components from the suspension L1 and to transport multiple types of dielectric particles P1 and P2 from the suspension L1. Unwanted components are components that are not needed in the separation of a specific type of dielectric particle P1 from the suspension L1. Examples of unwanted components include small cells P3 such as red blood cells contained in blood and solutions. The replacement liquid may be selected to be capable of transporting multiple types of dielectric particles P1 and P2 and not to hinder the application of dielectrophoretic force to multiple types of dielectric particles P1 and P2. In particular, the displacement solution is a liquid with lower conductivity than the suspension L1 solution in order to facilitate the separation of specific types of dielectric particles P1. The substrate 10a may be provided with an outlet for discharging unwanted components of the suspension L1 that have been replaced by the displacement solution.

[0070] Figure 12 is a schematic plan view of example 2 of the configuration of the flow channel chip of Embodiment 4. Hereinafter, the flow channel chip in Figure 12 will be denoted by reference numeral 10C2. The flow channel chip 10C2 in Figure 12 has a flow channel 30C that is different from the flow channel 30 of the flow channel chip 10A of Embodiment 2. The flow channel 30C in Figure 12 has a connecting passage 33 that connects the main flow channel 31 and the inlet 22.

[0071] Figure 13 is a schematic plan view of example 3 of the flow channel chip configuration of Embodiment 4. Hereinafter, the flow channel chip in Figure 13 will be denoted by reference numeral 10C3. The flow channel chip 10C3 in Figure 13 has a flow channel 30C that is different from the flow channel 30B of the flow channel chip 10B1 of Embodiment 3. The flow channel 30C in Figure 13 has a connecting passage 33 that connects the main flow channel 31 and the inlet 22.

[0072] As described above, in Embodiment 4, the flow path 30C may have a connecting passage 33 connected to the inlet 22 for introducing the displacement liquid. This makes it possible to remove unwanted components from the suspension L1.

[0073] As in Embodiment 4, when using a displacement solution, displacement by the displacement solution may not be sufficient. In such cases, the electrical resistance of the suspension L1 tends to become unstable. However, since Embodiment 4 is also equipped with sensor electrodes 60, 60A, and 60B, the voltage applied to the separation electrode 50 can be adjusted according to the measured electrical resistance of the suspension L1 by the sensor electrodes 60, 60A, and 60B, and the components of the suspension L1 supplied to the flow channel chips 10C1, 10C2, and 10C3 can be adjusted. If the measured electrical resistance of the suspension L1 by the sensor electrodes 60, 60A, and 60B is an abnormal value, the separation operation can be stopped. Therefore, with the flow channel chips 10C1, 10C2, and 10C3, the separation operation of specific types of dielectric particles P1 from the suspension L1 can be stabilized.

[0074] [2. Variant] The embodiments of this disclosure are not limited to those described above. The embodiments can be modified in various ways depending on the design, etc., as long as the objectives of this disclosure can be achieved. The following lists some modifications of the embodiments. The modifications described below can be combined and applied as appropriate.

[0075] In one modified example, the separation system 1 does not necessarily need to include the analysis device 13. The separation system 1 may include a flow channel tip 10 and a measuring device 12.

[0076] In one modified example, suspension L1 is not limited to blood. Suspension L1 is not particularly limited as long as it contains dielectric particles to be separated. The dielectric particles are not limited to the cells mentioned above. The dielectric particles may be, for example, membrane vesicles, microorganisms, fungi, spores, viruses, exosomes, or nucleic acids such as DNA and RNA.

[0077] In one modified example, the shapes of the flow channel tips 10, 10A, 10B1, 10B2, 10C1, 10C2, and 10C3 can be changed. In particular, the shape of the base body 10a is not limited to the above embodiment. The shape of the base body 10a can be set appropriately according to the flow channels 30, 30B, and 30C. The flow channels 30, 30B, and 30C may be curved rather than straight as in the above embodiment. Also, depending on the shape of the flow channels 30, 30B, and 30C, the collection unit 40 is not essential.

[0078] In one modified example, the number and shape of the separation electrodes 50 can be changed. The separation electrodes 50 only need to be able to generate dielectrophoretic force that guides a specific type of dielectric particle in a predetermined direction from multiple types of dielectric particles. Depending on the shape of the separation electrodes 50, the separation electrode pads 71 ​​and 72 can be omitted.

[0079] In one modified example, the shapes of the sensor electrodes 60, 60A, and 60B can be changed. The sensor electrodes 60, 60A, and 60B only need to be able to measure the electrical resistance of the suspension L1. Depending on the shape of the sensor electrodes 60, 60A, and 60B, the sensor electrode pads 81 and 82 can be omitted.

[0080] In one modified example, in the flow channel tips 10A and 10C2, the sensor electrode 60A does not need to be provided in all of the branched flow channels 32. The sensor electrode 60A only needs to be provided in at least one of the branched flow channels 32. In this case, it becomes possible to measure the electrical resistance of the suspension (L1) in each branched flow channel (32). In particular, by providing the sensor electrode 60A in only some of the branched flow channels 32 instead of all of them, the space and cost required for installing the sensor electrode 60A can be reduced.

