Cell potential measurement device

Abstract

[Problem] To ascertain the conductive state of a measurement electrode and measurement wiring in a cell potential measurement device. [Solution] A cell potential measurement device 1 comprises: a substrate 10 having insulating properties; measurement wiring 30 provided on the substrate 10; an insulation layer 50 provided on the substrate 10 and covering at least the surface of the measurement wiring 30; a measurement electrode 20 provided on the insulation layer 50 and electrically connected to the measurement wiring 30; and test wiring 40 provided on the substrate 10 and disposed at least partially under the measurement electrode 20 with the insulation layer 50 interposed therebetween.

Description

[Technical Field]

[0001] The technology disclosed herein relates to a cell potential measuring device. [Background technology]

[0002] Conventionally, the action potential of cells or tissues (hereinafter simply referred to as "cells") has been measured in vitro and non-invasively using a microarray electrode (multi-electrode array: MEA). For example, Patent Document 1 discloses a measurement device that has relatively low impedance reference electrodes located on an insulating substrate at multiple positions a predetermined distance away from multiple microelectrodes. Patent Document 1 describes that the noise level can be kept low by placing the reference electrodes as far away as possible from the microelectrodes that measure the action potential of the cells. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 11-187865 Summary of the Invention [Problem to be solved by the invention]

[0004] However, if there is a problem with the connection between the microelectrode (measurement electrode) and its lead-out wiring (measurement wiring), or if the lead-out wiring has defects such as breaks or constrictions, measurement signals may not be obtained or may vary. Therefore, with conventional microarray electrodes, it was not possible to determine whether such variation in measurement signals was caused by the microarray electrode or the cells themselves.

[0005] The technique disclosed herein has been made in consideration of the above circumstances, and aims to provide a cellular potential measuring device that can inspect the continuity state of a measuring electrode and measuring wiring. [Means for solving the problem]

[0006] (1) A cellular potential measuring device according to the present technology includes an insulating substrate, measurement wiring (first wiring) provided on the substrate, an insulating layer provided on the substrate and covering at least the surface of the measurement wiring, a measurement electrode (first electrode) provided on the insulating layer and electrically connected to the measurement wiring, and a testing wiring (second wiring) provided on the substrate, at least a portion of which is disposed below the measurement electrode via the insulating layer. Note that in this specification, "above" includes both the case where it is above via another object and the case where it is directly above without via another object.

[0007] (2) Furthermore, in one embodiment of the present technology, in addition to the configuration of (1) above, the inspection wiring may include an inspection electrode portion (second electrode portion) facing the measurement electrode and a wiring portion extending from the inspection electrode portion, and the distance between the measurement electrode and the inspection electrode portion may be 10 nm or more and 100 μm or less.

[0008] (3) In one embodiment of the present technology, in addition to the configuration of (1) or (2) above, the insulating layer may cover a surface of the inspection wiring.

[0009] (4) In one embodiment of the present technology, in addition to any one of the configurations (1) to (3) above, the inspection wiring may be provided directly on the substrate.

[0010] (5) In one embodiment of the present technology, in addition to any one of the configurations (1) to (3) above, the insulating layer may include a first insulating layer disposed between the substrate and the testing wiring, and a second insulating layer disposed between the testing wiring and the measurement electrode.

[0011] (6) In one embodiment of the present technology, in addition to any one of the configurations (1) to (3) above, the inspection wiring may include an inspection electrode portion (second electrode portion) facing the measurement electrode and a wiring portion extending from the inspection electrode portion, the wiring portion being provided directly on the substrate, and the insulating layer may include a first insulating layer arranged between the substrate and the inspection electrode portion and a second insulating layer arranged between the inspection electrode portion and the measurement electrode.

[0012] (7) In an embodiment of the present technology, in addition to the configuration of (6) above, the wiring portion and the inspection electrode portion may be made of different materials.

[0013] (8) In one embodiment of the present technology, in addition to any one of the configurations (1) to (7) above, the measurement electrode may contain at least one transparent conductive material selected from the group consisting of tin oxide, zinc oxide, indium zinc oxide, and indium tin oxide.

[0014] (9) In one embodiment of the present technology, in addition to any one of the configurations (1) to (8) above, at least a portion of the inspection wiring and the measurement wiring may contain at least one element selected from the group consisting of gold, silver, copper, aluminum, tantalum, tungsten, molybdenum, niobium, and titanium.

[0015] (10) In one embodiment of the present technology, in addition to any one of the configurations (1) to (9) above, the insulating layer may include a first insulating layer, at least a portion of which is provided directly on the substrate, and a second insulating layer, at least a portion of which is provided directly below the measurement electrode, and the first insulating layer and the second insulating layer each include a covering region arranged above the measurement wiring, and a conductive shielding layer may be provided between the first insulating layer and the second insulating layer in the covering region.

[0016] (11) In one embodiment of the present technology, in addition to any one of the configurations (1) to (10) above, the measurement electrode includes a first measurement electrode (third electrode) and a second measurement electrode (fourth electrode), the inspection wiring includes an inspection electrode portion (second electrode portion) facing the measurement electrode and a wiring portion extending from the inspection electrode portion, and the inspection electrode portion includes a first inspection electrode portion (third electrode portion) facing the first measurement electrode and a second inspection electrode portion (fourth electrode portion) facing the second measurement electrode, and the first inspection electrode portion and the second inspection electrode portion may be connected to one of the wiring portions.

[0017] (12) In one embodiment of the present technology, in addition to any one of the configurations (1) to (11) above, the measurement electrodes may include a plurality of first measurement electrodes (third electrodes) and a plurality of second measurement electrodes (fourth electrodes), the measurement wiring may include a plurality of first measurement wirings (third wirings) connected to each of the plurality of first measurement electrodes and a plurality of second measurement wirings (fourth wirings) connected to each of the plurality of second measurement electrodes, the inspection wiring may include an inspection electrode portion (second electrode portion) and a wiring portion, and the inspection electrode portion may include a plurality of first inspection electrode portions (third electrode portions) facing each of the plurality of first measurement electrodes via the insulating layer and a plurality of second inspection electrode portions (fourth electrode portions) facing each of the plurality of second measurement electrodes via the insulating layer, and the wiring portion may include a first wiring portion connected to each of the plurality of first inspection electrode portions and a second wiring portion connected to each of the plurality of second inspection electrode portions.

[0018] (13) In one embodiment of the present technology, in addition to the configuration of (12) above, one first measurement electrode among the plurality of first measurement electrodes and one second measurement electrode among the plurality of second measurement electrodes are arranged alternately with each other along a direction along the surface of the substrate, and the insulating layer includes a first insulating layer arranged between the substrate and the first wiring portion and the plurality of first inspection electrode portions, the plurality of second inspection electrode portions, and the second wiring portion, and a second insulating layer provided above the plurality of first inspection electrode portions, the plurality of second inspection electrode portions, and the second wiring portion and below the plurality of first measurement electrodes and the plurality of second measurement electrodes, and the first wiring portion and the plurality of first inspection electrode portions may be connected via a through portion that penetrates the first insulating layer.

[0019] (14) In one embodiment of the present technology, in addition to the configuration of (13) above, a first shield layer may be provided above the plurality of first measurement wirings and between the first insulating layer and the second insulating layer, the first shield layer being connected to one of the plurality of second inspection electrode portions that are close to each of the plurality of first measurement wirings, and a second shield layer may be provided above the plurality of second measurement wirings and between the first insulating layer and the second insulating layer, the second shield layer being connected to one of the plurality of first inspection electrode portions that are close to each of the plurality of second measurement wirings.

[0020] (15) In one embodiment of the present technology, in addition to any one of the configurations (1) to (13) above, a wall portion erected on the substrate so as to surround the measurement electrode may be further provided.

[0021] (16) In one embodiment of the present technology, in addition to any one of the configurations (1) to (14) above, a field effect transistor may be provided on the substrate and connected to the inspection wiring.

[0022] (17) In one embodiment of the present technology, in addition to any one of the configurations (1) to (15) above, a field effect transistor may be provided on the substrate and connected to the measurement wiring. [Effects of the Invention]

[0023] According to the technique disclosed herein, it is possible to inspect the continuity of the measurement electrodes and measurement wiring in a cellular potential measuring device. [Brief explanation of the drawings]

[0024] [Figure 1] FIG. 1 is a plan view schematically showing the main parts of the cellular potential measuring device according to the first embodiment. [Figure 2] FIG. 2 is a cross-sectional view of the cellular potential measuring device of FIG. 1 taken along line AA. [Figure 3] FIG. 3 is a schematic diagram showing how the local action potential of a cell is measured by the cell potential measuring device of FIG. [Figure 4] FIG. 4 is a graph illustrating an example of an input signal to the cellular potential measuring device. [Figure 5] FIG. 5 is a graph illustrating an example of an output signal output from the cellular potential measuring device in response to the input signal shown in FIG. [Figure 6] FIG. 6 is a plan view schematically showing the cellular potential measuring device according to the second embodiment. [Figure 7] FIG. 7 is a cross-sectional view of the cellular potential measuring device of FIG. 6 taken along line BB. [Figure 8] FIG. 8 is a plan view schematically showing the cellular potential measuring device according to the third embodiment. [Figure 9] FIG. 9 is a cross-sectional view of the cellular potential measuring device of FIG. 8 taken along line CC. [Figure 10] FIG. 10 is a diagram illustrating a cross section of a part of the cellular potential measuring device according to the fourth embodiment and an example of an output signal. [Figure 11] FIG. 11 is a diagram illustrating a cross section of a part of the cellular potential measuring device according to the third embodiment and an example of an output signal. [Figure 12] FIG. 12 is a plan view of the cellular potential measuring device according to the fifth embodiment. [Figure 13] FIG. 13 is a cross-sectional view of the cellular potential measuring device of FIG. 12 taken along line DD. [Figure 14]14 is a cross-sectional view of the cellular potential measuring device of FIG. 12 taken along line EE. [Figure 15] FIG. 15 is a plan view of the cellular potential measuring device according to the sixth embodiment. [Figure 16] FIG. 16 is a plan view of the cellular potential measuring device according to the seventh embodiment. [Figure 17] FIG. 17 is an enlarged view of the essential parts of the cellular potential measuring device of FIG. [Figure 18] FIG. 18 is a diagram showing a configuration including one test electrode of the cellular potential measuring device of FIG. [Figure 19] FIG. 19 is a cross-sectional view taken along line F1-F5 in FIG. [Figure 20] FIG. 20 is a diagram showing the operation of the cellular potential measuring device of FIG. [Figure 21] FIG. 21 is another diagram showing the operation of the cellular potential measuring device of FIG. [Figure 22] FIG. 22 is a plan view schematically showing a conventional cellular potential measuring device. [Figure 23] FIG. 23 is a cross-sectional view of the cellular potential measuring device of FIG. 22 taken along line GG. DETAILED DESCRIPTION OF THE INVENTION

