Imaging method, distance determination method, and, imaging apparatus
The imaging method in microfluidic devices addresses the challenge of focusing on few or no microscopic objects by using dielectrophoretic forces to trap and image particles, ensuring reliable imaging outcomes.
Patent Information
- Application Number
- JP2024018444
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-02-09
- Publication Date
- 2025-08-22
AI Technical Summary
Microfluidic devices face challenges in obtaining reliable imaging results when there are few or no microscopic objects, such as bacteria, due to difficulties in focusing the imaging unit.
An imaging method that captures dielectric particles in a fluidic chip using an imaging unit, focusing on an electrode and adjusting the focus position to a predetermined distance away along the optical axis, utilizing dielectrophoretic forces to trap and image particles.
Enables highly reliable imaging results regardless of the quantity and presence of dielectric particles by ensuring consistent focus and imaging conditions across multiple fluid chips.
Smart Images

Figure 2025122793000001_ABST
Abstract
Description
[Technical Field]
[0001] The present invention relates to an imaging method, a distance determination method, and an imaging device. [Background technology]
[0002] The microfluidic device described in Patent Document 1 is a platform for processing and manipulating minute objects such as biological cells. The microfluidic device includes one or more individual microfluidic circuits configured to hold fluids. Each microfluidic circuit includes regions, flow paths, channels, chambers, and / or pens.
[0003] Furthermore, the method for analyzing a fluid sample in Patent Document 1 includes processing at least a portion of a fluid sample drawn into a microfluidic device. Processing at least a portion of the fluid sample includes imaging the sample contained in the microfluidic chip. The imaging includes imaging a micro-object contained in at least a portion of the fluid sample. The micro-object is a biological micro-object (e.g., a cell). [Prior art documents] [Patent documents]
[0004] [Patent Document 1] Special Publication No. 2023-500623 Summary of the Invention [Problem to be solved by the invention]
[0005] However, depending on the purpose of use of the microfluidic device, there may be very few or no microscopic objects in the fluid drawn into the microfluidic device. For example, if the purpose of use of the microfluidic device is to check the sanitary environment of the site (to ensure that bacteria are not growing), there may be very few or no bacteria in the fluid drawn into the microfluidic device. In this case, it is difficult or impossible to focus the imaging unit on microscopic objects (subjects) such as bacteria.
[0006] An object of the present invention is to provide an imaging method, a distance determination method, and an imaging device that are capable of obtaining highly reliable imaging results regardless of the quantity and presence of subjects. [Means for solving the problem]
[0007] According to one aspect of the present invention, an imaging method captures an image of dielectric particles in a fluidic chip using an imaging unit. The fluidic chip has an electrode that applies a dielectrophoretic force to the dielectric particles contained in a fluid injected into the fluidic chip. The imaging method includes a step of focusing the imaging unit on the electrode and a step of changing the focusing position of the imaging unit to a position a predetermined distance away from the position of the electrode in a first direction. The first direction is a direction along the optical axis of the imaging unit, and indicates a direction from the inner bottom surface toward the inner top surface of the fluidic chip.
[0008] In one aspect of the present invention, in the imaging method, it is preferable that in the step of focusing the imaging unit, the imaging unit is focused on a top surface of the electrode.
[0009] In one aspect of the present invention, in the imaging method, the predetermined distance preferably indicates a length equal to or less than the sum of a thickness of an insulating film covering the electrode and a size of the dielectric particle, and the size is preferably expressed in units of length.
[0010] In one aspect of the present invention, in the imaging method, the predetermined distance preferably indicates a length equal to or less than the size of the dielectric particle, and the size is preferably expressed in units of length.
[0011] In one aspect of the present invention, in the imaging method, it is preferable that in the step of focusing the imaging unit, the imaging unit is focused on a bottom surface of the electrode.
[0012] In one aspect of the present invention, in the imaging method, the predetermined distance preferably indicates a length equal to or less than the sum of the thickness of the electrode, the thickness of the insulating film covering the electrode, and the size of the dielectric particle, and the size is preferably expressed in units of length.
[0013] In one aspect of the present invention, in the imaging method, the predetermined distance preferably indicates a length equal to or less than the sum of the thickness of the electrode and the size of the dielectric particle, and the size is preferably expressed in units of length.
[0014] In one aspect of the present invention, in the imaging method, it is preferable that the imaging unit is disposed at a position spaced apart from the fluidic chip in the first direction.
[0015] In one aspect of the present invention, in the imaging method, it is preferable that the imaging unit is disposed at a position spaced apart from the fluidic chip in a second direction opposite to the first direction.
[0016] In one aspect of the present invention, in the imaging method, the imaging unit preferably includes an imaging element and an imaging optical system. In the step of focusing the imaging unit, the imaging unit is preferably focused on the electrode by moving the entire imaging unit under control of an imaging control device. In the step of changing the position at which the imaging unit is to be focused, the imaging unit is preferably changed by moving the entire imaging unit by the predetermined distance in the first direction under control of the imaging control device.
[0017] According to another aspect of the present invention, an imaging method includes imaging dielectric particles in a fluidic chip using an imaging unit. The fluidic chip has an electrode that applies a dielectrophoretic force to the dielectric particles contained in a fluid injected into the fluidic chip. The imaging method includes a step of focusing the imaging unit on the electrode, and a step of focusing the imaging unit on the electrode, changing the focusing position of the imaging unit after focusing the imaging unit on the electrode, and imaging the dielectric particles captured by the electrode using the imaging unit.
[0018] According to yet another aspect of the present invention, a distance determination method determines an altered distance when changing the focusing position of an imaging unit that images a dielectric particle in a fluidic chip after focusing the imaging unit on an electrode of the distance-determination fluidic chip, The distance determination method includes a step of focusing the imaging unit on an electrode of the distance-determination fluidic chip, a step of focusing the imaging unit on a dielectric particle captured by the electrode of the distance-determination fluidic chip, and a step of determining the altered distance based on imaging conditions when the imaging unit is focused on the electrode of the distance-determination fluidic chip and imaging conditions when the imaging unit is focused on the dielectric particle.
[0019] According to yet another aspect of the present invention, an imaging device images dielectric particles trapped by an electrode of a fluidic chip that has an electrode that applies a dielectrophoretic force to the dielectric particles in a fluid. The imaging device includes an imaging unit and an autofocus mechanism. The imaging unit images the dielectric particles. The autofocus mechanism focuses the imaging unit on the electrode. The autofocus mechanism changes the focusing position of the imaging unit to a position that is a predetermined distance away from the position of the electrode in a first direction. The first direction is a direction along the optical axis of the imaging unit and indicates a direction from the inner bottom surface toward the inner top surface of the fluidic chip. [Effects of the Invention]
[0020] According to the present invention, highly reliable imaging results can be obtained regardless of the quantity and presence of subjects. [Brief explanation of the drawings]
[0021] [Figure 1] 1 is a diagram illustrating an inspection system according to an embodiment of the present invention. [Figure 2] 1A is a plan view showing the fluidic chip according to the present embodiment, and FIG. 1B is a cross-sectional view taken along line IIB-IIB in FIG. [Figure 3] 1A is a plan view showing a cover member of the fluidic chip according to the present embodiment, FIG. 1B is a plan view showing a spacer member of the fluidic chip according to the present embodiment, and FIG. 1C is a plan view showing an electrode member of the fluidic chip according to the present embodiment. [Figure 4] FIG. 2 is an enlarged plan view showing an electrode group of the fluidic chip according to the embodiment. [Figure 5] 5(a) to 5(c) are schematic cross-sectional views showing an imaging method according to the present embodiment. [Figure 6] 10 is a flowchart illustrating an example of an imaging method according to the present embodiment. [Figure 7] 5A to 5C are schematic cross-sectional views for explaining a distance determination method according to the present embodiment. [Figure 8] 10 is a flowchart illustrating an example of a distance determination method according to the present embodiment. [Figure 9] 10 is a flowchart showing an imaging method using an inspection system according to a first modified example of the present embodiment. [Figure 10] 10 is a flowchart showing a distance determination method using an inspection system according to a first modification of the present embodiment. [Figure 11] 10(a) to 10(c) are schematic cross-sectional views showing an imaging method using an inspection system according to a second modified example of the present embodiment. [Figure 12] FIG. 10 is a schematic cross-sectional view for explaining a distance determination method using an inspection system according to a second modified example of the present embodiment. [Figure 13] FIG. 10 is a schematic cross-sectional view showing an imaging method using an inspection system according to a third modified example of the present embodiment. [Figure 14] FIG. 10 is a schematic cross-sectional view for explaining a distance determination method using an inspection system according to a third modified example of the present embodiment. [Figure 15]1A shows an image captured by an inspection system according to an embodiment of the present invention when the imaging unit is focused on the line electrode, and FIG. 1B shows an image captured by an inspection system according to an embodiment of the present invention when the imaging unit is focused on a position that is a predetermined distance away from the line electrode. DETAILED DESCRIPTION OF THE INVENTION
[0022] Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the drawings, identical or corresponding parts are designated by the same reference numerals, and description thereof will not be repeated. In addition, in this specification, mutually orthogonal X-axis, Y-axis, and Z-axis may be described to facilitate understanding of the invention. Typically, the X-axis and Y-axis are parallel to the horizontal direction, and the Z-axis is parallel to the vertical direction. In addition, in this specification, a planar view typically refers to viewing an object from the vertical direction.
[0023] An inspection system 1 according to an embodiment of the present invention will be described with reference to FIGS. 1 to 8. FIG. 1 is a diagram showing the inspection system 1 according to this embodiment. The inspection system 1 shown in FIG. 1 inspects dielectric particles by utilizing dielectrophoresis of the dielectric particles contained in a fluid 2. In this case, the fluid 2 is, for example, a liquid. The liquid is, for example, a specimen liquid (sample liquid). The dielectric particles are, for example, microorganisms, cells, proteins, or nucleic acids. The microorganisms are, for example, bacteria, fungi, or viruses.
[0024] As shown in Fig. 1, the inspection system 1 includes a dielectrophoresis device 3, a control device 5, an imaging control device 7, a waste chamber 9, a tester 11, a connection unit 23, and a connection unit 25. In Fig. 1, the fluid 2 is indicated by hatching. In the inspection system 1, the dielectrophoresis device 3 is controlled by the control device 5 and the imaging control device 7, and the state of the dielectric particles captured by the dielectrophoresis device 3 is displayed on the imaging control device 7.
[0025] The dielectrophoresis device 3 includes a pump unit 13, a power supply unit 15, an imaging device 17, and a fluid chip 19. The imaging device 17 and the imaging control device 7 constitute an imaging system 21.
