CN105477780A - Implantable neuro-stimulation and recording photoelectrode and manufacturing method thereof - Google Patents

Abstract

The invention discloses an implantable photoelectrode for nerve stimulation and recording, which comprises: a support component, which includes an insertion end, and the insertion end is provided with a recording contact for generating electrical stimulation and recording nerve signals generated by the electrical stimulation; and , a light-emitting component, which is located at the insertion end and is used to generate light stimulation; wherein, the recording contacts are also used to record nerve signals generated by the light stimulation. In the present invention, a recording contact for generating electrical stimulation and recording the nerve signal generated by the electrical stimulation and a light-emitting component for generating light stimulation are arranged at the insertion end of the photoelectrode, and the recording contact is also used for recording the nerve signal generated by the light stimulation, thereby A photoelectrode with optical/electrical stimulation and multi-channel recording contacts is formed, and the recording of optical/electrical stimulation and optical/electrical stimulation nerve signals is completed through one photoelectrode, which simplifies equipment, saves materials, and is suitable for multi-site potentials Measurement, widely used.

Description

Implantable nerve stimulation and recording photoelectrode and its manufacturing method

technical field

The invention relates to the technical field of biomedical engineering, more specifically, the invention relates to an implantable nerve stimulation and recording photoelectrode and a manufacturing method thereof.

Background technique

Optogenetics, also known as light-stimulated genetic engineering, is a method of controlling cell behavior by using optical technology and genetic technology. Optogenetics technology overcomes many shortcomings of the traditional method of only using electrical stimulation to control the activities of cells or organisms, and provides a transformative research method for neuroscience. This technical method controls the emission or inhibition of cells expressing light-sensitive protein through light stimulation of a specific wavelength. At present, the most popular research method of optogenetics is that a laser or LED (Light Emitting Diode, Light Emitting Diode) light source emits light of a certain wavelength, which is transmitted to the brain of an experimental animal, usually a mouse or a rat, through an optical fiber. Optogenetic technology is used as a tool to excite neurons in animals. At the same time, it needs to cooperate with other instruments and electrodes to observe and record neuron discharge, behavioral changes and physiological changes in animals.

At present, most of the similar neuromodulation strategies are electrical stimulation through metal wires, optical stimulation through optical fibers with lasers as light sources, or direct output through LED light-emitting coupling optical fibers. Among them, the electrical stimulation technology is relatively mature and has been successfully applied in the treatment of central nervous system diseases such as Parkinson's. The electrical stimulation electrodes are generally implemented with metal foil wires as electrodes; optical stimulation can stimulate specific neurons more accurately. In the future, it may become a more effective treatment method than electrical stimulation. However, optical fiber-based stimulation has the disadvantages of limited luminous area, light source is limited by the type of external laser generator, and expensive. It cannot achieve multi-point stimulation of neural circuits and Nucleus stimulation and other application requirements; at the same time, although there are a few light-emitting diode-based optodes, their manufacturing process is relatively complicated and the price is high; in addition, light stimulation does not have the functions of electrical stimulation and nerve signal recording. If you need to record stimulation The generated nerve signals must be configured with other recording electrodes and hardware systems, and the electrode products are very expensive.

Contents of the invention

In view of the deficiencies in the above-mentioned technologies, the present invention provides an implantable nerve stimulation and recording photoelectrode and its manufacturing method, by setting the insertion end of the photoelectrode to generate electrical stimulation and record the neural signals generated by the electrical stimulation The recording contacts and the light-emitting parts that generate light stimulation, the recording contacts are also used to record the nerve signals generated by light stimulation, so as to form light/electric stimulation and a photoelectrode with multiple recording contacts in one, through a photoelectrode The optical/electrical stimulation and the recording of the nerve signal of the optical/electrical stimulation are respectively completed, the equipment is simplified, the material is saved, and it is suitable for multi-site potential measurement, and has a wide range of applications.

In order to realize these purposes and other advantages according to the present invention, the present invention realizes through the following technical solutions:

The photoelectrode for implantable nerve stimulation and recording according to the present invention includes:

a support member comprising an insertion end provided with recording contacts for generating electrical stimulation and recording neural signals generated by said electrical stimulation; and,

a light-emitting component located at the insertion end for generating light stimulation;

Wherein, the recording contacts are also used to record the nerve signals generated by the light stimulation.

