Flow path chip, dielectrophoresis device, and control voltage correction method

Abstract

A flow path chip (11) is provided with a substrate (21), a liquid receiving section (FW), a pair of first electrodes (33a), (33b), and a pair of second electrodes (43a), (43b). A sample liquid or a reference liquid can be injected into the liquid receiving unit (FW). When a control voltage is applied to the pair of first electrodes (33a, 33b), a dielectrophoretic force can act on dielectric particles (P1) contained in the sample liquid injected into the liquid receiving unit (FW). The pair of second electrodes (43a), (43b) are disposed at positions different from those of the pair of first electrodes (33a), (33b). The control voltage applied between the pair of first electrodes (33a), (33b) is corrected on the basis of the impedance between the pair of second electrodes (43a), (43b) measured via the reference liquid injected into the liquid receiving section (FW).

Description

Technical Field

[0001] The invention relates to a flow path chip, a dielectrophoresis device and a control voltage correction method. Background Art

[0002] Dielectrophoresis is effectively used as a particle control technology in micro spaces such as microfluidic devices. In the biological field, various research and development are carried out mainly on cells or microorganisms for characteristic analysis and separation and concentration. There are various forms, for example, Patent Document 1 can be cited.

[0003] The separation device described in Patent Document 1 is provided with a flow path for a sample liquid (sample liquid) containing cancer cells (dielectric particles) circulating in the blood to flow in a predetermined direction, a replacement part, an analysis part, and a separation part. The separation part is provided with a pair of electrodes, a power supply part, and a collection part. The power supply part generates an AC voltage and supplies it between the pair of electrodes. Thus, a positive dielectrophoretic force (gravitational force) acts on the cancer cells, and the cancer cells flow in the flow path along the extension direction of the pair of electrodes while being attracted by the pair of electrodes, and are collected by the collection part. That is, the separation device separates cancer cells from cells such as white blood cells and collects cancer cells.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Publication No. 2017-134020 Summary of the invention

[0007] Problems to be solved by the invention

[0008] However, in the separation device described in Patent Document 1, various parasitic components such as parasitic resistance and parasitic capacitance exist inside the separation unit. Therefore, the voltage value of the AC voltage actually applied to the sample liquid is smaller than the voltage value (set value) of the AC voltage output by the power supply unit. As a result, the separation performance and collection performance of cancer cells from white blood cells and other cells may be reduced.

[0009] The present invention has been made in view of the above problems, and an object of the present invention is to provide a flow channel chip, a dielectrophoresis device, and a control voltage correction method that can reduce the influence of parasitic components on the separation performance and collection performance of dielectric particles contained in a sample liquid.

[0010] Means for solving problems

[0011] According to one aspect of the present invention, a flow path chip comprises a substrate, a liquid receiving portion, a pair of first electrodes and a pair of second electrodes. The liquid receiving portion is arranged on a main surface side of the substrate, and can be injected with a sample liquid or a reference liquid. A pair of first electrodes are arranged between the main surface of the substrate and the liquid receiving portion, and by applying a control voltage, a dielectrophoretic force can be applied to the dielectric particles contained in the sample liquid injected into the liquid receiving portion. A pair of second electrodes are arranged between the main surface of the substrate and the liquid receiving portion at a position different from that of the pair of first electrodes. The control voltage applied between the pair of first electrodes is corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving portion.

[0012] In one embodiment of the present invention, it is preferred that the resistivity of the reference liquid is smaller than the resistivity of the second electrode.

[0013] In one embodiment of the present invention, the control voltage applied between the pair of first electrodes is preferably corrected based on a correction coefficient calculated based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving portion and the impedance between the pair of first electrodes measured via the sample liquid injected into the liquid receiving portion.

[0014] In one aspect of the present invention, the control voltage is preferably an AC voltage. The correction coefficient preferably has a value corresponding to a frequency of the control voltage.

[0015] In one embodiment of the present invention, the liquid receiving portion preferably includes a first flow path and a second flow path. The first flow path is preferably arranged on the main surface side of the substrate, and the sample liquid can be injected. The second flow path is preferably separated from the first flow path, arranged on the main surface side of the substrate, and the reference liquid can be injected. The pair of first electrodes is preferably arranged between the main surface of the substrate and the first flow path. The pair of second electrodes is preferably separated from the first flow path and the pair of first electrodes, and arranged between the main surface of the substrate and the second flow path. The control voltage applied between the pair of first electrodes is preferably corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the second flow path.

[0016] In one embodiment of the present invention, the liquid receiving portion preferably includes a first flow path and a storage portion. The first flow path is preferably arranged on the main surface side of the substrate, and the sample liquid can be injected. The storage portion is preferably separated from the first flow path, arranged on the main surface side of the substrate, and the reference liquid can be injected. The pair of first electrodes is preferably arranged between the main surface of the substrate and the first flow path. The pair of second electrodes is preferably separated from the first flow path and the pair of first electrodes, and arranged between the main surface of the substrate and the storage portion. The control voltage applied between the pair of first electrodes is preferably corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the storage portion.

[0017] In one embodiment of the present invention, the liquid receiving portion preferably includes a first flow path. The pair of first electrodes are preferably arranged between the main surface of the substrate and the first flow path, and by being applied with the control voltage, the dielectrophoretic force can act on the dielectric particles contained in the sample liquid injected into the first flow path when the reference liquid is not injected into the first flow path. The pair of second electrodes are preferably arranged between the main surface of the substrate and the first flow path at a position different from that of the pair of first electrodes. The control voltage applied between the pair of first electrodes is preferably corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the first flow path when the sample liquid is not injected into the first flow path.

[0018] According to another aspect of the present invention, a dielectrophoresis device includes a flow path chip and a voltage control device. The flow path chip includes a substrate, a liquid receiving portion, a pair of first electrodes and a pair of second electrodes. The liquid receiving portion is arranged on a main surface side of the substrate, and can be injected with a sample liquid or a reference liquid. A pair of first electrodes are arranged between the main surface of the substrate and the liquid receiving portion, and by applying a control voltage, a dielectrophoretic force can be applied to the dielectric particles contained in the sample liquid injected into the liquid receiving portion. A pair of second electrodes are arranged between the main surface of the substrate and the liquid receiving portion at a position different from that of the pair of first electrodes. The voltage control device corrects the control voltage applied between the pair of first electrodes based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving portion.

[0019] According to another aspect of the present invention, a control voltage correction method uses a flow path chip. The flow path chip includes a substrate, a liquid receiving portion, a pair of first electrodes, and a pair of second electrodes. The liquid receiving portion is arranged on one main surface side of the substrate, and can be injected with a sample liquid or a reference liquid. A pair of first electrodes are arranged between the main surface of the substrate and the liquid receiving portion, and by applying a control voltage, a dielectrophoretic force can be applied to the dielectric particles contained in the sample liquid injected into the liquid receiving portion. A pair of second electrodes are arranged between the main surface of the substrate and the liquid receiving portion at a position different from that of the pair of first electrodes. The control voltage correction method includes: a process of measuring the impedance between the pair of second electrodes via the reference liquid injected into the liquid receiving portion; and a process of correcting the control voltage applied between the pair of first electrodes based on the impedance between the pair of second electrodes.

[0020] In one embodiment of the present invention, in the control voltage correction method, preferably, the resistivity of the reference liquid is smaller than the resistivity of the second electrode.

[0021] In one embodiment of the present invention, the control voltage correction method preferably further includes the step of measuring the impedance between the pair of first electrodes via the sample liquid injected into the liquid receiving part. The step of correcting the control voltage preferably includes: the step of calculating a correction coefficient based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving part and the impedance between the pair of first electrodes measured via the sample liquid injected into the liquid receiving part; and the step of correcting the control voltage applied between the pair of first electrodes based on the correction coefficient.

[0022] In one aspect of the present invention, the control voltage is preferably an AC voltage. The step of calculating the correction coefficient and the step of correcting the control voltage are preferably performed every time the frequency of the control voltage is changed.

[0023] Effects of the Invention

[0024] According to the present invention, the influence of parasitic components on the separation performance and collection performance of dielectric particles contained in a sample liquid can be reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a plan view showing a dielectrophoresis device according to an embodiment of the present invention.

[0026] Figure 2 yes Figure 1 An enlarged view of the first electrode and the second electrode is shown.

[0027] Figure 3 It is along Figure 2Schematic cross-sectional view of the flow channel chip along line III-III.

[0028] Figure 4 It is along Figure 2 Schematic cross-sectional view of the flow channel chip along line IV-IV.

[0029] Figure 5 It is along Figure 2 Detailed cross-sectional view of the flow path chip of the VV line.

[0030] Figure 6 : is a flowchart showing the control voltage correction method according to the present embodiment.

[0031] Figure 7 : is a circuit diagram showing an equivalent circuit of the parasitic components of the flow channel chip according to the present embodiment.