[0081] In one modified example, a sensor electrode 60B may be provided between the inlet 21 and the separation electrode 50 in the flow channels 30, 30B, and 30C in the flow channel tips 10, 10A, 10C1, 10C2, and 10C3.

[0082] In one modified example, the flow path 30 may be equipped with a filter between the inlet 21 and the separation electrode 50. The filter removes, for example, particles smaller in size than multiple types of dielectric particles P1 and P2 from the suspension L1. The particles smaller in size than multiple types of dielectric particles P1 and P2 are particles smaller in size than the smallest dielectric particle among the multiple types of dielectric particles P1 and P2. The particles smaller in size than multiple types of dielectric particles P1 and P2 are, for example, small cells such as red blood cells contained in the suspension L1. Such a filter can separate multiple types of dielectric particles P1 and P2 from particles smaller in size than multiple types of dielectric particles P1 and P2 in the suspension L1 by the principle of hydrodynamic filtration (HDF).

[0083] [3. Appearance] As is clear from the above embodiments and modifications, this disclosure includes the following embodiments. In the following, reference numerals are enclosed in parentheses solely to indicate their correspondence with the embodiments.

[0084] The first embodiment is a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) comprising 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 particle (P1) is introduced, and a flow channel (30; 30B; 30C) through which the plurality of types of dielectric particles (P1, P2) of the suspension (L1) introduced from the inlet (21) flow; a separation electrode (50) located in the flow channel (30; 30B; 30C) to generate dielectrophoretic force to guide a specific type of dielectric particle (P1) among the plurality of types of dielectric particles (P1, P2) in a predetermined direction; and a sensor electrode (60; 60A; 60B) located in the flow channel (30; 30B; 30C) to measure the electrical resistance of the suspension (L1). According to this embodiment, the separation process of specific types of dielectric particles (P1) from a suspension (L1) can be stabilized.

[0085] The second embodiment is a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) based on the first embodiment. In the second embodiment, the separation electrode (50) and the sensor electrode (60; 60A; 60B) are separate electrodes. According to this embodiment, the separation electrode (50) and the sensor electrode (60) can be designed under conditions suitable for their respective purposes, thereby stabilizing the separation of specific types of dielectric particles (P1).

[0086] A third embodiment is a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) based on the first or second embodiment. In the third embodiment, the area of ​​the portion of the sensor electrode (60; 60A; 60B) located within the flow channel (30; 30B; 30C) is larger than the area of ​​the portion of the separation electrode (50) located within the flow channel (30; 30B; 30C). According to this embodiment, variations in performance in the flow channel chip 10 can be reduced, and the measurement performance by the sensor electrode (60) can be improved.

[0087] A fourth embodiment is a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) based on any one of the first to third embodiments. In the fourth embodiment, the impedance (or reactance and resistance) of the sensor electrodes (60; 60A; 60B) is smaller than the lower limit of the measurement range for the electrical resistance of the suspension (L1). According to this embodiment, performance variations in the flow channel chip 10 can be reduced.

[0088] The fifth embodiment is a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) based on the fourth embodiment. In the fifth embodiment, the impedance (or reactance and resistance) of the sensor electrodes (60; 60A; 60B) is 1 / 5 or less of the lower limit of the measurement range of the electrical resistance of the suspension (L1). According to this embodiment, variations in performance in the flow channel chip 10 can be reduced, and the measurement performance by the sensor electrodes (60) can be improved.

[0089] The sixth embodiment is a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) based on any one of the first to fifth embodiments. In the sixth embodiment, the sensor electrode (60; 60A; 60B) is a comb-shaped electrode having a plurality of teeth (611, 621) arranged along the length of the flow channel (30; 30B; 30C) on the bottom surface of the flow channel (30; 30B; 30C). According to this embodiment, the separation of a specific type of dielectric particle (P1) from a suspension (L1) can be stabilized.

[0090] The seventh embodiment is a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) based on any one of the first to sixth embodiments. In the seventh embodiment, the sensor electrodes (60; 60A; 60B) are located in the flow channel (30B) between the inlet (21) and the separation electrode (50), and in the flow channel (30B) on the side of the separation electrode (50) opposite the inlet (21). This embodiment allows for the stabilization of the separation of specific types of dielectric particles (P1) from the suspension (L1).

[0091] The eighth embodiment is a flow channel chip (10A; 10C2) based on any one of the first to seventh embodiments. In the eighth embodiment, the flow channel (30; 30C) includes a plurality of branched flow channels (32) connected to a plurality of collection units (40). The sensor electrode (60A) is provided in at least one of the plurality of branched flow channels (32). According to this embodiment, it is possible to measure the electrical resistance of the suspension (L1) in each branched flow channel (32). Here, by providing the sensor electrode (60A) in all of the plurality of branched flow channels (32), even if a distribution of the electrical resistance of the suspension (L1) occurs in the width direction of the flow channel (30), the influence of such a distribution of the electrical resistance of the suspension (L1) can be reduced, and a more accurate measurement of the electrical resistance of the suspension (L1) becomes possible. On the other hand, by providing the sensor electrode (60A) in only some of the branched flow channels (32) instead of all of the plurality of branched flow channels (32), the space and cost required for the installation of the sensor electrode (60A) can be reduced.

