JP6119128B2 - Living implanter - Google Patents

Description

The present invention relates to biological implantation UeSo location comprising an electrode which is implanted in living tissue.

  A visual reproduction assisting device is known as a device implanted in a living body. The visual reproduction assisting device is composed of an extracorporeal device that captures an image of the outside world and an in-vivo device that is electrically implanted in a living body and electrically stimulates cells constituting the retina of the patient in order to reproduce the vision of the patient. The intracorporeal device has a substrate in which an electrode formed of a conductive material such as metal is incorporated, and the substrate is attached to the eyeball through an incision formed on the retina, subretinal or sclera of the patient's eye. When an electrical stimulation pulse signal (charge) is output from each electrode in a state where the electrodes are attached to the eyeball, cells constituting the retina are electrically stimulated to promote visual reproduction. (For example, refer patent documents 1, 2, and 3) Moreover, the brain stimulation apparatus is known as a living body implantation apparatus. In the brain stimulating device, an electrode is implanted at a predetermined position of the brain, and a predetermined stimulation signal such as light is given to the patient's brain (for example, see Patent Document 4). In addition, investigation and research of response to brain stimulation by detecting response signals due to brain stimulation are being conducted.

JP 2002-325851 A JP 2006-068404 A JP 2009-501030 A Special table 2011-518629

  In the conventional biological implanting device, the substrate and the electrode are made of an opaque material, so that the light beam entering the living body is blocked by the substrate and the electrode, and the light beam reaches a normally functioning nerve cell. There was a problem that was not done.

In view of the problems of the prior art, and an object to provide a more accurate biological implantation UeSo location.

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

The biological implant device is formed of, for example, a transparent insulating material, a substrate at least a part of which is arranged on the surface of the retina, and a plurality of electrodes arranged in the part of the substrate, An electrode group comprising an electrode that is formed of a transparent conductive material, and that is provided on the surface of the retina together with the part of the substrate to apply electrical stimulation to cells constituting the retina; and A stimulation control unit for designating an electrode to be output from each of the electrodes, and the stimulation control unit is disposed on the substrate at a distance from the electrode group.

The present invention can provide a more accurate biological implantation UeSo location.

  An embodiment according to the present invention will be described with reference to the drawings. Hereinafter, a visual reproduction assisting device will be described as an example of the biological tissue stimulating device. FIG. 1 is an external view of a visual reproduction assisting device. 2A and 2B are explanatory views of the internal device of the visual reproduction assisting device. FIG. 2A is a front view of the internal device 20, and FIG.

  The visual reproduction assisting device 1 is composed of an extracorporeal device 10 that captures the outside world and an in-vivo device 20 that stimulates visual reproduction by applying electrical stimulation to cells constituting the retina. The extracorporeal device 10 includes spectacles 11 worn by a patient, an imaging device 12 attached to the spectacles 11, an external device 13, a transmission unit 14 having a primary coil and the like. The external device 13 has a data modulation means 13a having an arithmetic processing circuit such as a CPU, and a power source 13b for supplying power to the visual reproduction assisting apparatus 1 as a whole. The data modulation means 13a performs image processing on the subject image photographed by the photographing device 12, and generates electrical stimulation pulse data for visual reproduction. The transmission unit 14 modulates the electrical stimulation pulse data generated by the data modulation unit 13a and the power of the power source 13b, and transmits the modulated electromagnetic wave to the in-vivo device 20 side. The transmission means 14 includes a primary coil for transmitting and receiving signals and power between the extracorporeal device 10 and the intracorporeal device 20 by electromagnetic induction. A magnet is attached to the center of the primary coil, and the position with the secondary coil is fixed by magnetic force.