[0025] [Embodiment 1] Preferred embodiments of the technology disclosed herein are described below. Matters other than those specifically mentioned in this specification (e.g., the structure of the cell potential measuring device disclosed herein) that are necessary for implementing the technology (e.g., general matters related to the cells to be cultured, cell culture techniques, screening and preparation of pharmaceutical compositions, and general matters related to the microfabrication techniques involved in manufacturing the cell potential measuring device) can be understood as design matters of a person skilled in the art based on conventional technology in the fields of cytology, physiology, medicine, pharmacology, biochemistry, genetic engineering, protein engineering, materials engineering, semiconductor engineering, ultraprecision machining, MEMS engineering, etc. The technology can be implemented based on the content disclosed in this specification and the common general technical knowledge in the relevant fields.

[0026] (Cell potential measuring device) The cellular potential measuring device disclosed herein will be described with appropriate reference to Figures 1 to 5. Cellular potential measuring device 1 is a device for non-invasively recording electrical signals (action potentials) generated during the electrical activity of cells such as neurons, outside the cell. As shown in Figures 1 and 2, cellular potential measuring device 1 includes a substrate 10, a measurement electrode (first electrode) 20, measurement wiring (first wiring) 30, testing wiring (second wiring) 40, and an insulating layer 50.

[0027] The substrate 10 is an element that supports the measurement electrodes 20, the measurement wiring 30, the inspection wiring 40, and the insulating layer 50. The substrate 10 can also support the cells S (see FIG. 3) that are the measurement target, and can also serve as a stage for seeding and culturing the cells S. The substrate 10 of this embodiment is flat. The substrate 10 is made of an insulating material that has electrical insulation properties. The insulating material should have a volume resistivity of 10 or less at room temperature (for example, 25° C.). 7 Ωcm or more (e.g., 10 10 Ωcm or more, 10 12 Ωcm or more, even 10 15 Examples of materials that can be used include materials with a volume resistivity of Ωcm or higher, and may be organic or inorganic materials having the above-mentioned volume resistivities. Although the substrate 10 is not limited to this, it is preferable that the substrate 10 is made of a transparent material so that the cells S can be observed from below through the substrate 10. It is more preferable that the substrate 10 is colorless and transparent.

[0028] Materials constituting such a substrate 10 include, for example, various types of glass, synthetic resins, etc. Suitable examples of glass include soda-lime glass, borosilicate glass, and quartz glass. While not necessarily limited to these, alkali-free glass, which contains 0.1 mass % or less of alkali components calculated as oxides and in which the elution of alkali ions is highly suppressed, may also be used. As synthetic resins, for example, materials with a relatively high volume resistivity (for example, 10 10 Ωcm or more, 10 12 Ωcm or more, even 1015 Examples of suitable materials include synthetic resins such as polydimethylsiloxane (PDMS), polystyrene, polypropylene, polyethylene terephthalate (PET), polymethyl methacrylate, nylon, polyurethane, etc. There is no limitation on the thickness of the substrate 10, but a preferable example is about 0.2 to 1 mm (for example, 0.5 mm, 0.7 mm, etc.).

[0029] The measurement electrode 20 is an element for detecting (receiving) action potentials generated by the cell S. The measurement electrode 20 is made of an electrically conductive material. Details of the materials constituting the measurement electrode 20 will be described later. The measurement electrode 20 is layered and provided above the substrate 10. The planar shape of the measurement electrode 20 is not particularly limited and may be, for example, linear, rectangular, square, round, or irregular. The measurement electrode 20 of this embodiment is rectangular in plan view. At least a portion, preferably the entire upper surface 20A of the measurement electrode 20 is exposed on the surface of the cellular potential measuring device 1 to facilitate contact with the cell S. One or more measurement electrodes 20 may be provided per substrate 10. When multiple measurement electrodes 20 are provided per substrate 10, action potentials generated by the cell S can be detected while their occurrence site is locally identified. When multiple measurement electrodes 20 are provided per substrate 10, the multiple measurement electrodes 20 are preferably arranged regularly. The measurement electrode 20 is connected to a measurement wiring 30 .

[0030] There are no particular limitations on the shape and size of one measurement electrode 20. From the viewpoint of measuring the action potential of cells such as nerve cells, the size of the measurement electrode 20 is preferably a rectangle with one side measuring approximately 1 μm to 1000 μm (for example, approximately several tens of μm to 100 μm).

[0031] The measurement wiring 30 is an element for transmitting the action potential of the cell S received by the measurement electrode 20 to a connection position with a potential measuring instrument (not shown). The measurement wiring 30 is electrically connected to the measurement electrode 20. One measurement wiring 30 is provided for each measurement electrode 20. When multiple measurement electrodes 20 are provided on the substrate 10, one measurement wiring 30 is provided for at least one measurement electrode 20. Preferably, one measurement wiring 30 is provided for each of the multiple measurement electrodes 20. The measurement wiring 30 is made of an electrically conductive material. Details of the material constituting the measurement wiring 30 will be described later. The measurement wiring 30 is formed linearly in any pattern. The measurement wiring 30 typically extends from the position where the measurement electrode 20 is provided to the edge of the substrate 10. The end of the measurement wiring 30 opposite the end connected to the measurement electrode 20 may be connected to a connection terminal portion 38 that is wider than the measurement wiring 30 to ensure a reliable connection with the potential measuring instrument. The upper surface of the measurement wiring 30 is typically covered with an insulating layer 50 so as to prevent the action potential received by the measurement electrode 20 from being transmitted to other parts of the cell S. The measurement wiring 30 is typically provided directly on the substrate 10 (in other words, without any other layer therebetween), although this is not a limitation.

[0032] The inspection wiring 40 is an element for inspecting and understanding the electrical connection state of the measurement electrode 20 and the measurement wiring 30. The inspection wiring 40 is made of an electrically conductive material so that an inspection signal can be transmitted to the measurement electrode 20. Details of the material that makes up the inspection wiring 40 will be described later. The inspection wiring 40 includes an inspection electrode portion 42 and a wiring portion 44 that is electrically connected to the inspection electrode portion 42.

[0033] The inspection electrode portion 42 is provided on the substrate 10 so as to face the measurement electrode 20 while being electrically insulated from the measurement electrode 20. The inspection electrode portion 42 is typically arranged so as to face the measurement electrode 20 via an insulating layer 50, which will be described later. With this configuration, the inspection electrode portion 42 and the measurement electrode 20 form a capacitor, and inspection signals sent from the inspection wiring 40 can be propagated to the measurement electrode 20. The shape of the inspection electrode portion 42 is not particularly limited as long as it faces at least a portion of the measurement electrode 20. Furthermore, it is sufficient that at least a portion of the inspection electrode portion 42 faces the measurement electrode 20. In this embodiment, the inspection electrode portion 42 has a line shape that is narrower than the measurement electrode 20. From the viewpoint of forming a good capacitor with the measurement electrode 20, the inspection electrode portion 42 preferably has a side dimension of approximately 1 μm to 500 μm and a length of 1 μm to 1000 μm.

[0034] The wiring portion 44 is an element for transmitting a test signal output from a test device (not shown) to the test electrode portion 42. Typically, one wiring portion 44 is provided for each test electrode portion 42. The wiring portion 44 is formed linearly in any pattern. The wiring portion 44 typically extends from the position where the test electrode portion 42 is provided to the edge of the substrate 10. The end of the wiring portion 44 opposite to the end connected to the test electrode portion 42 may be connected to a connection terminal portion 48 that is wider than the wiring portion 44 in order to ensure a reliable connection with the test device.

[0035] Typically, one inspection wire 40 is provided for each measurement electrode 20. When a plurality of measurement electrodes 20 are provided on the substrate 10, one inspection wire 40 is provided for at least one measurement electrode 20. Preferably, one inspection wire 40 is provided for each of the plurality of measurement electrodes 20. The upper surface of the inspection wire 40 is typically covered with an insulating layer 50 so that the inspection signal to be sent to the measurement electrode 20 is not applied to the cells S, etc. Although not limited thereto, the inspection wire 40 of this embodiment, together with the inspection electrode portion 42 and the wiring portion 44, is provided directly on the substrate 10 (in other words, without any other layer interposed therebetween).

[0036] The insulating layer 50 is an element for insulating at least the measurement electrode 20 from the inspection wiring 40. The insulating layer 50 preferably also functions to insulate the top and side surfaces of the measurement wiring 30 and the inspection wiring 40 from the outside. Therefore, the insulating layer 50 is essentially disposed in a region including the portions where the measurement wiring 30 and the inspection wiring 40 are disposed and their peripheral portions in a planar view. The insulating layer 50 does not necessarily have to be provided in a region of the top surface 10A of the substrate 10 that is distant from the measurement wiring 30 and the inspection wiring 40 in a planar view. In a region distant from the measurement wiring 30 and the inspection wiring 40, for example, the top surface 10A of the substrate 10 may be exposed. Alternatively, in a region distant from the measurement wiring 30 and the inspection wiring 40, for example, the measurement electrode 20 may be provided directly on the top surface 10A of the substrate 10. However, in each plan view of the cellular potential measuring device 1 of the present application, the outline of the insulating layer 50 is omitted to facilitate understanding of the relative relationships between the measurement electrodes 20, the measurement wiring 30, and the testing wiring 40. This also applies to the following embodiments.

