JP4412970B2 - Method for producing biological tissue stimulation electrode - Google Patents

Description

  The present invention relates to a method for producing an electrode for applying electrical stimulation to a biological tissue and a biological tissue stimulation electrode obtained by the method.

  In recent years, as one of the blindness treatment techniques, an intraocular implantation device (internal device) having electrodes or the like is installed in the eye, and a living tissue (here, cells constituting the retina) is electrically stimulated with a plurality of electrodes. Research on visual reproduction assist devices that attempt to reproduce visual abilities is underway. Thus, when an intracorporeal device is installed (implanted) in the eye of a patient's eye in order to apply electrical stimulation to the living body, an insulating film with high biocompatibility is used in the body to support long-term implantation in the living body It is important to embed the entire device. However, since it is necessary to apply electrical stimulation to the cells constituting the retina with the electrode of the internal device, this electrode portion must be exposed.

As an electrode for performing multipoint stimulation on a living tissue using a plurality of electrodes, an integrated composite electrode for performing multipoint simultaneous stimulation / measurement of nerve cells can be cited as a technique. This integrated composite electrode that performs multi-point simultaneous stimulation / measurement is such that lead wires are formed on a substrate, an insulating photosensitive resin is applied to the substrate, and then the electrode is exposed by a photoetching technique. There is one in which an exposed electrode is formed by opening a hole and depositing a conductive metal material such as gold in the hole (for example, see Patent Document 1).
Japanese Patent Laid-Open No. 6-296595 (pages 4 to 5, FIG. 3 etc.)

In an intraocular implant device used for a visual regeneration assisting device, it is necessary to simultaneously realize complete embedding of a substrate to be implanted in the eye and an exposed electrode for stimulating living tissue. However, as disclosed in Patent Document 1, once the substrate is completely embedded, a method of forming a hole in the resin and forming an exposed electrode by vapor deposition has a problem of a decrease in insulation reliability due to the denseness due to the metal electrode. Yes, not suitable for long-term implantation in the body. Moreover, since a hole is formed in the embedding resin and an electrode is formed here, the exposed electrode surface may be lower than the embedding resin surface when the electrode is not sufficiently formed. In this case, there is a problem that the contact property to the living tissue may be lowered.
In view of the above-mentioned problems of the prior art, it is an object of the present invention to provide a method for producing an electrode for stimulating living tissue suitable for contact between the electrode and the living tissue and long-term implantation, and an electrode for stimulating living tissue using the method. And

In order to solve the above problems, the present invention is characterized by having the following configuration.
(1) a first step of forming a predetermined wiring circuit on the substrate, and a second step of forming a protrusion with a conductive Au-based noble metal material on the wiring circuit formed by the first step; A third step of coating the wiring circuit having at least the projections on the substrate with the projections formed by the second step with an insulating film having a good biocompatibility; and a coating by the third step . a fourth step you form an exposed electrode to expose the tip of the protrusion by a predetermined amount removed surface on which the projecting portion is formed to the substrate that has been in the thickness direction is, fourth step And a fifth step of forming a protrusion with a Pt-based noble metal material having conductivity on the exposed electrode formed by the step .

  According to the present invention, it is possible to obtain a biostimulation electrode suitable for contact with a living tissue and long-term implantation.

  Embodiments of the present invention will be described with reference to the drawings. The biological tissue stimulation electrode used in the present embodiment is an electrode for performing electrical stimulation on cells constituting the retina. FIG. 1 is a flowchart showing a procedure for manufacturing an electrode for stimulating living tissue manufactured in the present embodiment, FIG. 2 is a diagram showing a state where lead wires are formed on a substrate, and FIG. 3 is a diagram after forming the lead wires. It is sectional drawing which showed the mode for forming an electrode on a board | substrate.

  Reference numeral 1 denotes a substrate. The substrate 1 may be made of an insulating material. Preferably, a material having good biocompatibility in addition to the insulating property may be used. Moreover, since the electrode manufactured in the present invention is used for biological tissue stimulation, the substrate is preferably made of a soft material that bends along the electrode installation surface. Specific examples include silicon and polyimide. In this embodiment, polyimide is used. When a semiconductor material such as silicon is used as the substrate material, the silicon is oxidized to have insulating properties, or at least a wiring film forming surface side of the silicon substrate is formed with an insulating film, A wiring circuit may be formed on this film.

