Fluid flow devices

Abstract

To provide a technique of easily testing the conduction of an electrode even with no liquid in a flow passage device.SOLUTION: A flow passage device 1 includes: a measurement container 2 having a measurement chamber 100 as a flow passage inside; a porous film 30 located in the measurement chamber 100, the porous film being capable of supporting a cell tissue 9 and transmitting liquid; an upper action electrode 61 and an upper reference electrode 71 located upward away from the porous film 30; and a lower action electrode 63 and a lower reference electrode 73 located downward away from the porous film 30. The upper action electrode 61 includes: an upper first action part 611 and an upper second action part 612 vertically overlapping with the measurement chamber 100; and a first conductive pad part 616 and second conductive pad parts 617 and 618 exposed to the outside of the measurement container 2.SELECTED DRAWING: Figure 3

Description

Technical Field

[0001] The present invention relates to a channel device applicable to electrical resistance measurement of cell tissues. Background Art

[0002] Trans-epithelial electrical resistance (TEER) measurement is known as a method for evaluating the barrier function of a cell layer forming a membrane structure. In TEER measurement, a bottomed cylindrical insert whose bottom surface is formed of a porous membrane is disposed in a recess of a culture plate, and cells are cultured on the porous membrane. Further, a working electrode for applying an electric current and a reference electrode for measuring a potential difference are disposed inside and outside the insert. Then, the electrical resistance of the cell layer is calculated by measuring the potential difference generated between the reference electrodes while applying an electric current between the working electrodes.

[0003] For example, Patent Document 1 describes that electrical resistance is measured by inserting electrodes (10A, 10B) from one side into and out of a culture insert dish (21). However, when inserting electrodes from one side, it is necessary to open the upper portion of the culture insert dish (21). Therefore, it is difficult to apply the method of Patent Document 1 to a device that does not have such an upper opening.

[0004] On the other hand, Non-Patent Document 1 describes a channel device in which an electrode is disposed on a lid portion that closes the upper opening of a culture container. By disposing the electrode on the lid portion in this manner, the electrical resistance of a cell layer cultured in a measurement chamber can be measured. Prior Art Documents Patent Documents

[0005] Patent Document 1 Japanese Unexamined Patent Publication No. 2005-137307 Non-Patent Documents

[0006] Non-Patent Document 1 Booth R, Kim H. Characterization of a microfluidic in vitro model of the blood-brain barrier (mu BBB) Lab Chip. 2012 Apr. 24;12(10):1784-92. [Overview of the project] [Problems that the invention aims to solve]

[0007] However, with conventional fluidic devices, it is necessary to introduce liquid into the fluid channel to check the conductivity of the electrodes. Therefore, it has been structurally extremely difficult to detect conductivity problems such as broken electrodes without introducing liquid.

[0008] The object of the present invention is to provide a technology that allows for easy inspection of electrode conductivity in a flow channel device, even when no liquid is present. [Means for solving the problem]

[0009] To solve the above problems, the first embodiment provides a flow channel device applicable to measuring the electrical resistance of cell tissue, comprising: a measuring container having a measuring chamber which is a flow channel inside; a porous membrane located in the measuring chamber which is capable of supporting cell tissue and which is permeable to liquid; and a first electrode and a second electrode located away from the porous membrane in one of the first directions. 、 The system comprises a third electrode and a fourth electrode located away from the porous membrane in the other direction of the first direction, wherein the first electrode overlaps the measurement chamber in the first direction. and extending in a second direction intersecting the first direction It has a measuring electrode section and a first conductive pad section and a second conductive pad section that are exposed outside the measuring container, and the first conductive pad section It is electrically connected to one side of the second direction in the measuring electrode portion, The second conductive pad portion This is connected to the other end in the second direction of the measuring electrode portion. .

[0010] The second aspect is a flow channel device according to the first aspect. ,before The second conductive pad portion is located away from the first conductive pad portion in the second direction.

[0011] In a third aspect, the flow path device according to the second aspect is provided, wherein the second conductive pad portion is connected to an end portion of the measurement electrode portion in the second direction.

[0012] In a fourth aspect, the flow path device according to any one of the first to third aspects is provided, The first electrode is, further comprising a conductive portion positioned within the measurement container and extending in the first direction, implied , wherein the first conductive pad portion is connected to the Measuring electrode part via the conductive portion.

[0013] In a fifth aspect, the flow path device according to the fourth aspect is provided, further comprising: a wiring portion connecting the measurement electrode portion and the conductive portion; and a third conductive pad portion connected midway along the wiring portion and exposed to the outside of the measurement container. Effects of the Invention

[0014] According to the flow path device of the first aspect, poor conduction of the first electrode can be detected by inspecting conduction between the first conductive pad portion and the second conductive pad portion.