[0037] The insulating layer 50 is made of an insulating material. Details of the material constituting the insulating layer 50 will be described later. In this embodiment, the insulating layer 50 is laminated in a region where the measurement wiring 30 and the inspection wiring 40 are arranged and on the periphery thereof in a plan view, covering the top and side surfaces of the measurement wiring 30 and the inspection wiring 40. The insulating layer 50 in this embodiment is also provided in a position below the measurement electrode 20 so as to support the measurement electrode 20 in a position where the measurement wiring 30 and the inspection wiring 40 are not provided. The thickness of the insulating layer 50 between the measurement electrode 20 and the inspection electrode portion 42 (inspection wiring 40), in other words, the distance between the measurement electrode 20 and the inspection electrode portion 42 (inspection wiring 40), can be appropriately designed based on the relationship between the dielectric constant of the material constituting the insulating layer 50, the opposing area between the measurement electrode 20 and the inspection electrode portion 42, and the electrostatic capacitance required for the capacitor formed by the measurement electrode 20 and the inspection electrode portion 42. The distance between the measurement electrode 20 and the inspection electrode portion 42 is preferably, for example, 10 nm or more (preferably 30 nm or more) and 100 μm or less (preferably 20 μm or less).

[0038] In this embodiment, as described above, the measurement wiring 30 and the testing wiring 40 are provided on the substrate 10 without any other layers in between. The measurement electrode 20 is disposed above the testing wiring 40 with the insulating layer 50 interposed therebetween. A contact hole CH is provided in the insulating layer 50, and the measurement electrode 20 and the measurement wiring 30 are electrically connected by, for example, filling the contact hole CH with a material that constitutes the measurement electrode 20. In other words, the cellular potential measuring device 1 can be constructed as a layered structure of the insulating layer 50 and the conductive layers that constitute the measurement electrode 20, the measurement wiring 30, and the testing wiring 40.

[0039] The conductive layers (the measurement electrode 20, the measurement wiring 30, and the inspection wiring 40) can all be made of conductive materials. Examples of such conductive materials include metal materials, conductive resin materials, and conductive inorganic materials. Metal materials are preferred because of their excellent thermal stability and electrical conductivity. Examples of metal materials include gold (Au), silver (Ag), copper (Cu), titanium (Ti), aluminum (Al), nickel (Ni), chromium (Cr), molybdenum (Mo), niobium (Nb), tantalum (Ta), and tungsten (W), alloys containing such metals, and alloys containing two or more of these metals. Metals containing these elements have high electrical conductivity, which allows for reduced resistivity even when fine electrodes and wiring are formed. Suitable examples of metal materials include Au, Ag, Cu, W, Ti, Al, tantalum nitride (TaN), and molybdenum-tungsten alloy (MoW). The conductive layers (e.g., the measurement wiring 30 and the testing wiring 40) located closer to the substrate 10 and their portions in contact with the substrate 10 are preferably made of metals with relatively high melting points, such as Ta, W, Mo, Ni, and Ti. Furthermore, from the viewpoint of avoiding signal degradation, portions located relatively far from the substrate 10 are preferably made of metals with relatively low resistance, such as Au, Al, and Cr. To reduce wiring resistance, a single-layer structure using a low-resistance MoW alloy may be used, or a multilayer structure, such as W / TaN, Ti / Al / Ti, or Cu / Ti, may be used, from the top layer down, to achieve both adhesion to the base (e.g., the substrate) and low resistance. Suitable metal materials for the conductive layers located in the areas that may come into contact with the cells S include Au and Ti, which have low cytotoxicity. The measurement wiring 30 and the testing wiring 40 in this embodiment are made of these metal materials.

[0040] Suitable conductive resin materials include, for example, conductive polyacetylene, conductive polythiophene, conductive polyaniline, and conductive polyethylenedioxythiophene (PEDOT). Suitable conductive inorganic materials include semiconductor oxides (which may be metal oxides) with a band gap of 3 eV or greater, such as tin oxide (SnO; including tin oxide doped with antimony (Sb), ta, or fluorine (F)), zinc oxide (ZnO; including zinc oxide doped with gallium (Al), gallium (Ga), or the like), indium tin oxide (ITO), indium zinc oxide (IZO), and indium gallium zinc oxide (IGZO). These semiconductor oxides have been confirmed to be transparent and bioinert. As will be described in the following examples, the measurement electrode 20 can be fabricated to have a larger area than the measurement wiring 30 and the testing wiring 40. In such a case, it is preferable that the measurement electrode 20 is made of a material transparent to visible light, like the substrate 10, because the measurement electrode 20 does not block the cells S when the cultured cells S are observed from the underside of the substrate 10. For example, the measurement electrode 20 in this embodiment is made of ITO. By using such a material, a stable conductive layer with low cytotoxicity can be produced.

[0041] The insulating layer 50 can be made of a material having the same electrical insulating properties as the substrate 10, and any material that exhibits stable electrical insulating properties in a cell culture environment can be used without particular limitation. The insulating layer 50 is not limited to these, but considering that the measuring electrode 20, the measuring wiring 30, and the testing wiring 40 are in contact with each other and are insulated from each other, it is preferable to make the insulating layer 50 from, for example, silicon nitride (e.g., Si3N4), silicon oxide (e.g., SiO2), silicon oxynitride (e.g., Si2N2O), etc. The insulating layer 50 may have a single-layer structure made of any of these materials, or may have a laminate structure made of two or more of these materials. While the representative compositions of the above materials are shown in parentheses, the compositions of each material are not limited to these.

[0042] (Manufacturing method) The method for manufacturing the cellular potential measuring device 1 described above is not particularly limited, and it can be suitably manufactured, for example, by the following procedure. Specifically, first, a substrate 10 made of an alkali-free glass plate or the like is prepared, and measurement wiring 30 and inspection wiring 40 are fabricated in a predetermined pattern shape on one surface (top surface 10A) of this substrate 10. If connection terminals 38, 48 are provided, these measurement wiring 30 and inspection wiring 40 are also fabricated simultaneously. The measurement wiring 30 and inspection wiring 40 can be suitably formed, for example, by forming a conductive film made of the above-mentioned metal material on the entire top surface 10A of the substrate 10 by sputtering or vapor deposition, and then patterning the conductive film into a predetermined shape by lithography (e.g., photolithography, laser lithography, etc.). In photolithography, a photoresist pattern is typically formed by applying a resist solution to a film to be patterned (here, a conductive film), exposing it to light, and rinsing it. Then, by using this photoresist pattern as a mask to perform an etching process on the conductive film, the conductive film portions not covered by the mask can be removed, thereby obtaining a conductive film with the desired pattern shape. To reduce wiring resistance, the measurement wiring 30 and the inspection wiring 40 may have, for example, a single-layer structure made of a low-resistance MoW alloy, or a laminated structure such as W / TaN or Ti / Al / Ti. The thickness of each of the measurement wiring 30 and the inspection wiring 40 is not particularly limited, and may be, for example, approximately 10 nm or more (preferably 30 nm or more) and 1 μm or less (preferably 500 nm or less).

[0043] Next, the substrate 10 and the upper surfaces of the formed measurement wiring 30 and inspection wiring 40 are covered with an insulating layer 50. The insulating layer 50, formed in a plan view except for the areas where the measurement electrodes 20, the measurement wiring 30, and the inspection wiring 40 are arranged and their peripheral edges, is removed by etching or the like. At this time, the insulating layer 50 formed on the connection terminal portions 38, 48 is also removed by etching or the like. Furthermore, by partially removing the insulating layer 50 covering the measurement wiring 30, a contact hole CH is formed, exposing the measurement wiring 30. This allows the surfaces of the measurement wiring 30 and the inspection wiring 40 to be selectively covered with the insulating layer 50. The thickness of the insulating layer 50 is not particularly limited, and may be, for example, in the range of approximately 10 nm or more (preferably 30 nm or more) to 100 μm or less (preferably 20 μm or less).

[0044] Then, the measuring electrode 20 is formed in a predetermined shape on the insulating layer 50 so as to fill the contact hole CH. The measuring electrode 20 is made of a transparent conductive material such as ITO. The layer made of the transparent conductive material can be formed, for example, by sputtering. If the connection terminals 38, 48 are provided, the transparent conductive material may also be sputtered onto these connection terminals 38, 48. The thickness of the transparent conductive material (i.e., the measuring electrode 20) may be, for example, approximately 10 nm (preferably 30 nm or more) to 300 nm or less (preferably 100 nm or less). This prevents the layer made of the metal material from being exposed on the outermost surface, allowing the production of a cellular potential measuring device 1 with excellent chemical stability.

[0045] (Action and effect) In the above embodiment, the cellular potential measuring device 1 comprises an insulating substrate 10, measurement wiring 30 provided on the substrate 10, an insulating layer 50 provided on the substrate 10 and covering at least the surface of the measurement wiring 30, a measurement electrode 20 provided on the insulating layer 50 and electrically connected to the measurement wiring 30, and an inspection wiring 40 provided on the substrate 10, at least a portion of which is positioned below the measurement electrode 20 via the insulating layer 50.