Preferably, the insertion side of the insertion end is trapezoidal along the insertion direction.

Preferably, the support component includes an upper substrate layer, a lower substrate layer, and a shielding layer connected between the upper substrate layer and the lower substrate layer; the support component also includes a connection end connected to an external connector;

Wherein, the upper substrate layer includes a signal collection line for collecting neural signals, the recording contact, and a first pad and a second pad respectively located at the connection end; the lower substrate layer includes a power line; the recording The contact is connected to the first pad through the signal collection line, and the light emitting component is connected to the second pad through the power line.

Preferably, the connection end is provided with a first through hole, and the insertion end is provided with a second through hole; the second pad is connected to one end of the power line through the first through hole, and the power supply The other end of the wire is connected to the light emitting component through the second through hole.

Preferably, the insertion side of the insertion end is trapezoidal along the insertion direction.

Preferably, at least one of the recording contacts and at least one of the light-emitting components are arranged sequentially on the insertion side of the insertion end along the insertion direction; wherein at least one of the recording contacts is arranged on the insertion side perpendicular to the insertion direction. The insertion side of the insertion end; at least one of the light-emitting components is arranged sequentially on the insertion side of the insertion end along the insertion direction.

Preferably, one of the recording contacts and one of the light-emitting components are sequentially arranged on the insertion side of the insertion end along the insertion direction; wherein, one of the recording contacts generates electrical stimulation, and records the nerve signal generated by the electrical stimulation And record a neural signal generated by light stimulation of the light-emitting component.

Preferably, several of the recording contacts and at least one of the light-emitting components are sequentially arranged on the insertion side of the insertion end along the insertion direction; wherein, several of the recording contacts generate electrical stimulation, and the recording of the electrical stimulation generates neural signals and record the neural signals generated by light stimulation of at least one light-emitting component.

Preferably, several of the recording contacts and at least one of the light-emitting components are sequentially arranged on the insertion side of the insertion end along the insertion direction; wherein, several of the recording contacts include generating electrical stimulation and recording the electrical stimulation A first recording contact for neural signals generated and a second recording contact for recording at least one neural signal generated by said light stimulation.

A method for making an implantable nerve stimulation and recording photoelectrode, comprising the following steps:

S1, apply a layer of epoxy resin glue on the lower substrate made of polyimide, and attach a layer of copper foil with photoresist on the surface of the epoxy resin glue to form a shielding layer;

S2, using a mask for ultraviolet exposure, the exposed area is the shape of the photoelectrode shielding layer, and the unexposed area is removed with a developer after exposure;

S3, using an etching solution to remove the exposed copper foil, and then using a strong alkali solution to remove the photoresist, so that the top of the shielding layer is completely exposed;

S4, after coating epoxy resin glue on the top of the shielding layer, attaching an upper substrate layer made of polyimide on the top of the epoxy glue, thereby forming a supporting part of the photoelectrode;

S5, attaching copper foil to the upper and lower surfaces of the supporting part of the photoelectrode;

S7, performing drilling processing on the supporting part of the photoelectrode to form a first through hole and a second through hole;

S6, using an electroplating process to plate a layer of copper on the walls of the first through hole and the second through hole respectively;

S7, performing pattern transfer according to the methods of step S1, step S2, and step S3, and forming designed signal collection lines, power lines, first pads, and second pads on the upper surface and the lower surface of the photoelectrode support member;

S8, using laser cutting technology to cut the upper substrate layer and the lower substrate layer into the shape of the photoelectrode supporting part around the signal collection line, the power line, the first pad and the second pad, and welding the light emitting part to the insertion end of the supporting part The second through hole; forms the photoelectrode for implantable nerve stimulation and recording.