  The intracorporeal device 20 includes a receiving unit 30 that receives an electromagnetic wave transmitted from the extracorporeal device 10 and a stimulating unit 40 that electrically stimulates cells constituting the retina. The receiving unit 30 includes a secondary coil 31 that receives an electromagnetic wave transmitted from the extracorporeal device 10, a reception control unit 61, and a substrate 33 on which these are installed. The stimulation unit 40 includes a plurality of electrodes 44, a stimulation control unit 62 that outputs a stimulation signal from the electrode 44 based on a signal from the reception control unit 61, and a plurality of conductive wires that electrically connect the electrode 44 and the stimulation control unit 62. 41 and a substrate 43 on which these are installed.

The reception control unit 61 extracts a signal and power from the electromagnetic wave received by the secondary coil 31. Further, the reception control unit 61 converts the extracted signal into a control signal including an electrical stimulation pulse signal to be output from the electrode 44, an electrode designation signal for designating the electrode 44 to output the electrical stimulation pulse signal, and the like. The stimulation control unit 62 distributes the corresponding electrical stimulation pulse signal to each electrode 44 based on the control signal transmitted from the reception control unit 61. That is, the stimulation control unit 62 outputs an electrical stimulation pulse signal from each electrode 44 based on the signal from the reception control unit 61 by the (de) multiplexer function.
The secondary coil 31 and the reception control unit 61 of the reception unit 30 are formed on the substrate 33. The substrate 33 is made of a known resin material having biocompatibility. At the center of the secondary coil 31, a magnet for fixing the position with the one coil is provided.

  The plurality of electrodes 44 of the stimulation unit 40 are formed at one end of each of the plurality of conductive wires 41. The other end of each conducting wire 41 is connected to the stimulation control unit 62. The stimulus control unit 62 (terminal not shown) is connected to one end of a plurality of conducting wires 51 wired in the cable 50. As a result, the reception control unit 61 is electrically connected from the electrode 44, and the stimulation control unit 62 is driven and controlled based on the reception signal of the reception control unit 61, and from each electrode 44 based on the command signal from the stimulation control unit 62. An electrical stimulation pulse signal is output. In the present embodiment, a counter electrode (return electrode) 34 is attached on the substrate 43. In addition to this, the counter electrode 34 is provided at an arbitrary position where the stimulation signal output from the electrode 44 can be received.

In addition, the electrode 44 and the conducting wire 41 of this embodiment are formed of a transparent conductive material having biocompatibility and conductivity. Graphene, carbon nanotubes, or the like are used as the transparent conductive material. In addition, transparent conductive materials are materials that have biocompatibility, have flexibility that can be bent when implanted in the eye, and have a high electron transfer rate at room temperature. It is done. By forming the electrode 44 with a material having high conductivity such as graphene, at least the surface area of the electrode 44 is suitably electrically stimulated by cells constituting the retina, and the electrode 44 can be reduced in size.
The electrode 44 and the conductive wire 41 may be formed of a translucent conductive material having conductivity and biocompatibility. In addition to this, the electrode 44 and the conductive wire 41 may be formed of a conductive material that can transmit at least a part of the light beam incident on the eye.

The substrate 43 on which the electrodes 44 and the like are installed is formed of an insulating material having biocompatibility and transparency. For example, a known insulating material such as polydimethyl silicone (PDMS), parylene, epoxy resin, polyimide, polyethylene, or the like is used as the transparent insulating material. The substrate 43 may be formed of an insulating material having biocompatibility and translucency. In addition to this, the substrate 43 may be formed of an insulating material capable of transmitting at least a part of the light beam incident on the eye.
In this way, the entire stimulating unit 40 is formed of a transparent (translucent) material (conductive material, insulating material), so that light incident from the eye passes through the entire stimulating unit 40 and enters the retina. To be reached.

