Neural electrode and method for manufacturing the same

Abstract

To simplify manufacturing processes, shorten creation time, and improve mass productivity of a nerve electrode.SOLUTION: A nerve electrode 1 includes a cylindrical support 10 and a flexible substrate 20 provided in the support 10. The flexible substrate 20 includes one end having an electrode 23 and the other end connected to a connector. A wire 22 extending over the flexible substrate 20 connects the electrode 23 and the connector.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a nerve electrode and a method for manufacturing the nerve electrode. [Background technology]

[0002] Neuronal activity in the brain is driven by pulsed electrical signals called action potentials that are sent from the cell body along the axon. Action potentials can be induced by external light or electrical stimulation. A neural probe is a device that inserts an electrode needle into flexible biological tissues such as the brain or nerve bundles to measure neuronal activity and input information to the nervous system in order to investigate cellular activity. Furthermore, some neural probes have been developed that can be used in conjunction with optical fibers or endoscopes.

[0003] Patent Document 1 discloses a neural probe with multipoint stimulation capabilities that can be used in conjunction with optical fibers. The neural probe has a structure in which a stainless steel needle with an integrated optical fiber is inserted into a polyimide tube that is machined with a recording electrode, wiring, and a window for light irradiation, and measures the electrical activity that occurs during optical stimulation. The recording electrode and wiring on the polyimide tube are fabricated using non-planar photofabrication technology. Non-planar photofabrication technology is a processing method that uses photolithography, laser ablation, and other techniques to perform microfabrication on non-planar samples.

[0004] Non-Patent Document 1 discloses a neural probe that can be used in conjunction with a fluorescent endoscope. Six recording electrodes are arranged in a line around the circumference of the tube's tip. This neural probe is intended for measurements in layered areas such as the cortex of the brain. The wiring on the rigid tube is fabricated using non-planar photofabrication technology. This neural probe allows an endoscope or optical fiber to be inserted inside. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2016 / 204084 [Non-Patent Document 1] Naoto Ikeda, Wenguang Ro, Tadao Matsunaga, Noriko Tsuruoka, Hajime Mushiaki, Minoru Koyamauchi, Tomoichi Oshiro, and Yoichi Haga, "Thin Tube-Shaped Nerve Probe with Endoscopic Observation Function," 35th Symposium on Sensors, Micromachines and Application Systems, 31pm2-PS-154, 2018. Summary of the Invention [Problem to be solved by the invention]

[0006] In recent years, attempts have been made to elucidate the activity of neurons deep within the brain by using neural electrodes in combination with ultrafine fluorescent endoscopes. The neural electrodes of Non-Patent Document 1 shown in Figures 12(a) and (b) can be used in combination with endoscopes, but measurements cannot be performed unless the wires (electrode pads) provided along the tube are electrically connected one by one with conductive epoxy to the wires on the printed circuit board (PCB). This connection work must be done manually, requiring skill. Therefore, there are issues with time-consuming manufacturing and low mass-producibility.

[0007] The neural electrodes and the method for manufacturing the neural electrodes disclosed herein were devised in view of these problems, and one of the objectives is to simplify the manufacturing process of the neural electrodes, shorten the production time, and increase mass productivity. [Means for solving the problem]

[0008] The neural probe disclosed herein comprises a cylindrical support and a flexible substrate attached to the support. The flexible substrate has one end having an electrode and the other end connected to a connector. and, and wiring extending on the flexible substrate connects the electrodes and the connector. The flexible substrate has an electrode portion having a rectangular shape having the electrode, and a connector portion extending from an end of the electrode portion in a direction deviating from the outer circumferential surface of the support, and is L-shaped, the electrode portion is provided on the support so as to extend along the axial direction of the support, and is wound once in a circumferential direction along the outer periphery of the support, the ends of the electrode portions in the circumferential direction face each other with a gap therebetween or face each other without creating a gap, and the wiring extends in the electrode portion along the axial direction of the support. It is characterized by: A neural electrode characterized by:

[0009] The method for manufacturing a neural probe disclosed herein includes providing an electrode on one end of a flexible substrate, extending wiring on the flexible substrate that connects the electrode to a connector to which the other end of the flexible substrate is connected, and The electrode has a rectangular electrode portion having the electrode, and a connector portion extending from an end of the electrode portion in a direction deviating from the outer circumferential surface of the cylindrical support, of The aforementioned support The electrode portion is wound once in a circumferential direction around the outer periphery of the support body so that the wiring has a portion on the electrode portion that extends along the axial direction of the support body, and the electrode portions are arranged so that the ends of the electrode portions in the circumferential direction face each other with a gap therebetween or face each other without creating a gap. It is characterized in that it is adhered to the outer peripheral surface of the support. [Effects of the Invention]