[0092] The ninth embodiment is a flow channel chip (10; 10C1) based on any one of the first to seventh embodiments. In the ninth embodiment, the flow channel (30; 30C) includes a plurality of branched flow channels (32) connected to a plurality of collection units (40). The sensor electrode (60) is provided spanning the plurality of branched flow channels (32). According to this embodiment, the electrical resistance of all the suspension (L1) passing through the flow channel (30) can be measured, enabling more accurate measurement of the electrical resistance of the suspension (L1).

[0093] The tenth embodiment is a separation system (1) comprising a flow channel chip (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) based on any one of the first to ninth embodiments, and a measuring device (12) for measuring the electrical resistance of the suspension (L1) based on the output from the sensor electrodes (60; 60A; 60B). According to this embodiment, the separation of a specific type of dielectric particle (P1) from the suspension (L1) can be stabilized.

[0094] The eleventh embodiment is a separation system (1) based on the tenth embodiment. In the eleventh embodiment, the flow path tips (10; 10A; 10B1; 10B2; 10C1; 10C2; 10C3) are disposable. This embodiment prevents contamination and further improves the usability of the separation system (1). [Industrial applicability]

[0095] This disclosure applies to flow channel chips and separation systems. Specifically, this disclosure is applicable to flow channel chips and separation systems for separating specific types of dielectric particles from multiple types of dielectric particles contained in a suspension. [Explanation of Symbols]

[0096] 1 Separation System 10, 10A, 10B1, 10B2, 10C1, 10C2, 10C3 flow path tip 10a Base 12 Measuring device 21 Entrance 30, 30B, 30C channel 40-1 First Collection Department (Collection Department) 40-2 Second Collection Department (Collection Department) 50 Separate Electrodes 60, 60A, 60B sensor electrodes 611 First tooth region (tooth region) 621 Second tooth region (tooth region) L1 suspension P1, P2 dielectric particles

Claims

1. A substrate having an inlet into which a suspension containing multiple types of dielectric particles, including a specific type of dielectric particle, is introduced, and a channel through which the multiple types of dielectric particles of the suspension introduced from the inlet flow, A separation electrode located within the channel is provided to generate dielectrophoretic force that guides a specific type of dielectric particle from among the multiple types of dielectric particles in a predetermined direction. A sensor electrode located in the flow path is used to measure the electrical resistance of the suspension, Equipped with, The area of ​​the portion of the sensor electrode located within the flow path is larger than the area of ​​the portion of the separation electrode located within the flow path. Flow channel chip.

2. A substrate having an inlet into which a suspension containing multiple types of dielectric particles, including a specific type of dielectric particle, is introduced, and a channel through which the multiple types of dielectric particles of the suspension introduced from the inlet flow, A separation electrode located within the channel is provided to generate dielectrophoretic force that guides a specific type of dielectric particle from among the multiple types of dielectric particles in a predetermined direction. A sensor electrode located in the flow path is used to measure the electrical resistance of the suspension, Equipped with, The aforementioned flow path includes multiple branched flow paths connected to multiple collection units, The sensor electrode is provided in at least one of the plurality of branched flow paths. Flow channel chip.

3. A substrate having an inlet into which a suspension containing multiple types of dielectric particles, including a specific type of dielectric particle, is introduced, and a channel through which the multiple types of dielectric particles of the suspension introduced from the inlet flow, A separation electrode located within the channel is provided to generate dielectrophoretic force that guides a specific type of dielectric particle from among the multiple types of dielectric particles in a predetermined direction. A sensor electrode located in the flow path is used to measure the electrical resistance of the suspension, Equipped with, The aforementioned flow path includes multiple branched flow paths connected to multiple collection units, The sensor electrode is provided across the plurality of branched channels. Flow channel chip.

4. The separation electrode and the sensor electrode are separate electrodes. A flow channel tip according to any one of claims 1 to 3.

5. The sensor electrode is a comb-shaped electrode having a plurality of teeth arranged along the length of the flow path on the bottom surface of the flow path. A flow channel tip according to any one of claims 1 to 4.

6. The sensor electrode is located in the flow path between the inlet and the separation electrode, and in the flow path on the side of the flow path opposite the inlet to the separation electrode. A flow channel chip according to any one of claims 1 to 5.

7. A flow channel chip according to any one of claims 1 to 6, A measuring device for measuring the electrical resistance of the suspension based on the output from the sensor electrode, Equipped with, Separation system.

8. The aforementioned flow channel tip is disposable. The separation system according to claim 7.

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