[0015] According to the flow path device of the third aspect, conduction at an end portion of the measurement electrode portion can be inspected.

[0016] According to the flow path device of the fourth aspect, conduction of the conductive portion can be inspected.

[0017] According to the flow path device of the fifth aspect, poor conduction of the conductive portion can be detected by inspecting conduction between the first conductive pad portion and the third conductive pad portion. Brief Description of the Drawings

[0018] [Figure 1] FIG. 1 is a cross-sectional view of the flow path device according to the embodiment. [Figure 2] FIG. 2 is an exploded cross-sectional view of the flow path device according to the embodiment. [Figure 3] FIG. 3 is a top view showing upper surfaces of an upper working electrode and an upper reference electrode. [Figure 4] It is a diagram showing upper surfaces of a lower working electrode and a lower reference electrode. [Figure 5] It is a diagram showing a circuit for measuring electrical resistance of cell tissue. MODE FOR CARRYING OUT THE INVENTION

[0019] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. It should be noted that the constituent elements described in this embodiment are merely illustrative, and are not intended to limit the scope of the present invention only thereto. In the drawings, for ease of understanding, dimensions and numbers of respective parts may be exaggerated or simplified as necessary in the illustration.

[0020] <1. Embodiment> Fig. 1 is a cross-sectional view of a flow path device 1 according to an embodiment. Fig. 2 is an exploded cross-sectional view of the flow path device 1 according to the embodiment. The flow path device 1 is a so-called micro flow path device in which a measurement chamber 100 serving as an internal space is a closed space except for a fine first flow path 51 and a fine second flow path 53. The flow path device 1 is applicable to an apparatus that measures the electrical resistance (resistance, resistance or impedance) of cell tissue 9 cultured in the measurement chamber 100 by a four-terminal measurement method.

[0021] As shown in Fig. 1 and Fig. 2, the flow path device 1 includes a measurement container 2. The measurement container 2 includes an intermediate member 10, a first lid member 21, and a second lid member 22. The intermediate member 10, the first lid member 21, and the second lid member 22 are each plate-shaped. In the flow path device 1, the intermediate member 10 is positioned on an upper surface 220 of the second lid member 22. Further, the first lid member 21 is positioned on an upper surface of the intermediate member 10.

[0022] As shown in Figure 1, the measurement chamber 100 is located on the intermediate member 10. The measurement chamber 100 forms a flow path through which a liquid such as a culture medium can flow. As shown in Figures 1 and 2, the intermediate member 10 has a first intermediate member 11 and a second intermediate member 12. The second intermediate member 12 has an upper member 121 and a lower member 122. The upper member 121 is located on the upper surface of the lower member 122. The first intermediate member 11 is located above the second intermediate member 12.

[0023] The intermediate member 10 is made of, for example, PET (polyethylene terephthalate). The first intermediate member 11 is preferably translucent, and more preferably colorless and transparent. As shown in Figure 1, the intermediate member 10 has a through hole 10H that penetrates the intermediate member 10 vertically. The inner surface of the through hole 10H constitutes the inner surface of the measurement chamber 100.

[0024] The first lid member 21 and the second lid member 22 are transparent substrates made of, for example, quartz glass. As shown in Figure 1, the first lid member 21 closes the opening at the top of the measurement chamber 100. That is, the top of the measurement chamber 100 is closed by the first lid member 21. The second lid member 22 closes the opening at the bottom of the measurement chamber 100. That is, the bottom of the measurement chamber 100 is closed by the second lid member 22.

[0025] As shown in Figures 1 and 2, the flow channel device 1 has a porous membrane 30. The porous membrane 30 is a sheet-like permeable membrane that can allow liquid to pass through. The porous membrane 30 is made of, for example, PC (polycarbonate), PTFE (polytetrafluoroethylene), or PET. The porous membrane 30 is preferably light-transmitting. The porous membrane 30 is located between the first intermediate member 11 and the second intermediate member 12 in the vertical direction.

[0026] The porous membrane 30 divides the measurement chamber 100 (through-hole 10H) into an upper first chamber 101 and a lower second chamber 102. As shown in Figure 1, the cell tissue 9 is placed in the first chamber 101 of the measurement chamber 100 by being supported on the upper surface of the porous membrane 30 inside the measurement chamber 100. The upper surface of the portion of the porous membrane 30 that is placed inside the measurement chamber 100 (through-hole 10H) may be coated with a cell adhesion factor (such as collagen).

[0027] As shown in Figure 1, the first chamber 101 of the measurement chamber 100 is composed of the inner surface of the first through-hole 11H that penetrates the first intermediate member 11 vertically, the upper surface of the porous membrane 30, and the lower surface 210 of the first lid member 21. The second chamber 102 of the measurement chamber 100 is composed of the inner surface of the second through-hole 12H that penetrates the second intermediate member 12 vertically, the lower surface of the porous membrane 30, and the upper surface 220 of the second lid member 22.