[0010] According to the neural electrode and the method for manufacturing the neural electrode of the present disclosure, the manufacturing process of the neural electrode can be simplified, the manufacturing time can be shortened, and mass productivity can be improved. [Brief explanation of the drawings]

[0011] [Figure 1] 1A and 1B are schematic diagrams illustrating the structure of a neural electrode according to an embodiment. [Figure 2] 1A and 1B are schematic diagrams illustrating a flexible printed circuit (FPC) according to an embodiment. [Figure 3] 1 is a schematic cross-sectional view of the front end of a neural electrode according to an embodiment, viewed from the front to the rear. FIG. [Figure 4] FIG. 2 is a partially enlarged schematic view of FIG. 1 for explaining a recording electrode. [Figure 5] 1A to 1C are diagrams illustrating the manufacturing process of an FPC. [Figure 6] 1A to 1C are diagrams illustrating a bending process for an FPC. [Figure 7] 1A to 1C are diagrams illustrating a bonding process for a support body and an FPC. [Figure 8] FIG. 10 is a diagram showing the state at the end of the bonding process. [Figure 9] FIG. 10 shows the use of a neural electrode in conjunction with an implant. [Figure 10] This is a variation of the FPC winding method. [Figure 11] This is a modified FPC shape. [Figure 12] FIG. 1 is a diagram illustrating a conventional neural electrode. DETAILED DESCRIPTION OF THE INVENTION

[0012] A neural electrode and a method for manufacturing the neural electrode will be described as an embodiment with reference to the drawings. The embodiments shown below are merely examples, and are not intended to exclude various modifications or applications of techniques not explicitly stated in the following embodiments. Each configuration of this embodiment can be modified in various ways without departing from the spirit of the invention. Furthermore, they can be selected or combined as needed.

[0013] In the following explanation, with the neural electrode placed on a horizontal surface, the side where the electrode is provided is defined as the front, and the opposite direction is defined as the rear, and left and right are defined based on the front and back. Furthermore, the up and down directions are defined with the direction of gravity as the downward direction and the opposite direction as the upward direction. Furthermore, the direction toward the center of the longitudinal cross section along the front-to-back direction of the neural electrode is defined as the inside, and the direction toward the periphery of the longitudinal cross section is defined as the outside.

[0014] [1. Configuration] Here, a neural electrode that can be used in conjunction with a separate insert, such as an endoscope, will be described as an example. The neural electrode according to the embodiment is intended to measure the basal ganglia, which are located deep within the brain and are involved in the initiation and termination of movement. The neural electrode can also be placed on the brain surface or in the sulci of the brain. For this reason, the required specifications must satisfy the following conditions: (A) Ensuring a lumen of 350 to 550 μm (a) Six electrodes arranged at equal intervals on the circumference (60 degree angle between electrodes) (c) Minimizing invasiveness by minimizing the outer diameter (D) Rigidity that can withstand insertion into the brain (e) Biocompatibility

[0015] [1-1. Structure] The configuration of the neural electrode 1 according to this embodiment will be described with reference to Figures 1 to 4. Figure 1 is a schematic diagram illustrating the structure of the neural electrode 1. The neural electrode 1 of this embodiment comprises, from the inside to the outside, a cylindrical support 10 and a flexible substrate 20 provided on the support 10. Furthermore, the neural electrode 1 comprises a cylindrical protector 30 that partially covers the support 10 and the flexible substrate 20.

[0016] The support 10 is a skeletal member that supports the pressure load acting on the neural probe 1. The support 10 is cylindrical, and its longitudinal cross-sectional shape along the front-rear direction is formed into, for example, a circle or an ellipse, but is not limited to these. The outer diameter and length in the front-rear direction of the cross section of the support 10 are large enough to allow the neural probe 1 to be held by hand during use, and the inner diameter of the cross section is large enough to allow the insertion body 40, which will be described later, to be inserted. The support 10 according to this embodiment has an elongated cylindrical shape. Specifically, the support 10 is a zirconia ceramic tube (manufactured by Kyocera Corporation) with an outer diameter of 800 μm, an inner diameter of 550 μm, and a length of 40 mm.