The present invention at least includes the following beneficial effects:

1) By setting the recording contacts for generating electrical stimulation and recording the neural signals generated by the electrical stimulation at the insertion end of the photoelectrode and the light-emitting components for generating optical stimulation, the recording contacts are also used to record the neural signals generated by optical stimulation, thereby A photoelectrode that forms photo/electric stimulation and has multiple recording contacts in one, completes the recording of photo/electric stimulation and photo/electric stimulation nerve signals respectively through one photoelectrode, simplifies equipment and saves materials;

2) The insertion side of the insertion end has a trapezoidal shape along the insertion direction, and the trapezoidal shape of the insertion side is equivalent to a triangle without the tip, similar to an arc design, which reduces the damage to the nerve tissue when the insertion end is inserted;

3) The recording contacts and light-emitting components are arranged at the insertion end in sequence along the insertion direction; at least one recording contact is arranged at the insertion end perpendicular to the insertion direction, which can provide at least one electrical stimulation or at least one neural signal generated by recording light stimulation ; At least one light-emitting component is arranged sequentially at the insertion end along the insertion direction, and can provide light stimulation of at least one or at least one wavelength.

Other advantages, objectives and features of the present invention will partly be embodied through the following descriptions, and partly will be understood by those skilled in the art through the study and practice of the present invention.

Description of drawings

Fig. 1 is the structure schematic diagram of the photoelectrode of implantable nerve stimulation and recording according to the present invention;

Fig. 2 is the top view of the photoelectrode of implantable nerve stimulation and recording according to the present invention;

Fig. 3 is a right view of the photoelectrode for implantable nerve stimulation and recording according to the present invention.

In the picture:

10-support component; 11-insert end; 111-record contact; 11A-insert side; 12-connection end; 13-signal acquisition line; 14-first pad; 15-second pad; 16-power line ; 17-the first through hole; 18-the second through hole;

20 - Lighting component.

detailed description

The present invention will be further described in detail below in conjunction with the accompanying drawings, so that those skilled in the art can implement it with reference to the description.

It should be understood that terms such as "having", "comprising" and "including" used herein do not exclude the presence or addition of one or more other elements or combinations thereof.

Example 1

The neuromodulation function can be manifested in two ways. One can generate electrical pulse stimulation with adjustable parameters through electrode contacts, and the other can perform light stimulation on specific neural tissues expressing light-sensitive proteins through micro-optic electrodes of specific wavelengths. As shown in Fig. 1, Fig. 2 and Fig. 3, the present invention provides a photoelectrode for implantable nerve stimulation and recording, including: a supporting part 10, which includes an insertion end 11, and the insertion end 11 is provided with a The recording contact 111 of the nerve signal generated by stimulation; and the light-emitting component 20, which is located at the insertion end 11, for generating light stimulation; wherein, the recording contact 111 is also used for recording the nerve signal generated by light stimulation.

The photoelectrode for implantable nerve stimulation and recording provided by the present invention is provided with a recording contact 111 for generating electrical stimulation and recording nerve signals generated by electrical stimulation and a light-emitting component 20 for generating optical stimulation at the insertion end 11 of the photoelectrode, recording The contact 111 also records the nerve signal generated by light stimulation, thereby forming a light/electric stimulation and a photoelectrode with an integrated recording contact, that is, the light/electric stimulation and the light/electric stimulation nerve signal are respectively completed through one photoelectrode. Recording, not only has the precise stimulation of specific neurons stimulated by light, but also records the nerve signals of light stimulation in time through the recording contacts 111 that generate electrical stimulation, simplifies equipment, saves materials, and improves the measurement accuracy and convenience of photoelectrodes.

Wherein, the recording contact 111 not only generates electrical stimulation and records the nerve signal generated by the electrical stimulation, but also records the nerve signal generated by the light stimulation, so as to improve the utilization rate of the recording contact 111 . The light source of the light-emitting component 20 can be a laser generator that emits light waves to optically stimulate nerve tissue. In this embodiment, considering the size and application of the photoelectrode for implantable nerve stimulation and recording, it is preferable to generate light of a specific wavelength, Furthermore, the miniature light-emitting diodes that control the expression of light-sensitive proteins have a small active area and a large scattered light-emitting area, which can be applied to the potential measurement of multiple parts of the animal body, and expand the application range of photoelectrodes for implantable nerve stimulation and recording.

As another embodiment of the present invention, the support member 10 includes an upper substrate layer, a lower substrate layer, and a shielding layer connected between the upper substrate layer and the lower substrate layer; the support member 10 also includes a connection terminal 12 connected to an external connector ; Wherein, the upper substrate layer includes the signal acquisition line 13 for collecting nerve signals, the recording contact 111 and the first pad 14 and the second pad 15 respectively located at the connection end 12; the lower substrate layer includes the power line 16; the recording contact 111 is connected to the first pad 14 through the signal collection line 13 , and the light emitting component 20 is connected to the second pad 15 through the power line 16 . The first pad 14, the second pad 15, the signal collection line 13, and the power line 16 are all made of gold-plated copper material; the shielding layer is made of copper foil. The shielding layer provided between the upper substrate layer and the lower substrate layer of the support component 10 reduces the interference of the power line 16 driving the light-emitting component 20 on the signal collection line 13 .