[0032] Figure 8 Graphs showing the impedance measured via a sample liquid and the impedance measured via a reference liquid according to the present embodiment.

[0033] Fig. 9 This is a graph showing the difference between the impedance measured via the sample liquid and the impedance measured via the reference liquid according to the present embodiment.

[0034] Fig.10 : is a graph showing the frequency dependency of the voltage output efficiency in this embodiment.

[0035] Fig.11 This is a graph showing an example of the voltage value of the voltage actually applied to the sample liquid when the control voltage having a specific voltage value according to the present embodiment is applied to the first electrode.

[0036] Fig.12 This is a graph showing an example of voltage output efficiency in this embodiment.

[0037] Fig.13 This is a graph showing an example of the correction coefficient according to the present embodiment.

[0038] Fig.14 : is a graph showing the voltage value of the voltage actually applied to the sample liquid when the corrected control voltage of the present embodiment is applied to the first electrode.

[0039] Fig.15 It is a plan view showing a reservoir and a second electrode of a flow channel chip according to a first modified example of the present embodiment.

[0040] Fig.16 It is along Fig.15 Schematic cross-sectional view of the flow channel chip taken along line XVI-XVI.

[0041] Fig.17 It is a plan view showing a dielectrophoresis device according to a second modified example of the present embodiment. DETAILED DESCRIPTION

[0042] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In addition, the same reference numerals are given to the same or corresponding parts in the drawings, and the description thereof will not be repeated.

[0043] Reference Figures 1 to 12 The dielectrophoresis device 1 according to the embodiment of the present invention will be described. Figure 1 to Figure 5 The dielectrophoresis device 1 will be described. Figure 1 1 is a plan view showing the dielectrophoresis device 1 .

[0044] Figure 2 yes Figure 1 An enlarged view of the first electrodes 33a, 33b and the second electrodes 43a, 43b is shown. Figure 3 It is along Figure 2 Schematic cross-sectional view along line III-III. Figure 4 It is along Figure 2 Schematic cross-sectional view along line IV-IV. Figure 5 It is along Figure 2 Detailed cross-sectional view of the VV line.

[0045] like Figure 1 As shown, the dielectrophoresis device 1 separates the dielectric particles P1 from other components P2 and collects the dielectric particles P1 by applying the dielectrophoretic force to the dielectric particles P1 contained in the sample liquid (specimen liquid). The sample liquid is, for example, a body fluid such as blood. Blood is an example of a suspension. The dielectric particles P1 are, for example, cells, proteins, nucleic acids or microorganisms. Cells are, for example, cancer cells. Other components P2 are, for example, dielectric particles of a different type from the specific type of dielectric particles P1. As an example, the sample liquid is blood, the dielectric particles P1 are cancer cells, and the other components P2 are white blood cells.

[0046] Specifically, the dielectrophoresis device 1 includes a flow channel chip 11. The flow channel chip 11 causes dielectrophoretic force to act on dielectric particles P1 contained in the sample liquid to separate and collect the dielectric particles P1 from other components P2. The diameter of the dielectric particles P1 is, for example, several μm or more and several tens of μm or less.

[0047] The flow channel chip 11 includes a substrate 21, a liquid receiving part FW, a pair of first electrodes 33a, 33b, a pair of second electrodes 43a, 43b, a pair of first electrode pad parts 331a, 331b, and a pair of second electrode pad parts 431a, 431b.

[0048] The material of the substrate 21 is, for example, quartz glass. However, the material of the substrate 21 is not limited to quartz glass. The substrate 21 has a substantially rectangular flat plate shape. However, the shape of the substrate 21 is not limited to a substantially rectangular flat plate shape.

[0049] The liquid receiving portion FW is arranged on the side of one of the pair of main surfaces of the substrate 21. Figure 1 In the example, one principal surface 211 of the substrate 21 is the upper surface of the substrate 21 , and the other principal surface of the substrate 21 is the lower surface of the substrate 21 .

[0050] The sample liquid or the reference liquid can be injected into the liquid receiving part FW. The liquid receiving part FW receives the sample liquid or the reference liquid. The reference liquid is a liquid used as a reference when extracting parasitic components other than the parasitic components of the sample liquid from the parasitic components of the flow path chip 11. The parasitic component refers to one or more components of parasitic resistance, parasitic capacitance, and parasitic inductance. The details of the parasitic component will be described later.

[0051] The resistance of the reference liquid is lower than the resistance of the second electrodes 43a, 43b. Specifically, the resistivity of the reference liquid is lower than the resistivity of the second electrodes 43a, 43b. In addition, the resistance of the reference liquid is lower than the resistance of the sample liquid. Specifically, the resistivity of the reference liquid is lower than the resistivity of the sample liquid. The reference liquid is, for example, an aqueous solution of sodium chloride (NaCl) or an aqueous solution of potassium chloride (KCl). The conductivity of the reference liquid is, for example, greater than 100 μS / cm.

[0052] The liquid receiving part FW includes a first flow path 31. The sample liquid can be injected into the first flow path 31. The sample liquid flows in the first flow path 31. The first flow path 31 includes a separation flow path 311 and a pair of collection flow paths 313a and 313b. In addition, the flow path chip 11 further includes a first supply part 315, a first collection part 317a, and a second collection part 317b.

[0053] The separation channel 311 extends linearly along the direction D1. One end of the separation channel 311 is connected to the first supply unit 315. The first supply unit 315 supplies the sample liquid to the separation channel 311. The first supply unit 315 has, for example, an opening. The first supply unit 315 is connected to a supply source of the sample liquid, for example, through a tube.

[0054] In addition, the first flow path 31 is branched into a collection flow path 313 a and a collection flow path 313 b at the other end of the separation flow path 311 .

[0055] The collecting channel 313a is a channel into which the dielectric particles P1 from the separation channel 311 flow in. The collecting channel 313b is a channel into which the other components P2 from the separation channel 311 flow in. One end of the collecting channel 313a and one end of the collecting channel 313b are connected to the other end of the separation channel 311. The other end of the collecting channel 313a is connected to the first collecting section 317a. The other end of the collecting channel 313b is connected to the second collecting section 317b. The first collecting section 317a collects the dielectric particles P1 to be separated. The first collecting section 317a may, for example, have an opening to supply a solution containing the dielectric particles P1 from the channel chip 11 to the outside. The second collecting section 317b collects the other components P2 that are not to be separated. The second collecting section 317b may, for example, have an opening to supply a solution containing the other components P2 from the channel chip 11 to the outside.

[0056] By applying the control voltage Vcn, the first electrodes 33a and 33b can exert a dielectrophoretic force on the dielectric particles P1 contained in the sample liquid injected into the liquid receiving part FW. Figure 1 In the example of FIG. 1 , by applying the control voltage Vcn, the first electrodes 33a and 33b can exert a dielectrophoretic force on the dielectric particles P1 included in the sample liquid injected into the first channel 31. The material of the first electrodes 33a and 33b is a metal such as aluminum.

[0057] In addition, the first electrodes 33a and 33b can also apply a measurement voltage Vm1 to the sample liquid injected into the liquid receiving part FW. The measurement voltage Vm1 is an AC voltage. The measurement voltage Vm1 is a voltage for measuring the impedance IM1 between the first electrodes 33a and 33b. Figure 1 In the example of FIG. 1 , the first electrodes 33 a and 33 b apply a measurement voltage Vm1 to the sample liquid injected into the first channel 31 .

[0058] like Figure 2 As shown, the first electrodes 33a and 33b intersect the first channel 31 (separation channel 311) at an acute angle θ in a plan view. The first electrodes 33a and 33b are comb-teeth-shaped electrodes. The first electrode 33a is electrically isolated from the first electrode 33b.

[0059] The first electrode 33a includes a plurality of first line portions 333a. The plurality of first line portions 333a are arranged at equal intervals in the direction D1. The direction D1 indicates the direction in which the first flow path 31 (separation flow path 311) extends. The plurality of first line portions 333a intersect at an acute angle θ relative to the first flow path 31 (separation flow path 311) when viewed from above. That is, the plurality of first line portions 333a are inclined at an acute angle θ relative to the direction D1 when viewed from above. The inclination angle θ of the first line portion 333a relative to the direction D1 is, for example, greater than 10 degrees and less than 60 degrees. One end of one of the plurality of first line portions 333a is connected to the first electrode pad portion 331a. The other ends of the plurality of first line portions 333a are connected. The first line portion 333a extends between one side and the other side of the direction D3 in a manner that forms an acute angle θ relative to the direction D1. The direction D3 is substantially orthogonal to the direction D1 along the substrate 21.

[0060] The first electrode 33b includes a plurality of first line portions 333b. The plurality of first line portions 333b are arranged at equal intervals in the direction D1. The plurality of first line portions 333b intersect at an acute angle θ relative to the first flow path 31 (separation flow path 311) when viewed from above. That is, the plurality of first line portions 333b are inclined at an acute angle θ relative to the direction D1 when viewed from above. The inclination angle θ of the first line portion 333b relative to the direction D1 is, for example, greater than 10 degrees and less than 60 degrees. One end of the plurality of first line portions 333b is connected to the first electrode pad portion 331b. The first line portion 333b extends between one side and the other side of the direction D3 in a manner that forms an acute angle θ relative to the direction D1.