[0017] The cavity 11 provided in the support 10 extends from one end to the other in the front-rear direction and can accommodate the insert 40. The cavity 11 also functions as a flow path for collecting tissue fluid from the biological tissue and for injecting a medicinal solution into the biological tissue.

[0018] 2 is a schematic diagram illustrating the flexible substrate 20. The flexible substrate (hereinafter also referred to as FPC (Flexible Printed Circuit)) 20 is an electric circuit for measuring electrical signals in biological tissues and for applying electrical stimulation to the biological tissues.

[0019] The FPC 20 is made of a thermoplastic material that can be deformed and retain its shape when heated, such as a liquid crystal polymer (LCP) sheet. Specifically, an LCP sheet (ESPANEX L809-25-09NEL (manufactured by Nippon Steel Chemical & Material Co., Ltd.)) was used as the base material of the FPC 20.

[0020] A recording electrode (electrode) 23 is provided at one end of the FPC 20, and the other end is connected to a connector (not shown). A part of the FPC 20 including the part where the recording electrode 23 is provided is referred to as an electrode part 20a, and the other part of the FPC including the part connected to the connector is referred to as a connector part 20b.

[0021] Wiring 22 extends on the top surface (front surface) of the FPC 20, connecting the end having the recording electrodes 23 with the end connected to the connector. The wiring 22 extends continuously on the top surface of the FPC 20. The FPC 20 according to this embodiment is provided with six wirings 22, and the width of each wiring 22 and the spacing between the wirings (wiring spacing) are equal in both the electrode portion 20a and the connector portion 20b. Specifically, the wiring width of the electrode portion 20a is 100 μm, the wiring spacing is 320 μm, and the wiring width of the connector portion 20b is 300 μm, and the wiring spacing is 200 μm.

[0022] The FPC 20 has a rectangular shape or a combination of rectangular shapes. The FPC 20 according to this embodiment is formed in a shape that is a combination of rectangular shapes, i.e., a point-symmetrical L-shape. The dashed-dotted line in FIG. 2 indicates the boundary between the electrode portion 20a and the connector portion 20b of the FPC 20, with the portion extending in the front-rear direction being the electrode portion 20a and the portion extending in the left-right direction being the connector portion 20b. Specifically, the electrode portion 20a is 2.2 mm long in the left-right direction and 17 mm long in the front-rear direction, while the connector portion 20b is 2.8 mm long in the front-rear direction and 30 mm long in the left-right direction.

[0023] The electrode portion 20a is wrapped around the outer peripheral surface of the support body 10 and is adhered to the support body 10 by an adhesive 12 (see FIG. 3) applied between the support body 10 and the lower surface (back surface) of the electrode portion 20a. The adhesion method will be described later. The connector portion 20b extends from a part (e.g., an end) of the electrode portion 20a extending in the front-rear direction in a direction deviating from the outer peripheral surface (see FIG. 8). In this embodiment, the connector portion 20b extends approximately vertically to the left of the front-rear direction in which the electrode portion 20a extends.

[0024] FIG. 3 is a cross-sectional schematic diagram of the front end of the neural probe 1, viewed from the front to the rear. The connector portion 20b and the protector 30 are not shown. The FPC 20 includes an LCP (base material) 21 adhered to the outer periphery of the support 10, wiring 22 as a metal layer (first metal layer) formed on the LCP 21, recording electrodes 23 as a metal layer (second metal layer) formed on the first metal layer, and an insulating layer 24 partially covering the second metal layer. The recording electrodes 23 are evenly spaced, with an inter-electrode angle of 60 degrees. As shown in FIG. 3, there are portions of the support 10 that are not covered by the FPC 20, but these are merely small gaps due to the design. The gaps can be eliminated by matching the outer periphery of the support 10 with the left-right length of the electrode portion 20a.

[0025] 4 is a partially enlarged schematic diagram of FIG. 1 for explaining the recording electrodes 23. As shown in FIG. 4, a part of the front end of the FPC 20 is not covered with the insulating layer 24 so that the recording electrodes 23 are exposed. Also, as shown in FIG. 1, the end of the connector portion 20b on the connector connection side is not covered with the insulating layer 24 so that the wiring 22 can be connected to the connector. A method for producing the FPC 20 will be described later.