[0026] The pump unit 13 is, for example, a syringe pump. As an example, the pump unit 13 includes a drive unit 130, a syringe 131, and a plunger unit 132. The drive unit 130 includes, for example, a motor. The drive unit 130 is controlled by the control device 5. The syringe 131 contains the fluid 2. The syringe 131 is connected to the fluid chip 19 by a connection unit 23. The connection unit 23 is, for example, a tube through which the fluid 2 flows. The plunger unit 132 includes, for example, a rod and a gasket. The plunger unit 132 is driven by the drive unit 130. As a result, the plunger unit 132 delivers the fluid 2 contained in the syringe 131 to the fluid chip 19 through the connection unit 23. In other words, the fluid 2 is injected from the pump unit 13 into the fluid chip 19. In this case, the flow rate and flow rate of the fluid 2 are set by the control device 5 controlling the drive unit 130.
[0027] The fluid chip 19 includes a flow channel 600 through which the fluid 2 flows, and an electrode group 700. The electrode group 700 has a size on the order of micrometers, for example. The fluid 2 delivered from the pump unit 13 flows through the flow channel 600 in the fluid chip 19 and is discharged to the waste chamber 9 through the connection unit 25. The connection unit 25 is, for example, a tube through which the fluid 2 flows. The electrode group 700 is disposed in the flow channel 600. In the fluid chip 19, while the fluid 2 flows over the electrode group 700 in the flow channel 600, an AC voltage is applied from the power supply unit 15 to the electrode group 700. As a result, dielectric particles contained in the fluid 2 undergo dielectrophoresis and are captured by the electrode group 700.
[0028] The power supply unit 15 includes, for example, a function generator. The power supply unit 15 generates an AC voltage and supplies the AC voltage to the electrode group 700 of the fluid chip 19. The frequency and amplitude of the AC voltage are controlled by the control device 5.
[0029] The imaging device 17 includes an autofocus mechanism 170 (hereinafter referred to as "AF mechanism 170") and an imaging section 171. The AF mechanism 170 is a mechanism that automatically focuses the imaging section 171 on a subject under the control of the imaging control device 7. In this embodiment, the AF mechanism 170 is controlled by the imaging control device 7 and moves the imaging section 171 along a predetermined direction. In this embodiment, the predetermined direction is the vertical direction. In other words, the predetermined direction is the up-down direction. The AF mechanism 170 includes, for example, a ball screw and a motor.
[0030] The imaging unit 171 captures an image of the dielectric particles in the fluid chip 19. The dielectric particles 4 are contained in the fluid 2 injected into the fluid chip 19. Specifically, the imaging unit 171 captures an image of the dielectric particles captured by the electrode group 700 of the fluid chip 19. The dielectric particles are the subject of the imaging unit 171. The imaging unit 171 generates a captured image including an image of the dielectric particles, and outputs the captured image to the imaging control device 7.
[0031] The imaging unit 171 includes an imaging element 172 and an imaging optical system 173. The imaging element 172 captures an image of the dielectric particles captured by the electrode group 700 in the fluid chip 19. The imaging element 172 is, for example, a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal-Oxide-Semiconductor) image sensor.
[0032] The imaging optical system 173 includes a plurality of lenses. The imaging optical system 173 includes, for example, an objective lens 174. The imaging optical system 173 is, for example, an optical microscope module. The optical microscope module is, for example, a phase-contrast microscope or an epi-illumination microscope. Furthermore, the optical microscope module may be switchable between a phase-contrast microscope and an epi-illumination microscope by, for example, lens exchange. Furthermore, when performing fluorescent observation in the optical microscope module, for example, a fluorescent filter is used.
[0033] The control device 5 controls the dielectrophoresis device 3. Specifically, the control device 5 controls the drive unit 130 of the pump unit 13 and the power supply unit 15. The control device 5 is, for example, a computer. The control device 5 includes a processor such as a CPU (Central Processing Unit) and an MPU (Micro Processing Unit), and a storage device.
[0034] The storage device stores data and computer programs. The storage device includes a primary storage device such as a semiconductor memory and a secondary storage device such as a semiconductor memory, a solid-state drive, and / or a hard disk drive. The storage device may also include removable media. The storage device may function as a non-transitory computer-readable storage medium.
[0035] The processor of the control device 5 controls the dielectrophoresis device 3 by executing a computer program stored in the storage device.
[0036] The imaging control device 7 controls the dielectrophoresis device 3. Specifically, the imaging control device 7 controls the imaging device 17. More specifically, the imaging control device 7 controls the AF mechanism 170 and the imaging unit 171. The imaging control device 7 also includes a display unit 71. The display unit 71 is a liquid crystal display or an organic electroluminescence display. The display unit 71 displays the captured image generated by the imaging unit 171. The imaging control device 7 can also analyze the captured image.
[0037] The imaging control device 7 is, for example, a computer. Similar to the control device 5, the imaging control device 7 includes a processor 72 and a storage device 73. The processor 72 of the imaging control device 7 controls the dielectrophoresis device 3 by executing a computer program stored in the storage device 73.
[0038] The waste liquid chamber 9 stores the fluid 2 that has flowed through the fluid chip 19 of the dielectrophoresis device 3. The waste liquid chamber 9 may be incorporated inside the dielectrophoresis device 3.
[0039] The tester 11 is, for example, a digital tester or an analog tester. The tester 11 is electrically connected to the electrode group 700 of the fluid chip 19 and measures at least one of a voltage, a current, and a resistance value. For example, the tester 11 measures the conductance or impedance of the electrode group 700. The tester 11 may be incorporated inside the dielectrophoresis device 3.
[0040] Next, the fluid chip 19 will be described with reference to FIGS. 2 to 4. FIG. 2(a) is a plan view showing the fluid chip 19. FIG. 2(b) is a cross-sectional view taken along line IIB-IIB in FIG. 2(a). As shown in FIG. 2(a), the fluid chip 19 has a generally rectangular, flat plate shape in plan view. Hereinafter, the longitudinal direction of the fluid chip 19 may be referred to as the chip longitudinal direction A1, the width direction as the chip width direction A2, and the thickness direction as the chip thickness direction A3. The chip longitudinal direction A1, the chip width direction A2, and the chip thickness direction A3 are perpendicular to one another. The chip longitudinal directions A1 and A2 are generally parallel to the horizontal direction, and the chip thickness direction A3 is generally parallel to the vertical direction.
[0041] The fluidic chip 19 includes a flow channel 600, an electrode group 700, a plurality of electrode pads 730, 731, 732, and 733, a plurality of test ports 740, 741, 742, and 743, a plurality of wirings 750, 751, 752, and 753, a plurality of wirings 760, 761, 762, and 763, a notch 80, a notch 90, an inlet 510, and an outlet 520. The plurality of electrode pads 730 to 733 are exposed from the notch 80. The plurality of test ports 740 to 743 are exposed from the notch 90. The electrode group 700 includes a first electrode portion 710 and a second electrode portion 720. Each of the first electrode portion 710 and the second electrode portion 720 exerts a dielectrophoretic force on dielectric particles contained in the fluid 2 injected into the fluidic chip 19.
[0042] 2(b), the fluid chip 19 includes a cover member 50, a spacer member 60, and an electrode member 70. The cover member 50, the spacer member 60, and the electrode member 70 are stacked in the chip thickness direction A3. The spacer member 60 is disposed between the cover member 50 and the electrode member 70.
[0043] The flow channel 600 is surrounded by the cover member 50, the spacer member 60, and the electrode member 70. Specifically, the spacer member 60 defines the flow channel 600 between the cover member 50 and the electrode member 70. The spacer member 60 is bonded to the cover member 50 and the electrode member 70, and the height h1 of the flow channel 600 is determined by the thickness of the spacer member 60. The height h1 is, for example, 100 μm.
[0044] Fig. 3(a) is a plan view showing a cover member 50 of the fluidic chip 19. Fig. 3(b) is a plan view showing a spacer member 60 of the fluidic chip 19. Fig. 3(c) is a plan view showing an electrode member 70 of the fluidic chip 19.
[0045] As shown in FIGS. 2(b) and 3(a), the cover member 50 covers the flow path 600 in the fluid chip 19. The cover member 50 has a substantially flat plate shape. The cover member 50 is, for example, a transparent acrylic plate. The inlet 510 and the outlet 520 are through-holes that penetrate the cover member 50. The inlet 510 and the syringe 131 (FIG. 1) are connected by a connection part 23 (FIG. 1). The inlet 510 communicates with the flow path 600 (FIG. 2(a)). The outlet 520 and the waste chamber 9 (FIG. 1) are connected by a connection part 25 (FIG. 1). The outlet 520 communicates with the flow path 600. The cover member 50 also includes a notch 810 and a notch 910.
[0046] As shown in FIGS. 2(b) and 3(b), the spacer member 60 has a slot 610 extending in the chip longitudinal direction A1. The slot 610 penetrates the spacer member 60. The slot 610 defines the shape of the flow path 600. The spacer member 60 has a generally flat plate shape. The spacer member 60 is, for example, a transparent PET (polyethylene terephthalate) tape. The spacer member 60 also includes a notch 820 and a notch 920. The notch 820 of the spacer member 60 and the notch 810 of the cover member 50 overlap in the chip thickness direction A3, forming a notch portion 80. The notch 920 of the spacer member 60 and the notch 910 of the cover member 50 overlap in the chip thickness direction A3, forming a notch portion 90.
[0047] Furthermore, the flow path 600 includes a first flow path 611, a narrow path 612, and a second flow path 613. The width of the narrow path 612 is smaller than the widths of the first flow path 611 and the second flow path 613. The width indicates the length in the chip width direction A2.
[0048] 3(c), the electrode member 70 includes a substrate 705. The substrate 705 is, for example, a transparent glass substrate. On the upper surface of the substrate 705, an electrode group 700, electrode pads 730 to 733, test ports 740 to 743, wirings 750 to 753, and wirings 760 to 763 are provided.
[0049] The electrode group 700 is made of a conductive material. The electrode group 700 is formed of a metal material such as chromium by, for example, vapor deposition or sputtering. The electrode group 700 may be formed in a single-layer structure or a multi-layer structure. The same applies to the electrode pads 730-733, test ports 740-743, wiring 750-753, and wiring 760-763. For example, the color of the electrode group 700, electrode pads 730-733, test ports 740-743, wiring 750-753, and wiring 760-763 is black.
