JP2011030734A - Visual restoration aiding device and method of manufacturing the same - Google Patents

Visual restoration aiding device and method of manufacturing the same Download PDF

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JP2011030734A
JP2011030734A JP2009179331A JP2009179331A JP2011030734A JP 2011030734 A JP2011030734 A JP 2011030734A JP 2009179331 A JP2009179331 A JP 2009179331A JP 2009179331 A JP2009179331 A JP 2009179331A JP 2011030734 A JP2011030734 A JP 2011030734A
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electrode
electrodes
visual reproduction
surface
assisting device
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JP2011030734A5 (en
JP5578540B2 (en
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Yasuo Terasawa
Akihiro Uehara
昭宏 上原
靖雄 寺澤
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Nidek Co Ltd
株式会社ニデック
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of manufacturing a visual restoration aiding device and a visual restoration aiding device, simply increasing the surface area of an electrode. <P>SOLUTION: In this visual restoration aiding device, a plurality of electrodes are installed on a patient's eye, and predetermined electric stimulus pulse signals are output from the electrodes to thereby accelerate visual restoration. The electrodes each have a three-dimensional shape, and the surfaces are treated to have non-uniform and fine rugged shape. This method of manufacturing the visual restoration aiding device in which a plurality of electrodes are installed on a patient's eye, and predetermined electric stimulus pulse signals are output from the electrodes to thereby accelerate visual restoration includes: a first step of forming a plurality of electrodes having three-dimensional shape on a predetermined base plate; and a second step of conducting predetermined surface treatment for the electrodes formed on the base plate in the first step to thereby form non-uniform and fine rugged shape on the surfaces of the electrodes. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a visual reproduction assisting device that reproduces part or all of a patient's vision and a method for manufacturing the visual reproduction assisting device.

  In recent years, as one of the techniques for treating blindness, research on visual regeneration assisting devices that attempt to regenerate vision by implanting in-vivo devices with a substrate on which multiple electrodes are formed and electrically stimulating cells that make up the retina Has been. Such a visual reproduction assist device, for example, converts a video imaged using an extracorporeal device into a predetermined signal and transmits it to an in-vivo device installed in the body, and outputs an electrical stimulation pulse signal (charge) from the electrode. Devices that attempt to reproduce vision by electrically stimulating the cells constituting the retina are known. (For example, refer to Patent Document 1).

2009-082496

  In order to electrically stimulate the cells that make up the retina to obtain vision, it is necessary to inject a predetermined amount of charge from the stimulation electrode, but the ability of the stimulation electrode to transfer charge depends on the surface area of the electrode. Proportional. On the other hand, in order to perform suitable visual reproduction, it is necessary that the electrode density is high, and in order to increase the electrode density in a limited space in the living body, the size of the electrode is required to be small. . Therefore, it is desired to increase the surface area of the electrode in order to improve the charge injection capability without increasing the size of the electrode.

  In view of the above-described problems of the prior art, it is an object of the present invention to provide a method for manufacturing a visual reproduction assisting device and a visual reproduction assisting device that can easily increase the surface area of an electrode.

  In order to solve the above problems, the present invention is characterized by having the following configuration.

(1) In a visual reproduction assisting device that promotes visual reproduction by installing a plurality of electrodes on a patient's eye and outputting predetermined electrical stimulation pulse signals from the electrodes, the electrodes have a three-dimensional shape and the surface thereof is treated. It is characterized by having a non-uniform and fine uneven shape.
(2) In the visual reproduction assisting device according to (1), the electrode is surface-treated by an electrochemical oxidation-reduction reaction.
(3) In the visual reproduction assisting device according to (1), the electrode material forming the electrode has anisotropy.
(4) In the visual reproduction auxiliary device of (2), the electrode is formed by cold drawing of the electrode material.
(5) In a method for manufacturing a visual reproduction assisting device that promotes visual reproduction by installing a plurality of electrodes on a patient's eye and outputting a predetermined electrical stimulation pulse signal from the electrodes, a plurality of three-dimensional shapes on a predetermined substrate A first step of forming the electrode, and a predetermined surface treatment on the electrode formed on the substrate by the first step, thereby forming a non-uniform and fine uneven shape on the electrode surface. And 2 steps.
(6) In the visual reproduction assisting device according to (5), the surface treatment is a treatment for causing the electrode to perform an electrochemical redox reaction.