[0061] The first line portions 333a and the first line portions 333b are alternately arranged at intervals in the direction D1. The inclination angle θ of the first line portion 333a is substantially the same as the inclination angle θ of the first line portion 333b.

[0062] like Figure 2 as well as Figure 3 As shown, the first electrodes 33a and 33b are arranged on the main surface 211 of the substrate 21 and the liquid receiving part FW ( Figure 1 ). Figure 3 In the example of , the first electrodes 33a and 33b are arranged between the main surface 211 of the substrate 21 and the first channel 31 (separation channel 311). Specifically, the first line portions 333a and 333b are arranged between the main surface 211 of the substrate 21 and the first channel 31 (separation channel 311).

[0063] like Figure 3As shown, the first electrodes 33a and 33b are arranged on the main surface 211 of the substrate 21. In addition, the flow path chip 11 also includes an insulating protective film 23 and a flow path cover 25. Moreover, the insulating protective film 23 covers the first electrodes 33a and 33b. The insulating protective film 23 is, for example, an oxide film. The oxide film is, for example, a silicon oxide film (SiOx). In addition, the insulating protective film 23 is not particularly limited as long as it is an insulator, and may be, for example, a nitride film. The nitride film is, for example, a silicon nitride film. By covering the first electrodes 33a and 33b with the insulating protective film 23, the electrochemical reaction generated at the interface between the electrode metal and the liquid can be suppressed, and the degradation and wear of the electrode metal over time can be suppressed.

[0064] A flow path cover 25 is disposed on the upper surface of the insulating protective film 23. The flow path cover 25 is made of silicone such as PDMS (dimethyl polysiloxane). The flow path cover 25 has a concave flow path groove 251. The flow path groove 251 extends along the direction D1 ( Figure 2 ) extends. The width of the flow path groove 251 in the direction D3 is, for example, micrometer order. The first flow path 31 is formed by the flow path groove 251 and the upper surface of the insulating protection film 23. In this way, by installing the flow path cover 25 on the main surface 211 side of the substrate 2, the first flow path 31 is arranged on the main surface 211 side of the substrate 21.

[0065] return Figure 1 , the width of the substrate 21 in the direction D3 is greater than the width of the flow path cover 25 in the direction D3. In addition, the first electrode pad portions 331a, 331b are arranged separately from the first flow path 31 (separation flow path 311) on one side of the first flow path 31 in the direction D3. At least a portion of the first electrode pad portion 331a and at least a portion of the first electrode pad portion 331b are arranged outside the flow path cover 25. In addition, the portion of the first electrode pad portions 331a, 331b arranged outside the flow path cover 25 is not covered by the insulating protective film 23. Therefore, on the outside of the flow path cover 25, the first electrode pad portions 331a, 331b can be electrically connected to the voltage control device 100.

[0066] The first electrode pad portion 331a is connected to the first electrode 33a. The first electrode pad portion 331b is connected to the first electrode 33b.

[0067] The liquid receiving part FW also includes a second flow path 41. A reference liquid can be injected into the second flow path 41. The second flow path 41 extends linearly along a direction D2. The direction D2 is substantially parallel to the direction D1. The direction D2 indicates the direction in which the second flow path 41 extends. The second flow path 41 is separated from the first flow path 31 in a direction D3. The direction D3 is substantially orthogonal to the directions D1 and D2 along the main surface 211 of the substrate 21. The reference liquid flows in the second flow path 41. In addition, the flow path chip 11 also includes a second supply part 411 and a recovery part 413.

[0068] One end of the second flow path 41 is connected to the second supply unit 411. The second supply unit 411 supplies the reference liquid to the second flow path 41. The second supply unit 411, for example, has an opening. The second supply unit 411 is connected to a supply source of the reference liquid, for example, through a tube. The other end of the second flow path 41 is connected to the recovery unit 413. The recovery unit 413 recovers the reference liquid flowing in from the second flow path 41. The recovery unit 413, for example, may have an opening to supply the reference liquid from the flow path chip 11 to the outside.

[0069] The second electrodes 43a and 43b apply a measurement voltage Vm2 to the reference liquid injected into the liquid receiving part FW. The measurement voltage Vm2 is an AC voltage. The measurement voltage Vm2 is a voltage for measuring the impedance IM2 between the second electrodes 43a and 43b. Figure 1 In the example of FIG. 4 , the second electrodes 43a and 43b apply a measurement voltage Vm2 to the reference liquid injected into the second flow path 41. The material of the second electrodes 43a and 43b is a metal such as aluminum.

[0070] like Figure 2 As shown, the second electrodes 43a and 43b are separated from the first electrodes 33a and 33b and the first flow path 31 in the direction D3, and are arranged next to the first electrodes 33a and 33b. The second electrodes 43a and 43b are substantially orthogonal to the second flow path 41 when viewed from above. The second electrodes 43a and 43b are comb-shaped electrodes. The second electrode 43a is electrically separated from the second electrode 43b.

[0071] The second electrode 43a includes a plurality of second line portions 433a. The plurality of second line portions 433a are arranged at equal intervals in the direction D2. The plurality of second line portions 433a are substantially orthogonal to the second flow path 41 when viewed from above. One end of the plurality of second line portions 433a is connected. The other end of one of the plurality of second line portions 433a is connected to the second electrode pad portion 431a. The second line portion 433a extends between one side and the other side of the direction D3 in a manner substantially orthogonal to the direction D1.

[0072] The second electrode 43b includes a plurality of second line portions 433b. The plurality of second line portions 433b are arranged at equal intervals in the direction D2. The plurality of second line portions 433b are substantially orthogonal to the second flow path 41 when viewed from above. That is, the plurality of second line portions 433b are substantially orthogonal to the direction D2 when viewed from above. One end and the other end of the plurality of second line portions 433b are connected to the second electrode pad portion 431b. The second line portion 433b extends between one side and the other side of the direction D3 in a manner substantially orthogonal to the direction D1.

[0073] The second line portions 433 a and the second line portions 433 b are alternately arranged at intervals in the direction D2 .

[0074] like Figure 2 as well as Figure 4 As shown, the second electrodes 43a and 43b are formed on the main surface 211 of the substrate 21 and the liquid receiving portion FW ( Figure 1 ) and are arranged at positions different from the first electrodes 33a and 33b. Figure 4 In the example, the second electrodes 43a and 43b are arranged at positions different from the first electrodes 33a and 33b between the main surface 211 of the substrate 21 and the second flow path 41. Specifically, the second line portions 433a and 433b are arranged between the main surface 211 of the substrate 21 and the second flow path 41.

[0075] like Figure 4 As shown, the second electrodes 43a and 43b are arranged on the main surface 211 of the substrate 21. The second electrodes 43a and 43b are covered by the insulating protective film 23. When the second electrodes 43a and 43b are covered by the insulating protective film 23, the electrochemical reaction generated at the interface between the electrode metal and the liquid can be suppressed, and the degradation and wear of the electrode metal over time can be suppressed.

[0076] A flow path cover 25 is disposed on the upper surface of the insulating protective film 23. The flow path cover 25 has a flow path groove 251 ( Figure 3 ) The same concave flow channel 252. The flow channel 252 extends along the direction D2. The direction D3 ( Figure 2 ) has a width of, for example, micrometer order. The second flow path 41 is formed by the flow path groove 252 and the upper surface of the insulating protection film 23. In this way, by mounting the flow path cover 25 on the main surface 211 side of the substrate 2, the second flow path 41 is arranged on the main surface 211 side of the substrate 21.

[0077] return Figure 1 , the second electrode pad portions 431a, 431b are arranged separately from the second flow path 41 on the other side of the one side and the other side of the second flow path 41 in the direction D3. At least a portion of the second electrode pad portion 431a and at least a portion of the second electrode pad portion 431b are arranged outside the flow path cover 25. In addition, the portions of the second electrode pad portions 431a, 431b arranged outside the flow path cover 25 are not covered by the insulating protective film 23. Therefore, the second electrode pad portions 431a, 431b can be electrically connected to the measuring device 200 outside the flow path cover 25.

[0078] The second electrode pad portion 431a is connected to the second electrode 43a, and the second electrode pad portion 431b is connected to the second electrode 43b.

[0079] The dielectrophoresis device 1 further includes a voltage control device 100. The voltage control device 100 is electrically connected to the first electrode pad portions 331a and 331b.