[0050] Specifically, in the electrode group 700, the first electrode section 710 and the second electrode section 720 are arranged along the chip longitudinal direction A1. The second electrode section 720 is arranged downstream of the first electrode section 710 in the flow of the fluid 2. In other words, the second electrode section 720 is arranged downstream of the first electrode section 710 in the flow path 600.
[0051] Returning to FIG. 2(a), the roles of the first electrode unit 710 and the second electrode unit 720 will be explained. First, the power supply unit 15 applies an AC voltage to the first electrode unit 710. Therefore, a dielectrophoretic force acts on the dielectric particles to be inspected, among the various particles contained in the fluid 2. As a result, the first electrode unit 710 separates the dielectric particles to be inspected from the particles not to be inspected, among the various particles contained in the fluid 2, and captures the dielectric particles to be inspected. Note that in this case, the power supply unit 15 does not apply an AC voltage to the second electrode unit 720.
[0052] Next, the power supply unit 15 stops applying the AC voltage to the first electrode unit 710 and applies the AC voltage to the second electrode unit 720. Therefore, the dielectric particles to be inspected captured by the first electrode unit 710 flow toward the second electrode unit 720, and a dielectrophoretic force acts on the dielectric particles to be inspected at the second electrode unit 720. As a result, the second electrode unit 720 captures the dielectric particles to be inspected. Then, the imaging device 17 captures an image of the dielectric particles to be inspected captured by the second electrode unit 720.
[0053] As explained above with reference to Figure 2(a), the first electrode section 710 is an electrode for separating the dielectric particles to be inspected, and the second electrode section 720 is an electrode for imaging the dielectric particles to be inspected.
[0054] 4 is an enlarged plan view of the electrode group 700 of the fluid chip 19. As shown in FIG. 4, the second electrode portion 720 of the electrode group 700 is disposed corresponding to the narrow passage 612 and crosses the narrow passage 612. The second electrode portion 720 includes a pair of second pattern electrodes 721, 723.
[0055] As shown in FIGS. 3(c) and 4, the second pattern electrode 721 is connected to an electrode pad 733 by a wiring 753. The second pattern electrode 721 is connected to a test port 743 by a wiring 763. The second pattern electrode 721 has a comb-like shape. Specifically, the second pattern electrode 721 has a plurality of line electrodes 722. Each of the plurality of line electrodes 722 extends in the chip width direction A2. The plurality of line electrodes 722 are arranged at intervals in the chip longitudinal direction A1. The line electrodes 722 cross the flow channel 600 (narrow passage 612) in the chip width direction A2. In a plan view, the line electrodes 722 intersect with the flow channel 600 (narrow passage 612). For example, in a plan view, the line electrodes 722 are approximately perpendicular to the flow channel 600 (narrow passage 612).
[0056] The second pattern electrode 723 is connected to the electrode pad 732 by a wiring 752. The second pattern electrode 723 is connected to the test port 742 by a wiring 762. The second pattern electrode 723 has a comb-like shape. Specifically, the second pattern electrode 723 has a plurality of line electrodes 724. Each of the plurality of line electrodes 724 extends in the chip width direction A2. The plurality of line electrodes 724 are arranged at intervals in the chip longitudinal direction A1. The line electrodes 724 cross the flow channel 600 (narrow passage 612) in the chip width direction A2. In a plan view, the line electrodes 724 intersect with the flow channel 600 (narrow passage 612). For example, in a plan view, the line electrodes 724 are approximately perpendicular to the flow channel 600 (narrow passage 612).
[0057] The line electrodes 722 and the line electrodes 724 are alternately arranged along the chip longitudinal direction A1 at intervals in the chip longitudinal direction A1.
[0058] Next, the operation of the second electrode unit 720 will be described with reference to Figures 1, 2(a), and 4. The power supply unit 15 applies an AC voltage according to the type of dielectric particles to be inspected to the second electrode unit 720 (second pattern electrodes 721, 723) via the electrode pads 732 and 733. The AC voltage according to the type of dielectric particles is, for example, a frequency that generates an electric field that specifically applies a dielectrophoretic force (attractive force) to the dielectric particles to be inspected, and is a voltage of a magnitude that does not destroy the dielectric particles.
[0059] Specifically, the frequency of the AC voltage is set so that a positive dielectrophoretic force (attractive force) acts on the dielectric particles to be inspected by the electric field between the second pattern electrode 721 and the second pattern electrode 723. Therefore, a positive dielectrophoretic force acts on the dielectric particles, and the dielectric particles are attracted to the line electrodes 722, 724. In other words, the dielectric particles to be inspected contained in the fluid 2 are captured by the line electrodes 722, 724. On the other hand, the frequency of the AC voltage is set so that the dielectrophoretic force does not act, or barely acts, on particles not to be inspected contained in the fluid 2.
[0060] Next, the first electrode unit 710 will be described with reference to Fig. 4. As shown in Fig. 4, the first electrode unit 710 is disposed in correspondence with the first flow path 611 and crosses the first flow path 611. The first electrode unit 710 includes a pair of first pattern electrodes 711, 713.
[0061] As shown in FIGS. 3(c) and 4, the first pattern electrode 711 is connected to an electrode pad 731 by a wiring 751. The first pattern electrode 711 is connected to a test port 741 by a wiring 761. The first pattern electrode 711 has a comb-like shape. Specifically, the first pattern electrode 711 has a plurality of line electrodes 712. Each of the plurality of line electrodes 712 extends in the chip width direction A2. The plurality of line electrodes 712 are arranged at intervals in the chip longitudinal direction A1. The line electrodes 712 cross the flow channel 600 (first flow channel 611) in the chip width direction A2. In a plan view, the line electrodes 712 intersect with the flow channel 600 (first flow channel 611). For example, in a plan view, the line electrodes 712 are approximately perpendicular to the flow channel 600 (first flow channel 611).
[0062] The first pattern electrode 713 is connected to the electrode pad 730 by a wiring 750. The first pattern electrode 713 is connected to the test port 740 by a wiring 760. The first pattern electrode 713 has a comb-like shape. Specifically, the first pattern electrode 713 has a plurality of line electrodes 714. Each of the plurality of line electrodes 714 extends in the chip width direction A2. The plurality of line electrodes 714 are arranged at intervals in the chip longitudinal direction A1. The line electrodes 714 cross the flow channel 600 (first flow channel 611) in the chip width direction A2. In a plan view, the line electrodes 714 intersect with the flow channel 600 (first flow channel 611). For example, in a plan view, the line electrodes 714 are approximately perpendicular to the flow channel 600 (first flow channel 611).
[0063] The line electrodes 712 and the line electrodes 714 are alternately arranged along the chip longitudinal direction A1 at intervals in the chip longitudinal direction A1.
[0064] The operation of the first electrode unit 710 is the same as that of the second electrode unit 720. That is, the power supply unit 15 applies an AC voltage according to the type of dielectric particles to be inspected to the first electrode unit 710 (first pattern electrodes 711, 713) via the electrode pads 730, 731. The AC voltage applied to the first electrode unit 710 is the same as the AC voltage applied to the second electrode unit 720. Therefore, a positive dielectrophoretic force acts on the dielectric particles to be inspected, and the dielectric particles contained in the fluid 2 are attracted to the line electrodes 712, 714. On the other hand, particles not to be inspected that are contained in the fluid 2 pass through the line electrodes 712, 714.
[0065] The total number of line electrodes 722, 724 in the second electrode unit 720 is smaller than the total number of line electrodes 712, 714 in the first electrode unit 710. Furthermore, the line width of each of the line electrodes 712, 714, 722, 724 is, for example, 100 μm, and the thickness of each of the line electrodes 712, 714, 722, 724 is, for example, 1 μm. The line width indicates the length in the chip longitudinal direction A1, and the thickness indicates the length in the chip thickness direction A3.
[0066] Hereinafter, when it is not necessary to distinguish between the line electrode 722 and the line electrode 724, the line electrodes 722 and 724 may be collectively referred to as "line electrode 725." The imaging device 17 captures an image of the dielectric particles captured by the line electrode 725. Furthermore, when it is not necessary to distinguish between the line electrode 712 and the line electrode 714, the line electrodes 712 and 714 may be collectively referred to as "line electrode 715." The line electrodes 715 and 725 apply a dielectrophoretic force to the dielectric particles contained in the fluid 2 injected into the fluid chip 19.
[0067] The line electrode 725 corresponds to an example of the "electrode" of the present invention.
[0068] Next, an imaging method according to this embodiment will be described with reference to Fig. 1 and Fig. 5. In this imaging method, an image of dielectric particles 4 contained in a fluid 2 in a fluid chip 19 is captured by an imaging unit 171. The imaging method is performed by an imaging system 21. Figs. 5(a) to 5(c) are schematic cross-sectional views showing the imaging method according to this embodiment. Figs. 5(a) to 5(c) show a cross section of the fluid chip 19 taken along line VV in Fig. 4.
[0069] 5(a), the fluid chip 19 has a flow channel 600 between the cover member 50 and the electrode member 70. The line electrode 725 of the electrode member 70 is exposed in the flow channel 600.
[0070] 5(a) to 5(c), the imaging method includes steps S101 to S103. In steps S101 to S103, the position of the fluid chip 19 is fixed in each of the chip longitudinal direction A1, the chip width direction A2, and the chip thickness direction A3.
[0071] As shown in FIGS. 1 and 5(a), first, in step S101, the AF mechanism 170 focuses the imaging unit 171 on the line electrode 725 under the control of the imaging control device 7. In this embodiment, the AF mechanism 170 drives the imaging unit 171 under the control of the imaging control device 7, thereby focusing the imaging unit 171 on the line electrode 725. Specifically, the AF mechanism 170 moves the entire imaging unit 171 (the image sensor 172 and the imaging optical system 173) in the first direction D1 or the second direction D2, thereby focusing the imaging unit 171 on the line electrode 725. Therefore, compared to when a focusing operation is performed by adjusting the imaging optical system 173, a focusing operation can be performed with a simple configuration and control.
[0072] The first direction D1 is a direction along the optical axis AX of the imaging unit 171 (imaging optical system 173) and indicates the direction from the inner bottom surface 601 to the inner top surface 602 of the fluid chip 19. The inner bottom surface 601 indicates the bottom surface of the flow channel 600. The inner top surface 602 indicates the top surface of the flow channel 600. The second direction D2 indicates the direction opposite to the first direction D1. The first direction D1 and the second direction D2 are approximately parallel to the chip thickness direction A3.