[0028] As shown in Figures 1 and 2, the flow channel device 1 has a flat top member 40. The top member 40 is located on the upper surface of the first lid member 21. The top member 40 is made of, for example, PET. The top member 40 has an observation opening 41. The observation opening 41 is a hole that penetrates the top member 40 vertically. The observation opening 41 is located directly above the measurement chamber 100. That is, the observation opening 41 overlaps the measurement chamber 100 in the vertical direction.

[0029] As shown in Figure 1, the intermediate member 10 has a first flow path 51. The first flow path 51 communicates with the first chamber 101 of the measurement chamber 100. "Communication" means a state in which fluids are connected so that they can flow. The first flow path 51 is a flow path for supplying liquid such as culture medium to the first chamber 101 of the measurement chamber 100. The first flow path 51 is tubular in shape, passing through the first intermediate member 11 vertically and enclosed by the inner surface of a through hole extending in the width direction, the upper surface of the upper member 121 of the second intermediate member 12, and the lower surface 210 of the first lid member 21. The width direction is the direction that intersects with the vertical direction, and preferably the width direction is the direction perpendicular to the vertical direction.

[0030] As shown in Figure 1, the intermediate member 10 has a second flow path 53. The second flow path 53 communicates with the second chamber 102 of the measurement chamber 100. The second flow path 53 is a flow path for discharging liquid from the second chamber 102 of the measurement chamber 100. The second flow path 53 is tubular in shape, surrounded by the inner surface of a through hole that penetrates the upper member 121 of the second intermediate member 12 vertically and extends in the width direction, the lower surface of the first intermediate member 11, and the upper surface of the lower member 122 of the second intermediate member 12.

[0031] As shown in Figure 1, a portion of the upper end of the first channel 51 communicates with a first through-hole 43 that penetrates the top member 40 and the first lid member 21 vertically. Also, a portion of the upper end of the second channel 53 communicates with a second through-hole 45 that penetrates the top member 40 and the first lid member 21 vertically. Liquid can be supplied into the measurement chamber 100 from the first through-hole 43. Furthermore, the liquid in the measurement chamber 100 can be discharged from the second through-hole 45.

[0032] <Electrode> As shown in Figures 1 and 2, the flow channel device 1 comprises an upper working electrode 61, a lower working electrode 63, an upper reference electrode 71, and a lower reference electrode 73. The upper working electrode 61 and the upper reference electrode 71 are located on the lower surface 210 of the first lid member 21. The lower working electrode 63 and the lower reference electrode 73 are located on the upper surface 220 of the second lid member 22. Each electrode is formed by vacuum deposition or the like. A portion of each electrode (for example, the portion facing the inside of the measurement chamber 100) may be covered with an insulating film such as a silicon oxide film.

[0033] The upper working electrode 61, the lower working electrode 63, the upper reference electrode 71, and the lower reference electrode 73 have portions that overlap with the measurement chamber 100 in the vertical direction. That is, the upper working electrode 61, the lower working electrode 63, the upper reference electrode 71, and the lower reference electrode 73 have portions that overlap with the measurement chamber 100 in the vertical direction.

[0034] Figure 3 shows the upper surfaces of the upper working electrode 61 and the upper reference electrode 71. In Figure 3, the position of the measurement chamber 100 is indicated by a dashed line.

[0035] As shown in Figure 3, the upper working electrode 61 has an upper first working portion 611, an upper second working portion 612, a wiring portion 613, a first conductive pad portion 616, and second conductive pad portions 617, 618.

[0036] As shown in Figure 3, the measuring chamber 100 extends along the vertical direction (second direction). The vertical direction is the direction that intersects the vertical direction and the width direction. Preferably, the vertical direction is the direction perpendicular to the vertical direction and the width direction. The upper first working portion 611 and the upper second working portion 612 extend linearly along the vertical direction. The upper second working portion 612 is located away from the upper first working portion 611 in one direction in the width direction.

[0037] As shown in Figure 3, the upper first working portion 611 and the upper second working portion 612 overlap the measurement chamber 100 in the vertical direction (first direction). The lengths of the upper first working portion 611 and the upper second working portion 612 in the vertical direction are greater than the length of the measurement chamber 100 in the vertical direction. Furthermore, the upper first working portion 611 and the upper second working portion 612 extend from a position away from the measurement chamber 100 in one vertical direction to a position away from the measurement chamber 100 in the other vertical direction. In other words, the upper first working portion 611 and the upper second working portion 612 traverse the measurement chamber 100 in the vertical direction.