As another embodiment of the present invention, the connection end 12 is provided with a first through hole 17, and the insertion end 11 is provided with a second through hole 18; the second pad 15 is connected to one end of the power line 16 through the first through hole 17, The other end of the power line 16 is connected to the light emitting component 20 through the second through hole 18 . The first through hole 17 and the second through hole 18 provide convenient wiring for the light-emitting component 20 of the power-driven photoelectrode, and promote the reasonable wiring of the signal collection line 13 and the power line 16 . Wherein, the power line 16 is welded to the second pad 15 of the connecting end 12 through the first through hole 17; the light-emitting component 20 is welded to the inserting end 11 through the second through hole 18; Connected by welding.

As another embodiment of the present invention, the insertion side 11A of the insertion end 11 has a trapezoidal shape along the insertion direction. Usually, the insertion side of the photoelectrode insertion end 11 adopts a triangular shape with a sharp point to improve the convenience of the photoelectrode insertion into the living body. The width is 500um, the thickness of the insertion side 11A and the light-emitting component 20 is 300um, and the insertion side 11A of the insertion end 11 is trapezoidal along the insertion direction. Without affecting the work of the light-emitting component 20 and the recording contact, the damage to the nerve tissue caused by the insertion of the photoelectrode is reduced.

As another embodiment of the present invention, at least one recording contact 111 and at least one light-emitting component 20 are sequentially arranged on the insertion side 11A of the insertion end 11 along the insertion direction, so as to facilitate the recording contact 111, the light-emitting component 20, and the signal collection line 13 And while the power line 16 is reasonably laid out, the size of the insertion end of the photoelectrode is reduced to facilitate the insertion of the photoelectrode. In order to further improve the rationality of the layout and the convenience of insertion, it is preferred in this embodiment that at least one recording contact 111 is arranged in sequence on the insertion side 11A of the insertion end 11 along the direction perpendicular to the insertion direction: as shown in Figure 2, three recording contacts 111 The contacts 111 are sequentially arranged on the insertion side 11A of the insertion end 11 along the direction perpendicular to the insertion direction; at least one light-emitting component 20 is sequentially arranged on the insertion side 11A of the insertion end 11 along the insertion direction.

As another embodiment of the present invention, a recording contact 111 and a light-emitting component 20 are arranged sequentially on the insertion side 11A of the insertion end 11 along the insertion direction; Neural signals and recording of neural signals generated by light stimulation of a light-emitting component 20 . This embodiment is a one-to-one mode in which one recording contact 111 corresponds to one light-emitting component 20, which satisfies photoelectrode electrical stimulation/photostimulation recording, and at the same time saves materials to the greatest extent, has a high degree of integration, and improves the convenience of photoelectrode use sex.

As another embodiment of the present invention, several recording contacts 111 and at least one light-emitting component 20 are arranged sequentially on the insertion side 11A of the insertion end 11 along the insertion direction; wherein, several recording contacts 111 generate electrical stimulation, recording electrical Stimulating and recording the neural signals generated by the at least one light-emitting component 20 . This embodiment is a many-to-one mode in which several recording contacts 111 correspond to one light-emitting component 20 or a many-to-many mode in which several recording contacts 111 correspond to several light-emitting components 20: in the many-to-one mode of this embodiment, Several recording contacts 111 record the nerve signals generated by the light stimulation of the same light-emitting component 20, specifically, several recording contacts 111 record the nerve signals generated by the light-stimulation of one light-emitting component 20 from different channels, so that the photoelectrode has multiple Differential recording of channel nerve electrical signals and dual-mode neuromodulation function of electrical stimulation and light stimulation, multi-channel recording also improves the accuracy of nerve signal acquisition generated by light stimulation; in the many-to-many mode of this embodiment, the specific It means that when several recording contacts 111 respectively send out electrical stimulation and record the nerve signals generated by electrical stimulation, they also record the nerve signals generated by light stimulation of several light-emitting components 20, in order to record the nerve signals generated by light stimulation of a variety of different wavelengths. Provides a way to further improve the accuracy of photostimulation recordings.