[0073] In step S101, the AF mechanism 170 preferably focuses the imaging unit 171 on the top surface 726 of the line electrode 725. That is, the AF mechanism 170 focuses the imaging unit 171 on a position F1 in the chip thickness direction A3. Position F1 indicates the position of the top surface 726 of the line electrode 725 in the chip thickness direction A3. According to this preferred example, it is easy to focus the imaging unit 171 on the line electrode 725 when the imaging unit 171 is disposed at a position spaced apart from the fluidic chip 19 in the first direction D1. The AF mechanism 170 may also focus the imaging unit 171 on an edge portion 8 of the line electrode 725. The edge portion 8 is part of the top surface 726.
[0074] Next, as shown in FIGS. 1 and 5(b), in step S102, the AF mechanism 170, under the control of the imaging control device 7, changes the position at which the imaging unit 171 is focused to position F2, which is a predetermined distance dz away from position F1 of the line electrode 725 in the first direction D1. Position F2 indicates a position in the chip thickness direction A3. Position F2 indicates the position at which the imaging unit 171 is predicted to focus on the dielectric particle 4 when the dielectric particle 4 (FIG. 5(c)) is captured on the line electrode 725. The predetermined distance dz is stored in advance in the storage device 73 of the imaging control device 7.
[0075] In this embodiment, the AF mechanism 170, under the control of the imaging control device 7, drives the imaging unit 171 to change the position at which the imaging unit 171 is focused from position F1 of the line electrode 725 to position F2 that is a predetermined distance dz away in the first direction D1. Specifically, the AF mechanism 170 changes the position at which the imaging unit 171 is focused from position F1 to position F2 by moving the entire imaging unit 171 (the image sensor 172 and the imaging optical system 173) the predetermined distance dz in the first direction D1. Therefore, compared to changing the position at which the imaging unit 171 is focused by adjusting the imaging optical system 173, the position at which the imaging unit 171 is focused can be changed with a simpler configuration and control.
[0076] Next, as shown in FIG. 1 and FIG. 5(c), in step S103, the imaging unit 171, under the control of the imaging control device 7, images the dielectric particles 4 captured by the line electrode 725. In this case, an AC voltage is applied to the line electrode 725 by the power supply unit 15. The dielectric particles 4 are contained in the fluid 2 flowing through the flow path 600.
[0077] 5, according to this embodiment, before capturing an image of the dielectric particle 4, the position on which the imaging unit 171 is focused is changed to position F2, which is a predetermined distance dz away from position F1 on the line electrode 725 (step S102). Therefore, by setting the predetermined distance dz in advance in accordance with the size of the dielectric particle 4, when the dielectric particle 4 is captured by the line electrode 725, it is possible to immediately focus the imaging unit 171 on the dielectric particle 4 without performing a focusing operation on the dielectric particle 4 after capture (step S103).
[0078] Furthermore, according to this embodiment, as long as the same type of dielectric particles 4 are the test objects, the predetermined distance dz is set to be the same in multiple fluid chips 19. This is because the sizes of the same type of dielectric particles 4 are approximately the same, and the tendency of the capture locations of the same type of dielectric particles 4 by the line electrode 725 is common in multiple fluid chips 19. In this way, the same imaging conditions (focusing conditions) can be set in multiple fluid chips 19. Therefore, the reliability of the imaging results can be improved in multiple fluid chips 19. As a result, when the same type of dielectric particles 4 are the test objects, the reliability of the inspection of the dielectric particles 4 in multiple fluid chips 19 can be improved.
[0079] For example, when the dielectric particles 4 to be inspected are present in the fluid 2 of each fluid chip 19 in an amount sufficient to enable focus, imaging is performed under the same imaging conditions (focusing conditions) for the multiple fluid chips 19. This allows for more reproducible and stable imaging results to be obtained for the multiple fluid chips 19 compared to a typical imaging method. In other words, more reliable imaging results can be obtained. Note that, in a typical imaging method, for example, after the dielectric particles 4 are captured on the line electrode 725, an operator manually performs a focusing operation on the dielectric particles 4 for each fluid chip 19. In this case, the imaging results may depend on the operator's level of skill or the working environment. Also, in a typical imaging method, for example, after the dielectric particles 4 are captured on the line electrode 725, a typical autofocus mechanism automatically performs a focusing operation on the dielectric particles 4 for each fluid chip 19. Even in this case, the imaging results may depend on the operation of the typical autofocus mechanism for each fluid chip 19.
[0080] For example, in a typical imaging method, if the dielectric particles 4 to be inspected are substantially absent in the fluid 2, an image focused on the dielectric particles 4 cannot be obtained. The case of substantial absence means that the dielectric particles 4 to be inspected are very few in the fluid 2 or are not present in the fluid 2. However, in this embodiment, as long as the inspection targets are the same type of dielectric particles 4, even in such a case, imaging is performed under the same imaging conditions (focusing conditions) as those for the fluid chip 19 into which the fluid 2 containing the dielectric particles 4 to be inspected is injected, in which an amount of the dielectric particles 4 to be inspected that allows focus is present. Therefore, highly reliable imaging results can be obtained. As a result, the reliability of determining that the dielectric particles 4 to be inspected are substantially absent in the fluid 2 can be improved.
[0081] As a result of the above, in this embodiment, the imaging device 17 can obtain highly reliable imaging results regardless of the amount and presence of the dielectric particles 4 that are the subject.
[0082] Furthermore, according to this embodiment, by setting a predetermined distance dz corresponding to each of the different types of dielectric particles 4, it is possible to obtain highly reliable imaging results according to the type of dielectric particles 4, regardless of the amount or presence or absence of the dielectric particles 4 that are the subject. In this case, the storage device 73 of the imaging control device 7 stores the predetermined distance dz for each type of dielectric particles 4.
[0083] Furthermore, in this embodiment, for example, the dielectric particles 4 are captured on the top surface 726 of the line electrode 725. Typically, the dielectric particles 4 are captured on the edge portion 8 of the line electrode 725. This point has been verified by the inventors of the present application. The predetermined distance dz in step S102 is greater than zero and indicates a length equal to or less than the size of the dielectric particles 4. Therefore, when the imaging unit 171 is focused on the top surface 726 of the line electrode 725 in step S101, it is possible to reliably obtain an image focused on the dielectric particles 4 in step S103.
[0084] The predetermined distance dz can be determined based on the size of the dielectric particle 4 to be inspected, obtained from, for example, literature such as academic papers and books, or a website. The predetermined distance dz is preferably an actual measurement value when an image of the dielectric particle 4 captured by the line electrode 725 is captured. A preferable example of this will be described later.
[0085] The size of the dielectric particle 4 is expressed in units of length. The length of which part of the dielectric particle 4 is defined as the "size of the dielectric particle 4" is determined depending on the shape of the dielectric particle 4 and the posture of the dielectric particle 4 captured by the line electrode 725. For example, if the dielectric particle 4 is spherical (e.g., cocci), the predetermined distance dz indicates a length that is equal to or shorter than the diameter of the dielectric particle 4. For example, if the dielectric particle 4 is rod-shaped or spiral-shaped (e.g., bacilli or spiral bacteria), the predetermined distance dz indicates a length that is equal to or shorter than the minor axis of the dielectric particle 4.
[0086] Furthermore, in this embodiment, the imaging unit 171 is disposed at a position separated in the first direction D1 from the fluid chip 19. Therefore, this is preferable when a space for disposing the imaging unit 171 can be secured above the fluid chip 19.
[0087] Next, an example of an imaging method according to this embodiment will be described with reference to Fig. 1, Fig. 5, and Fig. 6. Fig. 6 is a flowchart showing an example of the imaging method according to this embodiment. As shown in Fig. 6, the imaging method includes steps S1 to S3.
[0088] 1, 5(a), and 6, in step S1, the imaging device 17, under the control of the imaging control device 7, causes the AF mechanism 170 to focus the imaging section 171 on the line electrode 725 of the second electrode section 720. Otherwise, step S1 is the same as step S101 in FIG.
[0089] Next, as shown in Figures 1, 5(b), 5(c), and 6, in step S2, the imaging device 17, under the control of the imaging control device 7, focuses the imaging section 171 on the line electrode 725, and then (after step S1) changes the position at which the imaging section 171 is focused by the AF mechanism 170, and images the dielectric particles 4 captured by the line electrode 725 using the imaging section 171.
[0090] Next, step S3 is performed. Step S3 will be described later. After step S3 is performed, the imaging method ends.
[0091] As described above with reference to FIG. 6 , according to the imaging method of this embodiment, in step S1, prior to step S2, which includes a process of imaging the dielectric particles 4, the imaging unit 171 is focused on the line electrode 725 where the dielectric particles 4 are captured. Therefore, by previously setting a predetermined distance dz corresponding to the size of the dielectric particles 4, in step S2, before capturing the dielectric particles 4, the position at which the imaging unit 171 is focused can be changed to position F2, which is the predetermined distance dz away in the first direction D1 from position F1 on the line electrode 725. As a result, the imaging unit 171 can be immediately focused on the dielectric particles 4 after capturing the dielectric particles 4 without performing a focusing operation. Furthermore, the imaging method of this embodiment makes it possible to obtain highly reliable imaging results regardless of the amount and presence of the dielectric particles 4 that are the subject.
[0092] Next, step S2 will be described in detail with reference to Figures 1, 4, 5, and 6. As shown in Figure 6, step S2 includes steps S21 to S27.
[0093] First, as shown in Figures 1, 5(b) and 6, in step S21, the AF mechanism 170, under the control of the imaging control device 7, drives the imaging unit 171 to change the position at which the imaging unit 171 is focused from position F1 of the line electrode 725 of the second electrode unit 720 to position F2 that is a predetermined distance dz away in the first direction D1.
[0094] Next, as shown in FIGS. 1, 4 and 6, in step S22, the power supply unit 15, under the control of the control device 5, applies an AC voltage to the line electrode 715 of the first electrode unit 710 for a first predetermined period T1.
[0095] 1 and 6, in step S23, the pump unit 13, under the control of the control device 5, delivers the fluid 2 toward the flow path 600 at a first delivery rate while an AC voltage is being applied to the first electrode unit 710 (step S22). The first delivery rate is indicated by the flow rate at which the pump unit 13 delivers the fluid 2 per unit time. Specifically, under the control of the control device 5, the drive unit 130 drives the plunger unit 132 so as to deliver the fluid 2 from the syringe 131 toward the flow path 600 at the first delivery rate.