[0038] As shown in Figure 3, the wiring section 613 is located away from the measurement chamber 100 in one longitudinal direction. The wiring section 613 extends in the width direction. The other end of the wiring section 613 in the width direction is connected to the first conductive pad section 616. The respective ends of the upper first working section 611 and the upper second working section 612 in one longitudinal direction are connected to the wiring section 613. That is, the upper first working section 611 and the upper second working section 612 are electrically connected to the first conductive pad section 616 via the wiring section 613. The first conductive pad section 616 is located away from the upper first working section 611 in the other width direction.

[0039] The second conductive pad portions 617 and 618 are located apart from the first conductive pad portion 616 in the other longitudinal direction. The second conductive pad portion 617 is connected to the other longitudinal end of the upper first working portion 611. The second conductive pad portion 618 is connected to the other longitudinal end of the upper second working portion 612. The second conductive pad portion 618 is located one side in the width direction of the upper second working portion 612. The second conductive pad portions 617 and 618 are located outside the measurement chamber 100.

[0040] The upper reference electrode 71 has an upper first reference portion 711, an upper second reference portion 712, a wiring portion 713, a first conductive pad portion 716, and second conductive pad portions 717, 718. The upper first reference portion 711 and the upper second reference portion 712 extend linearly along the longitudinal direction. The upper second reference portion 712 is located away from the upper first reference portion 711 in one direction in the width direction.

[0041] As shown in Figure 3, the upper first reference section 711 and the upper second reference section 712 extend from a position away from the measurement chamber 100 in one longitudinal direction to a position away from the measurement chamber 100 in the other longitudinal direction. In other words, the upper first reference section 711 and the upper second reference section 712 traverse the measurement chamber 100 in the longitudinal direction.

[0042] As shown in Figures 1 and 3, the upper first reference portion 711 and the upper second reference portion 712 are located in the width direction between the upper first working portion 611 and the upper second working portion 612. The upper first reference portion 711 is located away from the upper first working portion 611 in one direction in the width direction. The upper second reference portion 712 is located away from the upper second working portion 612 in the other direction in the width direction.

[0043] The wiring section 713 is located away from the measurement chamber 100 in the other longitudinal direction. The wiring section 713 extends in the width direction and is connected to the first conductive pad section 716. As shown in Figure 3, the ends of the upper first reference section 711 and the upper second reference section 712 on the other longitudinal side are connected to the wiring section 713. That is, the upper first reference section 711 and the upper second reference section 712 are electrically connected to the first conductive pad section 716 via the wiring section 713. The first conductive pad section 716 is located away from the upper second reference section 712 in one width direction.

[0044] The second conductive pad portions 717 and 718 are located one lengthwise away from the first conductive pad portion 716. The second conductive pad portion 717 is connected to one lengthwise end of the upper first reference portion 711. The second conductive pad portion 718 is connected to one lengthwise end of the upper second reference portion 712. In the width direction, the second conductive pad portions 717 and 718 are located between the upper first working portion 611 and the upper second working portion 612. The second conductive pad portions 717 and 718 are located outside the measurement chamber 100.

[0045] Figure 4 shows the upper surfaces of the lower working electrode 63 and the lower reference electrode 73. In Figure 4, the position of the measurement chamber 100 is indicated by a dashed line.

[0046] As shown in Figure 4, the lower working electrode 63 has a lower first working portion 631, a lower second working portion 632, a wiring portion 633, and a relay pad portion 634.

[0047] As shown in Figure 4, the lower first working portion 631 and the lower second working portion 632 extend linearly along the vertical direction. The lower first working portion 631 and the lower second working portion 632 overlap the measurement chamber 100 in the vertical direction. The lower first working portion 631 and the lower second working portion 632 traverse the measurement chamber 100 in the vertical direction.

[0048] The lower first working portion 631 and the lower second working portion 632 are the same size and shape as the upper first working portion 611 and the upper second working portion 612, respectively. The upper first working portion 611 and the upper second working portion 612 and the lower first working portion 631 and the lower second working portion 632 are symmetrical with respect to a plane perpendicular to the vertical direction and passing through the center of the measuring chamber.

[0049] In the vertical direction, the lower first working portion 631 faces the upper first working portion 611, and the lower second working portion 632 faces the upper second working portion 612. By positioning the upper working electrode 61 and the lower working electrode 63 in this way, a uniform voltage can be applied to the cell tissue 9 between the electrodes.

[0050] As shown in Figure 4, the wiring section 633 is located away from the measurement chamber 100 in one longitudinal direction. The wiring section 633 extends in the width direction. One end of the wiring section 633 in the width direction is electrically connected to the relay pad section 634. The respective ends of the lower first working section 631 and the lower second working section 632 in the longitudinal direction are connected to the wiring section 633. That is, the lower first working section 631 and the lower second working section 632 are connected to the relay pad section 634 via the wiring section 633. The relay pad section 634 is located away from the lower second working section 632 in one longitudinal direction.