FIG. 3 shows a flowchart of a procedure for creating the stimulation unit 40. FIG. 4 is an explanatory diagram of a procedure for creating the stimulation unit 40. FIG. 5 is an enlarged view of the stimulation unit 40, and FIG. 5A shows a front view and FIG. 5B shows a side view.
First, the base substrate 143 is prepared. As shown in FIG. 4A, the base substrate 143 is formed on the silicon wafer (Si) 143a, the SiO2 film (for example, about 200 nm thick) 143b formed thereon, and the SiO2 film 143b. And a copper (Cu) film (for example, having a thickness of 500 nm) 143c. The SiO2 film 143b and the copper (Cu) film 143c are each formed by sputtering.

  In step S101, in order to form the electrode 44 and the conductive wire 41, a graphene sheet (graphene sheet) 144 having a predetermined area is generated on the base substrate 143 as shown in FIG. The graphene sheet 144 is generated by a well-known chemical vapor deposition method (chemical vapor deposition, various CVD). Various CVD methods include a thermal CVD method, a plasma CVD method, a surface excitation microwave plasma CVD method, and the like.

  In FIG. 6, the example of the production | generation apparatus of the graphene sheet 144 is shown. The graphene sheet generating apparatus 100 includes a reaction vessel 110 and a heating furnace 120. A source gas inlet 111 is provided on the left side of the reaction vessel 110 and a discharge port 112 is provided on the right side of the page. In addition, a base substrate 143 coated with a carbon source 113 and a catalytic metal layer that forms a graphene sheet is provided inside the reaction vessel 110. For example, camphor is used as the carbon source 113. In addition, materials such as methane and acetylene are used for the carbon source 113. In addition, any organic compound having a distorted carbocyclic ring is used. As described above, the surface (entire) of the base substrate 143 is coated with the copper 143c that is the catalyst metal layer. In addition to this, a pure metal of any one of nickel, iron, cobalt, platinum, gold, silver and copper, or an alloy containing two or more kinds is used as the catalyst metal.

  In the graphene sheet generating apparatus 100 as described above, the heating furnace 120 is heated at a predetermined temperature while being filled with an inert gas such as argon gas from the inlet 111. Note that the heating furnace 120 is heated at a temperature higher than the boiling point or sublimation point of the carbon source 113 and capable of growing graphene on the base substrate 143. The gas that has passed through the reaction vessel 110 is discharged from the discharge port 112.

When the camphor that is the carbon source 113 evaporates, the graphene sheet 144 grows on the base substrate 143 with the graphene that is supplied into the reaction vessel 110 and decomposed and generated by the copper 143c as the catalyst metal layer as a nucleus. When the carbon source 113 is sufficiently evaporated and decomposed by the catalytic metal layer, and the graphene sheet 144 is sufficiently grown on the base substrate 143, the heating of the heating furnace 120 is stopped. Thereby, a graphene sheet (laminated film) 144 having a predetermined thickness is obtained. Note that the amount of the carbon source 113 and the heating temperature of the heating furnace 120 are such that the graphene sheet 144 of the present embodiment is a laminate (graphite) of four or more layers (more preferably eight or more layers) of graphene. Adjusted. By forming the graphene sheet 144 having a predetermined thickness, it is possible to ensure predetermined conductivity with respect to the living body.
Note that, in the above, an example in which the graphene sheet 144 is grown in a state where the reaction vessel 110 is filled with a predetermined inert gas is shown. In addition to this, the graphene sheet may be grown in a reduced pressure state in which the inside of the reaction vessel is sealed.

  For example, the graphene sheet 144 preferably has a transmittance of 80% or more. If the transmittance is less than 80%, there is a concern that the reaction of the retina may be reduced. Other than this, the transmittance of the graphene sheet 144 may be formed so that the patient's retina can sense light. The graphene sheet 144 is grown to a sheet resistance of about 20 kΩ / □ or less. More preferably, it is preferably grown to about 3 kΩ / □ or less. If the sheet resistance is 20 kΩ / □ or more, unnecessary power consumption may increase or it may be difficult to obtain a desired current value.