[0096] The pump unit 13 continues to discharge the fluid 2 at the first discharge speed (step S23) during the period in which the AC voltage is applied to the first electrode unit 710 (step S22). As a result, a positive dielectrophoretic force acts on the dielectric particles 4 (not shown in FIG. 4) flowing on the line electrode 715 of the first electrode unit 710 in FIG. 4, and the dielectric particles 4 continue to be captured by the line electrode 715.
[0097] 1, 4, and 6, in step S24, the power supply unit 15, under the control of the control device 5, stops applying AC voltage to the line electrode 715 of the first electrode unit 710 after a first predetermined period T1 has elapsed. As a result, the dielectric particles 4 (not shown in FIG. 4) captured by the line electrode 715 are released from the line electrode 715. The released dielectric particles 4 move from the first flow path 611 and the line electrode 715 toward the narrow path 612 and the line electrode 725 in accordance with the flow of the fluid 2.
[0098] Next, as shown in FIGS. 1 and 6 , in step S25, the pump unit 13, under the control of the control device 5, reduces the delivery rate of the fluid 2 from the first delivery rate to the second delivery rate. That is, the second delivery rate is smaller than the first delivery rate. The second delivery rate is represented by the flow rate at which the pump unit 13 delivers the fluid 2 per unit time. The reason for reducing the delivery rate of the fluid 2 is as follows. That is, because the width of the narrow passage 612 is narrower than the width of the first flow path 611, it is presumed that the flow rate of the fluid 2 in the narrow passage 612 is faster than the flow rate of the fluid 2 in the first flow path 611. Therefore, the delivery rate of the fluid 2 is reduced to make the flow rate of the fluid 2 in the narrow passage 612 approximately equal to the flow rate of the fluid 2 in the first flow path 611.
[0099] 1, 5(c), and 6, in step S26, under the control of the control device 5, the power supply unit 15 applies the same AC voltage as that in step S22 to the line electrode 725 of the second electrode unit 720 for a second predetermined period T2. As a result, a positive dielectrophoretic force acts on the dielectric particles 4 flowing on the line electrode 725 of the second electrode unit 720, causing the dielectric particles 4 to be captured by the line electrode 725. The pump unit 13 continues to deliver the fluid 2 at the second delivery rate (step S25) during the period in which the AC voltage is applied to the second electrode unit 720 (step S26).
[0100] Next, in step S27, the imaging unit 171, under the control of the imaging control device 7, images the dielectric particles 4 captured by the line electrode 725 of the second electrode unit 720. Then, the imaging unit 171 generates a captured image showing the imaging results of the dielectric particles 4, and outputs the captured image to the imaging control device 7. Then, the processing of step S2 (steps S21 to S27) is completed, and the processing proceeds to step S3.
[0101] Next, in step S3, the power supply unit 15, under the control of the control device 5, stops applying the AC voltage to the line electrode 725 of the second electrode unit 720 after the second predetermined period T2 has elapsed. Then, the imaging method ends.
[0102] Next, a distance determination method according to this embodiment will be described with reference to Figures 1 and 7. In the distance determination method, a change distance is determined when the position at which the imaging unit 171, which images the dielectric particles 4 in the fluid chip 19, is focused on the line electrode 725 of the fluid chip 19 and then changed. In this case, the change distance indicates the predetermined distance dz (Figure 5). Therefore, the distance determination method is a method for determining the predetermined distance dz used in the imaging method according to this embodiment (Figures 5 and 6). Hereinafter, in the description of the distance determination method, the change distance will be referred to as "change distance dz."
[0103] The distance determination method uses a fluid chip having the same configuration as the fluid chip 19 (FIGS. 1 to 5). Hereinafter, the fluid chip used in the distance determination method will be referred to as the "distance determination fluid chip 190." Because the configuration of the distance determination fluid chip 190 is the same as the configuration of the fluid chip 19, the components of the distance determination fluid chip 190 will be described using the same reference numerals as those used for the components of the fluid chip 19. Furthermore, in describing the distance determination fluid chip 190, the fluid chip 19 in FIGS. 1 to 5 will be described as the distance determination fluid chip 190.
[0104] Fig. 7 is a schematic cross-sectional view for explaining the distance determination method according to this embodiment. Fig. 7 shows an enlarged view of the line electrode 725 and its surroundings shown in Fig. 5(c). However, Fig. 7 shows a cross-section when the distance determination method is executed, not the imaging method of Fig. 5(c).
[0105] As shown in FIG. 7, in the distance determination method, the AF mechanism 170 moves the entire imaging unit 171 in a first direction D1 or a second direction D2, thereby focusing the imaging unit 171 on the line electrode 725. The rest of the process of focusing the imaging unit 171 on the line electrode 725 is the same as step S101 in FIG. 5(a) and step S1 in FIG. 6. The position of the imaging unit 171 when the imaging unit 171 is focused on the line electrode 725 is referred to as "position P1." In FIG. 7, as an example, the tip 175 of the objective lens 174 of the imaging unit 171 is defined as the position of the imaging unit 171. In the example of FIG. 7, the tip 175 is the lower end of the objective lens 174.
[0106] Furthermore, the AF mechanism 170 moves the entire imaging unit 171 by a first predetermined distance d1 in the first direction D1 from position P1 to position p1, thereby changing the position at which the imaging unit 171 is focused to position f1, which is the first predetermined distance d1 away from position F1 of the line electrode 725 in the first direction D1. Position F1 of the line electrode 725 indicates the position of the top surface 726 of the line electrode 725. Then, the imaging unit 171 performs imaging processing at position p1 and generates a captured image that indicates the result of the imaging processing. In other words, the captured image is an image obtained by focusing the imaging unit 171 on position f1. The imaging unit 171 outputs the captured image to the imaging control device 7.
[0107] The first predetermined distance d1 is set to a value smaller than the size of the dielectric particle 4. For example, in the example of FIG. 7, the first predetermined distance d1 is set to "1 / M" of the diameter D of the dielectric particle 4. M is, for example, an integer equal to or greater than 2. In the example of FIG. 7, M=7.
[0108] Furthermore, the AF mechanism 170 moves the entire imaging unit 171 in the first direction D1 from position p1 to position p2 by a first predetermined distance d1, thereby changing the position at which the imaging unit 171 is focused to position f2, which is away from position f1 by the first predetermined distance d1 in the first direction D1. Then, the imaging unit 171 performs imaging processing at position p2 and generates a captured image that shows the result of the imaging processing. In other words, the captured image is an image obtained by focusing the imaging unit 171 on position f2. The imaging unit 171 outputs the captured image to the imaging control device 7.
[0109] Thereafter, the AF mechanism 170 gradually moves the entire imaging unit 171 from position p2 to position p7 in the first direction D1 by the first predetermined distance d1 at a time, thereby gradually changing the position at which the imaging unit 171 is focused in the first direction D1 from position f2 to position f7 in a time step by step, by the first predetermined distance d1 at a time. The imaging unit 171 then performs imaging processing at each of positions p3 to p7 and generates captured images that show the results of the imaging processing. In other words, each captured image is an image obtained by focusing the imaging unit 171 at each of positions f3 to f7. The imaging unit 171 outputs each captured image to the imaging control device 7.
[0110] Next, the imaging control device 7 identifies an image in focus on the dielectric particles 4 from among a plurality of images (seven images in the example of FIG. 7) obtained by focusing the imaging unit 171 on positions f1 to f7. Then, the imaging control device 7 stores, as the changed distance dz, in the storage device 73, a distance dz from the position of the imaging unit 171 when the image in focus on the dielectric particles 4 was obtained (hereinafter referred to as "position pz") to position P1 of the imaging unit 171 when the imaging unit 171 is focused on the line electrode 725. In the example of FIG. 7, position pz is position p4.
[0111] In this embodiment, the change distance dz is the same as the distance dz from the position (hereinafter referred to as "position fz") at which the imaging unit 171 is focused when an image focused on the dielectric particle 4 is obtained to the position F1 of the line electrode 725. In the example of Fig. 7, the position fz is position f4.
[0112] Furthermore, the change distance dz is expressed by the absolute value of the difference between the first distance H1 and the second distance H2. The first distance H1 indicates the distance between the line electrode 725 (top surface 726) and the imaging unit 171 (tip 175) when the imaging unit 171 is focused on the line electrode 725. The second distance H2 indicates the distance between the line electrode 725 (top surface 726) and the imaging unit 171 (tip 175) when the imaging unit 171 is focused on the dielectric particle 4.
[0113] The positions P1, p1 to p7, F1, and f1 to f7 indicate positions in the chip thickness direction A3.
[0114] As described above with reference to FIG. 7 , according to this embodiment, the imaging unit 171 is focused on the line electrode 725 of the distance-determination fluidic chip 190. In addition, the imaging unit 171 is focused on the dielectric particle 4 captured on the line electrode 725. Then, the change distance dz is determined based on the imaging conditions when the imaging unit 171 is focused on the line electrode 725 (positions P1 and F1 in the example of FIG. 7 ) and the imaging conditions when the imaging unit 171 is focused on the dielectric particle 4 (positions p4 and f4 in the example of FIG. 7 ). As described above, in the distance determination method, the change distance dz (predetermined distance dz) used in the imaging method according to this embodiment (FIGS. 5 and 6 ) is determined based on the actual imaging result of the dielectric particle 4. In other words, the change distance dz is an actual measurement value when the dielectric particle 4 captured on the line electrode 725 is imaged. Therefore, compared to when the change distance dz is obtained from literature (e.g., academic papers or books) and websites, the imaging method according to this embodiment makes it possible to obtain a more focused image of the dielectric particles 4.
[0115] In this embodiment, the second predetermined distance d2 is set to be equal to or less than the size of the dielectric particle 4. In the example of FIG. 7, the second predetermined distance d2 is approximately equal to the diameter D of the dielectric particle 4. In this embodiment, the positions f1 to f7 at which the imaging unit 171 is focused are changed within a range within the second predetermined distance d2. In other words, the positions p1 to p7 to which the imaging unit 171 is moved are changed within a range within the second predetermined distance d2. Therefore, when executing the distance determination method, unnecessary execution of imaging processing can be prevented. Note that even if the imaging processing is executed by focusing the imaging unit 171 at a position spaced apart from the dielectric particle 4 in the first direction D1, the dielectric particle 4 will not be focused on.
[0116] Next, an example of a distance determination method according to this embodiment will be described with reference to Fig. 1, Fig. 7, and Fig. 8. Fig. 7 is a flowchart showing an example of a distance determination method according to this embodiment. As shown in Fig. 8, the distance determination method includes steps S31 to S33.