[0026] Returning to FIG. 1 , the protector 30 will be described. The protector 30 is a protective member that protects the FPC 20 from the outside and enhances the insulation of the FPC 20. The protector 30 has a cylindrical shape, and its longitudinal cross section along the anterior-posterior direction is formed, for example, as a circle or an ellipse. The outer diameter and anterior-posterior length of the cross section of the protector 30 are large enough to allow the neural probe 1 to be held by hand during use, but are shorter than the anterior-posterior lengths of the support 10 and FPC 20 so as to expose the recording electrode 23 of the FPC 20. The inner diameter of the cross section is large enough to enclose the support 10 and FPC 20. Specifically, the protector 30 was fabricated using a polyimide tube (PIT-S, manufactured by Furukawa Electric Co., Ltd.) with an outer diameter of 1080 μm, an inner diameter of 1000 μm, and a length of 1.5 to 1.6 mm.

[0027] A cavity (not shown) provided in the protector 30 extends from one end to the other in the front-rear direction and can enclose a part of the support 10 on which the FPC 20 is provided. The protector 30 also partially covers the FPC 20. In other words, the protector 30 covers the part of the electrode section 20a on which the recording electrodes 23 are not provided.

[0028] Furthermore, a slit 31 is provided at one end of the protector 30. As shown in Fig. 1, the protector 30 covers the FPC 20 so as to expose the recording electrodes 23 of the electrode portion 20a of the FPC 20 and to expose the connector portion 20b of the FPC 20 through the slit 31.

[0029] [1-2. Manufacturing method] Next, a method for manufacturing the neural probe 1 will be described with reference to Figures 5 to 8. The manufacturing method is roughly divided into a process for producing the FPC 20 and a process for assembling the support 10 and the FPC 20.

[0030] [1-2-1. Manufacturing process] FIG. 5 is a diagram illustrating the manufacturing process of the FPC 20.

[0031] <1st step> Attaching to the board In the first step, Cu foil 23a for wiring 22 is formed on LCP 21, which is bonded to the outer peripheral surface of cylindrical support 10. The procedure involves attaching a thermal release sheet 25 to a printed circuit board 26, and then attaching Cu foil 23a, LCP 21, and Cu foil 23a, in that order, on top of that. A thermal release sheet is a sheet that has the characteristic of losing its adhesive strength when a certain amount of heat is applied. LCP 21 is an example of a substrate, and Cu foil 23a is an example of a first metal layer. In this embodiment, a thermal release sheet (Revalpha No. 319-4H, Nitto Denko Corporation) cut to 3.5 cm x 3.5 cm was attached to a printed circuit board cut to 4 cm x 4 cm, and an LCP cut to 3 cm x 3 cm was attached to the thermal release surface. This process is performed to keep the FPC flat during wiring patterning. If necessary, the thickness of the LCP 21 may be locally reduced by machining, laser processing, etching, or the like, or a perforation process may be locally performed on the LCP 21. This facilitates bending, as described below, and improves the adhesion of the FPC 20 to the support 10.

[0032] <2nd process> Resist coating In the second step, a resist layer 27 is formed on the entire surface on which the Cu foil 23a is formed. The procedure is as follows: the uppermost Cu foil 23a obtained in the first step is spin-coated with a positive resist (resist layer 27) and then pre-baked. Specifically, a spin coater (1H-D7, Mikasa Co., Ltd.) was used to coat the substrate with a positive resist, OFPR-800 LB (200 cp, Tokyo Ohka Kogyo Co., Ltd.), under the following conditions: 1 second acceleration → 700 rpm, 3 seconds → 3 second acceleration → 3000 rpm, 20 seconds → 3 second deceleration Thereafter, the substrate was heated (pre-baked) in a thermostatic chamber at 90°C for 30 minutes.

[0033] <3rd step> Exposure and development In the third step, the resist layer 27 is exposed to light using a first mask on which a predetermined shape has been drawn, and the exposed resist layer 27 is developed to process the resist layer 27 into a shape including a wiring region. The procedure involves placing a mask on the resist layer 27, performing flat exposure, developing, and post-baking. The thermal release sheet 25 is peeled off by the post-baking. Specifically, a mask alignment device (MA-20, Mikasa Co., Ltd.) was used to place a mask fabricated according to the wiring design on the sample, and 150 mJ / cm 2 The film was then developed for 2 minutes using NMD3 (Tokyo Ohka Kogyo Co., Ltd.), washed twice with pure water, and heated (post-baked) in a thermostatic chamber at 145°C for 30 minutes. During this process, the LCP was simultaneously peeled off from the thermal release sheet.