[0051] As shown in Figure 1, the lower working electrode 63 further comprises a conductive portion 635 and a first conductive pad portion 636. The conductive portion 635 is a conductive member extending in the vertical direction. The conductive portion 635 is, for example, silver paste. It is located within a hole that penetrates the first intermediate member 11, the second intermediate member 12, and the porous membrane 30 in the vertical direction. The first conductive pad portion 636 is a conductive membrane provided on the lower surface 210 of the first lid member 21. The first conductive pad portion 636 overlaps the relay pad portion 634 in the vertical direction. As shown in Figure 1, the lower end of the conductive portion 635 is in contact with the relay pad portion 634, and the upper end of the conductive portion 635 is in contact with the first conductive pad portion 636. The relay pad portion 634 and the first conductive pad portion 636 are electrically connected via the conductive portion 635.

[0052] As shown in Figure 4, the lower working electrode 63 has second conductive pad portions 637 and 638. The second conductive pad portions 637 and 638 are located on the upper surface 220 of the second cover member 22. The second conductive pad portions 637 and 638 are located away from the intermediate pad portion 634 in the other direction in the vertical direction. Also, the second conductive pad portions 637 and 638 are located away from the first conductive pad portion 636 in the other direction in the vertical direction.

[0053] The second conductive pad portion 637 is connected to the other end in the vertical direction of the lower first working portion 631. The second conductive pad portion 638 is connected to the other end in the vertical direction of the lower second working portion 632. The second conductive pad portion 637 is located on the other side in the width direction of the lower first working portion 631. The second conductive pad portions 637 and 638 are located outside the measurement chamber 100.

[0054] As shown in Figure 4, the lower working electrode 63 has a third conductive pad portion 639. The third conductive pad portion 639 is located on the upper surface 220 of the second cover member 22. The third conductive pad portion 639 is connected in the middle of the wiring portion 633. Specifically, the third conductive pad portion 639 is connected at a position between the portion of the wiring portion 633 to which the lower second working portion 632 is connected and the portion of the wiring portion 633 to which the relay pad portion 634 is connected.

[0055] As shown in Figure 4, the lower reference electrode 73 has a lower first reference portion 731, a lower second reference portion 732, a wiring portion 733, and a relay pad portion 734.

[0056] As shown in Figure 4, the lower first reference section 731 and the lower second reference section 732 extend linearly along the vertical direction. The lower first reference section 731 and the lower second reference section 732 overlap the measurement chamber 100 in the vertical direction. The lower first reference section 731 and the lower second reference section 732 traverse the measurement chamber 100 in the vertical direction.

[0057] The lower first reference section 731 and the lower second reference section 732 are the same size and shape as the upper first reference section 711 and the upper second reference section 712, respectively. The upper first reference section 711 and the upper second reference section 712, and the lower first reference section 731 and the lower second reference section 732 are symmetrical with respect to a plane perpendicular to the vertical direction and passing through the center of the measurement chamber. In the vertical direction, the lower first reference section 731 faces the upper first reference section 711, and the lower second reference section 732 faces the upper second reference section 712.

[0058] As shown in Figure 4, the wiring section 733 is located away from the measurement chamber 100 in the other longitudinal direction. The wiring section 733 extends in the width direction. The other end of the wiring section 733 in the width direction is connected to the relay pad section 734. The other ends of the lower first reference section 731 and the lower second reference section 732 in the other longitudinal direction are connected to the wiring section 733. That is, the lower first reference section 731 and the lower second reference section 732 are electrically connected to the relay pad section 734 via the wiring section 733. The relay pad section 734 is located away from the lower first reference section 731 in the other longitudinal direction.

[0059] The lower reference electrode 73 has a conductive portion 735 (see Figure 4). The conductive portion 735 is a conductive member that extends in the vertical direction. The conductive portion 735 is, for example, silver paste. The conductive portion 735, like the conductive portion 635, is located within a hole (not shown) that penetrates the first intermediate member 11, the second intermediate member, and the porous membrane 30 in the vertical direction. The lower end of the conductive portion 735 is in contact with the relay pad portion 734. The upper end of the conductive portion 735 is in contact with a first conductive pad portion (not shown) located on the lower surface 210 of the first lid member 21. The first conductive pad portion of the lower reference electrode 73 is exposed to the outside of the measuring container 2 through a through hole (not shown) provided in the measuring container 2.

[0060] As shown in Figure 4, the lower reference electrode 73 has second conductive pad portions 737 and 738. The second conductive pad portions 737 and 738 are located on the upper surface 220 of the second cover member 22. The second conductive pad portions 737 and 738 are located away from the intermediate pad portion 734 in one longitudinal direction. Also, the second conductive pad portions 737 and 738 are located away from the first conductive pad portion of the lower reference electrode 73 in one longitudinal direction.