  Reference numeral 2 denotes a wiring circuit (lead wire) formed on the substrate 1. As a material used for the wiring circuit 2, for example, a material generally used for a wiring circuit such as Cr, Cu, Au, Al, and Pt is used. The wiring circuit 2 has a thickness of about 1.0 to 100 μm. These materials are stacked on the substrate 1 by vapor deposition, sputtering, or the like, and a desired wiring pattern (wiring circuit) is formed by etching using a photoresist. . Further, each lead wire end 2a constituting the wiring circuit 2 has a circular shape of about φ50 μm to φ100 μm, and an electrode is formed here. In the present embodiment, the wiring circuit 2 is used to form a total of 25 electrodes of 5 × 5. However, the present invention is not limited to this, and if a wiring circuit corresponding to the number of electrodes according to need is formed. Good. An integrated circuit chip on which electrode pads for forming metal protrusions are formed can also be used as the substrate. In this case, the function of the wiring circuit 2 can be realized not only by an integrated circuit on the silicon substrate, but also various electrical and optical processing functions such as detection, amplification, and signal processing.

  After the desired wiring circuit 2 is formed on the substrate 1, as shown in FIG. 3A, the protrusion 3 made of a conductive material is formed on each lead wire end 2 a of the wiring circuit 2. As the conductive material used for forming the protrusions 3, a metal material having good biocompatibility such as Au and Pt can be used. In the present embodiment, Au stud bumps are formed as the protrusions 3. Such protrusions 3 may be formed one by one by a wire bonding method (a method using a ball bonder) or may be formed by plating. In addition, when forming bumps by the wire bonding method, it is possible to use not a metal aggregated from a liquid phase or a gas phase, but a bulk metal having a small number of holes formed by rolling, etc. I can expect.

  Further, the height of the projection 3 is preferably about 10 μm to 500 μm, and more preferably 50 μm to 300 μm. Since the protrusion 3 is then scraped by a predetermined amount by polishing, polishing becomes difficult unless the height is less than 10 μm. Further, although the height of the protrusion 3 may exceed 500 μm, it is not preferable because it takes time to form the protrusion 3, the covering operation of the substrate 1 with an insulating material, and subsequent polishing.

  After the protrusions 3 are formed on each lead wire end 2a of the wiring circuit 2, as shown in FIG. 3B, the entire substrate 1 is embedded (covered) with a material having good biocompatibility and insulating properties. Then, the coating layer 4 is formed. Examples of the insulating material for embedding the substrate 1 include polyimide and silicon nitride. In the present embodiment, the coating layer 4 is formed using polyimide. Conventional methods such as vapor deposition, sputtering, and coating can be used as the coating method. In this embodiment, the coating layer 4 is formed by applying a polyimide precursor for dropping application to the substrate 1, drying and baking. Further, when covering the surface on which the protrusions 3 are formed, the covering layer 4 is formed so as to be sufficiently higher than the height of the protrusions 3.

  After the substrate 1 is embedded with an insulating material, the coating layer 4 and a part of the projection 3 are scraped off by polishing a predetermined amount of the projection 3 forming surface side of the substrate 1. What is necessary is just to carry out the amount cut away to such an extent that the desired electrode height is obtained. In the present embodiment, the coating layer 4 and part of the protruding part 3 are scraped off by polishing. However, the present invention is not limited to this, and part of the covering layer 4 and the protruding part 3 is scraped from the projecting part 3 forming surface side ( It is sufficient if a predetermined amount can be removed). For example, the coating layer 4 and a part of the protrusion 3 may be removed by cutting using a plane, laser light, or the like, or by etching.