[0117] 1, 7, and 8, in step S31, the imaging device 17, under the control of the imaging control device 7, causes the AF mechanism 170 to focus the imaging section 171 on the line electrode 725 of the second electrode section 720. Otherwise, the processing in step S31 is the same as the processing in step S101 in FIG. 5 and step S1 in FIG. 6.
[0118] Next, in step S32, the imaging device 17 is controlled by the imaging control device 7 to cause the AF mechanism 170 to focus the imaging section 171 on the dielectric particles 4 captured by the line electrode 725 of the second electrode section 720.
[0119] Next, in step S33, the imaging control device 7 determines the changed distance dz based on the imaging conditions when the imaging unit 171 was focused on the line electrode 725 of the second electrode unit 720 in step S31 and the imaging conditions when the imaging unit 171 was focused on the dielectric particle 4 in step S32. The imaging control device 7 stores the changed distance dz in the storage device 73 as the predetermined distance dz to be used in the imaging method. Then, the distance determination method ends.
[0120] Next, step S32 will be described in detail with reference to Fig. 1, Fig. 7, and Fig. 8. As shown in Fig. 8, step S32 includes steps S321 to S330. Steps S321 to S325 are similar to steps S22 to S26 in Fig. 6, respectively.
[0121] As shown in Figures 1, 7, and 8, in step S326, the AF mechanism 170, under the control of the imaging control device 7, drives the imaging unit 171 to change the position at which the imaging unit 171 is focused to a position that is a first predetermined distance d1 away in the first direction D1.
[0122] Next, in step S327, the imaging unit 171 executes imaging processing and generates a captured image under the control of the imaging control device 7. The imaging unit 171 outputs the captured image to the imaging control device 7. The imaging control device 7 stores the captured image in the storage device 73.
[0123] Next, in step S328, the imaging control device 7 determines whether the movement distance of the imaging unit 171 relative to the position P1 of the imaging unit 171 when the imaging unit 171 is focused on the line electrode 725 of the second electrode unit 720 exceeds a second predetermined distance d2. The movement distance indicates the distance in the chip thickness direction A3.
[0124] If it is determined in step S328 that the movement distance does not exceed the second predetermined distance d2 (No), the process proceeds to step S326.
[0125] On the other hand, if it is determined in step S328 that the movement distance has exceeded the second predetermined distance d2 (Yes), the process proceeds to step S329. Therefore, steps S326 and S327 are repeated until it is determined in step S328 that the movement distance has exceeded the second predetermined distance d2.
[0126] Next, in step S329, the power supply unit 15, under the control of the control device 5, stops applying the AC voltage to the line electrode 725 of the second electrode unit 720.
[0127] Next, in step S330, the imaging control device 7 specifies a captured image in which the dielectric particles 4 are in focus from among the plurality of captured images obtained in step S327.
[0128] Next, in step S33, the imaging control device 7 determines the changed distance dz based on the imaging conditions in step S31 and the imaging conditions of the captured image (step S330) focused on the dielectric particles 4. Specifically, in step S33, the imaging control device 7 stores, as the changed distance dz, the distance dz from the position pz of the imaging unit 171 when the captured image focused on the dielectric particles 4 is obtained to the position P1 of the imaging unit 171 when the imaging unit 171 is focused on the line electrode 725 in the storage device 73. Then, the distance determination method ends.
[0129] (First Modification) An inspection system 1 according to a first modified example of this embodiment will be described with reference to Figures 1, 5, 7, 9, and 10. The first modified example differs from the embodiment described above with reference to Figures 6 and 8 mainly in that it does not use the first electrode unit 710. That is, in the first modified example, an AC voltage is not applied to the first electrode unit 710. Below, the differences between the first modified example and the embodiment will be mainly described.
[0130] 9 is a flowchart showing an imaging method using the inspection system 1 according to a first modified example of this embodiment. As shown in FIG. 9, the imaging method according to the first modified example includes steps S41 to S43. The imaging method according to the first modified example differs mainly from the imaging method described with reference to FIG. 6 in that the first electrode section 710 is not used. The following mainly describes the differences between the first modified example and the imaging method of FIG. 6.
[0131] First, step S41 is executed, which is the same as step S1 in FIG.
[0132] Next, as shown in Figures 1, 5(b), 5(c), and 9, in step S42, the imaging device 17, under the control of the imaging control device 7, focuses the imaging section 171 on the line electrode 725, and then (after step S41) changes the position on which the imaging section 171 is focused by the AF mechanism 170, and images the dielectric particles 4 captured by the line electrode 725 using the imaging section 171.
[0133] Next, step S43 is performed. Step S43 is similar to step S3 in Fig. 6. After step S3 is performed, the imaging method ends.
[0134] Next, step S42 will be described in detail with reference to Figures 1, 5, and 9. As shown in Figure 9, step S42 includes steps S421 to S424.
[0135] First, as shown in Figures 1, 5(b) and 9, in step S421, the AF mechanism 170, under the control of the imaging control device 7, drives the imaging unit 171 to change the position at which the imaging unit 171 is focused from position F1 of the line electrode 725 of the second electrode unit 720 to position F2 that is a predetermined distance dz away in the first direction D1.
[0136] Next, in step S422, under the control of the control device 5, the power supply unit 15 applies an AC voltage to the line electrode 725 of the second electrode unit 720 for a third predetermined period T3.
[0137] Next, in step S423, the pump unit 13, under the control of the control device 5, sends out the fluid 2 toward the flow path 600 at a third sending speed while an AC voltage is being applied to the second electrode unit 720 (step S422). As a result, a positive dielectrophoretic force acts on the dielectric particles 4 contained in the fluid 2 flowing over the line electrode 725 of the second electrode unit 720, and the dielectric particles 4 are captured by the line electrode 725. The third sending speed is indicated by the flow rate at which the pump unit 13 sends out the fluid 2 per unit time.
[0138] Next, as shown in Fig. 1, Fig. 5(c) and Fig. 9, in step S424, the imaging unit 171, under the control of the imaging control device 7, images the dielectric particles 4 captured by the line electrode 725 of the second electrode unit 720. Then, the imaging unit 171 generates a captured image showing the imaging results of the dielectric particles 4 and outputs the captured image to the imaging control device 7. Then, the processing of step S42 (steps S421 to S424) is completed, and the processing proceeds to step S43.
[0139] As described above with reference to FIG. 9, in the imaging method according to the first modified example, the first electrode section 710 is not used, but the second electrode section 720 is used.
[0140] Next, a distance determination method using the inspection system 1 according to the first modified example will be described with reference to FIGS. 1, 7, and 10. FIG. 10 is a flowchart showing the distance determination method according to the first modified example. As shown in FIG. 10, the distance determination method includes steps S51 to S53. The distance determination method according to the first modified example differs mainly from the distance determination method described with reference to FIG. 8 in that the first electrode unit 710 is not used. Below, the differences between the first modified example and the distance determination method of FIG. 8 will be mainly described.
[0141] First, step S51 is executed, which is the same as step S31 in FIG.
[0142] Next, in step S52, the imaging device 17 is controlled by the imaging control device 7 to cause the AF mechanism 170 to focus the imaging section 171 on the dielectric particles 4 captured by the line electrode 725 of the second electrode section 720.
[0143] Next, in step S53, the imaging control device 7 determines and stores the changed distance dz (predetermined distance dz) based on the imaging conditions when the imaging unit 171 was focused on the line electrode 725 of the second electrode unit 720 in step S51 and the imaging conditions when the imaging unit 171 was focused on the dielectric particle 4 in step S52. Then, the distance determination method ends.
[0144] Next, step S52 will be described in detail with reference to Fig. 1, Fig. 7, and Fig. 10. As shown in Fig. 10, step S52 includes steps S521 to S527. Steps S521 and S522 are similar to steps S422 and S423, respectively, in Fig. 9. Furthermore, steps S523 to S527 are similar to steps S325 to S330, respectively, in Fig. 8.
[0145] In step S53, the imaging control device 7 determines the changed distance dz based on the imaging conditions in step S51 and the imaging conditions of the captured image (step S527) focused on the dielectric particles 4. Otherwise, step S53 is the same as step S33 in Fig. 8. Then, the distance determination method ends.
[0146] As described above with reference to FIG. 10, in the distance determination method according to the first modification, the first electrode section 710 is not used, but the second electrode section 720 is used.
[0147] (Second Modification) 1, 11, and 12, an inspection system 1 according to a second modified example of the present embodiment will be described. The second modified example differs mainly from the above embodiment in that the imaging unit 171 is arranged below the fluid chip 19. Below, the differences between the second modified example and the above embodiment will be mainly described.
[0148] First, an imaging method according to the second modified example will be described with reference to Fig. 1 and Fig. 11. Below, differences between the imaging method according to the second modified example and the imaging method of Fig. 5 will be mainly described.
[0149] 11(a) to 11(c) are schematic cross-sectional views showing an imaging method using an inspection system 1 according to a second modified example of this embodiment. As shown in Fig. 11(a), the imaging unit 171 is disposed at a position spaced apart from the fluid chip 19 in a second direction D2 opposite to the first direction D1. Therefore, this is suitable when a space for disposing the imaging unit 171 can be secured below the fluid chip 19.
[0150] As shown in FIGS. 11(a) to 11(c), the imaging method according to the second modification includes steps S201 to S203.
[0151] 1 and 11(a), first, in step S201, the AF mechanism 170, under the control of the imaging control device 7, focuses the imaging section 171 on the line electrode 725. Specifically, the AF mechanism 170 moves the entire imaging section 171 (the imaging element 172 and the imaging optical system 173) in the first direction D1 or the second direction D2, thereby focusing the imaging section 171 on the line electrode 725. Otherwise, step S201 is similar to step S101 in FIG.
[0152] In step S201, the AF mechanism 170 preferably focuses the imaging unit 171 on the bottom surface 727 of the line electrode 725. That is, the AF mechanism 170 focuses the imaging unit 171 on a position F1 in the chip thickness direction A3. Position F1 indicates the position of the bottom surface 727 of the line electrode 725 in the chip thickness direction A3. According to this preferred example, it is easy to focus the imaging unit 171 on the line electrode 725 when the imaging unit 171 is disposed at a position spaced apart from the fluidic chip 19 in the second direction D2. The AF mechanism 170 may also focus the imaging unit 171 on an edge portion 12 of the line electrode 725. The edge portion 12 is part of the bottom surface 727.
[0153] 1 and 11(b), in step S202, the AF mechanism 170, under the control of the imaging control device 7, changes the position at which the imaging unit 171 is focused to a position F2 that is a predetermined distance dz away in the first direction D1 from the position F1 on the line electrode 725. Position F2 indicates the position at which the imaging unit 171 is predicted to focus on the dielectric particle 4 when the dielectric particle 4 (FIG. 11(c)) is captured by the line electrode 725.