[0080] The voltage control device 100 applies a control voltage Vcn corresponding to the dielectric particle P1 to the first electrodes 33a and 33b via the first electrode pad portions 331a and 331b. That is, the voltage control device 100 applies a control voltage Vcn corresponding to the dielectric particle P1 between the first electrode 33a and the first electrode 33b via the first electrode pad portions 331a and 331b. The control voltage Vcn is an AC voltage. The control voltage Vcn corresponding to the dielectric particle P1 is a frequency that generates an electric field that specifically acts on the dielectric particle P1 with a dielectrophoretic force (attraction), and is a voltage of a magnitude that does not destroy the dielectric particle P1.

[0081] Specifically, the frequency of the control voltage Vcn is set to act on the dielectric particle P1 through the first electrodes 33a and 33b with a positive dielectrophoretic force (attraction). Therefore, the positive dielectrophoretic force (attraction) acts on the dielectric particle P1, and the dielectric particle P1 is attracted by the first electrodes 33a and 33b (first line portions 333a and 333b) while flowing in the separation channel 311 along the extension direction of the first electrodes 33a and 33b (first line portions 333a and 333b), and is collected by the first collection portion 317a through the collection channel 313a. On the other hand, the frequency of the control voltage Vcn is set so that the dielectrophoretic force does not act on the other component P2, or even if the positive or negative dielectrophoretic force (attraction or repulsion) acts on the other component P2, the dielectrophoretic force is relatively small. Therefore, the other component P2 flows through the flow in the direction D1 in the separation channel 311, and is collected by the second collection portion 317b through the collection channel 313b.

[0082] Above, as reference Figure 1 As described above, the positive dielectrophoretic force (attractive force) acts on the dielectric particles P1, so that the dielectric particles P1 are separated from other components P2, and the dielectric particles P1 are collected in the first collecting part 317a.

[0083] Next, refer to Figure 5 The principle of separating the dielectric particles P1 from other components P2 will be described. Figure 5 It is along Figure 2 Detailed cross-sectional view of the VV line. Figure 5 As shown in FIG. 1 , the separation of the dielectric particles P1 from the other components P2 is performed by capturing the dielectric particles P1. In this case, the capturing force for the dielectric particles P1 is determined by the balance between the moving force of the sample liquid SP in the direction D1 and the electric attraction caused by the electric field EF generated by the pair of first electrodes 33a and 33b. The direction D1 represents the flow direction of the sample liquid SP in the first flow path 31 (separation flow path 311). In addition, the inclination angle θ ( Figure 2) also contributes to the capture and separation of the dielectric particles P1. In the following, in this embodiment, the capture and separation of the dielectric particles P1 are focused on the electric attraction (electric binding force). Specifically, in this embodiment, the control voltage Vcn applied between the first electrodes 33a and 33b is focused on to suppress the attenuation of the control voltage Vcn caused by the parasitic components of the flow path chip 11. The details are described later.

[0084] return Figure 1 The voltage control device 100 can also apply the measurement voltage Vm1 to the first electrodes 33a and 33b via the first electrode pads 331a and 331b and measure the impedance IM1 between the first electrodes 33a and 33b via the sample liquid. In this case, the voltage control device 100 measures the impedance IM1 for each frequency while changing the frequency of the measurement voltage Vm1.

[0085] The voltage control device 100 includes a power supply unit 101 , a control unit 102 , and a measurement unit 103 .

[0086] The control unit 102 controls the power supply unit 101 and the measuring unit 103. The control unit 102 includes, for example, a processor and a storage device. The processor is, for example, a CPU (Central Processing Unit) or an MPU (Micro Processing Unit). The storage device stores data and computer programs. The storage device includes a main storage device such as a semiconductor memory and an auxiliary storage device such as a semiconductor memory, a solid-state drive and / or a hard disk drive. The storage device may also include a removable medium. The storage device is equivalent to an example of a non-transient computer-readable storage medium.

[0087] The power supply unit 101 generates a control voltage Vcn or a measurement voltage Vm1 corresponding to the dielectric particles P1 to be separated. The power supply unit 101 applies the control voltage Vcn or the measurement voltage Vm1 to the first electrodes 33a and 33b via the first electrode pads 331a and 331b. The power supply unit 101 is, for example, a signal generator such as a function generator.

[0088] In a state where the measurement voltage Vm1 is applied between the first electrodes 33a and 33b by the power supply unit 101, the measurement unit 103 measures the impedance IM1 between the pair of first electrodes 33a and 33b via the sample liquid injected into the liquid receiving part FW. Figure 1In the example of , the measuring unit 103 measures the impedance IM1 between the pair of first electrodes 33a and 33b via the sample liquid injected into the first flow path 31. Specifically, the measuring unit 103 measures the current flowing between the first electrodes 33a and 33b via the first electrodes 33a and 33b in a state where the measuring voltage Vm1 is applied between the first electrodes 33a and 33b by the power supply unit 101. The measuring unit 103 calculates the impedance IM1 between the first electrodes 33a and 33b based on the measuring voltage Vm1 and the current measured via the first electrodes 33a and 33b. The measuring unit 103 is, for example, a measuring instrument such as an oscilloscope.

[0089] The voltage control device 100 may be formed of, for example, a source measurement unit.

[0090] The dielectrophoresis device 1 further includes a measuring device 200. The measuring device 200 is electrically connected to the second electrode pad portions 431a and 431b.

[0091] The measuring device 200 applies a measuring voltage Vm2 to the second electrodes 43a and 43b via the second electrode pads 431a and 431b, and measures the impedance IM2 between the second electrodes 43a and 43b via the reference liquid. In this case, the measuring device 200 measures the impedance IM2 at each frequency while changing the frequency of the measuring voltage Vm2.

[0092] The measuring device 200 includes a power supply unit 201 , a control unit 202 , and a measuring unit 203 .

[0093] The control unit 202 controls the power supply unit 201 and the measuring unit 203. The configuration of the control unit 202 is the same as that of the control unit 102.

[0094] The power supply unit 201 generates a measurement voltage Vm2. The power supply unit 201 applies the measurement voltage Vm2 to the second electrodes 43a and 43b via the second electrode pad units 431a and 431b. The power supply unit 201 is, for example, a signal generator such as a function generator.

[0095] In a state where the measurement voltage Vm2 is applied between the second electrodes 43a and 43b by the power supply unit 201, the measurement unit 203 measures the impedance IM2 between the pair of second electrodes 43a and 43b via the reference liquid injected into the liquid receiving part FW. Figure 1In the example of , the measuring unit 203 measures the impedance IM2 between the pair of second electrodes 43a and 43b via the reference liquid injected into the second flow path 41. Specifically, the measuring unit 203 measures the current flowing between the second electrodes 43a and 43b via the second electrodes 43a and 43b in a state where the measuring voltage Vm2 is applied between the second electrodes 43a and 43b by the power supply unit 201. The measuring unit 203 calculates the impedance IM2 between the second electrodes 43a and 43b based on the measuring voltage Vm2 and the current measured via the second electrodes 43a and 43b. The measuring unit 203 is, for example, a measuring instrument such as an oscilloscope.

[0096] The measuring unit 203 outputs data indicating the frequency of the measurement voltage Vm2 and the impedance IM2 between the second electrodes 43 a and 43 b to the control unit 102 of the voltage control device 100 .

[0097] The measuring device 200 may be constituted by a source measurement unit, for example.

[0098] Above, as reference Figure 1 As described, according to the present embodiment, the first flow path 31 into which the sample liquid is injected is separated from the second flow path 41 into which the reference liquid is injected. Furthermore, the impedance IM1 of the sample liquid and the impedance IM2 of the reference liquid are measured separately. Therefore, the first flow path 31 can be prevented from being contaminated by the reference liquid, and the second flow path 41 can be prevented from being contaminated by the sample liquid. In addition, the measurement of the impedance IM1 and the measurement of the impedance IM2 can also be performed in parallel. As a result, the throughput of the separation and collection process of the dielectric particles P1 can be improved.

[0099] Next, refer to Figure 1 and Figure 6 The control voltage correction method of this embodiment is described. In the control voltage correction method, the flow path chip 11 is used. The control voltage correction method is performed by the dielectrophoresis device 1. In this embodiment, by performing the control voltage correction method, in the flow path chip 11, the influence of the parasitic components of the flow path chip 11 on the separation performance and collection performance of the dielectric particles P1 from other components P2 can be reduced.

[0100] Figure 6 is a flow chart showing the control voltage correction method of this embodiment. Figure 6 As shown, the control voltage correction method includes steps S1 to S7.

[0101] like Figure 1 and Figure 6 As shown, first, in step S1, a reference liquid is injected into the liquid receiving part FW. In the present embodiment, in step S1, the second supply part 411 injects the reference liquid into the second flow path 41.

[0102] Next, in step S2, the power supply unit 201 of the measuring device 200 applies a measuring voltage Vm2 between the pair of second electrodes 43a and 43b, and the measuring unit 203 of the measuring device 200 measures the impedance IM2 between the pair of second electrodes 43a and 43b via the reference liquid injected into the liquid receiving part FW. In the present embodiment, in step S2, the measuring unit 203 measures the impedance IM2 between the pair of second electrodes 43a and 43b via the reference liquid injected into the second flow path 41. The measuring voltage Vm2 has a specific voltage value Vx. The measuring voltage Vm2 is an AC voltage. Therefore, the specific voltage value Vx is represented by an effective value.