As another embodiment of the present invention, several recording contacts 111 and at least one light-emitting component 20 are sequentially arranged on the insertion side 11A of the insertion end 11 along the insertion direction; wherein, several recording contacts 111 include generating electrical stimulation and recording A first recording contact for neural signals generated by electrical stimulation and a second recording contact for recording at least one neural signal generated by optical stimulation. Dividing the first recording contact only for generating electrical stimulation and recording the neural signal generated by electrical stimulation from the second recording contact only for recording at least one neural signal generated by optical stimulation improves the optical stimulation/electrical Accuracy of stimulus recording.

Example 2

On the basis of Embodiment 1, this embodiment provides a method for manufacturing an implantable nerve stimulation and recording photoelectrode described in Embodiment 1, which is characterized in that it includes the following steps:

S1, apply a layer of epoxy resin glue on the lower substrate made of polyimide, and attach a layer of copper foil with photoresist on the surface of the epoxy resin glue to form a shielding layer;

S2, using a mask for ultraviolet exposure, the exposed area is the shape of the photoelectrode shielding layer, and the unexposed area is removed with a developer after exposure;

S3, using an etching solution to remove the exposed copper foil, and then using a strong alkali solution to remove the photoresist, so that the top of the shielding layer is completely exposed;

S4, after coating epoxy resin glue on the top of the shielding layer, attaching an upper substrate layer made of polyimide on the top of the epoxy glue, thereby forming a supporting part of the photoelectrode;

S5, attaching copper foil to the upper and lower surfaces of the supporting part of the photoelectrode;

S7, performing drilling processing on the supporting part of the photoelectrode to form a first through hole and a second through hole;

S6, using an electroplating process to plate a layer of copper on the walls of the first through hole and the second through hole respectively;

S7, performing pattern transfer according to the methods of step S1, step S2, and step S3, and forming designed signal collection lines, power lines, first pads, and second pads on the upper surface and the lower surface of the photoelectrode support member;

S8, using laser cutting technology to cut the upper substrate layer and the lower substrate layer into the shape of the photoelectrode supporting part around the signal collection line, the power line, the first pad and the second pad, and welding the light emitting part to the insertion end of the supporting part The second through hole; forms the photoelectrode for implantable nerve stimulation and recording.

Wherein, the main component of developing solution is sodium carbonate. The main components of the etching solution are hydrogen peroxide and hydrochloric acid. The main component of strong alkaline solution is sodium hydroxide. The first pad 14, the second pad 15, the signal collection line 13, and the power line 16 are made of gold-plated copper material, and a layer of copper is plated on the walls of the first through hole 17 and the second through hole 18, thereby realizing the support component 10 The electrical connection between the recording contact 111 between the upper substrate layer, the lower substrate layer and the shielding layer and the first pad 14 , and the electrical connection between the light emitting component 20 and the second pad 15 . The light-emitting component 20 is soldered to the second through hole 18 of the insertion end 11 of the supporting component 10 by lead-free low-temperature solder paste.

The embodiment of the present invention provides a method for manufacturing an implantable photoelectrode for nerve stimulation and recording. The photoelectrode for implantable nerve stimulation and recording produced by the method is flexible and bendable, and is suitable for both epidermis and It is suitable for deep tissues, and the photoelectrode can be freely placed in the nerve tissue, which improves the flexibility of the photoelectrode and broadens the application range of the photoelectrode.

Although embodiments of the present invention have been disclosed above, it is not limited to the applications set forth in the specification and examples. It can be fully applied to various fields suitable for the present invention. Additional modifications can be readily effected by those skilled in the art. Therefore, the invention should not be limited to the specific details and examples shown and described herein, without departing from the general concept defined by the claims and their equivalents.

Claims (9)

1. implantable nerve stimulates the optoelectronic pole with record, it is characterized in that, comprising:

Support component, it comprises insertion end, and described insertion end is provided with the record contact producing electricity irritation and record the nerve signal that described electricity irritation produces; And,

Luminous component, it is positioned at described insertion end, for generation of photostimulation;

Wherein, described record contact is also for recording the nerve signal that described photostimulation produces.