[0034] <4th step> Cu layer etching, resist removal The Cu foil 23a on which the resist layer 27 is formed in the third step is wet etched to remove the resist layer 27. The procedure is as follows: the Cu foil 23a is etched, and the remaining resist layer 27 is removed with acetone. Specifically, the wiring was immersed in Cu etching solution (H-1000A, Sanhayato) with the side without resist for 5 minutes, then turned over and etched until the copper foil was gone, then washed twice with pure water.To remove the remaining resist, the sample was immersed in a dish containing acetone for about 2 minutes, then immersed in a dish containing ethacol for 2 minutes, then washed about 10 times with pure water, and then dried.

[0035] <5th step> Ni, Au plating In a fifth step, Ni 23b and Au 23c for the recording electrode 23 are formed on the Cu foil 23a. The procedure involves electrolytic plating of Ni 23b and Au 23c in that order, which will become the recording electrode 23. Ni 23b and Au 23c are an example of a second metal layer. Specifically, Ni plating was performed first and then Au plating was performed on the portions that would become the electrode portions 20a of the FPC 20. The plating conditions are shown in Table 1. [Table 1]

[0036] <6th step> Board preparation In the sixth step, a thermal release sheet 25 is attached to the entire surface of the LCP 21 opposite to the side on which the Cu foil 23a is formed. As in the first step, the thermal release sheet 25 is attached to the printed circuit board 26, and the LCP 21 layer obtained up to the sixth step is then attached thereon. Specifically, a printed circuit board and a thermal release sheet of the same size as those in the specific example of step 1 were prepared, and an LCP was attached to them. To prevent the insulating layer used in the subsequent step 7 from coating the connector part 20b, the thermal release sheet was attached to the wiring surface with the thermal release surface facing down.

[0037] <7th step> Insulation layer coating In the seventh step, the entire surface on the Au 23c side is coated with the insulating layer 24. As a procedure, a spin coater is used to coat photosensitive polyimide as the insulating layer 24. Specifically, a spin coater was used to coat the substrate with PW1200 (Photoneece, Toray Industries, Inc.), a photosensitive polyimide, under the following conditions: 1 second acceleration → 700 rpm, 10 seconds → 3 second acceleration → 2400 rpm, 30 seconds → 3 second deceleration Thereafter, the substrate was heated (pre-baked) in a thermostatic chamber at 110°C for 5 minutes.

[0038] <8th step> Exposure and development In the eighth step, the insulating layer 24 is exposed to light using a second mask on which a predetermined shape has been drawn, and the exposed insulating layer 24 is developed to process the insulating layer 24 into a shape that exposes the areas of the recording electrodes 23. The procedure involves exposing, developing, and heating the areas that will become the recording electrodes 23. The electrodes were exposed using a proprietary maskless exposure machine. The exposure conditions are shown in Table 2. The exposure radius can be determined by the aperture and objective lens magnification, and in this case the radius was set to 5 μm. [Table 2] Then, as in the third process, the FPC was developed with NMD-3, washed twice with pure water, and heated in a thermostatic chamber at 145°C for 5 minutes to remove the thermal release sheet. After removing the sheet, the four corners of the FPC were fixed to a stainless steel plate with polyimide tape to prevent the FPC from curling due to the difference in thermal expansion coefficients of each material, and then placed in an electric oven, where the temperature was raised to 140°C over 1 hour, held there for 1 hour, then raised to 300°C over 2 hours, and held there for 1 hour.

[0039] [1-2-2. Assembly process] 6 to 8, the assembly process for integrating the support body 10 and the FPC 20 will be described. The assembly process is divided into a bending process, a bonding process, and an insertion process.

[0040] <Bending process> 6 is a diagram illustrating the bending process of the FPC 20. The FPC 20 produced by the above-described manufacturing process is cut to a predetermined size, and the FPC 20 is wound around a cylindrical member (e.g., a metal pipe), and the entire electrode portion 20a is clamped and fixed with the reverse action tweezers 50. Furthermore, the entire clamped electrode portion 20a together with the reverse action tweezers 50 is heated. Specifically, the fabricated FPC was cut into an L-shape by cutting a portion of the square FPC sheet using a razor along the wiring, then wrapped around a metal pipe, clamped and fixed with reverse action tweezers, and heated on a hot plate at 150°C for 30 minutes. The inner corners of the L-shaped cut FPC may be chamfered to maintain strength. By bending the FPC 20, the FPC 20 is preliminarily formed into a shape close to a cylinder, which makes it easier to bond the FPC 20 to the support 10 and prevents the FPC 20 from peeling off from the support 10 after bonding.