  According to the present invention, it is possible to easily increase the surface area of the electrode used in the visual reproduction assisting device.

  Embodiments of the present invention will be described with reference to the drawings. FIG. 1 is a schematic diagram showing an external appearance of a visual reproduction assistance device, and FIG. 2 is a diagram showing an in-vivo device in the visual reproduction assistance device.

  As shown in FIGS. 1 and 2, the visual reproduction assisting device 1 includes an extracorporeal device 10 for photographing the outside world, and an in-vivo device 20 that promotes visual reproduction by applying electrical stimulation to cells constituting the retina. The extracorporeal device 10 includes a visor 11 on which a patient is placed, an imaging device 12 including a CCD camera attached to the visor 11, an external device 13, a transmission unit 14 including a primary coil, and the like.

  The external device 13 is provided with a data modulation means 13a having an arithmetic processing circuit such as a CPU, and a battery 13b for supplying power to the visual reproduction auxiliary device 1 (external device 10 and internal device 20). The data modulation unit 13a performs image processing on the subject image captured by the image capturing device 12, and further converts the obtained image processed data into electrical stimulation pulse data for reproducing vision. The transmission means 14 transmits the electrical stimulation pulse data converted by the data modulation means 13a and the power for driving the in-vivo device 20 described later to the in-vivo device 20 side as a predetermined signal, in this embodiment, an electromagnetic wave ( Wireless transmission). On this electromagnetic wave, electrical stimulation pulse data and power are superimposed. A magnet (not shown) is attached to the center of the transmission means 14. The magnet is used to fix the position with the receiving means 31 described later.

  The visor 11 has an eyeglass shape, and can be used by being mounted in front of the patient's eyes as shown in FIG. The photographing device 12 is attached to the front surface of the visor 11 and can photograph a subject to be visually recognized by the patient.

  Next, the configuration of the intracorporeal device 20 will be described. 2A shows an external appearance of the in-vivo device 20, and FIG. 2B shows a cross section of the stimulation unit 40. As shown in FIG. The in-vivo device 20 is roughly divided into a receiving unit (receiving unit) 30 that receives data and electric power for electrical stimulation pulse signals transmitted from the extracorporeal device 10 by electromagnetic waves, and a stimulating unit (stimulating unit) that electrically stimulates cells constituting the retina ) 40. The receiving unit 30 is provided with a receiving unit 31 including a secondary coil that receives electromagnetic waves from the extracorporeal device 10 and a control unit 32. The control unit 32 separates the electrical stimulation pulse data and the power received by the receiving unit 31, and based on the electrical stimulation pulse data, an electrical stimulation pulse signal for obtaining vision, an electrical stimulation pulse signal, It has a role for converting to a control signal including an electrode designation signal for designating a corresponding electrode (for outputting an electrical stimulation pulse signal) and transmitting the control signal to the stimulation unit 40.

  These receiving means 31 and control unit 32 are formed on a substrate 33. The receiving unit 30 is provided with a magnet (not shown) for fixing the position of the transmitting unit 14. The counter electrode (return electrode) 34 is a member for opposing each electrode 44 to efficiently electrically stimulate cells and the like.

  The stimulation unit 40 includes a plurality of electrodes 44 that output electrical stimulation pulse signals, a stimulation control unit 42 (control means), and a substrate 43 on which these are installed. Each electrode 44 is connected to the stimulation control unit 42. The stimulation control unit 42 has a multiplexer function that distributes the corresponding electrical stimulation pulse signal to each of the electrodes 44 based on the control signal (including the electrode designation signal) sent from the control unit 32.

  The electrode 44 is made from a mechanically extended rod-like platinum bulk material. When the platinum bulk material is mechanically stretched by cold drawing or the like in the manufacturing process of the platinum bulk material, the platinum metal crystal grains constituting the platinum bulk material are stretched in the major axis direction, and are one-dimensional in the stretching direction (axial direction). Anisotropy occurs. The electrode 44 is formed such that when the platinum bulk material is cut along a cross section perpendicular to the axial direction (the cross section includes many crystal grain boundaries), the cut surface becomes the electrode upper portion 44c (see FIG. 3). Is done. Here, the electrode 44 is formed in a three-dimensional bullet shape having an outer diameter of 100 to 500 μm and a height of 100 to 500 μm.