2. implantable nerve as claimed in claim 1 stimulates the optoelectronic pole with record, it is characterized in that, the screen layer that described support component comprises upper substrate layer, lower substrate layer and is connected between described upper substrate layer and described lower substrate layer; Described support component also comprises the link connecting external connector;

Wherein, described upper substrate layer comprises the signals collecting line gathering nerve signal, described record contact and lays respectively at the first pad and second pad of described link; Described lower substrate layer comprises power line; Described record contact is connected to described first pad by described signals collecting line, and described luminous component is connected to described second pad by described power line.

3. implantable nerve as claimed in claim 2 stimulates the optoelectronic pole with record, it is characterized in that,

Described link is provided with the first through hole, and described insertion end is provided with the second through hole; Described second pad is connected to described power line one end by described first through hole, and the described power line other end is connected to described luminous component by described second through hole.

4. implantable nerve as claimed in claim 1 stimulates the optoelectronic pole with record, and it is characterized in that, the inserting side of described insertion end is trapezoidal shape along direction of insertion.

5. implantable nerve as claimed in claim 4 stimulates the optoelectronic pole with record, it is characterized in that, records contact and described at least one, luminous component is sequentially arranged in the inserting side of described insertion end along direction of insertion described at least one;

Wherein, contact is recorded described at least one along the inserting side being sequentially arranged in described insertion end perpendicular to direction of insertion; Luminous component described at least one is sequentially arranged in the inserting side of described insertion end along direction of insertion.

6. implantable nerve as claimed in claim 5 stimulates the optoelectronic pole with record, it is characterized in that, a described record contact and described luminous component are sequentially arranged in the inserting side of described insertion end along direction of insertion;

Wherein, a described record contact produces electricity irritation, records the nerve signal that described electricity irritation produces and the nerve signal recording a described luminous component photostimulation generation.

7. implantable nerve as claimed in claim 5 stimulates the optoelectronic pole with record, it is characterized in that,

Contact is recorded and luminous component described at least one is sequentially arranged in the inserting side of described insertion end along direction of insertion described in several;

Wherein, record contact described in several to produce electricity irritation, record the nerve signal that described electricity irritation produces and the nerve signal recording luminous component photostimulation generation described at least one.

8. implantable nerve as claimed in claim 5 stimulates the optoelectronic pole with record, it is characterized in that,

Contact is recorded and luminous component described at least one is sequentially arranged in the inserting side of described insertion end along direction of insertion described in several;

Wherein, record described in several contact comprise only for generation of electricity irritation and record the nerve signal that described electricity irritation produces the first record contact and only for recording the second record contact of the nerve signal that photostimulation described at least one produces.

9. the implantable nerve according to any one of claim 1-8 stimulates the manufacture method with the optoelectronic pole of record, it is characterized in that, comprises the following steps:

S1, above the infrabasal plate that polyimides is made, be coated with one deck epoxide-resin glue, above epoxide-resin glue, coating surface posts the Copper Foil of one deck photoresist, forms screen layer;

S2, utilize mask to carry out ultraviolet exposure, exposure area is the shape of optoelectronic pole screen layer, is removed by unexposed area after exposure with developer solution;

S3, utilizes etching liquid to be removed by exposed Copper Foil, and photoresist is removed by recycling strong base solution, allows above screen layer and exposes completely;

S4, on the shielding layer after square epoxy resin coating glue, the upper substrate layer that polyimides of fitting above epoxy natural gum is made, thus the support unit forming optoelectronic pole;

S5, at the support unit upper and lower surface laminating Copper Foil of optoelectronic pole;

S7, carries out boring process to the support unit of optoelectronic pole, forms the first through hole and the second through hole;

S6, plates one deck copper respectively with electroplating technology on the hole wall of the first through hole and the second through hole;

S7, carries out Graphic transitions according to the method for step S1, step S2, step S3, forms designed signals collecting line, power line, the first pad and the second pad at the upper surface of optoelectronic pole support unit and lower surface;

S8, utilizes laser cutting technique, around signals collecting line, power line, the first pad and the second pad, upper substrate layer and lower substrate layer are cut into the shape of optoelectronic pole support unit jointly, luminous component is welded on the second through hole of support unit insertion end; Form implantable nerve and stimulate the optoelectronic pole with record.