[0154] Specifically, the AF mechanism 170 moves the entire imaging unit 171 (the imaging element 172 and the imaging optical system 173) a predetermined distance dz in the first direction D1, thereby changing the position at which the imaging unit 171 is focused from position F1 to position F2. Otherwise, step S202 is similar to step S102 in FIG. 5.
[0155] Next, as shown in FIGS. 1 and 11(c), in step S203, the imaging section 171, under the control of the imaging control device 7, captures an image of the dielectric particles 4 captured by the line electrode 725.
[0156] 11, according to the imaging method of the second modified example, in step S201, the imaging unit 171 is focused on the line electrode 725, in step S202 the position at which the imaging unit 171 is focused is changed to position F2 that is a predetermined distance dz away from position F1, and in step S203 an image of the dielectric particles 4 is captured. Therefore, according to the imaging method of the second modified example, similar to the imaging method of the above embodiment described with reference to Fig. 5, the imaging device 17 can obtain highly reliable imaging results regardless of the amount and presence or absence of the dielectric particles 4 that are the subject.
[0157] Furthermore, in the second modified example, for example, the dielectric particles 4 are captured on the top surface 726 of the line electrode 725. Typically, the dielectric particles 4 are captured on the edge portion 8 of the line electrode 725. The predetermined distance dz in step S202 is greater than the thickness d3 of the line electrode 725 and is equal to or less than the sum of the thickness d3 of the line electrode 725 and the size of the dielectric particles 4. Therefore, when the imaging unit 171 is focused on the bottom surface 727 of the line electrode 725 in step S201, it is possible to reliably obtain an image focused on the dielectric particles 4 in step S203. The thickness d3 of the line electrode 725 indicates the thickness of the line electrode 725 in the chip thickness direction A3.
[0158] The imaging method according to the second modified example can be shown by the flowchart of FIG. 6 or FIG.
[0159] Next, a distance determination method according to a second modified example will be described with reference to Fig. 1 and Fig. 12. Below, differences between the distance determination method according to the second modified example and the distance determination method in Fig. 7 will be mainly described. Fig. 12 is a schematic cross-sectional view for explaining a distance determination method that uses an inspection system 1 according to a second modified example of the present embodiment.
[0160] 1 and 12, in the distance determination method according to the second modification, the AF mechanism 170 moves the entire imaging unit 171 in the first direction D1 or the second direction D2, thereby focusing the imaging unit 171 on the line electrode 725. The position of the imaging unit 171 when the imaging unit 171 is focused on the line electrode 725 is referred to as "position P1." In FIG. 12, as an example, the tip 175 of the objective lens 174 of the imaging unit 171 is defined as the position of the imaging unit 171. In the example of FIG. 12, the tip 175 is the upper end of the objective lens 174.
[0161] Furthermore, the AF mechanism 170 moves the entire imaging unit 171 by a first predetermined distance d1 in the first direction D1 from position P1 to position p1, thereby changing the position at which the imaging unit 171 is focused to position f1, which is the first predetermined distance d1 away from position F1 of the line electrode 725 in the first direction D1. Position F1 of the line electrode 725 indicates the position of the bottom surface 727 of the line electrode 725. Then, the imaging unit 171 performs imaging processing at position p1 and generates a captured image that indicates the results of the imaging processing. In other words, the captured image is an image obtained by focusing the imaging unit 171 on position f1.
[0162] Thereafter, the AF mechanism 170 gradually moves the entire imaging unit 171 from position p1 to position p9 in the first direction D1 by the first predetermined distance d1 at a time, thereby gradually changing the position at which the imaging unit 171 is focused in the first direction D1 from position f1 to position f9 in a time step by step, by the first predetermined distance d1 at a time. The imaging unit 171 then performs imaging processing at each of positions p2 to p9 and generates captured images that indicate the results of the imaging processing. In other words, each captured image is an image obtained by focusing the imaging unit 171 at each of positions f2 to f9.
[0163] Next, the imaging control device 7 identifies an image in focus on the dielectric particle 4 from among a plurality of images (nine images in the example of FIG. 12) obtained by focusing the imaging unit 171 on positions f1 to f9. Then, the imaging control device 7 stores in the storage device 73, as the changed distance dz (predetermined distance dz), a distance dz from the position of the imaging unit 171 when the image in focus on the dielectric particle 4 was obtained (hereinafter referred to as "position pz") to position P1 of the imaging unit 171 when the imaging unit 171 is focused on the line electrode 725. In the example of FIG. 12, position pz is position p6.
[0164] In the second modified example, the change distance dz is represented by the absolute value of the difference between the first distance H1 and the second distance H2. The first distance H1 indicates the distance between the line electrode 725 (bottom surface 727) and the imaging unit 171 (tip 175) when the imaging unit 171 is focused on the line electrode 725. The second distance H2 indicates the distance between the line electrode 725 (bottom surface 727) and the imaging unit 171 (tip 175) when the imaging unit 171 is focused on the dielectric particle 4.
[0165] The distance determination method according to the second modified example can be shown by the flowchart of FIG. 8 or FIG.
[0166] 12, according to the second modified example, the changed distance dz (predetermined distance dz) is an actual measurement value when capturing an image of the dielectric particle 4 captured by the line electrode 725. Therefore, the imaging method according to the second modified example makes it possible to obtain a more focused image of the dielectric particle 4.
[0167] Here, in the second modified example, the second predetermined distance d2 is set to be equal to or less than the sum of the thickness d3 of the line electrode 725 and the size of the dielectric particle 4. In the example of FIG. 12, the second predetermined distance d2 is approximately equal to the sum of the thickness d3 of the line electrode 725 and the diameter D of the dielectric particle 4. In the second modified example, the positions f1 to f9 at which the imaging unit 171 is focused are changed within a range within the second predetermined distance d2. In other words, the positions p1 to p9 to which the imaging unit 171 is moved are changed within a range within the second predetermined distance d2. Therefore, when executing the distance determination method, it is possible to prevent unnecessary execution of imaging processing.
[0168] (Third Modification) 1, 13, and 14, an inspection system 1 according to a third modified example of the present embodiment will be described. The third modified example differs mainly from the above embodiment in that the electrode group 700 of the fluid chip 19 is covered with an insulating film. Below, the differences between the third modified example and the above embodiment will be mainly described.
[0169] First, an imaging method according to the third modified example will be described with reference to Fig. 1 and Fig. 13. Below, differences between the imaging method according to the third modified example and the imaging method of Fig. 5 will be mainly described.
[0170] 13(a) to 13(c) are schematic cross-sectional views showing an imaging method using an inspection system 1 according to a third modified example of this embodiment. As shown in FIGS. 13(a) to 13(c), the imaging method according to the third modified example includes steps S301 to S303. The fluid chip 19 also includes an insulating film 85. The line electrodes 725 are covered with the insulating film 85. The upper surface of the insulating film 85 faces the flow path 600. In the third modified example, the electrode group 700 in FIG. 3 is covered with the insulating film 85. The insulating film 85 is, for example, an oxide film or a nitride film. The oxide film is, for example, a silicon oxide film (SiOx). The nitride film is, for example, a silicon nitride film. The insulating film 85 is, for example, transparent.
[0171] 1 and 13(a), first, in step S301, the AF mechanism 170, under the control of the imaging control device 7, focuses the imaging unit 171 on the line electrode 725 covered with the insulating film 85. Otherwise, step S301 is the same as step S101 in FIG.
[0172] 1 and 13(b), in step S302, the AF mechanism 170, under the control of the imaging control device 7, changes the position at which the imaging unit 171 is focused to a position F2 that is a predetermined distance dz away in the first direction D1 from the position F1 of the line electrode 725. Otherwise, step S302 is the same as step S102 in FIG.
[0173] 1 and 13(c), in step S303, the imaging unit 171, under the control of the imaging control device 7, images the dielectric particles 4 captured on the line electrode 725 covered with the insulating film 85. In this case, the line electrode 725 captures the dielectric particles 4 via the insulating film 85.
[0174] Here, in the third modified example, for example, the dielectric particles 4 are trapped near the top surface 726 of the line electrode 725. Typically, the dielectric particles 4 are trapped near the edge portion 8 of the line electrode 725. This point has been verified by the inventors of the present application. The predetermined distance dz in step S302 is greater than the thickness d4 of the insulating film 85 and is equal to or less than the sum of the thickness d4 of the insulating film 85 and the size of the dielectric particles 4. Therefore, when the imaging unit 171 is focused on the top surface 726 of the line electrode 725 in step S301, it is possible to reliably obtain an image focused on the dielectric particles 4 in step S303.
[0175] The thickness d4 of the insulating film 85 indicates the thickness of the insulating film 85 in the chip thickness direction A3. The thickness d4 of the insulating film 85 also indicates the thickness of the insulating film 85 covering the top surface 726 of the line electrode 725. In other words, the thickness d4 indicates the thickness of the insulating film 85 on the top surface 726.
[0176] The imaging method according to the third modified example can be shown by the flowchart of FIG. 6 or FIG.
[0177] Next, a distance determination method according to a third modified example will be described with reference to Fig. 1 and Fig. 14. Below, differences between the distance determination method according to the third modified example and the distance determination method in Fig. 7 will be mainly described. Fig. 14 is a schematic cross-sectional view for explaining a distance determination method that uses an inspection system 1 according to a third modified example of the present embodiment.
[0178] As shown in FIG. 14, the distance determination method according to the third modification is the same as the distance determination method shown in FIG. 7, and therefore a description thereof will be omitted.
[0179] In the third modification, the second predetermined distance d2 is set to be equal to or less than the sum of the thickness d4 of the insulating film 85 and the size of the dielectric particles 4. In the example of FIG. 14, the second predetermined distance d2 is approximately equal to the sum of the thickness d4 of the insulating film 85 and the diameter D of the dielectric particles 4. In the third modification, the positions f1 to f8 at which the imaging unit 171 is focused are changed within a range within the second predetermined distance d2. In other words, the positions p1 to p8 to which the imaging unit 171 is moved are changed within a range within the second predetermined distance d2. Therefore, when the distance determination method is executed, unnecessary execution of imaging processing can be prevented.
[0180] The distance determination method according to the third modified example can be shown by the flowchart of FIG. 8 or FIG.