  In addition, although the case where platinum is used for the electrode material which comprises the electrode 44 is demonstrated here, besides this, metals with high biocompatibility, for example, gold, titanium nitride, pure iridium or iridium oxide, Tantalum or the like can be used.

  Further, the electrode 44 is formed into a rough surface state (a state in which irregularities including a plurality of grooves are formed on the surface) by a surface treatment described later. By increasing the surface area as compared with the case where the surface treatment is not performed and the surface of the electrode 44 is smooth, the charge injection capability of the electrode 44 is enhanced. At this time, since the electrode 44 is formed so that the cut surface of the platinum bulk material becomes the electrode upper portion 44c as described above, the surface area of the electrode 44 can be efficiently increased by the surface treatment. A detailed description of the surface treatment method of the electrode 44 will be described later.

  FIG. 3 is a schematic cross-sectional view in the vicinity of the electrode 44. The electrode 44 includes a base 44a and a column member 44b extending in a columnar shape (convex shape) with the base 44a as a base. The substrate 43 includes a base portion 43a serving as a first substrate and a cover portion 43b serving as a second substrate. Between the base portion 43a and the cover portion 43b, a base 44a and a base 44a are provided. The connected wire 41 is clamped. The front end portion of the column member 44b penetrates the cover portion 43b and protrudes from the substrate 43 (base portion 43a).

  Here, a method of creating the electrode 44 will be briefly described. As described above, the electrode 44 formed in a bullet shape from a platinum bulk material is electrically connected to the base 44a and the wire 41 by an existing joining technique such as laser welding, resistance welding, or crimping. Connected to. In a state where the electrode 44 and the wire 41 are connected, the cylindrical portion 44b of the electrode unit 44 is passed through a through hole (not shown) formed in the resin cover portion 43b formed in a flat plate shape. The through holes are formed to have a size enough to penetrate the cylindrical portion 44b by laser processing or machining, and are formed in accordance with the number of electrodes 44 at a predetermined position.

  Next, using the existing vapor deposition technique, the same kind of resin as the cover portion 43b is vapor-deposited on the base 44a until a predetermined thickness is obtained, thereby forming a flat plate-like base portion 43a having flexibility. Thereby, the base 45 a and the wire 41 are sandwiched (embedded) by the cover portion 43 b and the base portion 43 a, and the cylindrical portion 45 b is formed on the substrate 43 in a convex shape.

  Since the substrate 43 used in the present embodiment is installed in the eye, particularly in a layered eye tissue, it preferably conforms to the shape of the eyeball, and even if it is implanted in the interlayer (in the layer) for a long period of time, it is a burden on the patient. It is preferable that there is little. For this reason, the substrate 43 is formed by processing a material that is highly biocompatible and can be bent at a predetermined thickness, such as parylene, polypropylene, polyimide, and silicone, into a flat plate shape extending in the longitudinal direction. The thickness of the substrate 43 is 10 to 100 μm. On this substrate 43, a wire 41, which is a conductive wire that electrically connects the electrode 44 and the stimulation control unit 42, is disposed. The wire 41 is made of a metal having high biocompatibility, such as gold or platinum, and the surface thereof is biocompatible and also has an insulating material such as parylene, polyimide, Teflon (registered trademark Teflon), silicone. It coats with resin. The thickness (diameter) of the wire 41 is set to a thickness preferable for the flexibility and long-term installation of the substrate 43, for example, 10 to 100 μm. The stimulation control unit 42 mounted on the substrate 43 is connected to a plurality of electrodes 44 formed on the substrate 43 through wires 41. The wire 41 is covered with a substrate 43. Since the metal portion of the wire 41 is double covered with the insulating coating, even if body wire or the like is infiltrated into the wire 41 portion, the possibility of leakage or the like is reduced.

  The stimulus control unit 42 is a semiconductor integrated circuit that performs a function by a combination of semiconductor elements, and is bonded to the surface of the semiconductor substrate on which the pattern wiring for functioning the integrated circuit is formed. Although detailed description is omitted, the stimulus control unit 42 is covered with plating or the like to reduce infiltration from a living body. The stimulus control unit 42 may be configured to be sealed using an airtight case formed of ceramics or metal. In such a case, the stimulus control unit 42 is connected to the wire 41 via a via provided in the case.