[0046] Using this cellular potential measuring device 1, the electrical connection between the measurement electrode 20 and the measurement wiring 30 can be inspected. Specifically, as shown in FIG. 3, when measuring the action potential of a cell, a test signal with a pulse waveform as shown in FIG. 4 is input in advance from a test device (not shown) to the test electrode unit 42 via the connection terminal unit 48 and the wiring unit 44. Here, the measurement electrode 20 and the test electrode unit 42 (test wiring 40) form a capacitor, so that the test signal can be propagated between the measurement electrode 20 and the test wiring 40 while maintaining electrical insulation between them. For example, when a charge is accumulated in the test electrode unit 42 by the test signal, a corresponding charge of the opposite polarity is accumulated in the measurement electrode 20. When the charge in the test electrode unit 42 disappears, the opposite polarity charge in the measurement electrode 20 also disappears. This allows the test signal to be propagated to the measurement electrode 20. At this time, if the electrical connection between the measurement electrode 20 and the measurement wiring 30 and the contact hole portion connecting them is good and there is no break or other problem in either the measurement electrode 20 or the measurement wiring 30, the test signal from the measurement electrode 20 is detected by a potential meter (not shown) via the measurement wiring 30 and the connection terminal portion 38. As a result, it can be confirmed that there are no electrical defects in the measurement electrode 20 and the measurement wiring 30 and that a continuity state is ensured. Also, for example, as shown in FIG. 3, the measurement wiring 30b is broken. At this time, even if a test signal is input to the test wiring 40, no test signal is detected from the measurement wiring 30b. In this way, the fact that the potential meter does not detect a response test signal can be used to confirm that continuity between the measurement electrode 20 and the measurement wiring 30 is not ensured.

[0047] In addition, by comparing the input waveform of the test signal to the test wiring 40 (see FIG. 4) with the output waveform from the measurement wiring 30 (see FIG. 5), electrical characteristics such as the resistance, signal delay, and signal attenuation of each measurement electrode 20 and measurement wiring 30 can be determined. For example, the better the conduction state between the measurement electrodes 20a-20d and the measurement wiring 30a-30d, the closer the shape and magnitude of the output waveform to the input waveform. Conversely, the worse the conduction state between the measurement electrodes 20a-20d and the measurement wiring 30a-30d, the more the shape of the output waveform changes relative to the input waveform and the greater the attenuation may be. In this way, by comparing the output waveform from each measurement wiring 30a-30d with the input waveform of the test signal, the conduction characteristics between the measurement electrodes 20a-20d and the measurement wiring 30a-30d can be evaluated.

[0048] The results of measuring the action potential of cell S using the cellular potential measuring device 1 are shown schematically as graphs (a) to (d) at the bottom of FIG. 3. For ease of explanation, it is assumed that the same action potential is input from cell S to each of measurement electrodes 20a to 20d. In graph (b) of FIG. 3, which shows the measurement results using measurement electrode 20b connected to disconnected measurement wiring 30b, no test signal is detected. This cellular potential measuring device 1 can determine that the electrical continuity between measurement electrode 20b and measurement wiring 30b is poor in a previous electrode test. Therefore, the lack of a test signal in graph (b) can be understood to be due to poor electrical continuity, such as a disconnection, between measurement electrode 20b and measurement wiring 30b, rather than due to cell S not generating a local action potential at the position of measurement electrode 20b. Furthermore, the relatively large test signal detected in graph (a) can be understood to be due to cell S generating a local action potential at the position of measurement electrode 20a.

[0049] Furthermore, although not specifically shown, a more detailed evaluation of the activity of cell S can be performed by analyzing the signals detected in graphs (a), (c), and (d) over time. Specifically, for example, in biological tissue, the transmission of information from one neuron to another is accompanied by a sharp electrical change (impulse) lasting less than 1 millisecond. It is known that the magnitude of this action potential does not depend on the magnitude of the information stimulus, but the number of impulses fired per unit time increases as the information stimulus increases. By using the cellular potential measuring device 1 according to the present technology, the state of information transmission (activity) between such neurons can be quantified and understood over time and two-dimensionally. Furthermore, by feeding back the evaluation results of the electrical characteristics of each measurement electrode 20 and measurement wiring 30 (e.g., characteristics related to signal attenuation and delay) to the analysis of the cellular action potential, more accurate measurement of cellular activity is possible.

[0050] In a conventional cellular potential measuring device 1X (see FIGS. 22 and 23 ) that does not include a test wiring, if a test signal is input to the test wiring 40X and the desired detection result is not obtained from the measurement wiring 30X, it is impossible to determine whether the cause is a problem with the cellular potential measuring device 1X or the cell itself. In the cellular potential measuring device 1 of this embodiment, when a test signal is input to the test wiring 40, the signal detected from the measurement wiring 30 can be used to determine the continuity state, including whether the electrical connection from the measurement electrode 20 to the measurement wiring 30 is secured. This allows for testing whether cellular potential measurement can be performed normally. Furthermore, the detection signal detected from the measurement wiring 30 can be analyzed with higher accuracy. This configuration can be particularly effective when the number of electrodes is increased to measure the activity state of cells in detail with high sensitivity.

[0051] In the above embodiment, the inspection wiring 40 includes an inspection electrode portion 42 that faces the measurement electrode 20, and a wiring portion 44 that extends from the inspection electrode portion 42. The distance between the measurement electrode 20 and the inspection electrode portion 42 is 10 nm or more and 100 μm or less. This configuration is preferable because it allows the capacitor structure formed by the measurement electrode 20 and the inspection electrode portion 42 (inspection wiring 40) to be configured in a manner suitable for determining the electrical continuity between the measurement electrode 20 and the measurement wiring 30.

[0052] In the above embodiment, the insulating layer 50 covers the surface of the testing wire 40. With this configuration, even if the cell S to be observed placed in the cellular potential measuring device 1 is located above the testing wire 40, the cell S is insulated from the testing wire 40. As a result, the action potential generated by the cell S is prevented from propagating to the testing wire 40. In other words, the action potential generated by the cell S is prevented from being received by the testing wire 40 and propagated as noise to the measurement electrode 20 and the measurement wiring 30. Furthermore, when a testing signal is sent through the testing wire 40 to determine the electrical continuity between the measurement electrode 20 and the measurement wiring 30, the testing signal is prevented from being applied to the cell S as an electrical stimulus. This prevents unintended electrical stimuli from being applied to the cell S. Ultimately, the action potential of the cell S can be measured more accurately. With this configuration, the cellular potential measuring device 1, which includes multiple combinations of the measurement electrode 20, the measurement wiring 30, and the testing wire 40, can locally identify the location of the cell emitting the detected action potential with high accuracy.

[0053] In the above embodiment, the entire testing wiring 40 is provided directly on the substrate 10. With this configuration, when the cellular potential measuring device 1 is fabricated using, for example, lithography technology, the testing wiring 40 can be formed on the substrate 10 using the same material as the measurement wiring 30 and in the same process. Furthermore, the lithography technology is also preferable in that providing the testing wiring 40 directly on the substrate 10 allows the testing wiring 40 to be suitably formed from a metal material with high electrical conductivity.

[0054] In the above embodiment, the measurement electrode 20 is made of ITO (an example of a transparent conductive material). This configuration allows the measurement electrode 20 to be transparent. For example, when the area of ​​the measurement electrode 20 is enlarged and a portion of the measurement electrode 20 is disposed directly on the glass substrate 10, the transparency of the portion of the glass substrate 10 where the measurement electrode 20 is disposed directly can be maintained. As a result, when measuring the action potential of the cell S, the cell S can be observed, for example, from the underside of the glass substrate 10 through the transparent measurement electrode 20. Furthermore, ITO is an inorganic conductive material, and is suitable for its low cytotoxicity and high chemical stability in a cell culture environment.

[0055] In the above embodiment, the measurement electrode 20 includes a plurality of measurement electrodes 20a to 20d (an example of a first measurement electrode (third electrode) and a second measurement electrode (fourth electrode)). The testing wiring 40 includes a testing electrode portion (second electrode portion) 42 facing the measurement electrode 20 and a wiring portion 44 extending from the testing electrode portion 42. The testing electrode portion 42 includes a plurality of testing electrode portions 42a to 42d (an example of a first testing electrode portion (third electrode portion) and a second testing electrode portion (fourth electrode portion)) facing the plurality of measurement electrodes 20a to 20d, respectively. The plurality of testing electrode portions 42a to 42d are connected to one wiring portion 44. With this configuration, one cellular potential measuring device 1 can measure the action potential of a cell using two or more measurement electrodes 20, and can test the continuity of each of the plurality of measurement electrodes 20 and the measurement wiring 30. Furthermore, since the plurality of test electrode units 42a to 42d are connected to one wiring unit 44, test signals can be easily input. This allows, for example, action potentials of a plurality of cells to be easily measured. Also, action potentials of different parts of a single cell can be easily measured.

[0056] [Embodiment 2] Embodiment 2 will be described with reference to FIGS. 6 and 7. In Embodiment 1, both the inspection electrode portion 42 and the wiring portion 44 of the inspection wiring 40 were provided directly on the substrate 10. The insulating layer 50 was configured as a single layer (however, this single layer may have a laminated structure). In contrast, in the cellular potential measuring device 100 of Embodiment 2, the insulating layer 150 includes a first insulating layer 152 disposed on the upper surface 10A of the substrate 10 and a second insulating layer 154 disposed above the first insulating layer 152. In addition, in the inspection wiring 140, both the inspection electrode portion 142 and the wiring portion 144 are provided on the first insulating layer 152. The other configurations, functions, and effects are the same as those of Embodiment 1, and therefore, redundant description will be omitted.