[0103] Preferably, the measuring unit 203 measures the impedance IM2 between the pair of second electrodes 43a and 43b via the reference liquid according to the frequency while changing the frequency of the measuring voltage Vm2. Furthermore, the storage device of the control unit 202 stores the impedance IM2 between the pair of second electrodes 43a and 43b for each frequency of the measuring voltage Vm2. The control unit 202 outputs data indicating the impedance IM2 for each frequency to the voltage control device 100. Then, in the voltage control device 100, the storage device of the control unit 102 stores the impedance IM2 for each frequency of the measuring voltage Vm2.

[0104] Next, in step S3, the sample liquid is injected into the liquid receiving part FW. In the present embodiment, in step S3, the first supply part 315 injects the sample liquid into the first channel 31 (separation channel 311).

[0105] Next, in step S4, the power supply unit 101 of the voltage control device 100 applies a measurement voltage Vm1 between the pair of first electrodes 33a and 33b, and the measurement unit 103 of the voltage control device 100 measures the impedance IM1 between the pair of first electrodes 33a and 33b via the sample liquid injected into the liquid receiving part FW. In the present embodiment, in step S4, the measurement unit 103 measures the impedance IM1 between the pair of first electrodes 33a and 33b via the sample liquid injected into the first flow path 31 (separation flow path 311). The measurement voltage Vm1 is an AC voltage. The measurement voltage Vm1 has the same specific voltage value Vx as the measurement voltage Vm2.

[0106] Preferably, the measuring unit 103 measures the impedance IM1 between the pair of first electrodes 33a and 33b via the sample liquid while changing the frequency of the measuring voltage Vm1. The storage device of the control unit 102 stores the impedance IM1 between the pair of first electrodes 33a and 33b for each frequency of the measuring voltage Vm1.

[0107] Next, in step S5 , the control unit 102 of the voltage control device 100 corrects the control voltage Vcn applied between the pair of first electrodes 33a , 33b based on the impedance IM2 between the pair of second electrodes 43a , 43b measured in step S2 and the impedance IM1 between the pair of first electrodes 33a , 33b measured in step S4 .

[0108] Specifically, step S5 includes step S51 and step S52.

[0109] In step S51, the control unit 102 calculates the correction coefficient C based on the impedance IM2 between the pair of second electrodes 43a and 43b measured via the reference liquid injected into the liquid receiving part FW (the second flow path 41) and the impedance IM1 between the pair of first electrodes 33a and 33b measured via the sample liquid injected into the liquid receiving part FW (the first flow path 31). In this case, the impedance IM1 is the impedance between the first electrodes 33a and 33b measured when the measurement voltage Vm1 of the specific frequency fx is applied between the first electrodes 33a and 33b. Similarly, the impedance IM2 is the impedance between the second electrodes 43a and 43b measured when the measurement voltage Vm2 of the specific frequency fx is applied between the second electrodes 43a and 43b. The specific frequency fx of the measurement voltage Vm1 is the same as the specific frequency fx of the measurement voltage Vm2.

[0110] The correction coefficient C uses the voltage output efficiency VOE, which is expressed by formula (1). The voltage output efficiency VOE is expressed by formula (2). Therefore, the voltage output efficiency VOE represents the ratio of "the voltage value actually applied to the sample liquid when the control voltage Vcn having a specific voltage value Vx is applied to the first electrodes 33a, 33b" to "the target value of the voltage applied to the sample liquid, that is, the specific voltage value Vx".

[0111] C=1 / VOE…(1)

[0112] VOE=(IM1-IM2) / IM1…(2)

[0113] Next, in step S52, the control unit 102 corrects the control voltage Vcn applied between the pair of first electrodes 33a and 33b based on the correction coefficient C. Specifically, the control unit 102 corrects the control voltage Vcn having a specific voltage value Vx based on the correction coefficient C. That is, the control unit 102 corrects the specific voltage value Vx based on the correction coefficient C and calculates the corrected voltage value Vy. Specifically, the control unit 102 calculates the corrected voltage value Vy by formula (3). Then, the control unit 102 controls the power supply unit 101 to output the control voltage Vcn having the corrected voltage value Vy and the specific frequency fx. The specific voltage value Vx represents the target value of the voltage applied to the sample liquid.

[0114] Vy=C×Vx…(3)

[0115] Next, in step S6, the power supply unit 101 applies the corrected control voltage Vcn between the first electrodes 33a and 33b. The corrected control voltage Vcn is a control voltage having a corrected voltage value Vy and a specific frequency fx.

[0116] Next, in step S7 , the control unit 102 determines whether an instruction to change the frequency of the control voltage Vcn has been received.

[0117] If it is determined in step S7 that an instruction to change the frequency has been received (Yes), the process proceeds to step S51. Then, in step S51, the control unit 102 recalculates the correction coefficient C based on the impedances IM1 and IM2 measured with the measurement voltages Vm1 and Vm2 having the changed frequency. In this case, the control unit 102 sets the changed frequency to the specific frequency fx.

[0118] On the other hand, when it is determined in step S7 that the instruction to change the frequency has not been received (No), the control voltage correction method ends.

[0119] Above, as reference Figure 6 As described, according to the present embodiment, the voltage control device 100 corrects the control voltage Vcn applied between the pair of first electrodes 33a and 33b based on the impedance IM2 between the pair of second electrodes 43a and 43b measured via the reference liquid injected into the liquid receiving part FW (the second flow path 41) (step S5). Therefore, in the flow path chip 11, the influence of the parasitic component on the separation performance and collection performance of the dielectric particles P1 from the other components P2 contained in the sample liquid can be reduced. The parasitic component is a parasitic component existing inside the flow path chip 11.

[0120] According to the present embodiment, step S51 of calculating the correction coefficient C and step S52 of correcting the control voltage Vcn are performed every time the frequency of the control voltage Vcn is changed (step S7). Therefore, the control voltage Vcn can be appropriately corrected according to the frequency for each frequency of the control voltage Vcn.

[0121] Next, refer to Figure 7 to Figure 10 The reasons why the influence of parasitic components on the separation performance and collection performance of the dielectric particles P1 in the flow channel chip 11 can be reduced will be described in detail. Figure 7 1 is a circuit diagram showing an equivalent circuit of a parasitic component of the flow channel chip 11 (hereinafter referred to as “in-device parasitic component PR”). Figure 8 : is a graph showing the impedance IM1 measured via the sample liquid and the impedance IM2 measured via the reference liquid. Fig. 9 The frequency is shown as 104 Hz and above and 10 6 Graph of the difference DF between impedance IM1 and impedance IM2 in the range below Hz. Figure 8 and Fig. 9 A double logarithmic graph is shown, where the horizontal axis represents the frequency [Hz] of the measurement voltages Vm1 and Vm2 and the vertical axis represents the impedance [Ω]. Fig.10 is a graph showing the frequency dependence of the voltage output efficiency VOE. Fig.10 In the figure, the horizontal axis represents the frequency [Hz] of the measurement voltages Vm1 and Vm2, and the vertical axis represents the voltage output efficiency VOE [%]. Fig.10 In order to facilitate understanding, the voltage output efficiency VOE is expressed as a percentage [%).

[0122] First, refer to Figure 7 , to explain the parasitic component PR in the device. Figure 7 As shown, the parasitic component PR in the device includes the parasitic component PR1 of the electrode metal, the parasitic component PR2 of the insulating protection film 23, the parasitic component PR3 of the liquid interface, and the parasitic component PR4 of the liquid. The parasitic component PR1 of the electrode metal represents the parasitic resistance R of the first electrodes 33a, 33b or the parasitic resistance R of the second electrodes 43a, 43b. The parasitic component PR2 of the insulating protection film 23 represents the parasitic resistance R and the parasitic capacitance C of the insulating protection film 23. The parasitic component PR3 of the liquid interface represents the parasitic resistance R and the parasitic capacitance C at the interface between the first electrodes 33a, 33b and the sample liquid, or the parasitic resistance R and the parasitic capacitance C at the interface between the second electrodes 43a, 43b and the reference liquid. The parasitic component PR4 of the liquid represents the parasitic resistance R and the parasitic capacitance C of the sample liquid, or the parasitic resistance R and the parasitic capacitance C of the reference liquid.

[0123] In this embodiment, the device basic parasitic component PR0 is extracted using the reference liquid. The device basic parasitic component PR0 is the parasitic components PR1, PR2, and PR3 other than the parasitic component PR4 of the liquid among the parasitic components PR in the device.