[0181] Next, the present invention will be described in detail based on examples, but the present invention is not limited to the following examples. [Example]
[0182] An embodiment of the present invention will be described with reference to Figures 1, 2, 9, 14, and 15. In the embodiment, the imaging method of Figure 9 was performed using the inspection system 1 of Figure 1 and the fluid chip 19 of Figure 2. The line electrode 725 of the fluid chip 19 was covered with an insulating film 85 (Figure 14). The fluid chip 19 was an ELESTA chip manufactured by AFI Technology. A 60x lens and a 0.5x lens barrel were used as the imaging optical system 173, and the experiment was performed at a total magnification of 30x. The dielectric particles 4 to be inspected were "C. albicans". The fluid 2 was ultrapure water.
[0183] 15(a) shows a captured image 200 obtained when the imaging unit 171 was focused on the line electrode 725 in the inspection system 1 according to the embodiment of the present invention. Specifically, the imaging unit 171 was driven by the AF mechanism 170 to focus the imaging unit 171 on the edge portion 8 of the line electrode 725 (step S41 in FIG. 9). As a result, a captured image 200 was obtained in which the edge portion 8 of the line electrode 725 was in focus. Note that even when "E. coli," "S. aureus," "B. subtilis," "B. cereus," "L. lactis," and "P. aeruginosa" were used as the dielectric particles 4, captured images in which the edge portion of the line electrode was in focus were obtained, similar to the case of "C. albicans."
[0184] FIG. 15(b) shows a captured image 210 obtained in the inspection system 1 according to the embodiment of the present invention, when the position where the imaging unit 171 is focused is changed to a position that is a predetermined distance dz away from the position of the line electrode 725. Specifically, the AF mechanism 170 drives the imaging unit 171, and the position where the imaging unit 171 is focused is changed to a position that is a predetermined distance dz away from the position of the line electrode 725 in the first direction D1 (step S421 in FIG. 9). The predetermined distance dz was 5 μm. Then, as a result of performing an imaging process using the imaging unit 171, a captured image 210 in which the dielectric particles 4 were focused was obtained. Note that even when "E. coli," "S. aureus," "B. subtilis," "B. cereus," "L. lactis," and "P. aeruginosa" were used as the dielectric particles 4, captured images in which the dielectric particles 4 were focused were obtained, similar to the case of "C. albicans."
[0185] The embodiments of the present invention have been described above with reference to the drawings. However, the present invention is not limited to the above embodiments and can be implemented in various forms without departing from the spirit of the present invention. Furthermore, the components disclosed in the above embodiments can be modified as appropriate. For example, some of the components shown in one embodiment may be added to the components of another embodiment, or some of the components shown in one embodiment may be deleted from the embodiment.
[0186] Furthermore, the drawings mainly show each component in a schematic manner to facilitate understanding of the invention, and the thickness, length, number, spacing, etc. of each component shown in the drawings may differ from the actual ones due to the convenience of creating the drawings. Furthermore, the configuration of each component shown in the above embodiment is merely an example and is not particularly limited, and it goes without saying that various modifications are possible within a range that does not substantially deviate from the effects of the present invention.
[0187] (1) In the imaging method according to the second modified example shown in FIG. 11, the fluid chip 19 shown in FIG. 13 having the insulating film 85 may be used as the fluid chip 19.
[0188] In this case, the predetermined distance dz in Figure 11 is greater than the sum of the thickness d3 of the line electrode 725 (Figure 14) and the thickness d4 of the insulating film 85 (Figure 14), and is less than the sum of the thickness d3 of the line electrode 725, the thickness d4 of the insulating film 85, and the size of the dielectric particle 4.
[0189] In the distance determination method according to the second modified example shown in FIG. 12, the distance determination fluidic chip 190 shown in FIG. 14 having the insulating film 85 may be used as the distance determination fluidic chip 190.
[0190] In this case, the second predetermined distance d2 in FIG. 12 is set to be equal to or less than the sum of the thickness d3 (FIG. 14) of the line electrode 725, the thickness d4 (FIG. 14) of the insulating film 85, and the size of the dielectric particles 4. As an example, the second predetermined distance d2 is approximately equal to the sum of the thickness d3 of the line electrode 725, the thickness d4 of the insulating film 85, and the diameter D of the dielectric particles 4. In this case, the position at which the imaging unit 171 is focused is changed within a range within the second predetermined distance d2. In other words, the position to which the imaging unit 171 is moved is changed within a range within the second predetermined distance d2.
[0191] 7, 8, 10, 12, and 14, and the distance determination method shown in (1) above, after focusing the imaging unit 171 on the line electrode 725, the imaging unit 171 may be moved a second predetermined distance d2 in the first direction D1 and stopped. Then, the imaging unit 171 may be moved in the second direction D2 by the first predetermined distance d1 at a time.
[0192] (3) Even when the imaging unit 171 is disposed above the fluid chip 19, the imaging unit 171 may be focused on the bottom surface 727 of the line electrode 725, rather than the top surface 726 of the line electrode 725. Also, even when the imaging unit 171 is disposed below the fluid chip 19, the imaging unit 171 may be focused on the top surface 726 of the line electrode 725, rather than the bottom surface 727 of the line electrode 725.
[0193] (4) The line electrodes 715 and 725 (FIG. 4) are generally perpendicular to the flow channel 600, but may be inclined with respect to the flow channel 600.
[0194] (5) The AF mechanism 170 focuses the imaging unit 171 on the line electrode 725 and changes the position where the imaging unit 171 is focused by moving the entire imaging unit 171 in the first direction D1 or the second direction D2. However, the AF mechanism 170 may focus the imaging unit 171 on the line electrode 725 and change the position where the imaging unit 171 is focused by adjusting the imaging optical system 173. In this case, the AF mechanism 170 may be incorporated into the imaging unit 171. Alternatively, the AF mechanism 170 may focus the imaging unit 171 on the line electrode 725 and change the position where the imaging unit 171 is focused by moving a stage on which the fluid chip 19 or the distance-determining fluid chip 190 is placed in the first direction D1 or the second direction D2. In this case, the position of the imaging unit 171 is fixed.
[0195] (6) The fluid chip 19 has a flow path 600. However, the fluid chip 19 may have a storage portion for storing the fluid 2 instead of the flow path 600. In this case, in the description of FIGS. 1 to 14, the flow path 600, the first flow path 611, the narrow path 612, and the second flow path 613 are appropriately read as storage portions. The flow path 600 and the storage portion can be collectively referred to as a "fluid receiving portion." The fluid receiving portion receives the fluid. [Industrial Applicability]
[0196] The present invention relates to an imaging method, a distance determination method, and an imaging device, and has industrial applicability. [Explanation of symbols]
[0197] 2 fluid 4. Dielectric particles 7. Imaging control device 17 Imaging device 19 Fluidic Chip 85 insulating film 170 Autofocus mechanism 171 Imaging unit 172 image sensor 173 Imaging Optical System 722, 724, 725 Line electrodes (electrodes)
Claims
1. An imaging method for imaging dielectric particles in a fluid chip by an imaging unit, comprising: the fluid chip has electrodes that apply a dielectrophoretic force to the dielectric particles contained in the fluid injected into the fluid chip; focusing the imaging unit on the electrode; changing the position at which the imaging unit is focused to a position spaced a predetermined distance in a first direction from the position of the electrode; Including, An imaging method, wherein the first direction is a direction along an optical axis of the imaging unit and indicates a direction from an inner bottom surface toward an inner top surface of the fluidic chip.
2. The imaging method according to claim 1 , wherein the step of focusing the imaging unit focuses the imaging unit on a top surface of the electrode.
3. the predetermined distance is equal to or less than the sum of the thickness of the insulating film covering the electrode and the size of the dielectric particles, The imaging method of claim 2 , wherein the size is expressed in units of length.
4. the predetermined distance indicates a length equal to or less than the size of the dielectric particle, The imaging method of claim 1 , wherein the size is expressed in units of length.
5. The imaging method according to claim 1 , wherein the step of focusing the imaging unit focuses the imaging unit on a bottom surface of the electrode.
6. the predetermined distance is equal to or less than the sum of the thickness of the electrode, the thickness of the insulating film covering the electrode, and the size of the dielectric particle; The imaging method of claim 5 , wherein the size is expressed in units of length.
7. the predetermined distance is equal to or less than the sum of the thickness of the electrode and the size of the dielectric particles, The imaging method of claim 5 , wherein the size is expressed in units of length.
8. The imaging method according to claim 1 , wherein the imaging unit is disposed at a position spaced apart from the fluidic chip in the first direction.
9. The imaging method according to claim 1 , wherein the imaging unit is disposed at a position spaced apart from the fluidic chip in a second direction opposite to the first direction.
10. the imaging unit includes an imaging element and an imaging optical system; In the step of focusing the imaging unit, the imaging unit is moved as a whole under the control of an imaging control device, thereby focusing the imaging unit on the electrode; 8. The imaging method according to claim 1, wherein in the step of changing the position at which the imaging unit is focused, the position at which the imaging unit is focused is changed by moving the entire imaging unit by the predetermined distance in the first direction under the control of the imaging control device.
11. An imaging method for imaging dielectric particles in a fluid chip by an imaging unit, comprising: the fluid chip has electrodes that apply a dielectrophoretic force to the dielectric particles contained in the fluid injected into the fluid chip; focusing the imaging unit on the electrode; a step of focusing the imaging unit on the electrode and then changing the position at which the imaging unit is focused, and capturing an image of the dielectric particles captured by the electrode by the imaging unit; An imaging method comprising:
12. 1. A distance determination method for determining a change distance when changing a position at which an imaging unit that captures an image of a dielectric particle in a fluid chip is focused on an electrode of the fluid chip, the method comprising: focusing the imaging unit on an electrode of a distance-determining fluidic chip; focusing the imaging unit on the dielectric particles captured by the electrodes of the distance-determining fluidic chip; determining the changed distance based on imaging conditions when the imaging unit is focused on the electrode of the distance-determination fluidic chip and imaging conditions when the imaging unit is focused on the dielectric particle; A distance determination method comprising:
13. 1. An imaging device for imaging dielectric particles captured by electrodes of a fluid chip that has electrodes that apply a dielectrophoretic force to dielectric particles in a fluid, the imaging device comprising: an imaging unit that images the dielectric particles; an autofocus mechanism that focuses the imaging unit on the electrode; Equipped with the autofocus mechanism changes a position at which the imaging unit is focused to a position that is a predetermined distance away from the position of the electrode in a first direction; The first direction is a direction along an optical axis of the imaging unit, and indicates a direction from an inner bottom surface toward an inner top surface of the fluid chip.
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System for operating a microfluidic device
JP2023500623A