[0057] The first insulating layer 152 is provided in a plan view on the measurement electrode 20, the measurement wiring 30, the inspection wiring 140, and the peripheral areas thereof. The first insulating layer 152 covers the measurement wiring 30 from above in the portion where the measurement wiring 30 is provided. The first insulating layer 152 is disposed between the substrate 10 and the inspection wiring 140 in the portion where the inspection wiring 140 is provided. The second insulating layer 154 is provided in a plan view on the region where the measurement electrode 20, the measurement wiring 30, and the inspection wiring 140 are provided, and on the peripheral areas thereof. The second insulating layer 154 covers the inspection wiring 140 from above in the portion where the inspection wiring 140 is provided. The second insulating layer 154 covers the first insulating layer 152 from above in the portion where the inspection wiring 140 is not provided. The second insulating layer 154 is disposed between the inspection electrode 142 and the measurement electrode 20. The first insulating layer 152 and the second insulating layer 154 can each independently be made of the insulating material listed in embodiment 1. The first insulating layer 152 and the second insulating layer 154 may each independently have a laminated structure.

[0058] (Manufacturing method) The cellular potential measuring device 100 described above can be suitably fabricated using, for example, known lithography techniques, as in the first embodiment. Specifically, first, the measurement wiring 30 is fabricated in a predetermined pattern on one surface (top surface 10A) of the substrate 10. The measurement wiring 30 of this embodiment is configured with a laminated structure containing aluminum (for example, Ti / Al / Ti laminated from the top). Next, a first insulating layer 152 is laminated on the top surface of the substrate 10 in an area where the measurement electrodes 20, the measurement wiring 30, and the inspection wiring 140 are arranged in plan view, as well as on the periphery thereof. Thereafter, the inspection wiring 140 (the inspection electrode portion 142 and the wiring portion 144) is laminated in a predetermined pattern on the top surface of the first insulating layer 152. The inspection wiring 140 of this embodiment is configured with a laminated structure containing aluminum (for example, Ti / Al / Ti laminated in this order). Next, second insulating layer 154 is laminated on the upper surfaces of first insulating layer 152 and testing wiring 140. After that, first insulating layer 152 and second insulating layer 154 covering measurement wiring 30 are partially removed to form contact hole CH and expose measurement wiring 30. Then, measurement electrode 20 is formed in a predetermined shape on the upper surface of second insulating layer 154, filling contact hole CH. This establishes electrical continuity between measurement electrode 20 and measurement wiring 30, completing cellular potential measuring device 100.

[0059] With the above configuration, inspection electrode portion 142 can be disposed below measurement electrode 20 without contacting substrate 10. This allows for a wider range of choices for the material that constitutes inspection electrode portion 142 (inspection wiring 140). For example, when cellular potential measuring device 100 is formed using lithography technology, heat from substrate 10 is less likely to be transmitted to inspection wiring 140, so inspection wiring 140 can be suitably formed using a material that is relatively poor in thermal stability and substrate conformability but has low resistance.

[0060] In the above embodiment, the measurement wiring 30 and the inspection wiring 140 are respectively configured by laminating Ti / Al / Ti in that order from the top layer and Ti / Al / Ti in that order. This configuration is preferable because it is possible to narrow the line width of the measurement wiring 30 and the inspection wiring 140 and to increase the thickness to reduce the resistance.

[0061] [Embodiment 3] Embodiment 3 will be described with reference to Figures 8 and 9. In Embodiments 1 and 2, the inspection electrode portions 42, 142 and wiring portions 44, 144 of the inspection wiring 40, 140 were all fabricated on the substrate 10 or the first insulating layer 152 in the same process (in other words, at the same level). Furthermore, the inspection electrode portions 42, 142 and wiring portions 44, 144 were all made of the same material. In contrast, the cellular potential measuring device 200 of Embodiment 3 differs from the above embodiments in the configuration of the insulating layer 250 and the inspection wiring 240. The other configurations, actions, and effects are the same as those of Embodiments 1 and 2, and therefore, redundant description will be omitted.

[0062] The inspection wiring 240 includes an inspection electrode portion 242 facing the measurement electrode 20 and a wiring portion 244 extending from the inspection electrode portion 242. Like the measurement wiring 30, the wiring portion 244 is provided directly on the substrate 10. The inspection electrode portion 242 is provided on an insulating layer 250. The insulating layer 250 also includes a first insulating layer 252 disposed between the substrate 10 and the inspection electrode portion 242, and a second insulating layer 254 disposed between the inspection electrode portion 242 and the measurement electrode 20. The first insulating layer 252 is provided in a region where the measurement electrode 20, the measurement wiring 30, and the wiring portion 244 are disposed and on the periphery thereof in a plan view. The first insulating layer 252 covers the measurement wiring 30 and the wiring portion 244 from above in the region where the measurement wiring 30 and the wiring portion 244 are provided. The first insulating layer 152 abuts against the substrate 10 in a portion where the measurement wiring 30 and the wiring portion 244 are not provided. The inspection electrode portion 242 is provided on the first insulating layer 252 below the measurement electrode 20. The second insulating layer 254 is provided in a region overlapping the first insulating layer 252 in a plan view. The second insulating layer 254 covers the inspection electrode portion 242 from above in a portion where the inspection electrode portion 242 is provided on the first insulating layer 252. The second insulating layer 254 abuts against the first insulating layer 252 in a portion where the inspection electrode portion 242 is not provided. The inspection electrode portion 242 and the wiring portion 244 are connected via a contact hole CH.

[0063] (Manufacturing method) The cellular potential measuring device 100 described above can be suitably fabricated using, for example, known lithography techniques, as in the first embodiment. Specifically, first, the measurement wiring 30 and wiring portion 244 are fabricated in a predetermined pattern on one surface (upper surface 10A) of the substrate 10. In this embodiment, the measurement wiring 30 and wiring portion 244 are made of a metallic material. Next, a first insulating layer 252 is laminated on the upper surfaces of the substrate 10, the measurement wiring 30, and the wiring portion 244. Then, contact holes CH are formed by partially removing the first insulating layer 252 covering the wiring portion 244, thereby exposing the wiring portion 244. In this state, the test electrode portion 242 is fabricated in a predetermined pattern on the upper surface of the first insulating layer 252, filling the contact holes CH. In this embodiment, the test electrode portion 242 is fabricated from a metallic material. As a result, the test electrode portion 242 and the wiring portion 244 are connected via the contact holes CH. Next, a second insulating layer 254 is laminated on the upper surfaces of the first insulating layer 252 and the testing electrode portion 242. After that, the first insulating layer 252 and the second insulating layer 254 covering the measurement wiring 30 are partially removed to form contact holes CH and expose the measurement wiring 30. Then, the measurement electrode 20 is formed in a predetermined shape on the upper surface of the second insulating layer 254 by filling the contact holes CH. In this embodiment, the measurement electrode 20 is made of a transparent conductive material (e.g., ITO). This establishes electrical conduction between the measurement electrode 20 and the measurement wiring 30, completing the cellular potential measuring device 200.

[0064] According to the above configuration, the wiring portion 244 and the measurement wiring 30 of the inspection wiring 240 are provided with the first insulating layer 252 and the second insulating layer 254, respectively, thereby providing more reliable insulation to prevent propagation of an action potential from the cell S to be observed. Furthermore, the wiring portion 244 can be made of a material different from that of the inspection electrode portion 242 and is provided on the substrate 10 together with the measurement wiring 30. Therefore, the wiring portion 244 of the inspection wiring 240 can be made of a metal material with high electrical conductivity. The inspection electrode portion 242 is disposed below the measurement electrode 20 so as not to abut the substrate 10, and can be made of a transparent conductive material (e.g., ITO). As a result, when observing the cell S from the underside of the substrate 10, the cell S can be observed without being obstructed by the measurement electrode 20 and the inspection electrode portion 242. This allows for more accurate electrode inspection and cell action potential measurement.

[0065] [Embodiment 4] Embodiment 4 will be described with reference to Figures 10 and 11. In Embodiments 2 and 3, first insulating layers 152, 252 and second insulating layers 154, 254 are laminated directly above measurement wiring 30. In contrast, cellular potential measuring device 300 of Embodiment 4 differs from the above embodiments in that shielding layer 346 is interposed between first insulating layer 352 and second insulating layer 354 above measurement wiring 330. Other configurations, actions, and effects may be the same as those of Embodiments 1 to 3, and redundant description will be omitted.

[0066] The shield layer 346 is made of a conductive material having electrical conductivity. The shield layer 346 is provided above the measurement wiring 330, between the first insulating layer 352 and the second insulating layer 354, and is an element that shields the measurement wiring 330 from noise. The shield layer 346 is insulated from the measurement electrodes 320. The shield layer 346 is formed wide so as to cover the multiple measurement wirings 330 in the width direction in a plan view. Although not limited to this, the shield layer 346 is preferably connected to a ground potential.

[0067] When a cell culture environment, such as a cell culture solution or cell culture medium, is placed on cellular potential measuring device 300, there is a concern that action potentials generated by the cells may propagate to measurement wiring 330 via the culture solution or medium and be detected as noise. According to the above configuration, shield layer 346 is present between first insulating layer 352 and second insulating layer 354. Therefore, a first capacitor is formed by a laminated structure made up of second insulating layer 354 and shield layer 346. Furthermore, a second capacitor is formed by a laminated structure made up of shield layer 346, first insulating layer 352, and measurement wiring 330. This effectively prevents noise from propagating from the cell culture environment to measurement wiring 330.

[0068] [Embodiment 5] Embodiment 5 will be described with reference to FIGS. 12 to 14. In Embodiment 4, testing wiring 340 is configured as a single system of wiring in which multiple testing electrode sections 342 are connected to one wiring section, and measurement wiring 30 is shielded by shield layer 346. In contrast, cellular potential measuring device 400 of Embodiment 5 differs from Embodiment 4 in that testing wiring 440 is configured as two systems of wiring (first testing wiring 440A and second testing wiring 440B) and the configuration of shield layer 446 is changed. Other configurations, actions, and effects may be the same as those of Embodiments 1 to 4, and redundant explanations will be omitted.