  In addition, the receiving unit 30 and the stimulating unit 40 placed at positions separated from each other in the body are electrically connected by a plurality of wires (conductive wires) 50. The wire 50 preferably has elasticity and durability corresponding to eye movement when placed in the body, and is made of the same material as the wire 41 described above. The wire 50 having one end connected to the receiving unit 30 is connected to the end portion of the wire 41 arranged in the stimulating unit 40. Although detailed description is omitted, the wire 50 and the wire 41 are connected by welding, pressure bonding, or the like. Further, the wire 50 is housed in a cable 51 made of a material having high biocompatibility, for example, silicone, parylene, etc. so as to be easily handled.

  In addition, although illustration is abbreviate | omitted, the receiving part 30 takes out the cable 51 and the counter electrode 34, is accommodated in a highly airtight container, and the lid | cover of the container is sealed. Furthermore, it is coated from above the container with a resin having good biocompatibility and insulating properties. Thereby, the receiver 30 is hermetically sealed.

  Next, a method for increasing the surface area by subjecting the electrode 44 formed on the substrate 43 to surface treatment will be described. FIG. 4 shows a configuration of the surface treatment apparatus 100 for etching the surface of the electrode 44 to form a rough surface state having a fine uneven shape.

  A container (cell) 101 such as a glass beaker contains an aqueous solution 101a for performing electrolysis. As the aqueous solution 101a, a solution in which a medium containing a chloride salt capable of dissolving platinum, such as saline and hydrochloric acid, is used in addition to a mild saline solution of phosphoric acid.

  The stimulation unit 40 (electrode 44), the counter electrode 103, and the reference electrode 104 are immersed in the aqueous solution 101a. At this time, the stimulating unit 40 is placed in the cell 101 so that all the electrodes 44 are immersed in the aqueous solution 101a. The counter electrode 103 is made of a material that does not corrode by the aqueous solution 101a, such as platinum, tantalum, titanium, or carbon electrode. As the reference electrode (reference electrode) 104, for example, a silver-silver chloride reference electrode, a saturated calomel electrode, an Ag / AgCl electrode, or the like is used.

  The stimulating unit 40 (electrode 44), the counter electrode 103, and the reference electrode 104 are arranged with a certain distance in the aqueous solution 101a. Here, the stimulation unit 40 and the reference electrode 104 are fixed with silicon rubber 107 so as to maintain a predetermined interval. Further, the electrode 44 and the counter electrode 103 of the stimulating unit 40 are disposed so as to face each other and are disposed in parallel.

  In addition, although the case where the surface treatment is performed in a state where the electrode 44 is incorporated in the stimulation unit 40 will be described here, the surface treatment may be performed only in the state of the electrode 44 (a state before being incorporated in the stimulation unit 40). good.

  The stimulation unit 40 (electrode 44), the counter electrode 103, and the reference electrode 104 are connected to a potentiostat (potentiostat) 105, which is a voltage control means for outputting a constant voltage (constant current), via wiring. Each electrode 44 is electrically connected to the potentiostat 105 by connecting the wire 50 of the stimulating unit 40 to the wiring via a clip or the like. (When the electrode 44 is surface-treated alone, wiring is connected to the base 44a of the electrode 44 via a clip or the like).

The potentiostat 105 is connected to a signal source 106 that outputs a predetermined voltage waveform. The output from the signal source 106 is made a constant voltage (constant current) by the potentiostat 105 and applied between the stimulation unit 40 (electrode 44) and the counter electrode 103.
As described above, the surface treatment apparatus 100 does not require special chemicals or special equipment, and can be configured simply and inexpensively.

  Next, a method for performing surface treatment (etching) of the electrode 44 using the surface treatment apparatus 100 having the above configuration will be described based on experiments. As an experimental condition, an electrode 44 having a bullet shape having a diameter of about 500 μm and a height of about 500 μm was used. As the aqueous solution 101a, mild phosphate sanitary physiologic saline (having a mild phosphate phosphate with a 0.9% sodium chloride solution) was used, and surface treatment was performed at room temperature (23 degrees). As the potentiostat 105, Wavefactory WF1946 manufactured by NF Corporation was used. As the signal source 106, HA-151 manufactured by Hokuto Denko Corporation was used.