  In addition, when it is difficult to obtain such characteristics with a single layer of graphene sheet 144, a graphene sheet 144 having a plurality of layers can be obtained by repeating a growth process (the process of step S <b> 101 described above) by a CVD method described later a plurality of times. It may be formed. Note that the transparency of the graphene sheet 144 decreases as the layer thickness increases, and the resistance value of the graphene sheet 144 increases as the layer thickness decreases. In consideration of the above characteristics, the graphene sheet 144 having the desired transparency and resistance value may be formed according to the shape. Through the above process, a graphene sheet 144 having a predetermined area (for example, 5 × 5 mm or more) is obtained.

  Next, in step S102, as shown in FIG. 4B, a wiring board that omits the conductor pattern width (for example, 5 to 20 μm) at a predetermined wiring pitch (for example, 10 to 50 μm) by lithography. A (conductor substrate) 150 is prepared. Then, the wiring substrate 150 on which the wiring pattern is formed is covered with a thin polydimethylsilicone 151 using a spin coater or the like.

  Next, in step S103, as shown in FIG. 4C, the copper (Cu) film 143c is peeled off and etched away from the SiO2 film 143b of the silicon wafer 143a, and the wiring by the graphene sheet 144 is made into a polydimethylsilicone thin film. Transcript to. At this time, an adhesion promoter is applied between the graphene sheet 144 and the polydimethylsilicone 151 as necessary. As shown in FIG. 4D, the graphene transfer surface (conductive layer) 144a is thinly coated with polydimethyl silicone by the same method as described above to completely insulate the graphene. (In this step, instead, parylene may be vapor-grown on both the front and back surfaces to form an insulating coating film). As a result, a substrate 43 having a conductive layer of graphene inside is formed.

  Next, in step S104, as shown in FIG. 4E, a part of the insulating coating is opened by etching to expose the graphene layer (conductive layer). Then, the stimulus control unit 62 and the electrode 44 are connected to the exposed portion. For example, the stimulus control unit 62 forms gold bumps on a pad (not shown), performs a flattening process, and mounts it on the substrate 43 with a conductive adhesive (attached to the conductive layer). The electrode 44 is formed by fixing a parylene resin coated with a platinum ball or graphene, and is attached to the graphene layer. Thereby, a three-dimensional electrode is formed. And the counter electrode 34 is attached on the board | substrate 43, the terminal which abbreviate | omits illustration of the stimulation control part 62, and the end of the conducting wire 41 are electrically connected, and the stimulation part 40 is completed. In addition, the stimulating unit 40 and the receiving unit 30 are electrically connected via the conducting wire 51 of the cable 50, whereby the in-vivo device 20 is completed.

  In step S101 described above, the base substrate 143 in the reaction vessel 110 is formed according to the shape of the electrode 44 and the conductive wire 41, and the process of step S101 is performed, whereby the electrode 44 and The conducting wire 41 may be formed. In this case, the process of step S102 is omitted.

  In the above, an example of an apparatus for producing graphene by a thermal CVD method is shown. In addition to this, for example, when producing graphene at a low temperature, it may be preferable to produce the graphene by a surface excitation microwave plasma CVD method. That is, when graphene is grown at a low temperature, it is necessary to lower the gas pressure. Therefore, in a general plasma CVD method, it may be difficult to generate plasma due to a decrease in gas pressure. Thus, by using surface-excited microwave plasma CVD, graphene is suitably generated using plasma even at a low temperature. For example, in the surface excitation microwave plasma CVD method, a cylindrical quartz tube with an antenna inside is arranged, and an alternating voltage with a predetermined frequency (for example, 2.45 GHz) is applied thereto to generate plasma. In addition to this, the microwave that has passed through the waveguide is guided into the reaction vessel through a quartz window or the like, and a gas (carbon source) is excited to generate plasma.