[0124] Specifically, the resistivity (resistance) of the reference liquid is smaller than the resistivity (resistance) of the second electrodes 43a, 43b. In other words, the conductivity of the reference liquid is greater than the conductivity of the second electrodes 43a, 43b. Figure 8 As shown in FIG. 1 , the impedance IM2 between the second electrodes 43a and 43b measured by the measuring device 200 via the reference liquid represents the device basic parasitic component PR0. Thus, in this embodiment, the device basic parasitic component PR0 of the flow path chip 11 can be easily extracted. The resistance of the reference liquid is, for example, 10 4 Hz and above and 10 610 in the range below Hz 3 The resistance of the reference liquid is, for example, 10 5 Hz and above and 10 6 10 in the range below Hz 2 Ω or less.

[0125] On the other hand, Figure 8 As shown, the impedance IM1 between the first electrodes 33a and 33b measured by the voltage control device 100 via the sample liquid represents the parasitic component PR in the device, including the basic parasitic component PR0 of the device. Figure 8 In the example, the frequency of the measuring voltage Vm1 is about 10 4 When the frequency is above 10 Hz, the impedance IM1 is approximately constant. 4 The impedance IM1 at Hz or higher mainly represents the resistance of the sample liquid. This is because the reactance, which is the imaginary part of the impedance, has frequency dependence, but the resistance, which is the real part of the impedance, has no frequency dependence.

[0126] Therefore, if Fig. 9 As shown, at a frequency of 10 4 Hz and above and 10 6 In the range below Hz, the difference DF (= IM1 - IM2) obtained by subtracting the impedance IM2 from the impedance IM1 represents the parasitic component PR4 ( Figure 7 ) is the "parasitic resistance (resistance) of the sample liquid". Figure 8 In the example of , the difference DF representing the parasitic resistance (resistance) of the sample liquid is approximately 1 kΩ.

[0127] Using the difference DF (= IM1 - IM2), the voltage output efficiency VOE can be calculated by the above formula (2). Fig.10 It can be seen that the voltage output efficiency VOE is 50% or more when the frequency is about 10 kHz or more. Even when the frequency is about 10 kHz or more, the voltage output efficiency VOE depends on the frequency.

[0128] The voltage output efficiency VOE represents the ratio of "the voltage value actually applied to the sample liquid when the control voltage Vcn having a specific voltage value Vx is applied to the first electrodes 33a and 33b" to "the specific voltage value Vx, which is the target value of the voltage applied to the sample liquid". The device basic parasitic component PR0 exists in the flow channel chip 11, so the voltage output efficiency VOE is not 100%. That is, the control voltage Vcn having a specific voltage value Vx is attenuated by the device basic parasitic component PR0, so the voltage output efficiency VOE is not 100%.

[0129] Therefore, the voltage value of the control voltage Vcn is corrected by adding the voltage value attenuated by the device basic parasitic component PR0 to the specific voltage value Vx. As a result, the voltage value of the voltage actually applied to the sample liquid can be made to be the specific voltage value Vx as the target value. That is, in this embodiment, the influence of the device basic parasitic component PR0 on the separation performance and collection performance of the dielectric particles P1 from other components P2 contained in the sample liquid in the flow path chip 11 can be reduced.

[0130] Specifically, as shown in the above-mentioned formula (1) and formula (3), the control unit 102 calculates the correction coefficient C based on the voltage output efficiency VOE, and multiplies the correction coefficient C by the specific voltage value Vx to calculate the correction voltage value Vy. The correction coefficient C is the inverse of the voltage output efficiency VOE, so by multiplying the correction coefficient C by the specific voltage value Vx, it is possible to obtain the correction voltage value Vy obtained by adding the voltage value attenuated by the device basic parasitic component PR0 to the specific voltage value Vx. The correction coefficient C is a real number greater than 1. Then, the control unit 102 controls the power supply unit 101 to apply the control voltage Vcn having the correction voltage value Vy to the first electrodes 33a and 33b. As a result, the power supply unit 101 applies the control voltage Vcn having the correction voltage value Vy to the first electrodes 33a and 33b. According to this embodiment, by measuring the impedances IM1 and IM2 and calculating the correction coefficient C, the control voltage Vcn can be easily corrected.

[0131] Here, when manufacturing a plurality of flow path chips 11, manufacturing variations may occur within tolerances between the plurality of flow path chips 11. For example, when manufacturing a plurality of flow path chips 11, variations in thickness and structure of the insulating protective film 23 may occur within tolerances between the plurality of flow path chips 11. In particular, the parasitic component PR2 ( Figure 7 ) is a high reactance component. Therefore, if the insulating protective film 23 is biased, especially between the plurality of flow path chips 11, the differential voltage between the control voltage Vcn applied to the first electrodes 33a and 33b and the voltage actually applied to the sample liquid may also be biased. As a result, if no correction is made, the separation performance and collection performance of the dielectric particles P1 to be separated may also be biased between the plurality of flow path chips 11.

[0132] Therefore, in this embodiment, the voltage value of the control voltage Vcn is corrected by adding the voltage value attenuated by the device basic parasitic component PR0 including the parasitic component PR2 of the insulating protection film 23 to the specific voltage value Vx. That is, the correction coefficient C is calculated by equations (1) to (3), and the control voltage Vcn is corrected by the correction coefficient C, thereby reducing the influence of the device basic parasitic component PR0. As a result, even if there is a manufacturing deviation of the insulating protection film 23 and the like between the plurality of flow path chips 11, the deviation of the performance of the plurality of flow path chips 11 can be suppressed.

[0133] Next, refer to Figure 11 to Figure 13 , a specific example is given to illustrate the correction process of the control voltage Vcn. Figure 11 to Figure 13 In the description of FIG. 1 , as an example, a specific voltage value Vx which is a target value of a voltage applied to a sample liquid is set to “12 V”.

[0134] Fig.11 The graph shows the voltage value Vr0 of the voltage actually applied to the sample liquid when the control voltage Vcn having a specific voltage value Vx is applied to the first electrodes 33a and 33b. The horizontal axis shows the frequency [MHz] of the control voltage Vcn, and the vertical axis shows the voltage [V]. Fig.12 It means Fig.11 The curve diagram of the voltage output efficiency VOE corresponding to the voltage value Vr0. The horizontal axis represents the frequency of the control voltage Vcn [MHz], and the vertical axis represents the voltage output efficiency VOE [%]. Fig.12 In order to facilitate understanding, the voltage output efficiency VOE is expressed as a percentage [%). Fig.13 is a graph showing the correction coefficient C. Fig.13 In order to facilitate understanding, the correction coefficient C is expressed as a percentage [%]. As shown in the above formula (1), the correction coefficient C is expressed by the inverse of the voltage output efficiency VOE (1 / VOE) (C = 1 / VOE). The horizontal axis represents the frequency [MHz] of the control voltage Vcn, and the vertical axis represents the correction coefficient C [%]. Fig.14 Graph showing voltage value Vr1 of voltage actually applied to the sample liquid when the corrected control voltage Vcn is applied to the first electrodes 33a and 33b. The horizontal axis shows the frequency [MHz] of the control voltage Vcn, and the vertical axis shows the voltage [V].

[0135] like Fig.11 As shown in FIG. 1 , when the power supply unit 101 applies the control voltage Vcn having the specific voltage value Vx (=12 V) to the first electrodes 33a and 33b, the voltage attenuation occurs due to the influence of the device basic parasitic component PR0, and the voltage value Vr0 of the voltage actually applied to the sample liquid is smaller than the specific voltage value Vx (=12 V). In addition, the voltage value Vr0 changes according to the frequency of the control voltage Vcn.

[0136] Therefore, if Fig.12 As shown, the control unit 102 calculates the voltage output efficiency VOE for each frequency. The voltage output efficiency VOE is obtained by Fig.11 The voltage value shown corresponds to the value Vr0.

[0137] And, if Fig.13 As shown, the control unit 102 calculates for each frequency Fig.12 The inverse of the voltage output efficiency VOE shown is the correction coefficient C. Then, the control unit 102 calculates the correction voltage value Vy for each frequency using the correction coefficient C and the specific voltage value Vx according to the above formula (3). As a result, the power supply unit 101 applies the control voltage Vcn having the correction voltage value Vy to the first electrodes 33a and 33b.

[0138] Therefore, if Fig.14 As shown in FIG. 1 , when the corrected control voltage Vcn is applied to the first electrodes 33a and 33b, the voltage value Vr1 of the voltage actually applied to the sample liquid is substantially constant regardless of the frequency. Specifically, the voltage value Vr1 of the voltage actually applied to the sample liquid is substantially consistent with the specific voltage value Vx (=12V) as the target value. In this way, the influence of the device basic parasitic component PR0 can be reduced, and a voltage of the specific voltage value Vx (voltage value Vr1) as the target value can be applied to the sample liquid.