[0041] <Adhesion process> 7 is a diagram illustrating the bonding step of bonding the FPC 20 (electrode portion 20a) to the support body 10. The bonding is performed by pressing the bonding portion against the base 51. First, adhesive 12 is applied to the center of the electrode portion 20a that has been bent by the above-described bending process (step 1), and the support 10 is pressed against it, applying force until it adheres (step 2). After adhesion is confirmed, adhesive 12 is applied to the gap between the support 10 and the electrode portion 20a (step 3). The support 10 is rotated while applying pressure from above so that the adhesive 12 spreads over the outer circumferential surface of the support 10, and the electrode portion 20a is wound around the support 10. Furthermore, one lateral end of the electrode portion 20a is pressed against the outer circumferential surface of the support 10 until it adheres (step 4). The other lateral end of the electrode portion 20a is also adhered to the outer circumferential surface of the support 10 using the same method as in steps 3 and 4 (steps 5 and 6). Specifically, the bonding process used a Teflon sheet (PTFE film, Furon Kogyo; "Teflon" is a registered trademark) as a base, and the bonding area was pressed against the base. First, to increase the adhesive strength, the bent FPC bonding surface was moistened with pure water using an industrial cotton swab (HUBY340, Sanyo Co., Ltd.), and then liquid adhesive (Aron Alpha A, Sankyo) was applied parallel to the wiring near the center axis of the bonding surface. A ceramic tube was placed on the FPC and moved two or three times to spread the adhesive, then pressed down until it bonded. Next, adhesive was applied to the gap between the tube and FPC, and the tube was rotated while applying pressure from above, spreading the adhesive around the periphery. When the razor-cut end reached the bottom, pressure was applied from above, and the FPC was held in place until bonded. This process was repeated until both left and right end faces were bonded to the tube.

[0042] Fig. 8 is a diagram showing the state at the end of the bonding step. The state shown in Fig. 8 is achieved by the bending step and bonding step described above, and then the insertion step described below is carried out.

[0043] <Insertion process> Finally, the support 10 to which the FPC 20 is attached is covered with a protector 30. The protector 30 covers the support so that the wiring 22 of the connector portion 20b is exposed to the outside through the slits 31 and the recording electrodes 23 of the electrode portion 20a are exposed. Specifically, a polyimide tube with a 5 mm long slit cut in the front-to-back direction to allow the connector wiring to be exposed was placed over the ceramic tube with the FPC attached.The gap between the polyimide tube and the FPC was then filled with non-conductive epoxy (EPO-TEK 301, Rikei Corporation), which was then heated and cured on a hot plate at 70°C for 1 hour. The above-described insertion process results in the neural electrode 1 shown in FIG.

[0044] FIG. 9 is a diagram showing a case where the neural electrode 1 is used in combination with an insert 40. As shown in FIG. 9, the insert 40 can be inserted into the cavity 11 of the neural electrode 1. The insert 40 can move in the front-to-back direction (longitudinal direction) within the cavity 11. Examples of the insert 40 include an endoscope and an optical fiber. Using the neural electrode 1 in combination with the insert 40 improves the accuracy of measuring the activity of nerve cells.

[0045] As an example, we will explain an example in which the neural probe 1 is used in conjunction with a fluorescence endoscope 40. A commercially available fluorescence endoscope for the brain is the Ultra-thin Fluorescence Endoscope Imaging System (U-FEIS), a minimally invasive system. The U-FEIS includes an ultra-fine endoscope unit and a dedicated, compact imaging system consisting of an image capture camera and a fluorescent dye excitation laser. In particular, the ultra-fine endoscope unit 40 includes an image fiber 41, a microlens 42 attached to the tip of the image fiber 41, and a protective metal tube 43 that protects the image fiber 41 and the microlens 42 from the outside. Specifically, the diameters of the image fiber 41 and the microlens 42 are approximately 450 μm, and the diameter of the protective metal tube 43 is approximately 450 μm. The ultra-fine endoscope unit 40 has a spatial resolution of 2 μm, allowing for sufficient recognition of cellular activity.

[0046] [2. Actions and Effects] (1) The neural probe 1 described above comprises a cylindrical support 10 and a flexible substrate 20 provided on the support 10. The flexible substrate 20 has one end having a recording electrode 23 and the other end connected to a connector, and wiring 22 extending on the flexible substrate 20 connects the recording electrode 23 to the connector. As a result, the flexible substrate 20 has wiring 22 that connects the recording electrodes 23 to the connector, eliminating the need to manually connect the wiring as in the prior art. This allows for greater freedom in wiring, reduces the number of fabrication processes, and shortens manufacturing time. This ultimately improves mass productivity.