The case where the visual reproduction auxiliary device 1 having the above configuration is implanted in a living body will be described. FIG. 7 shows an explanatory view of a cross section in a state where the intracorporeal device 20 is implanted in the eye. In FIG. 7, a retina E1, a choroid E2, and a sclera E3.
The bendable stimulation part 40 is inserted into the eye through a notch (port) (not shown) while being bent. When a part of the stimulation unit 40 is inserted into the eye, the stimulation unit 40 is restored to the original shape in the eye by the restoring force of the material of the substrate 43. A part (electrode 44 and substrate 34) of the stimulating part 40 spreading in the eye is attached on the retina. On the other hand, as shown in the figure, the stimulus control unit 42 is preferably placed outside the eyeball. Since the opaque stimulus control unit 42 is placed outside the eyeball in this way, the light beam entering the eye can suitably reach the retina. The stimulus control unit 62 may be placed in the eye. In this case, the stimulus control unit 62 is attached to a blind spot such as an optic disc. In this way, the light beam that has passed through the stimulating unit 40 is suitably projected onto the retina while suppressing the influence of the light blocking of the light beam by the stimulus control unit 62. Although not shown, the receiving unit 30 is installed outside the eye via the cable 50. In this way, by placing the substrate 43 on the patient's retina, it is possible to reduce the burden on the patient at the time of surgery rather than below the retina. In addition, since the entire member placed on the retina is transparent, it enters from the eye and passes through 43 etc. and reaches the retina.

  In the above description, an example in which the substrate 43 is placed on the retina of the patient has been shown. In addition to this, when the substrate 43 is placed under the retina E3 and in the incision of the sclera E1, the thickness of the substrate 43 is formed so as to reduce the burden on the patient associated with the operation. it can. In addition, the surgeon can easily perform an operation when implanting the visual reproduction assisting device 1 in the living body.

Furthermore, in this embodiment, a fine electrode is formed using graphene. Therefore, for example, it is possible to stimulate the cells constituting the retina individually by forming the electrode shape in a cell level size. By providing a plurality of such fine electrodes, it is expected that the appearance closer to that of a healthy person can be obtained.
Furthermore, the precision of visual reproduction is improved by forming the thin substrate 43 so as to cover the retina and forming many fine electrodes on the substrate 43. The substrate 43 may be formed by connecting a plurality of substrates 43.

  Next, the operation of the visual reproduction assisting device having the above configuration will be described. FIG. 8 shows a block diagram of a control system of the visual reproduction assisting device. Shooting data (image data) of a subject photographed by the photographing device 12 is sent to the data conversion means 13a. The data conversion means 13a converts the photographed subject into a signal (electric stimulation pulse data) within a predetermined band necessary for the patient to visually recognize, and transmits the signal as electromagnetic waves from the transmission means 14 to the in-vivo device 20 side.

  On the intracorporeal device 20 side, the electromagnetic wave received by the secondary coil 31 is modulated, whereby electrical stimulation pulse data and power are generated and sent to the reception control unit 61. The reception control unit 61 generates an electrical stimulation pulse to be distributed to each electrode 44 and a multiplexer control signal for controlling the distribution of the electrical stimulation pulse based on the extracted electrical stimulation pulse data, and the stimulation control unit via the cable 50 Send to 42. The stimulation control unit 42 outputs an electrical stimulation pulse from each electrode 44. The cells constituting the retina are electrically stimulated by the electrical stimulation pulse output from each electrode 44, and the patient obtains vision.

The light transmitted through the substrate 43 or the like is absorbed by retinal pigment cells (photocells) through transparent nerve fibers, cellular nerve layers, and the like. The photoreceptor cell converts light into a stimulus signal. The stimulus signal output from the photoreceptor cell is subjected to complicated processing from various nerve cells existing in the retina, and then transmitted from the ganglion cell existing on the surface of the retina to the brain center via the optic nerve.
In this way, all the members such as the substrate 43 placed on the retina are formed of a transparent material, so that cells involved in signal transmission such as ganglion cells function normally by transmitted light, and more healthy eyes. It is expected that visual reproduction will be performed in a state close to.