[0061] The second conductive pad portion 737 is connected to one end in the vertical direction of the lower first reference portion 731. The second conductive pad portion 738 is connected to one end in the vertical direction of the lower second reference portion 732. The second conductive pad portions 737 and 738 are located in the width direction between the lower first working portion 631 and the lower second working portion 632. The second conductive pad portions 737 and 738 are located outside the measurement chamber 100.

[0062] As shown in Figure 4, the lower reference electrode 73 has a third conductive pad portion 739. The third conductive pad portion 739 is located on the upper surface 220 of the second cover member 22. The third conductive pad portion 739 is connected in the middle of the wiring portion 733. Specifically, the third conductive pad portion 739 is connected at a position between the portion of the wiring portion 733 to which the lower first reference portion 731 is connected and the portion of the wiring portion 733 to which the relay pad portion 734 is connected.

[0063] As shown in Figure 1, the measuring container 2 has conductive holes 81 and 82. The conductive holes 81 and 82 consist of the inner surface of a hole that penetrates the intermediate member 10, the porous membrane 30, and the second lid member 22 in the vertical direction, and the lower surface 210 of the first lid member 21 that closes the upper part of the through hole. Conductive hole 81 is located away from the measuring chamber 100 in the other direction in the width direction. Conductive hole 82 is located away from the measuring chamber 100 in one direction in the width direction. As shown in Figure 1, conductive probe pins 90 (external electrodes) can be inserted into the conductive holes 81 and 82.

[0064] As shown in Figure 1, the first conductive pad portion 616 of the upper working electrode 61 is located inside the conductive hole 81. The first conductive pad portion 636 of the lower working electrode 63 is located inside the conductive hole 82. In other words, the first conductive pad portions 616 and 636 are exposed to the outside of the measuring container 2 through the conductive holes 81 and 82, respectively.

[0065] The measuring container 2 has conductive holes (not shown) that expose the second conductive pad portions 617 and 618 of the upper working electrode 61 to the outside of the measuring container 2. The measuring container 2 also has conductive holes (not shown) that expose the second conductive pad portions 637 and 638 and the third conductive pad portion 639 of the lower working electrode 63 to the outside of the measuring container 2.

[0066] The measuring container 2 has conductive holes (not shown) that expose the first conductive pad portion 716 and the second conductive pad portions 737 and 738 of the upper reference electrode 71 to the outside of the measuring container 2. The measuring container 2 also has conductive holes (not shown) that expose the first conductive pad portion 736, the second conductive pad portions 737 and 738 and the third conductive pad portion 739 of the lower reference electrode 73 to the outside of the measuring container 2.

[0067] As shown in Figure 1, probe pins 90 are inserted into each of the conductive holes, including conductive holes 81 and 82, provided in the measuring container 2. This electrically connects the conductive pads of the upper working electrode 61, lower working electrode 63, upper reference electrode 71, and lower reference electrode 73 to the external device.

[0068] In this embodiment, the upper working electrode 61 is an example of a "first electrode," the upper reference electrode 71 is an example of a "second electrode," the lower working electrode 63 is an example of a "third electrode," and the lower reference electrode 73 is an example of a "fourth electrode." Furthermore, the upper first working portion 611 and the upper second working portion 612 are examples of "measuring electrode portions."

[0069] Alternatively, the upper reference electrode 71 can be considered as the "first electrode," and the upper first reference section 711 and upper second reference section 712 as the "measuring electrode section." In this case, the upper working electrode 61 corresponds to the "second electrode," and the lower working electrode 63 and lower reference electrode 73 correspond to the "third electrode" and "fourth electrode," respectively.

[0070] Alternatively, the lower working electrode 63 can be considered the "first electrode," and the lower first working portion 631 and lower second working portion 632 can be considered the "measuring electrode portion." In this case, the lower reference electrode 73 corresponds to the "second electrode," and the upper working electrode 61 and upper reference electrode 71 correspond to the "third electrode" and "fourth electrode," respectively.

[0071] Furthermore, the lower reference electrode 73 can be considered the "first electrode," and the lower first reference section 731 and lower second reference section 732 can be considered the "measuring electrode section." In this case, the lower working electrode 63 corresponds to the "second electrode," and the upper working electrode 61 and upper reference electrode 71 correspond to the "third electrode" and "fourth electrode," respectively.

[0072] <Continuity Test> According to the flow channel device 1, the continuity of the upper working electrode 61, lower working electrode 63, upper reference electrode 71, and lower reference electrode 73 can be checked even if there is no liquid such as culture medium in the flow channel, which is the measurement chamber 100.