[0047] (2) Furthermore, the flexible substrate 20 includes an LCP 21 that is adhered to the outer peripheral surface of the cylindrical support 10, a first metal layer 23a for wiring 22 formed on the LCP 21, second metal layers 23b, 23c for recording electrodes 23 formed on the first metal layer 23a, and an insulating layer 24 that partially covers the second metal layers 23b, 23c. The flexible substrate 20 having such a configuration can be mass-produced because the manufacturing process can be simplified and the manufacturing time can be shortened.

[0048] (3) The flexible substrate 20 has an electrode portion 20a having a recording electrode 23 and adhered to the outer peripheral surface of the support 10, and a connector portion 20b extending from a part of the electrode portion 20a in a direction deviating from the outer peripheral surface of the support 10. The L-shaped flexible substrate 20 allows the entire neural probe 1 to be made compact.

[0049] (4) The flexible substrate 20 is made of a thermoplastic material. This allows a planar circuit to be transformed into a three-dimensional shape.

[0050] (5) The neural probe 1 has a cylindrical protective body 30 that partially covers the flexible substrate 20. This makes it possible to protect the support body 10 and the flexible substrate 20.

[0051] (6) Protector 30 has slit 31 at one end, and protector 30 covers the portion of electrode portion 20a where recording electrode 23 is not provided, with connector portion 20b exposed through slit 31. The protector 30 has a shape that fits the flexible substrate 20, allowing the entire neural probe 1 to be made compact.

[0052] (7) The support 10 has a cavity 11 therein into which the insert 40 is inserted, and the insert 40 is movable in the cavity 11 in the longitudinal direction. (8) The insert 40 is characterized by being made up of either an endoscope or an optical fiber. This allows for the measurement of nerve cells with improved accuracy by using measuring instruments and optical stimulation devices in combination with the neural electrode 1.

[0053] (9) The manufacturing process of the flexible substrate 20 includes a first step of forming a first metal layer 23a for wiring on a base material 21 that is adhered to the outer peripheral surface of the cylindrical support 10; a second step of forming a resist layer 27 over the entire surface on which the first metal layer 23a is formed; a third step of exposing the resist layer 27 using a first mask on which a predetermined shape is drawn, developing the exposed resist layer 27, and processing the resist layer 27 into a shape that includes a wiring region; and a fourth step of wet-etching the first metal layer 23a on which the resist layer 27 obtained in the third step is formed, and removing the resist layer 27. Furthermore, the manufacturing process of the flexible substrate 20 includes a fifth step of forming second metal layers 23b, 23c for electrodes on the first metal layer 23a, a sixth step of attaching a thermal release sheet 25 to the entire side of the substrate 21 opposite to the side on which the first metal layer 23a is formed, a seventh step of coating the entire surface on the second metal layer 23c side with an insulating layer 24, and an eighth step of exposing the insulating layer 24 using a second mask on which a predetermined shape has been drawn, developing the exposed insulating layer 24, and processing the insulating layer 24 into a shape that exposes the electrode area. This process is easy to fabricate and shortens the manufacturing time, improving mass productivity. In addition, the flexible substrate 20 fabricated by this process has higher wiring position accuracy than the prior art where wiring is connected manually.

[0054] [3. Modifications] The above-described configuration of the neural probe 1 is one example. The above-described materials are also one example, and other materials that provide similar properties and effects can be used.

[0055] In the above-described embodiment, as shown in FIG. 8, only the electrode portion 20a is adhered to the support 10. However, not only the electrode portion 20a but also the connector portion 20b may be adhered onto the electrode portion 20a. FIG. 10 shows a modified example of the winding method of the FPC 20. As shown in FIG. 10, the connector portion 20b may be wound around the electrode portion 20a by one turn, and the gap between the electrode portion 20a and the connector portion 20b may be fixed with adhesive 12. This prevents the FPC 20 from breaking at the bent portion of the wiring 22. Furthermore, although the FPC 20 described above is wound around the support 10 clockwise, it may also be wound counterclockwise, as in the example of FIG. 10.