  In this embodiment, since the electrode 44 is directly disposed on the retina, the stimulation signal from the electrode 44 is directly transmitted to the retina. For this reason, the cells constituting the retina are efficiently electrically stimulated without the stimulation signal output from the electrode 44 being attenuated. Therefore, the surface area of the electrode 44 can be further reduced.

  Further, in the development stage of the apparatus, the reaction of the ganglion cell of the eye (normal eye) may be acquired using the visual regeneration auxiliary device as described above (the reaction of the subject to the stimulation pulse signal may be acquired). good). And based on a detection result, you may set the stimulation conditions of the stimulation pulse signal produced | generated with respect to the picked-up image image | photographed with the camera 12 based on reaction of a ganglion cell. As described above, by setting the stimulation conditions of the stimulation pulse signal in accordance with the stimulation response of the healthy eye in advance, the quality of visual reproduction (QOV) can be improved as compared with the visual reproduction auxiliary device of the prior art.

  For example, an electrode provided on the intracorporeal device 20 side is used as a detection unit (for example, an electrode) that detects a change in response signal from a nerve cell (temporal intensity change amount). Then, the change amount of the response signal from the nerve cell detected by the detection unit and the information of the stimulation pulse signal are associated and stored in a storage unit such as a memory (not shown). Then, when the visual reproduction assistance device is used for a patient, a stimulation pulse signal is output from an electrode implanted in the eye based on information stored in the storage unit.

  Furthermore, the biological implanting device having the above-described configuration may be used for detecting response signals of various nerve fibers. For example, in recent years, research has been conducted to apply a stimulus signal such as light from the outside with electrodes embedded in a patient's brain and detect the response signal to use for treatment of a living body. In such research and development, when the configuration of the present invention is applied, a change in the response signal to a stimulus (for example, a light beam) irradiated to a local region of the brain is suitably acquired. In this case, an electrode implanted in the brain is used as a detection unit that detects a change in response signal from a nerve cell (temporal intensity change amount). When a predetermined stimulus signal (for example, light) is applied to the brain from the outside, and a neuron in the brain responds to the stimulus, a change in the response signal is detected via the electrode. At this time, since the brain is preferably stimulated by light or the like through the transparent substrate, it is expected that the response signal of the brain nerve cells will be suitably detected through the electrodes. Is done. It is also expected that more detailed information at the cell level can be obtained by providing a large number of finely shaped electrodes.

It is an external view of a visual reproduction auxiliary device. It is explanatory drawing of the internal body apparatus of a visual reproduction assistance device. It is a flowchart of the preparation procedure of a stimulation part. It is explanatory drawing of the preparation procedure of a stimulation part. It is an enlarged view of a stimulation part. It is an example of a graphene sheet production | generation apparatus. It is explanatory drawing of the cross section of the state which implanted the intracorporeal apparatus in eyes. It is a block diagram of the control system of a visual reproduction auxiliary device.

DESCRIPTION OF SYMBOLS 10 Extracorporeal device 20 Intracorporeal device 30 Receiving part 40 Stimulation part 41 Conductor 43 Board | substrate 44 Electrode 62 Stimulation control part

Claims (2)

A substrate formed of a transparent insulating material and at least partially disposed on the surface of the retina;
A plurality of electrodes arranged on the part of the substrate , formed of a transparent conductive material, and a cell constituting the retina while being arranged on the surface of the retina together with the part of the substrate An electrode group comprising electrodes for applying electrical stimulation to
A stimulation control unit for designating an electrode to which electrical stimulation is output from each of the electrodes, and
The stimulation control unit is a living body implanting device arranged on the substrate with a space from the electrode group.   The living body implanter according to claim 1, wherein the stimulation control unit designates the electrode based on an image captured by an imaging device that is arranged outside the body and images the outside world.

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