By cutting off part of the coating layer 4 and the protrusion 3, the protrusion 3 is exposed from the coating layer 4 as shown in FIG. As an apparatus used for polishing, a planarization apparatus (polishing apparatus) or the like for polishing and planarizing an existing semiconductor wafer or the like may be used. The exposed surface of the protruding portion 3 thus exposed is used as the exposed electrode 3a. By performing the steps as described above, it is possible to produce an electrode for stimulating living tissue that is excellent in insulation and can be implanted in the living body for a long period of time. Moreover, since the projection 3 is exposed by polishing the coating layer 4 to form an exposed electrode, the electrode surface does not become lower than the coating layer 4.
Further, by manufacturing the exposed electrode through the above steps, the exposed electrode surface does not become lower than the covering layer 4 and the contact between the living tissue and the electrode is improved. It is also possible to form the convex electrode 5 on the exposed electrode surface by plating, screen printing, wire bonding or the like with an electrode material such as Au. Thus, it can be expected that the contact between the living tissue and the electrode is further improved by forming the convex electrode 5 on the exposed electrode surface.

  In the above embodiment, Au (gold) is used as the material of the exposed electrode. However, the present invention is not limited to this. Precious metals can also be used. By introducing such a fine wire made of a Pt-based noble metal into a stud bump forming apparatus used for wiring of a semiconductor device or an LSI, a stud bump using a Pt-based noble metal is replaced with a stud bump using Au on the substrate 1. Can be formed. Such a Pt-based noble metal is superior to an Au-based noble metal in terms of corrosion resistance and the amount of injected charge per unit area.

  In addition, since Pt-based noble metals are harder than Au-based noble metals, if there is a risk of destroying the substrate surface during stud bump formation, the conductive material used for the protrusions formed on the substrate is relatively soft and the substrate surface Bumps made of Pt-based noble metal may be further formed on the formed protrusions using a material that is difficult to break. Specifically, a stud bump made of an Au-based noble metal material may be formed on the substrate 1, and a stud bump made of a Pt-based noble metal may be provided thereon. By using such a forming method, the protrusion 3 shown in FIG. 3D is made of Au (Au-based noble metal), and the electrode 5 is formed of a Pt-based noble metal. As a result, a Pt-based noble metal material excellent in corrosion resistance and the like can be used as an electrode without destroying the substrate surface.

  In the present embodiment, the substrate 3 is embedded with an insulating material after the protrusion 3 is formed on the lead wire end 2a of the wiring circuit 2. However, the present invention is not limited to this. For example, after the wiring circuit 2 is formed on the substrate 1, the wiring circuit 2 is once covered with an insulating material, then a hole is formed in the covering portion on the lead wire terminal 2 a, and then the protrusion 3 may be formed. . After the formation of the protrusions 3, the entire substrate 1 is embedded with an insulating material and polished as described above to produce an exposed electrode. By providing the coating layer in two stages as described above, it is expected that the insulating property is further improved.

Next, as an example of an apparatus using the biostimulation electrode obtained by the above-described process, a visual reproduction assisting apparatus that is implanted and used in the eye for artificial reproduction of vision is based on FIGS. 4 and 5. Will be described below. Note that components having the same functions as those shown in FIG. 3 are given the same reference numerals, and detailed descriptions thereof are omitted.
The visual reproduction assisting device 10 shown in FIG. 4 is roughly composed of a power acquisition unit 20 and a visual reproduction unit 30 that are mounted on the substrate 1. The visual reproduction unit 30 is electrically connected to the power acquisition unit 20 via the electric wire 21.
The substrate 1 uses a material having translucency and good biocompatibility, and polyimide is used as described above. The substrate 1 is composed of a disc portion 1a and a long plate portion 1b. A power acquisition unit 20 is attached to the disc portion 1a, and a visual reproduction unit 30 is attached to the tip of the long plate portion 1b.

  The power acquisition unit 20 includes a magnetic core 20a made of a ring-shaped magnetic body that is provided with a through hole in the center and is hollow, and a secondary coil 20b that is wound around the magnetic core 20a. Yes. In the hollow portion of the magnetic core 20a of the present embodiment, an optical member 22 (lens) instead of a crystalline lens is installed, and an image of an object point located at a predetermined distance in front of the eyes is described later. It is possible to form an image on 30 light receiving surfaces. If the lens is not removed when the intracorporeal device 20 is placed in the eye, the lens 22 need not be provided.