[0073] For example, in the upper working electrode 61, poor continuity in the upper first working portion 611 and the wiring portion 613 can be detected by checking the continuity between the first conductive pad portion 616 and the second conductive pad portion 617 shown in Figure 3. Also, poor continuity in the upper second working portion 612 and the wiring portion 613 can be detected by checking the continuity between the first conductive pad portion 616 and the second conductive pad portion 618.

[0074] By checking the continuity between the first conductive pad portion 716 and the second conductive pad portion 717 shown in Figure 3 at the upper reference electrode 71, poor continuity in the upper first reference portion 711 and the wiring portion 713 can be detected. Furthermore, by checking the continuity between the first conductive pad portion 716 and the second conductive pad portion 718, poor continuity in the upper second reference portion 712 and the wiring portion 713 can be detected.

[0075] By checking the continuity between the second conductive pad portion 637 and the third conductive pad portion 639 shown in Figure 4 at the lower working electrode 63, poor continuity in the lower first working portion 631 and the wiring portion 633 can be detected. Furthermore, by checking the continuity between the second conductive pad portion 638 and the third conductive pad portion 639, poor continuity in the lower second working portion 632 and the wiring portion 633 can be detected.

[0076] Furthermore, by inspecting the continuity between the first conductive pad portion 636 and the third conductive pad portion 639 in the lower working electrode 63, it is possible to detect poor continuity (poor contact or open circuit, etc.) in the intermediate pad portion 634, the conductive portion 635, and the first conductive pad portion 636.

[0077] It is possible to detect poor conductivity between each pad portion by inspecting the conductivity between the second conductive pad portion 637 or the second conductive pad portion 638 and the first conductive pad portion 636. However, it is difficult to distinguish between poor conductivity in the lower first working portion 631 or the lower second working portion 632 and poor conductivity in the conductive portion 635. In contrast, by providing the third conductive pad portion 639, it is possible to inspect for poor conductivity in the lower first working portion 631 or the lower second working portion 632 and poor conductivity in the conductive portion 635 separately. Therefore, the location of the poor conductivity can be easily identified.

[0078] By checking the continuity between the second conductive pad portion 737 and the third conductive pad portion 739 shown in Figure 4 at the lower reference electrode 73, poor continuity in the lower first reference portion 731 and the wiring portion 733 can be detected. Furthermore, by checking the continuity between the second conductive pad portion 738 and the third conductive pad portion 739, poor continuity in the lower second reference portion 732 and the wiring portion 733 can be detected.

[0079] Furthermore, by inspecting the continuity between the first conductive pad portion (not shown) and the third conductive pad portion 739 at the lower reference electrode 73, poor continuity (poor contact or open circuit, etc.) in the intermediate pad portion 734, the conductive portion 735, and the first conductive pad portion can be detected.

[0080] <Electrical Resistance Measurement> Figure 5 shows a circuit for measuring the electrical resistance of cell tissue 9. When measuring the electrical resistance of cell tissue 9, a power supply 91 and a voltmeter 92 are connected to the flow channel device 1. Specifically, the output terminal of the power supply 91 is electrically connected to the upper working electrode 61 and the lower working electrode 63 via a wire 94a. The input terminal of the voltmeter 92 is electrically connected to the upper reference electrode 71 and the lower reference electrode 73 via a wire 94b. The wires 94a and 94b are connected to each electrode via probe pins 90.

[0081] Cell tissue 9 is held on the upper surface of the porous membrane 30 inside the measurement chamber 100. A supply tube is connected to the first through-hole 43 of the top member 40 to supply liquid (such as culture medium) into the measurement chamber 100. Liquid is supplied to the first channel 51 and the measurement chamber 100 via this supply tube. A discharge tube is connected to the second through-hole 45 of the top member 40. Liquid is discharged from the measurement chamber 100 and the second channel 53 via this discharge tube. As a result, liquid exchange (or circulation) is performed as appropriate in the first chamber 101 and the second chamber 102 of the measurement chamber 100.

[0082] In Figure 5, resistance Rm corresponds to the electrical resistance of the porous membrane 30 portion within the measurement chamber 100 and the cell tissue 9 supported by the porous membrane 30 (hereinafter referred to as the "cell portion"). Resistance Rw1 corresponds to the electrical resistance of the liquid between the upper working electrode 61 and the cell portion (specifically, the liquid in the first chamber 101 of the measurement chamber 100). Resistance Rw2 corresponds to the electrical resistance of the liquid between the lower working electrode 63 and the cell portion (specifically, the liquid in the second chamber 102).

[0083] In Figure 5, resistance Rr1 corresponds to the electrical resistance of the liquid between the upper reference electrode 71 and the cell (specifically, the liquid in the first chamber 101 of the measurement chamber 100). Resistance Rr2 corresponds to the electrical resistance of the liquid between the lower reference electrode 73 and the cell (specifically, the liquid in the second chamber 102 of the measurement chamber 100).