[0139] In addition, even when there is a manufacturing variation of the insulating protective film 23 or the like among the plurality of flow path chips 11, the voltage value Vr1 of the voltage actually applied to the sample liquid is substantially consistent with the specific voltage value Vx (=12 V) as the target value. In this way, by reducing the influence of the device basic parasitic component PR0 including the parasitic component PR2 of the insulating protective film 23, the variation of the separation performance and the collection performance of the dielectric particles P1 caused by the flow path chip 11 among the plurality of flow path chips 11 can be suppressed.

[0140] And, if Fig.13 As shown in FIG. 1 , the correction coefficient C has a value corresponding to the frequency of the control voltage Vcn. Therefore, according to the present embodiment, the control voltage Vcn can be appropriately corrected according to the frequency for each frequency of the control voltage Vcn. As a result, Fig.14 As shown, in a wide frequency range, the voltage value Vr1 of the voltage actually applied to the sample liquid can be made substantially consistent with the specific voltage value Vx (=12 V) as the target value.

[0141] (First Modification)

[0142] Reference Fig.15 and Fig.16, a flow path chip 11 of a first modified example of the present embodiment is described. The flow path chip 11 of the first modified example includes a reservoir 41A instead of the second flow path 41 ( Figure 1 ), in this point, the first variant is mainly different from the above-mentioned embodiment. The following mainly describes the differences between the first variant and the above-mentioned embodiment.

[0143] Fig.15 1 is a plan view showing the reservoir 41A and the second electrodes 43 a and 43 b of the channel chip 11 according to the first modification. Fig.16 It is along Fig.15 Schematic cross-sectional view along line XVI-XVI. Fig.15 and Fig.16 Only the periphery of the reservoir 41A and the reservoir 41A in the flow channel chip 11 are shown.

[0144] like Fig.15 and Fig.16 As shown, the flow channel chip 11 includes a storage portion 41A instead of Figure 1 The second flow path 41 shown in FIG. 4A can store a reference liquid. The storage portion 41A is connected to the first flow path 31 ( Figure 1 ) separation. Fig.16 As shown in FIG. 1 , the storage section 41A is disposed on the main surface 211 side of the substrate 21. The storage section 41A is formed by a through hole provided in the flow channel cover 25. In addition, the flow channel cover 25 has an opening 412 for injecting a reference liquid into the storage section 41A. The storage section 41A is not like the second flow channel 41 ( Figure 3 ) is not a slender tubular flow path surrounded by walls on all sides, but is constructed as a concave hole with an opening on the top.

[0145] like Fig.15 as well as Fig.16 As shown, the flow channel chip 11 has a pair of second electrodes 43a, 43b. The pair of second electrodes 43a, 43b and the first flow channel 31 ( Figure 1 ) and a pair of first electrodes 33a, 33b ( Figure 1 ) are separated and arranged between the main surface 211 of the substrate 21 and the reservoir 41A. The second electrodes 43a and 43b are covered by the insulating protection film 23.

[0146] The second electrode 43a has a plurality of second line portions 433a arranged in a comb-tooth shape. The second electrode 43b has a plurality of second line portions 433b arranged in a comb-tooth shape. The plurality of second line portions 433a and the plurality of second line portions 433b extend along the direction D1. The plurality of second line portions 433a are arranged at equal intervals in the direction D3. The plurality of second line portions 433b are arranged at equal intervals in the direction D3. The second line portions 433a and the second line portions 433b are alternately arranged at intervals in the direction D3.

[0147] In the case of the flow path chip 11 of the first variant, the measuring device 200 measures the impedance IM2 between the second electrodes 43a and 43b in a state where a reference liquid is injected into the storage part 41A. Moreover, the control voltage Vcn applied between the pair of first electrodes 33a and 33b is corrected based on the impedance IM2 between the pair of second electrodes 43a and 43b measured via the reference liquid injected into the storage part 41A. Therefore, according to the first variant, similarly to the above-mentioned embodiment, in the flow path chip 11, the influence of parasitic components on the separation performance and collection performance of the dielectric particles P1 from other components P2 contained in the sample liquid can be reduced. In addition, between multiple flow path chips 11, the deviation of the separation performance and collection performance of the dielectric particles P1 caused by the flow path chip 11 can be suppressed.

[0148] Specifically, the control voltage Vcn applied between the pair of first electrodes 33a and 33b is corrected based on the impedance IM2 between the pair of second electrodes 43a and 43b measured via the reference liquid injected into the reservoir 41A and the impedance IM1 between the pair of first electrodes 33a and 33b measured via the sample liquid injected into the first flow path 31.

[0149] In addition, according to the first variant, the first flow path 31 into which the sample liquid is injected is separated from the storage portion 41A into which the reference liquid is injected. Furthermore, the impedance IM1 of the sample liquid and the impedance IM2 of the reference liquid are measured separately. Therefore, the first flow path 31 can be prevented from being contaminated by the reference liquid, and the storage portion 41A can be prevented from being contaminated by the sample liquid. In addition, the measurement of the impedance IM1 and the measurement of the impedance IM2 can also be performed in parallel. As a result, the throughput of the separation and collection process of the dielectric particles P1 can be improved.

[0150] (Second Modification)

[0151] Reference Fig.17 , a dielectrophoresis device 1 according to a second variation of the present embodiment is described. The second variation mainly differs from the above embodiment in that the flow path chip 11A of the second variation includes first electrodes 33a, 33b and second electrodes 43a, 43b in the first flow path 31. The differences between the second variation and the above embodiment are mainly described below.

[0152] Fig.17 FIG. 2 is a plan view showing a dielectrophoresis device 1 according to a second modified example. Fig.17 As shown, the liquid receiving part FW includes a first flow path 31 .

[0153] The pair of first electrodes 33a and 33b can cause the dielectrophoretic force to act on the dielectric particles P1 contained in the sample liquid injected into the first flow channel 31 in a state where the reference liquid is not injected into the first flow channel 31. That is, the voltage control device 100 (power supply unit 101) applies the control voltage Vcn to the first electrodes 33a and 33b in a state where the reference liquid is not injected into the first flow channel 31 and the sample liquid is injected into the first flow channel 31.

[0154] In addition, the voltage control device 100 (power supply unit 101) can also apply the measurement voltage Vm1 to the first electrodes 33a and 33b in a state where the reference liquid is not injected into the first flow channel 31 but the sample liquid is injected into the first flow channel 31. In this case, the voltage control device 100 (measurement unit 103) measures the impedance IM1 between the pair of first electrodes 33a and 33b in a state where the sample liquid is injected into the first flow channel 31.

[0155] On the other hand, a pair of second electrodes 43a and 43b are formed on the main surface 211 ( Figure 3 ) and the first flow path 31( Figure 3 ) are arranged at a position different from a pair of first electrodes 33a, 33b.

[0156] The measuring device 200 (power supply unit 201) applies a measuring voltage Vm2 to the second electrodes 43a and 43b in a state where the sample liquid is not injected into the first flow channel 31 but the reference liquid is injected into the first flow channel 31. Then, the measuring device 200 (measuring unit 203) measures the impedance IM2 between the pair of second electrodes 43a and 43b in a state where the reference liquid is injected into the first flow channel 31.

[0157] The control voltage Vcn applied between the pair of first electrodes 33a and 33b is corrected based on the impedance IM2 between the pair of second electrodes 43a and 43b measured via the reference liquid injected into the first flow path 31 when the sample liquid is not injected into the first flow path 31. Therefore, according to the second modification, similarly to the above-mentioned embodiment, in the flow path chip 11A, the influence of the parasitic component on the separation performance and collection performance of the dielectric particles P1 from the other components P2 contained in the sample liquid can be reduced. In addition, among the plurality of flow path chips 11A, the deviation of the separation performance and collection performance of the dielectric particles P1 caused by the flow path chip 11A can be suppressed.

[0158] Specifically, the control voltage Vcn applied between the pair of first electrodes 33a and 33b is corrected based on the impedance IM2 between the pair of second electrodes 43a and 43b measured via the reference liquid injected into the first flow path 31 and the impedance IM1 between the pair of first electrodes 33a and 33b measured via the sample liquid injected into the first flow path 31.

[0159] Next, refer to Fig.17 The second electrodes 43a and 43b are described below. The second electrodes 43a and 43b are separated from the first electrodes 33a and 33b in the direction D1. The second electrodes 43a and 43b are separated from the first electrodes 33a and 33b by the insulating protective film 23 ( Figure 3 )cover.

[0160] The second electrode 43a has a plurality of second line portions 433a arranged in a comb shape. The second electrode 43b has a plurality of second line portions 433b arranged in a comb shape. The plurality of second line portions 433a and the plurality of second line portions 433b extend along the direction D3. The second line portions 433a and the second line portions 433b are alternately arranged at intervals in the direction D1.

[0161] Part of the plurality of second line portions 433a is substantially orthogonal to the collecting channel 313a in a plan view and is arranged at equal intervals in the direction D1. Part of the plurality of second line portions 433b is substantially orthogonal to the collecting channel 313a in a plan view and is arranged at equal intervals in the direction D1.