[0069] In this embodiment, the multiple shield layers 446 are each connected to the test electrode portion 442. In other words, the shield layers 446 are configured by extending the test electrode portions 442. However, if the shield layers 446 and the test electrode portions 442 were simply connected, a test signal would also be transmitted to the measurement wiring 430 when testing the conductivity of the measurement electrodes 420 and the measurement wiring 430, making it impossible to determine whether the contact between the measurement electrodes 420 and the measurement wiring 430 is good. Therefore, the cellular potential measuring device 400 has test wiring 440 configured as follows.

[0070] The cell potential measuring device 400 includes a plurality of measuring electrodes 420 n ,420 n+1 ,420 n+2 ,420 n+3 , ... (n is an integer of 1 or more). n ,420 n+1 ,420 n+2 ,420 n+3 When the plurality of measurement electrodes 420 are collectively referred to, they are simply referred to as "a plurality of measurement electrodes 420." The plurality of measurement electrodes 420 are arranged in one direction. The plurality of measurement electrodes 420 are arranged in a plurality of adjacent first measurement electrodes 420. n ,420 n+2 , ... and the second measurement electrode 420 n+1 ,420 n+3 , .... The plurality of measurement electrodes 420 n ,420 n+1 ,420 n+2 ,420 n+3 , . . . each have a plurality of measurement wirings 430 n ,430 n+1 ,430 n+2 ,430 n+3 ,... are connected.

[0071] The plurality of measurement wirings 430 are connected to the first measurement electrode 420. n ,420 n+2 , . . . the first measurement wiring (third wiring) 430 connected to n ,430 n+2 , ... and the second measurement electrode 420 n+1 ,420 n+3 , . . . the second measurement wiring (fourth wiring) 430 connected to n+1 ,430 n+3 , . . . The plurality of shield layers 446 can also be divided into the first measurement wiring 430 n ,430 n+2 , . . . a first shield layer 446 for shielding the n ,446 n+2 , ... and the second measurement wiring 430 n+1 ,430 n+3 , . . . a second shield layer 446 for shielding the n+1 ,446n+3 ,... and can be divided into.

[0072] The inspection wiring 440 includes an inspection electrode portion 442 facing the measurement electrode 420 and a wiring portion 444 extending from the inspection electrode portion 442. The inspection electrode portion 442 is connected to the plurality of first measurement electrodes 420. n ,420 n+2 , . . . a plurality of first test electrode portions 442 respectively facing n ,442 n+2 , ...and a plurality of second measurement electrodes 420 n+1 ,420 n+3 , . . . n+1 ,442 n+3 , . . . The wiring portion 444 includes the first test electrode portion 442. n ,442 n+2 , . . . and a first wiring portion 444A connected to the second test electrode portion 442 n+1 ,442 n+3 , . . . and a second wiring portion 444B connected to the first test electrode portion 442 n ,442 n+2 , ... and the first wiring portion 444A have the same structure as the inspection wiring 140 in the second embodiment. n+1 ,442 n+3 , ... and the second wiring portion 444B have the same structure as the inspection wiring 240 in embodiment 3. That is, the inspection wiring 440 includes a first inspection wiring 440A including the first wiring portion 444A, and a second inspection wiring 440B including the second wiring portion 444B.

[0073] The first measurement electrodes 420 in the first inspection wiring 440A n ,420 n+2 , ... and the plurality of second measurement electrodes 420 in the second inspection wiring 440B. n+1 ,420 n+3 , ... are alternately arranged in one direction along the surface of the substrate 10. In other words, the first test electrode portions 442 n ,442 n+2 , ... and the second test electrode portion 442 n+1,442 n+3 , ... are arranged alternately with one another along one direction in a plan view.

[0074] The first wiring portion 444A of the first testing wiring 440A and the plurality of measurement wirings 430 are provided directly on the substrate 10. The insulating layer 450 includes a first insulating layer 452 and a second insulating layer disposed above the first insulating layer 452. Here, the first insulating layer 452 is provided in the area where the plurality of measurement electrodes 420, the plurality of measurement wirings 430, and the testing wiring 440 are disposed and on the periphery thereof in plan view, and covers the first wiring portion 444A and the measurement wiring 430 from above.

[0075] A plurality of first test electrode portions 442 in the first test wiring 440A n ,442 n+2 , and the second inspection wiring 440B (i.e., the plurality of second inspection electrode portions 442 n+1 ,442 n+3 , ..., and second wiring portion 444B) are provided on first insulating layer 452. In this embodiment, a plurality of shield layers 446 are additionally provided on first insulating layer 452 at positions overlapping the plurality of measurement wirings 430. Note that the first wiring portion 444A constituting the first inspection wiring 440A and the plurality of first inspection electrode portions 442 n ,442 n+2 , . . . are connected via contact holes CH formed through the first insulating layer 452.

[0076] The second insulating layer 454 is formed between the plurality of first test electrode portions 442. n ,442 n+2 , . . . , the second inspection wiring 440B and the plurality of shield layers 446 are provided on the first insulating layer 452 so as to cover them from above. A plurality of first measurement electrodes 420 are provided on the second insulating layer 454. The plurality of first measurement electrodes 420 and the plurality of measurement wirings 430 are connected to each other via contact holes CH formed through the first insulating layer 452 and the second insulating layer 454.

[0077] When an inspection signal is sent to the first inspection wiring 440A, the inspection signal is transmitted to the first wiring portion 444A, the plurality of first inspection electrode portions 442 n ,442 n+2 , ..., a plurality of first measurement electrodes 420 n ,420 n+2 , ...... through the first measurement wiring 430 n ,430 n+2 ,... is sent. When an inspection signal is sent to the second inspection wiring 440B, the inspection signal is transmitted to the second wiring portion 444B, the plurality of second inspection electrode portions 442 n+1 ,442 n+3 , ..., a plurality of second measurement electrodes 420 n+1 ,420 n+3 , ..., through the second measurement wiring 430 n+1 ,430 n+3 ,... is sent. When the test is performed using the first test wiring 440A, the plurality of second measurement electrodes 420 n+1 ,420 n+3 , . . . , and when the inspection is performed using the second inspection wiring 440B, the plurality of first inspection electrode portions 442 n ,442 n+2 ,..., no test signal is sent.

[0078] Therefore, the first shield layer 446 n ,446 n+2 , ... are set to a plurality of second measurement electrodes 420 n+1 ,420 n+3 , . . . , respectively, and the second wiring portion 444B can be grounded when testing is performed using the first testing wiring 440A. With this configuration, when testing is performed using the first testing wiring 440A, the first measurement wiring 430 n ,430 n+2 ,... can be effectively shielded from noise. In addition, the second shield layer 446 n+1 ,446 n+3 , ... are arranged as a plurality of first measurement electrodes 420 n ,420 n+2, ..., respectively, so that the first wiring portion 444A can be grounded when testing is performed using the second testing wiring 440B. With this configuration, when testing is performed using the second testing wiring 440B, the second measurement wiring 430 n+1 ,430 n+3 ,... can be effectively shielded from noise.

[0079] In the above embodiment, the measurement electrode 420 includes a plurality of first measurement electrodes and a plurality of second measurement electrodes. The measurement wiring 430 includes a plurality of first measurement wirings connected to each of the plurality of first measurement electrodes and a plurality of second measurement wirings connected to each of the plurality of second measurement electrodes. The inspection wiring 440 includes an inspection electrode portion and a wiring portion, and the inspection electrode portion 442 includes a plurality of first inspection electrode portions facing each of the plurality of first measurement electrodes via the insulating layer 450 and a plurality of second inspection electrode portions facing each of the plurality of second measurement electrodes via the insulating layer 450. The inspection wiring portion includes a first wiring portion 444A connected to each of the plurality of first inspection electrode portions and a second wiring portion 444B connected to each of the plurality of second inspection electrode portions. This configuration is convenient because, even when a large number of measurement electrodes 420 and measurement wirings 430 are provided on the substrate 10, the inspection wiring 440 can be divided into a plurality of systems (two systems in this case). Furthermore, if multiple measurement electrodes 420 and measurement wiring 430 are to be inspected using a single system of measurement wiring 430, it may become impossible to inspect all of them if there is a defect in any part of the measurement wiring 430. In contrast, by dividing the inspection wiring 440 into multiple systems, this risk can be reduced.

[0080] In the above embodiment, one of the plurality of first measurement electrodes and one of the plurality of second measurement electrodes are alternately arranged in one direction along the surface of the substrate. The insulating layer 450 includes a first insulating layer 452 arranged between the substrate 10 and the first wiring portion 444A and the plurality of first test electrode portions, the plurality of second test electrode portions, and the second wiring portion 444B, and a second insulating layer 454 provided above the plurality of first test electrode portions, the plurality of second test electrode portions, and the second wiring portion 444B and below the plurality of first measurement electrodes and the plurality of second measurement electrodes. The first wiring portion 444A and the plurality of first test electrode portions are connected via a through portion penetrating the first insulating layer 452. This configuration allows the first test wiring 440A and the second test wiring 440B to be formed in an appropriate manner while suppressing the occurrence of short circuits, etc.

[0081] In the above embodiment, one first measurement wiring 430 n ,430 n+2 , . . . and between the first insulating layer 452 and the second insulating layer 454, a first measurement wiring 430 is provided. n ,430 n+2 , . . . one second inspection electrode portion 442 adjacent to n+1 ,442 n+3 , . . . the first shield layer 446 n ,446 n+2 , ... are provided. Also, one second measurement wiring 430 n+1 ,430 n+3 , . . . and between the first insulating layer 452 and the second insulating layer 454, a second measurement wiring 430 n+1 ,430 n+3 , . . . one first inspection electrode portion 442 adjacent to n+2 ,442 n+4 , . . . the second shield layer 446 n+1 ,446 n+3, .... This configuration allows the first testing electrode portion and the second shield layer to be continuous, and the second testing electrode portion and the first shield layer to be continuous, which is suitable for fabrication using lithography technology. Furthermore, the first shield layer and the second shield layer can be connected to the ground potential at any time using the testing wiring 440, allowing for highly accurate testing of the continuity state and measurement of the action potential.