[0084] The power supply unit 91 applies a voltage between the upper working electrode 61 and the lower working electrode 63. The voltmeter 92 measures the voltage between the upper reference electrode 71 and the lower reference electrode 73. From the measured voltage values, a computer (not shown) calculates the exact voltage value between the upper working electrode 61 and the lower working electrode 63. The resistance Rm of the cell region is also calculated from the calculated voltage value. The electrical resistance of the cell tissue 9 is determined by subtracting the resistance of the porous membrane 30 from the resistance Rm of the cell region. The resistance of the porous membrane 30 is determined by measuring the electrical resistance in the absence of the cell tissue 9.

[0085] When a voltage is applied between the upper working electrode 61 and the lower working electrode 63, oxidation and reduction reactions of the liquid may occur on the surfaces of the upper working electrode 61 and the lower working electrode 63, potentially forming an electrical double layer. When an electrical double layer is formed, the voltage applied between the upper working electrode 61 and the lower working electrode 63 may differ from the output voltage of the power supply 91. In response to this, an upper reference electrode 71 and a lower reference electrode 73 are positioned near the upper working electrode 61 and the lower working electrode 63 within the measurement chamber 100. Therefore, the voltage between the upper working electrode 61 and the lower working electrode 63 can be approximately obtained from the measured voltage between the upper reference electrode 71 and the lower reference electrode 73. This allows for accurate measurement of the cell resistance Rm.

[0086] <2. Variant Example> Although embodiments have been described above, the present invention is not limited to those described above, and various modifications are possible.

[0087] For example, the conductive portion 635 of the lower working electrode 63 may be omitted. In this case, for example, a through hole for exposing the intermediate pad portion 634 to the outside of the measuring container 2 may be provided in the measuring container 2, thereby allowing the intermediate pad portion 634 to function as the first conductive pad portion 636.

[0088] Although this invention has been described in detail, the above description is illustrative in all respects, and the invention is not limited thereto. It is understood that countless variations not illustrated can be envisioned without falling outside the scope of this invention. The components described in each of the above embodiments and variations can be combined or omitted as appropriate, as long as they do not contradict each other. [Explanation of Symbols]

[0089] 1. Flow channel device 100 measurement room 2. Measuring container 30 Porous membrane 61 Upper working electrode 611 Upper first action part 612 Upper 2nd action part 613 Wiring section 616 First conductive pad section 617, 618 Second conductive pad section 63 Lower working electrode 631 Lower first action part 632 Lower 2nd action part 633 Wiring section 634 Relay Pad Section 635 Conductive part 636 First conductive pad section 637, 638 Second conductive pad section 639 Third conductive pad section 71 Upper reference electrode 711 Upper 1st reference section 712 Upper 2nd reference section 713 Wiring section 716 First conductive pad section 717,718 Second conductive pad section 73 Lower reference electrode 731 Lower 1st reference section 732 Lower 2nd reference part 733 Wiring section 735 Conductive part 736 First conductive pad section 737,738 Second conductive pad section 739 Third conductive pad section 9 Cell organization

Claims

1. A fluid channel device applicable to measuring the electrical resistance of cell tissues, A measuring container having a measuring chamber which is a flow path inside, A porous membrane located in the aforementioned measurement chamber, capable of supporting cell tissue and permeable to liquid, A first electrode and a second electrode are located away from the porous membrane in one direction in the first direction, A third electrode and a fourth electrode are located away from the porous membrane in the other direction of the first direction, Equipped with, The first electrode is A measuring electrode section overlaps the measuring chamber in a first direction and extends in a second direction intersecting the first direction, The first conductive pad portion and the second conductive pad portion are exposed outside the measuring container, It has, The first conductive pad portion is electrically connected to one side of the measuring electrode portion in the second direction, The second conductive pad portion is a flow channel device connected to the other end of the measuring electrode portion in the second direction.

2. A flow channel device according to claim 1, The second conductive pad portion is a flow channel device located away from the first conductive pad portion in the second direction.

3. A flow channel device according to claim 2, The second conductive pad portion is a flow channel device connected to the end of the measuring electrode portion in the second direction.

4. A flow channel device according to any one of claims 1 to 3, The first electrode is located inside the measuring container and has a conductive portion extending in the first direction. It further includes, The first conductive pad portion is connected to the measuring electrode portion via the conductive portion, and is a flow channel device.

5. A flow channel device according to claim 4, A wiring section connecting the measuring electrode section and the conductive section, A third conductive pad portion is connected in the middle of the wiring portion and is exposed outside the measuring container, A flow channel device that further incorporates these features.

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