[0056] Figure 11 shows modified shapes of the FPC 20. As shown in Figure 11(a), by providing a groove on the lower surface of the LCP 21 of the FPC 20, the FPC 20 can be easily curved when fitted along the outer peripheral surface of the support 10 (see Figure 11(b)), thereby making it possible to more firmly adhere it to the support 10. Also, as shown in Figure 11(c), by providing a concave groove on the upper surface of the LCP 21 of the FPC 20 and a convex groove on the lower surface, the grooves fit together when the FPC 20 is wrapped around the support 10 (see Figure 11(d)), thereby making it possible to more firmly adhere it to the support 10. [Explanation of symbols]

[0057] 1. Neural electrodes 10 Support 11 Cavity 12 Adhesive 20 FCP (Flexible Printed Circuit) 20a Electrode part 20b Connector part 21 LCP (liquid crystal polymer, base material) 22 Wiring 23 Recording electrode (electrode) 23a Cu foil (first metal layer) 23b Ni (second metal layer) 23c Au (second metal layer) 24 insulating layer 25 Thermal release sheet 26 Printed Circuit Board 27 Resist (positive resist, resist layer) 30 Protective Body 31 Slit 40 Insert 41 Image Fiber 42 Microlenses 43 Protective metal tube 50 Reverse Action Tweezers 51 Foundation

Claims

1. A cylindrical support; a flexible substrate provided on the support; Equipped with the flexible substrate has one end having an electrode and the other end connected to a connector; Wiring extending on the flexible substrate connects the electrodes and the connector, the flexible substrate has a rectangular electrode portion having the electrode, and a connector portion extending in a direction deviating from an outer peripheral surface of the support at an end of the electrode portion on the opposite side to an arrangement portion of the electrode, and the flexible substrate is L-shaped; the electrode portions are provided on the support body so as to extend along an axial direction of the support body, and the electrode portions are wound around the outer periphery of the support body in the circumferential direction so that ends of the electrode portions in the circumferential direction along the outer periphery of the support body face each other with a gap therebetween or face each other without the gap, the wiring has a portion in the electrode portion that extends along the axial direction of the support body; A neural electrode characterized by:

2. The flexible substrate is a substrate adhered to the outer peripheral surface of the support; a first metal layer for wiring formed on the base material; a second metal layer for the electrode formed on the first metal layer; an insulating layer partially covering the second metal layer; 2. The neural electrode according to claim 1, comprising:

3. The flexible substrate is made of a thermoplastic material.

3. The neural electrode according to claim 1 or 2.

4. A cylindrical protector that partially covers the flexible substrate The neural electrode according to any one of claims 1 to 3, characterized in that

5. The protector has a slit at one end, the protector covers a portion of the electrode portion where the electrode is not provided, The connector portion is exposed from the slit.

5. The nerve electrode according to claim 4, wherein the nerve electrode is a conductor.

6. The support has a cavity therein for receiving an insert, the insert being longitudinally movable within the cavity. The neural electrode according to any one of claims 1 to 5, characterized in that

7. The insert comprises either an endoscope or an optical fiber.

7. The nerve electrode according to claim 6,

8. An electrode is provided on one end of the flexible substrate, and a wiring is extended on the flexible substrate to connect the electrode and a connector to which the other end of the flexible substrate is connected; The flexible substrate has a rectangular electrode portion having the electrode, and a connector portion extending in a direction deviating from the outer peripheral surface of a cylindrical support at an end of the electrode portion opposite the electrode arrangement portion of the electrode portion, the flexible substrate is L-shaped, the electrode portion extends along the axial direction of the support, the wiring has a portion on the electrode portion that extends along the axial direction of the support, and the electrode portion is wound around the outer periphery of the support in the circumferential direction and bonded to the outer peripheral surface of the support so that ends of the electrode portions in the circumferential direction along the outer periphery of the support face each other with a gap therebetween or face each other without the gap. A method for manufacturing a neural electrode.

9. The flexible substrate is a first step of forming a first metal layer for wiring on a base material adhered to an outer peripheral surface of the support; a second step of forming a resist layer on the entire surface on which the first metal layer is formed; a third step of exposing the resist layer using a first mask on which a predetermined shape is drawn, developing the exposed resist layer, and processing the resist layer into a shape including a wiring region; a fourth step of wet-etching the first metal layer on which the resist layer formed in the third step is formed, and removing the resist layer; a fifth step of forming a second metal layer for an electrode on the first metal layer; a sixth step of attaching a thermal release sheet to the entire surface of the base material opposite to the side on which the first metal layer is formed; a seventh step of coating an insulating layer on the entire surface of the second metal layer side; an eighth step of exposing the insulating layer using a second mask on which a predetermined shape is drawn, developing the exposed insulating layer, and processing the insulating layer into a shape that exposes an electrode region; Made with 9. The method for manufacturing a neural electrode according to claim 8.

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