On the other hand, the visual reproduction unit 30 performs a predetermined process based on the electrode 5, the light receiving element 31 including a photodiode, and the light reception signal from the light receiving element 31, and generates a stimulation current for reproducing the visual from the electrode 5. A control circuit 32 and the like are provided and have an IC (Integration Circuit) configuration. The light receiving element 31 is formed in a two-dimensional array on the surface on the substrate 1 facing the anterior eye portion (the surface capable of receiving the light beam incident on the eye) when the visual reproduction assisting device 10 is installed (implanted) in the eye. Many are installed. Further, a large number of electrodes 5 are arranged in a two-dimensional array corresponding to each of the light receiving elements 31 on the surface of the substrate 1 opposite to the installation surface of the light receiving elements 31 (the back side of the paper in FIG. 4).
The visual reproduction assisting device 10 is entirely covered with a biocompatible material such as polyimide, and prevents direct contact with the body fluid or the like. Moreover, the electrode 5 is a convex electrode protruding from the surface where the coating layer is polished by using the manufacturing method described above. Therefore, when the visual reproduction assisting device 10 is installed in the eye of a patient's eye, the tip of the electrode 5 can directly contact the retina.

FIG. 5 is a diagram showing a state in which the visual reproduction assisting device 10 is installed in the eye. As shown in the figure, the power acquisition unit 20 is installed on the back side of the iris. At this time, the lens 22 is placed in the pupil. The long plate portion 1b is placed along the retina, and the visual reproduction unit 30 at the tip of the long plate portion 1b is fixed by the tack 33 in a state in contact with a predetermined position of the retina. In this state, the electrode 5 is always in contact with the retina, and visual regeneration can be performed by electrically stimulating cells constituting the retina such as bipolar cells and retinal ganglion cells.
Reference numeral 40 denotes a visor worn by a patient, and a hollow magnetic core 41 and a primary coil 42 are attached to the visor 40. The primary coil 42 transmits power from the power supply device 43 to the secondary coil 20b by electromagnetic induction. The visual reproduction assisting device 10 uses the power obtained by the secondary coil 20b as power for driving the device.

  In this embodiment, the electrodes are placed on the retina. However, the present invention is not limited to this. Cells that constitute the retina from the photoreceptor side by inserting the substrate under the retina (between the retina and the choroid). You may make it give an electrical stimulus to. In such a case, the electrode may be formed on the surface opposite to the above-described formation surface.

  In the above embodiment, after forming the protrusion on the substrate, the protrusion is completely filled (embedded) with an insulating material (resin) such as polyimide, and then exposed by polishing the resin. Although an electrode is obtained, the present invention is not limited to this. Another embodiment of the present invention is listed below.

  FIG. 6 is a view showing a case where the thickness of the resin to be embedded is made thinner than the height of the protrusion 3 and the tip of the protrusion 3 is exposed during or after embedding to form an electrode. As shown in FIG. 6 (a), after forming the protrusion 3 (stud bump) made of Pt-based noble metal on the lead wire end 2a, the polyimide 3 is formed with such a thickness that the tip of the protrusion 3 is exposed. By forming the coating layer 4 to be formed on the substrate, an electrode exposed from the coating layer 4 can be formed without performing polishing or the like. The coating layer 4 may be formed by applying the dripping coating polyimide precursor to the substrate 1 as described above, followed by drying and baking. Further, as shown in FIG. 6B, after forming the protrusion 3 on the substrate 1, the coating layer 4 is once formed on the entire substrate 1 and the protrusion 3 with a thickness thinner than the height of the protrusion 3. Then, the resin covering the tip of the protrusion 3 can be removed by polishing, cutting, or pressing from above to form an exposed electrode. As a method for forming the coating layer 4 on the substrate 1 and the entire projection 3 with a thickness smaller than the height of the projection 3, for example, after applying a dripping-applied polyimide precursor to the substrate 1, nitrogen is applied before curing. A method in which an excess resin is allowed to flow by spraying an inert gas such as the like onto the coated surface and then cured is exemplified.