[0162] Another portion of the plurality of second line portions 433a is substantially orthogonal to the collecting channel 313b in a plan view and is arranged at equal intervals in the direction D1. Another portion of the plurality of second line portions 433b is substantially orthogonal to the collecting channel 313b in a plan view and is arranged at equal intervals in the direction D1.

[0163] According to the second modification, the first electrodes 33a and 33b and the second electrodes 43a and 43b are arranged corresponding to the first flow channels 31. Therefore, the flow channel chip 11A can be miniaturized compared to the case where the second flow channels 41 and the reservoirs 41A are provided separately.

[0164] The embodiments of the present invention are described above with reference to the accompanying drawings. However, the present invention is not limited to the above-mentioned embodiments and can be implemented in various ways without departing from the scope of the present invention. In addition, the multiple components disclosed in the above-mentioned embodiments can be appropriately changed. For example, a certain component of all the components shown in a certain embodiment can be added to the components of other embodiments, or some components of all the components shown in a certain embodiment can be deleted from the embodiment.

[0165] In addition, in the drawings, in order to facilitate the understanding of the invention, each component is schematically shown as the main body, and the thickness, length, number, spacing, etc. of each component shown in the drawings are sometimes different from the actual ones for the convenience of making the drawings. In addition, the structure of each component shown in the above-mentioned embodiment is an example and is not particularly limited. Of course, various changes can be made within the scope that does not substantially deviate from the effect of the present invention.

[0166] (1) In reference Figure 1 , Fig.15 as well as Fig.17 In the present embodiment, the first modification, and the second modification described above, the dielectrophoresis device 1 only needs to include any one of the voltage control device 100 and the measuring device 200. When the dielectrophoresis device 1 includes the voltage control device 100 but does not include the measuring device 200, the voltage control device 100 is connected to the second electrode pad portions 431a and 431b, so that the impedance IM2 between the second electrodes 43a and 43b is measured by the voltage control device 100. In addition, when the dielectrophoresis device 1 includes the measuring device 200 but does not include the voltage control device 100, the measuring device 200 is connected to the first electrode pad portions 331a and 331b, so that the impedance IM1 between the first electrodes 33a and 33b is measured by the measuring device 200. In addition, the control voltage Vcn is applied between the first electrodes 33a and 33b by the measuring device 200.

[0167] (2) In reference Figure 1 and Fig.15 In the present embodiment and the first modification described above, when a pair of second electrodes 43a and 43b are used as a group to form an electrode unit, the flow path chip 11 may also include a plurality of electrode units. In this case, the plurality of electrode units are arranged at intervals in the direction D2. Furthermore, the correction coefficient C may also be calculated based on the average value of the plurality of impedances IM2 measured by the plurality of electrode units.

[0168] (3) In reference Fig.17 In the second modification described above, the second electrodes 43a and 43b are arranged downstream of the first electrodes 33a and 33b in the direction D1. However, the second electrodes 43a and 43b may be arranged upstream of the first electrodes 33a and 33b in the direction D1.

[0169] In addition, the second electrodes 43a and 43b may be arranged corresponding to either the collecting channel 313a or the collecting channel 313b.

[0170] (4) In reference Figure 6 In the control voltage correction method described above, steps S3 and S4 may be performed before steps S1 and S2.

[0171] Industrial Applicability

[0172] The present invention relates to a flow channel chip, a dielectrophoresis device and a control voltage correction method, and has industrial applicability.

[0173] Explanation of symbols

[0174] 11. 11A flow path chip,

[0175] 21 substrate,

[0176] 31 first flow path,

[0177] 41 Second flow path,

[0178] 41A Storage Department,

[0179] 33a, 33b first electrode,

[0180] 43a, 43b second electrode,

[0181] 100 voltage control device,

[0182] FW liquid receiving part.

Claims

1. A flow channel chip, characterized in that: have: substrate; a liquid receiving portion, which is arranged on one main surface side of the substrate and can be injected with a sample liquid or a reference liquid; a pair of first electrodes disposed between the main surface of the substrate and the liquid receiving portion, and capable of causing a dielectrophoretic force to act on dielectric particles contained in the sample liquid injected into the liquid receiving portion by applying a control voltage thereto; as well as a pair of second electrodes disposed between the main surface of the substrate and the liquid receiving portion at positions different from those of the pair of first electrodes; The control voltage applied between the pair of first electrodes is corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving part.

2. The flow path chip according to claim 1, characterized in that: The resistivity of the reference liquid is lower than the resistivity of the second electrode.

3. The flow channel chip according to claim 1 or 2, characterized in that: correcting the control voltage applied between the pair of first electrodes based on a correction coefficient, The correction coefficient is calculated based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving part and the impedance between the pair of first electrodes measured via the sample liquid injected into the liquid receiving part.

4. The flow path chip according to claim 3, characterized in that: The control voltage is an AC voltage. The correction coefficient has a value corresponding to a frequency of the control voltage.

5. The flow channel chip according to claim 1 or 2, characterized in that: The liquid receiving part comprises: a first flow path, which is arranged on the main surface side of the substrate and can inject the sample liquid; and a second flow path, which is separated from the first flow path and is disposed on the main surface side of the substrate, and is capable of injecting the reference liquid; The pair of first electrodes are arranged between the main surface of the substrate and the first flow path, The pair of second electrodes are separated from the first flow path and the pair of first electrodes and are arranged between the main surface of the substrate and the second flow path. The control voltage applied between the pair of first electrodes is corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the second flow path.

6. The flow channel chip according to claim 1 or 2, characterized in that: The liquid receiving part comprises: a first flow path, which is arranged on the main surface side of the substrate and can inject the sample liquid; and a storage portion, which is separated from the first flow path and is disposed on the main surface side of the substrate and is capable of injecting the reference liquid, The pair of first electrodes are arranged between the main surface of the substrate and the first flow path, The pair of second electrodes are separated from the first flow path and the pair of first electrodes and are arranged between the main surface of the substrate and the storage portion. The control voltage applied between the pair of first electrodes is corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the reservoir.

7. The flow channel chip according to claim 1 or 2, characterized in that: The liquid receiving portion includes a first flow path, The pair of first electrodes are arranged between the main surface of the substrate and the first flow path, and by applying the control voltage, the dielectrophoretic force can act on the dielectric particles contained in the sample liquid injected into the first flow path in a state where the reference liquid is not injected into the first flow path. The pair of second electrodes are arranged between the main surface of the substrate and the first flow path at positions different from those of the pair of first electrodes. The control voltage applied between the pair of first electrodes is corrected based on the impedance between the pair of second electrodes measured via the reference liquid injected into the first flow channel in a state where the sample liquid is not injected into the first flow channel.

8. A dielectrophoresis device, characterized in that: Equipped with flow path chip and voltage control device, The flow path chip comprises: substrate; a liquid receiving portion, which is arranged on one main surface side of the substrate and can be injected with a sample liquid or a reference liquid; a pair of first electrodes disposed between the main surface of the substrate and the liquid receiving portion, and capable of causing a dielectrophoretic force to act on dielectric particles contained in the sample liquid injected into the liquid receiving portion by applying a control voltage thereto; and a pair of second electrodes disposed between the main surface of the substrate and the liquid receiving portion at positions different from those of the pair of first electrodes; The voltage control device corrects the control voltage applied between the pair of first electrodes based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving part.

9. A control voltage correction method using a flow path chip, characterized in that: The flow path chip comprises: substrate; a liquid receiving portion, which is arranged on one main surface side of the substrate and can be injected with a sample liquid or a reference liquid; a pair of first electrodes disposed between the main surface of the substrate and the liquid receiving portion, and capable of causing a dielectrophoretic force to act on dielectric particles contained in the sample liquid injected into the liquid receiving portion by applying a control voltage thereto; and a pair of second electrodes disposed between the main surface of the substrate and the liquid receiving portion at positions different from those of the pair of first electrodes; The control voltage correction method comprises the following steps: a step of measuring the impedance between the pair of second electrodes via the reference liquid injected into the liquid receiving part; and The control voltage applied between the pair of first electrodes is corrected based on the impedance between the pair of second electrodes.

10. The control voltage correction method according to claim 9, characterized in that: The resistivity of the reference liquid is lower than the resistivity of the second electrode.

11. The control voltage correction method according to claim 9 or 10, characterized in that: The control voltage correction method further includes the step of measuring the impedance between the pair of first electrodes via the sample liquid injected into the liquid receiving part, The process of correcting the control voltage includes: a step of calculating a correction coefficient based on the impedance between the pair of second electrodes measured via the reference liquid injected into the liquid receiving part and the impedance between the pair of first electrodes measured via the sample liquid injected into the liquid receiving part; and The control voltage applied between the pair of first electrodes is corrected based on the correction coefficient.

12. The control voltage correction method according to claim 11, characterized in that: The control voltage is an AC voltage. The process of calculating the correction coefficient and the process of correcting the control voltage are performed every time the frequency of the control voltage is changed.

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