[0082] [Embodiment 6] A sixth embodiment will be described with reference to FIG. 15. In a cellular potential measuring device 500 of the sixth embodiment, a plurality of (16 in the figure) measurement electrodes 520 are arranged in a matrix (e.g., 4 rows x 4 columns) in the center of a substantially square substrate 510. Although not specifically shown, one measurement wire 530 and one inspection wire 540 (i.e., an inspection electrode portion and a wiring portion) are provided on the substrate 10 for each measurement electrode 520, and an insulating layer (not shown) is provided to appropriately insulate these. The configurations, functions, and effects of the measurement electrode 520, the measurement wire 530, and the inspection wire 540 may be the same as those of any of the first to fifth embodiments, and redundant description will be omitted.

[0083] Furthermore, ends of the plurality of measurement wires 530 extend to a pair of side edges of substrate 510, respectively. Connection terminal groups 538A and 538B are provided on the pair of side edges of substrate 510, and ends of the plurality of measurement wires 530 are connected to connection terminal groups 538A and 538B, respectively. Ends of the plurality of inspection wires 540 extend to another pair of side edges of substrate 510, respectively. Connection terminal groups 548A and 548B are provided on the other pair of side edges of substrate 510, and ends of the plurality of inspection wires 540 are connected to connection terminal groups 548A and 548B, respectively.

[0084] A ring-shaped wall 560 is provided on the substrate 510 so as to surround all of the measurement electrodes 520. The wall 560 is a partition for forming a cell culture environment therein. The configuration of the wall 560 is not particularly limited. The wall 560 is preferably made of the above-mentioned transparent and biocompatible material so as to be suitable for cell culture and observation. The wall 560 is installed watertightly, for example, via an adhesive or the like, on the upper surface of the substrate 510 or on the insulating layer 550 covering each wiring.

[0085] According to the above configuration, the action potential of cells can be suitably measured while the cells are being cultured in cellular potential measuring device 500. Furthermore, cellular potential measuring device 500 is suitable because it can test the state of conduction between each of measurement electrodes 520 and measurement wiring 530 at any timing while the cells are being cultured.

[0086] [Embodiment 7] Embodiment 7 will be described with reference to Figures 16 to 21. In the figures, X and Y indicate the column and row directions along the surface of the substrate 610, respectively, which are perpendicular to each other. However, these directions are merely defined for convenience and should not be interpreted in a restrictive manner. Furthermore, for multiple identical components, a reference symbol may be assigned to one component, and the reference symbols for the other components may be omitted.

[0087] In the cellular potential measuring device 500 of the sixth embodiment, a plurality of (e.g., 16, typically less than 100) measuring electrodes 520 are provided on a substantially square substrate 510. In contrast, in the cellular potential measuring device 500 of the seventh embodiment, as shown in FIG. 16 , a large number of (typically 100 or more, e.g., 200 or more, e.g., 500 or more) measuring electrodes 620 are provided on a substantially square substrate 610. The number of measuring electrodes 620 provided on the substrate 610 is determined taking into consideration the size of the substrate (i.e., the size of the cell culture area), the dimensions of each measuring electrode 620, the spacing (pitch) between adjacent measuring electrodes 620, and the like. Although not specifically shown, the plurality of measuring electrodes 620 are arranged in a matrix (e.g., 100 rows x 100 columns) in the center of the substrate 610. Matters other than those described below may be the same as those in any of the first to sixth embodiments, and redundant description will be omitted.

[0088] 17 is an enlarged view of the region in which four measurement electrodes 620 are arranged in cellular potential measuring device 600. Wiring portions 644 of a plurality of test wirings 640 and a plurality of signal wirings GL are provided along the column direction on substrate 610. Also, a plurality of source wirings SL and a plurality of detection wirings DL are provided along the row direction on substrate 610. A rectangular region surrounded by these four wirings 644, GL, SL, and DL, constitutes one measurement region A, and one measurement region A is provided with one measurement electrode 620 and one test electrode portion 642 facing this measurement electrode 620.

[0089] As shown in FIGS. 18 and 19 , the wiring portion 644 is connected to a plurality of inspection electrode portions 642. The inspection electrode portion 642 of this embodiment includes an opposing portion 642A and a capacitance portion 642B. The opposing portion 642A faces the measurement electrode 620 via insulating layers 652 and 654, thereby forming a capacitor. The capacitance portion 642B is a charge storage portion that is provided so that a large amount of charge can be instantaneously supplied to the opposing portion 642A during wiring inspection. The capacitance portion 642B is located closer to the wiring portion 644 than the opposing portion 642A, and does not face the measurement electrode 620.

[0090] Note that the measurement electrode 620 faces the facing portion 642A in some regions and does not face the facing portion 642A in other regions. Although not limited to this, the measurement electrode 620 of this embodiment has a large non-facing region that does not face the facing portion 642A (test electrode portion 642), so the insulating layers 652 and 654 are not provided in the non-facing region. The insulating layers 652 and 654 are provided in areas where it is necessary to ensure insulation between the wiring 644, GL, SL, and DL and the outside. The non-facing region of the measurement electrode 620 is provided directly on the substrate 610. In this embodiment, the area of ​​the non-facing region of the measurement electrode 620 (approximately equal to the area where the measurement electrode 620 abuts on the substrate 610) accounts for 50% or more (e.g., 80% or more) of the area of ​​the measurement electrode 620. Furthermore, this non-facing region accounts for 30% or more (e.g., 50% or more) of one measurement region A.

[0091] The signal wiring GL cooperates with the wiring portion 644 and the source wiring SL to send a testing signal to the testing electrode portion 642. First, the source wiring SL will be described. The source wiring SL includes a main wiring portion SL1, a plurality of capacitance electrode portions 643, and a plurality of switch wiring portions SL2. The main wiring portion SL1 extends along the row and column direction. The plurality of capacitance electrode portions 643 and the plurality of switch wiring portions SL2 are provided one per measurement area A.

[0092] The switch wiring section SL2 includes a first switching element Tr1 and is connected to the second switching element Tr2. Both the first switching element Tr1 and the second switching element Tr2 are configured by thin film transistors TFT (an example of a field effect transistor). More specifically, the switch wiring section SL2 connects the main wiring section SL1 and the capacitive electrode section 643, and is an element for driving the second switching element Tr2 of the measurement wiring 630 (described later). The switch wiring section SL2 interposes the first switching element Tr1 between the main wiring section SL1 and the capacitive electrode section 643. The source S1 of the first switching element Tr1 is connected to the main wiring section SL1. The drain D1 of the first switching element Tr1 is connected to the capacitive electrode section 643 and the gate G2 of the second switching element Tr2. The gate G1 of the first switching element Tr1 is connected to the signal wiring GL. As shown in FIG. 20, when a drive signal for the first switching element Tr1 is sent from the signal line GL, the source S1 and drain D1 of the first switching element Tr1 are electrically connected, and charge is sent from the source line SL to the capacitive electrode portion 643.

[0093] The capacitive electrode portion 643 is an element for storing charge in the capacitive portion 642B of the inspection electrode portion 642. The capacitive electrode portion 643 is disposed opposite the capacitive portion 642B via an insulating layer (not shown). The capacitive electrode portion 643, the insulating layer, and the capacitive portion 642B form a capacitor. When a charge is supplied to the capacitive electrode portion 643, a charge is also induced in the capacitive portion 642B through the wiring portion 644. This allows a charge to be stored in the capacitive portion 642B. Furthermore, when a sufficient charge is stored in the capacitive electrode portion 643, the potential of the switch wiring portion SL2 is increased, and as shown in FIG. 21, the second switching element Tr2 is driven.

[0094] The detection wiring DL includes a main wiring section DL1 and a plurality of measurement wiring sections 630. The main wiring section DL1 extends along the row direction. The plurality of measurement wiring sections 630 are provided one for each measurement area A. One end of each of the measurement wiring sections 630 is connected to the main wiring section DL1. The other end of each of the measurement wiring sections 630 is connected to the measurement electrode 620. A second switching element Tr2 is interposed in the measurement wiring section 630. As described above, the gate G2 of the second switching element Tr2 is connected to the switch wiring section SL2. The source S2 of the second switching element Tr2 is connected to the measurement electrode 620. The drain D2 of the second switching element Tr2 is connected to the main wiring section DL1. When a sufficient charge is stored in the capacitive electrode section 643, an inspection signal is sent to the measurement electrode 620, and the second switching element Tr2 is driven.

[0095] According to the above configuration, the electrical continuity between the measurement electrode 620 and the measurement wiring 630 can be inspected by the following procedure. First, the potential of the main wiring section SL1 of the source wiring SL is adjusted so that a sufficient charge is stored in the capacitive electrode section 643 to drive the second switching element Tr2. Next, a drive signal for the first switching element Tr1 is sent from the signal wiring GL. This drives the first switching element Tr1 of the switch wiring section SL2 (see FIG. 20). As a result, charge moves from the main wiring section SL1 of the source wiring SL to the capacitive electrode section 643, and charge is stored between the capacitive electrode section 643 and the capacitive section 642B, driving the second switching element Tr2 (see FIG. 21). After charging, the drive signal from the signal wiring GL is stopped, and the conduction of the first switching element Tr1 is interrupted.