  Thus, even if the thickness of the resin to be embedded is made thinner than the height of the protrusion and the tip of the protrusion is exposed during or after embedding, the electrode and the resin are in close contact. Therefore, infiltration of body fluid into the substrate during implantation in the body is suppressed. In addition, since the electrode tip is less likely to be lower than the coating layer, the contact with the living tissue is good.

  FIG. 7 is a diagram showing a method for obtaining an exposed electrode by forming a coating layer by press-bonding a resin film to a substrate instead of using a liquid insulating material. As shown in FIG. 7A, after forming the protrusions 3 on the substrate 1, the protrusions 3 are covered with an insulating film 100 such as polyimide, and the film is then covered with a crimping jig 101 from above. 100 is pressed from above. The thickness of the film to be used is thinner than the height of the protrusion 3. By pressing the crimping jig 101, the tip of the protrusion 3 penetrates the film 100 and is exposed on the upper surface of the resin (film 100) embedded on the substrate 1, and the film 100 is firmly adhered to the substrate 1 and covered. Acts as a layer. In addition, after the film 100 is pressure-bonded, a release agent or the like is applied to the film contact surface of the pressure-bonding jig 100 in advance or the pressure-bonding is performed so that the film 100 can be easily separated from the pressure-bonding jig 101. Peeling can be facilitated by, for example, coating the surface of the jig 100 with Teflon. Further, as a technique for pressure bonding such a film, a pressure bonding technique of NCF (non-conductive film) used in semiconductor chip mounting can be used.

  Further, as shown in FIG. 7B, a recess 101a is formed on the film 100 contact surface side of the crimping jig 101, and the tip of the projection 3 is applied to the recess 101a while the film 100 is interposed. In this manner, the film 100 can be pressure-bonded to the substrate 1. In this way, by pressing the film 100 to the substrate 1, it is possible to obtain a convex exposed electrode in which the tip of the protrusion 3 penetrates the film 100 and the tip protrudes from the coating layer formed by the film 100. it can. As shown in FIGS. 7A and 7B, bumps (protrusions) are formed in advance on a substrate with a Pt-based or Au-based material, and then a resin film is pressure-bonded to the substrate, so that the protrusions By obtaining the exposed electrode by penetrating the tip from the film, the electrode and the resin are brought into close contact with each other as described above, and infiltration of body fluid into the substrate during implantation in the body is suppressed. In addition, since the electrode tip is less likely to be lower than the coating layer, the contact with the living tissue is good. In addition, as shown in FIG.7 (c), the crimping | compression-bonding jig | tool 101 in which the recessed part 101a was formed was made to fit the recessed part 101a and the front-end | tip of the projection part 3 in the state where the film 100 does not intervene, and it is liquid in the clearance gap. The exposed electrode can also be obtained by pouring and embedding the resin 100 ′ and then curing the resin 100 ′.

It is the flowchart which showed the procedure of electrode preparation. It is the figure which showed the state which formed the lead wire on the board | substrate. It is the figure which showed a mode that an electrode was formed on a board | substrate. It is the figure which showed schematic structure of the visual reproduction assistance apparatus. It is the figure which showed the state which embedded the visual reproduction auxiliary | assistance apparatus in the eye. It is the figure which showed the example of a change in this invention. It is the figure which showed the example of a change in this invention.

Explanation of symbols

1 Substrate 2 Wiring circuit 2a Lead wire end 3 Projection 3a Exposed electrode

Claims (1)

A first step of forming a predetermined wiring circuit on the substrate, a second step of forming a protrusion with a conductive Au-based noble metal material on the wiring circuit formed by the first step; A third step of coating the wiring circuit having at least the protrusions on the substrate with the protrusions formed in two steps with an insulating film having a good biocompatibility; and the coating in the third step a fourth step you form an exposed electrode to expose the tip of the protrusion by a predetermined amount removed surface on which the projecting portion with respect to the substrate is formed in the thickness direction, is formed by the fourth step And a fifth step of forming a protrusion on the exposed electrode with a Pt-based noble metal material having conductivity .

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