  A square wave with an amplitude of ± 5 V and a duty ratio of 50% is output from the signal source 106, and the potential of the electrode 44 is held at +5 V for 1 second and −5 V for 1 second via the potentiostat 105 (frequency 0. 5 Hz) was applied for 5 hours to cause an electrochemical oxidation-reduction reaction to the electrode 44 to form a fine uneven shape on the surface. In this document, unless otherwise noted, the voltage is a value based on a silver-silver chloride reference electrode.

  FIG. 5 shows a photographed image of the electrode 44 by a scanning electron microscope SEM as an experimental result. 5A is an image obtained by photographing the electrode 44 before the surface treatment from an oblique direction (magnification: 150 times), and FIG. 5B is an image obtained by photographing the electrode 44 after the surface treatment from an oblique direction (magnification: 150 times). 5 (c) is an enlarged image (magnification: 1000 times) of the electrode upper part 44c before the surface treatment, and FIG. 5 (d) is an enlarged image (magnification: 1000 times) of the electrode upper part 44c after the surface treatment.

  5B and 5D, it can be seen that a plurality of grooves are formed on the surface of the electrode 44 by etching with the surface treatment apparatus 100. In this experiment, a plurality of grooves having a diameter of about 2 to 8 μm and a depth of about 2 to 8 μm are formed, and the surface of the electrode 44 has a fine uneven shape.

By using a cyclic voltammogram (not shown) obtained by cyclic voltammetry (electronic scan speed 0.05 V / second, voltage range +1.1 V to -0.85 V) not shown, the electrode 44 before and after the surface treatment The surface areas were compared. As a result, the surface area of the electrode 44 after the surface treatment shown in FIGS. 5B and 5D is about 4.3 compared with the surface area of the electrode 44 before the surface treatment shown in FIGS. It turned out that it has increased by a factor of two.
That is, the surface area of the electrode 44 can be easily increased by using the surface treatment apparatus having a simple configuration as described above.

  5B and 5D, the surface of the electrode 44 is not uniformly etched as a whole, and the electrode upper portion 44c (the surface that contacts the cells constituting the patient's retina). ) Are concentrated and etched.

  This is because, since the electrode material was extended by cold drawing during the electrode formation, the platinum molecules constituting the electrode 44 had anisotropy (crystal grain boundaries), and as a result, the etching rate in the extension direction of the electrode upper portion 44c. However, this is considered to be faster than the electrode side surface. That is, by forming the electrode 44 with a material having anisotropy, a specific direction can be easily etched (difficult).

  Note that the surface area of the electrode upper portion 44c is further increased by etching, so that the amount of charge released from the electrode upper portion 44c is further increased, and the cells constituting the retina can be electrically stimulated more efficiently. On the other hand, the side surface of the electrode 44 is made difficult to be etched, so that a gap is hardly formed between the substrate 43 and the electrode 44, and the insulation of the stimulating unit 40 is further maintained.

  Even when the surface treatment is performed only with the electrode 44 (in a state where the electrode 44 is not incorporated in the stimulating portion 40), the increase in the surface area of the electrode upper surface 44c is increased by utilizing the anisotropy of the electrode material. In addition, the side surface of the electrode 44 can be made difficult to be etched. Thereby, the surface of the electrode 44 can be brought into a surface state where electrical stimulation can be performed more efficiently, and a gap between the electrode 44 and the substrate 43 can be hardly generated.

  In addition, in order to etch the electrode 44, the polarity of the voltage applied to the electrode 44 should just be reversed with a fixed period. For example, the frequency of the voltage waveform may be set to about 0.5 Hz to 10 Hz. (If the frequency is high, etching is difficult. On the other hand, if the frequency is low, etching takes time.)

  In the above description, the case where the amplitude of the voltage is set to +5 V on the plus side and −5 V on the minus side is described as the experimental condition. However, the amplitude of the voltage is +1.5 to +5.0 V on the plus side and − on the minus side. You may set in the range of 5.0V--1.5V. If the absolute value of the voltage amplitude is smaller than 1.5V, etching is difficult. On the other hand, when the absolute value of the voltage amplitude is larger than 5V, there is a concern that gas generated by electrolysis adheres to the surface of the electrode 44 and leads to etching spots.