[0096] In this state, an inspection signal is transmitted from the inspection electrode portion 642 (opposing portion 642A) to the measurement electrode 620. Furthermore, the measurement electrode 620 and the measurement wiring 630 are electrically connected. Therefore, when an inspection signal is input to the inspection electrode portion 642 through the wiring portion 644, if the electrical connection between the measurement electrode 620 and the measurement wiring 630 is good, the inspection signal is output and sent to the main wiring portion DL1 of the detection wiring DL through the second switching element Tr2. The output of the inspection signal has a waveform corresponding to the electrical connection between the measurement electrode 620 and the measurement wiring 630, and analyzing the waveform allows the electrical connection state to be grasped in more detail. On the other hand, if the electrical connection between the measurement electrode 620 and the measurement wiring 630 is not good, the inspection signal is not output to the main wiring portion DL1 of the detection wiring DL. This allows abnormalities in the electrical connection state to be confirmed. Furthermore, in the measurement area A to which no drive signal or charge is sent from the signal wiring GL and source wiring SL, the first switching element Tr1 and the second switching element Tr2 are not driven, and no inspection signal is sent from the wiring section 644. This makes it possible to select the measurement electrode 620 (measurement area A) to be inspected from the multiple measurement electrodes 620.

[0097] Furthermore, when a cell generates an action potential, the action potential can be detected by the following procedure. That is, for the desired measurement area A (measurement electrode 620), similar to the above-described continuity test, an electric charge is applied between the capacitive electrode section 643 and the capacitive section 642B, and the second switching element Tr2 is driven (set to the ON state). In this state, when a cell generates an action potential, the action potential is conducted to the measurement electrode 620. As a result, the action potential signal received by the measurement electrode 620 is sent to the main wiring section DL1 of the detection wiring DL via the second switching element Tr2. This allows the cell potential to be measured with high accuracy using an electrode whose continuity has been tested.

[0098] A ring-shaped wall portion 660 is erected on the substrate 610 so as to surround the plurality of measurement electrodes 620. A plurality of connection terminals 662 are provided on the periphery of the substrate 610. The plurality of wiring portions 644, the plurality of signal lines GL, the plurality of source lines SL, and the plurality of detection lines DL are led out to the periphery of the substrate 610 and connected to these connection terminals 662. A drive signal and an inspection signal for the first switching element Tr1 can be transmitted from these connection terminals 662. Transmission of the drive signal for the first switching element Tr1, transmission of the inspection signal, and analysis of the output of the inspection signal can be performed using, for example, conventionally known liquid crystal panel inspection techniques.

[0099] <Other embodiments> The technology disclosed herein is not limited to the embodiments described above and illustrated in the drawings, and the following embodiments, for example, are also included within the technical scope.

[0100] (1) In the above embodiment, the substrate 10 is made of a colorless and transparent glass plate. However, the configuration of the substrate 10 is not limited to this example. For example, when cells as targets for action potential measurement are observed by emitting chemiluminescence or fluorescence, the substrate may be made of a white or black material.

[0101] (2) In the above embodiments, the cellular potential measuring device is mainly composed of a substrate, measurement electrodes, measurement wiring, and testing wiring. The cellular potential measuring device may also include layers other than the measurement electrodes, measurement wiring, and testing wiring, as long as the essential features of the present technology are not impaired. Examples of such layers include a protective layer.

[0102] (3) In the above-described first to fourth embodiments, the insulating layer is provided in the area occupied by the measurement electrode in plan view and in the surrounding area. However, the insulating layer does not have to be provided between the measurement electrode and the substrate as long as the insulation between the measurement electrode and the inspection wiring portion can be ensured.

[0103] (4) The cellular potential measuring device including the thin film transistor in the above embodiment can be fabricated by suitably applying known TFT array manufacturing techniques.

[0104] (5) In the above embodiments, the cellular potential measuring device mainly includes a substrate, measurement electrodes, measurement wiring, and testing wiring. However, the cellular potential measuring device may additionally include a processing device for processing signals related to action potentials acquired through the electrodes, a display for displaying analysis results, and the like. This processing device may be configured, for example, by a microcomputer, and may be configured to execute an analysis program for analyzing signal data acquired from the electrodes, thereby, for example, counting neural activity (spikes), detecting bursts, and even performing intercellular network analysis in measuring action potentials over a long period of time for nerve cells. Furthermore, for muscle cells such as cardiac muscle, the processing device may be capable of measuring extracellular potentials and analyzing response potential data related to various reactions due to cardiac contraction and relaxation. [Explanation of symbols]

[0105] 1,100,200,300,400,500,600... Cell potential measuring device, 10,510610... Substrate, 10A... Upper surface, 20,320,420,520,620... Measuring electrode (first electrode), 20A... Upper surface, 30,330,430,530,630... Measurement wiring (first wiring), 38,48... Connection terminal portion, 40,140,240,340,440,540,640... Test wiring (second wiring), 42,142,242 , 342,442,642...inspection electrode portion (second electrode portion), 442n...first inspection electrode portion (third electrode portion), 442n...second inspection electrode portion (fourth electrode portion), 44,144,444,644...wiring portion, 346,446...shield layer, 50,150,250,450,550...insulating layer, 152,252,352,452...first insulating layer, 154,254,354,454...second insulating layer, 560,660...wall portion, 662...connection terminal

Claims

1. an insulating substrate; a first wiring provided on the substrate; an insulating layer provided on the substrate and covering at least a surface of the first wiring with a through hole; a first electrode provided on the insulating layer and electrically connected to the first wiring through the through hole; a second wiring provided on the substrate, at least a portion of which is disposed below the first electrode via the insulating layer; Equipped with the first electrode is a measurement electrode for measuring a cell potential; the first wiring is a measurement wiring that is a lead wiring of the measurement electrode, The cellular potential measuring device, wherein the second wiring is a test wiring for testing an electrical connection state between the measurement electrode and the measurement wiring.

2. The second wiring is a second electrode portion facing the first electrode; a wiring portion extending from the second electrode portion, The cellular potential measuring device according to claim 1 , wherein the distance between the first electrode and the second electrode portion is not less than 10 nm and not more than 100 μm.

3. the insulating layer covers a surface of the second wiring; The cell potential measuring device according to claim 1 or 2.

4. The second wiring is provided directly on the substrate. The cell potential measuring device according to any one of claims 1 to 3.

5. The insulating layer includes a first insulating layer disposed between the substrate and the second wiring, and a second insulating layer disposed between the second wiring and the first electrode. The cell potential measuring device according to any one of claims 1 to 3.

6. The second wiring is a second electrode portion facing the first electrode; a wiring portion extending from the second electrode portion, the wiring portion is provided directly on the substrate, the insulating layer includes a first insulating layer disposed between the substrate and the second electrode portion, and a second insulating layer disposed between the second electrode portion and the first electrode. The cell potential measuring device according to any one of claims 1 to 3.

7. The cellular potential measuring device according to claim 6 , wherein the wiring portion and the second electrode portion are made of different materials.

8. The cell potential measuring device according to any one of claims 1 to 7, wherein the first electrode comprises at least one transparent conductive material selected from the group consisting of tin oxide, zinc oxide, indium zinc oxide, and indium tin oxide.

9. A cell potential measuring device as described in any one of claims 1 to 8, wherein at least a portion of the second wiring and the first wiring contain at least one element selected from the group consisting of gold, silver, copper, aluminum, tantalum, tungsten, molybdenum, niobium, and titanium.

10. The insulating layer is a first insulating layer at least a portion of which is disposed directly on the substrate; a second insulating layer at least a portion of which is provided directly under the first electrode; the first insulating layer and the second insulating layer each include a covering region disposed above the first wiring; a conductive shield layer is provided between the covering region of the first insulating layer and the covering region of the second insulating layer; The cell potential measuring device according to any one of claims 1 to 9.

11. a third electrode and a fourth electrode, each of which is the first electrode; the second wiring includes a plurality of second electrode portions facing the first electrode and wiring portions extending from the second electrode portions; the plurality of second electrode portions include a third electrode portion facing the third electrode and a fourth electrode portion facing the fourth electrode, the third electrode portion and the fourth electrode portion are connected to one of the wiring portions; The cell potential measuring device according to any one of claims 1 to 10.

12. a plurality of third electrodes, each of which is the first electrode; and a plurality of fourth electrodes, each of which is the first electrode; a plurality of third wirings, each of which is the first wiring and connected to each of the plurality of third electrodes; and a plurality of fourth wirings, each of which is the first wiring and connected to each of the plurality of fourth electrodes; one of the second wirings and another of the second wirings; The second wiring includes a second electrode portion and a wiring portion, the one second wiring includes a plurality of third electrode portions, each of which is the second electrode portion and faces the plurality of third electrodes, and a first wiring portion, which is the wiring portion and is connected to each of the plurality of third electrode portions; The other second wirings each include a plurality of fourth electrode portions that are the second electrode portion and that face the plurality of fourth electrodes, respectively, and a second wiring portion that is the wiring portion and that is connected to the plurality of fourth electrode portions, respectively. The cell potential measuring device according to any one of claims 1 to 10.

13. the plurality of third electrodes and the plurality of fourth electrodes are alternately arranged in one direction along the surface of the substrate, The insulating layer is a first insulating layer provided on the substrate and the second wiring portion and below the third electrode portions, the fourth electrode portions, and the first wiring portion; a second insulating layer provided on the third electrode portions, the fourth electrode portions, and the first wiring portion and below the third electrodes and the fourth electrodes, the second wiring portion and the plurality of fourth electrode portions are connected via through portions that penetrate the first insulating layer. The device for measuring cellular potential according to claim 12.

14. a first shield layer connected to one of the plurality of fourth electrode portions adjacent to each of the plurality of third wirings is provided above the plurality of third wirings and between the first insulating layer and the second insulating layer; a second shield layer connected to one of the third electrode portions adjacent to each of the fourth wirings is provided above the fourth wirings and between the first insulating layer and the second insulating layer; The device for measuring cellular potential according to claim 13.

15. The semiconductor device further includes a wall portion erected on the substrate so as to surround the first electrode. The cell potential measuring device according to any one of claims 1 to 14.

16. The cellular potential measuring device according to any one of claims 1 to 15, further comprising a field effect transistor provided on the substrate and connected to the second wiring.

17. The cellular potential measuring device according to any one of claims 1 to 16, further comprising a field effect transistor provided on the substrate and connected to the first wiring.

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