  As described above, the method for increasing the surface area of the electrode 44 by electrolysis has been described. However, as another method for easily increasing the surface area of the electrode 44, a machine using a file (not shown) is used as a surface treatment apparatus. There is a way to do it. A type of file that forms a groove with a depth of several μm on the surface of the electrode 44 is used. The surface of the electrode 44 (especially in the vicinity of the upper side 44c) is polished with a file to form irregularities, thereby increasing the surface area of the electrode 44.

  Alternatively, a laser light source may be used as a surface treatment device to increase the surface area by forming grooves on the surface of the electrode 44 by laser irradiation. As the laser light source, a type capable of metal processing is used. For example, the groove is formed by melting the surface of the electrode 44 with heat using a carbonic acid (CO2) laser. Similarly, a groove is formed on the surface of the electrode 44 using a YAG laser.

  Furthermore, as shown in FIG. 6 (FIG. 6A is a schematic cross-sectional view and FIG. 6B is a schematic top view), holes 46 are formed in advance to increase the surface area. When the above surface treatment method is applied to the electrode 44 having a shape, the surface area can be increased without changing the size of the electrode 44.

  A plurality of openings 46 a are formed in the electrode 44, and holes 46 having a predetermined depth are formed from the openings 46 a toward the substrate 43. The hole 46 is formed in a columnar shape with an inner diameter D <b> 2 so as to be substantially perpendicular to the substrate 43. The height of the hole 46 (the depth from the tip of the electrode 44 to the low) is approximately the same as the height at which the electrode 44 protrudes from the substrate 43. Thereby, the surface area in the hole 46 formed corresponding to the opening 46a is made as wide as possible. Thus, by forming the shape of the electrode 44 in advance so as to increase the surface area, and performing any of the above surface treatments, the surface area with respect to the size of the electrode 44 can be further increased. The charge injection capability of the electrode 44 can be improved.

It is the schematic which showed the external appearance of the visual reproduction auxiliary | assistance apparatus. It is a figure which shows the internal body apparatus in a visual reproduction assistance device. It is a typical sectional view near an electrode. It is an example of a surface treatment apparatus. It is the picked-up image of the electrode by a scanning electron microscope. It is an example of a change of an electrode shape.

DESCRIPTION OF SYMBOLS 1 Visual reproduction | regeneration assistance apparatus 10 External device 20 In-vivo device 30 Receiving part 40 Stimulation part 44 Electrode 100 Surface treatment apparatus

Claims (6)

  1. In a visual reproduction assisting device in which a plurality of electrodes are installed on a patient's eye and a predetermined electrical stimulation pulse signal is output from the electrodes to promote visual reproduction, the electrodes have a three-dimensional shape and the surface thereof is processed. A visual reproduction assisting device characterized by having a non-uniform and fine uneven shape.
  2. 2. The visual reproduction assisting device according to claim 1, wherein the electrode is surface-treated by an electrochemical oxidation-reduction reaction.
  3. 2. The visual reproduction assisting device according to claim 1, wherein the electrode material forming the electrode has anisotropy.
  4. 3. The visual reproduction assisting device according to claim 2, wherein the electrode is formed by cold drawing of the electrode material.
  5. In a method for manufacturing a visual reproduction assisting device that promotes visual reproduction by installing a plurality of electrodes on a patient's eye and outputting a predetermined electrical stimulation pulse signal from the electrodes, a plurality of electrodes having a three-dimensional shape are formed on a predetermined substrate. A first step of forming, and a second step of applying a predetermined surface treatment to the electrode formed on the substrate by the first step, thereby forming a non-uniform and fine uneven shape on the electrode surface; A method for manufacturing a visual reproduction assisting device, comprising:
  6. 6. The visual reproduction assisting device according to claim 5, wherein the surface treatment is a process of causing the electrode to perform an electrochemical redox reaction.
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US10207108B2 (en) 2014-10-22 2019-02-19 Oculeve, Inc. Implantable nasal stimulator systems and methods
US10252048B2 (en) 2016-02-19 2019-04-09 Oculeve, Inc. Nasal stimulation for rhinitis, nasal congestion, and ocular allergies
US10426958B2 (en) 2015-12-04 2019-10-01 Oculeve, Inc. Intranasal stimulation for enhanced release of ocular mucins and other tear proteins

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