CN110367977B

CN110367977B - Photoelectric integrated stretchable flexible nerve electrode and preparation method thereof

Info

Publication number: CN110367977B
Application number: CN201910560592.5A
Authority: CN
Inventors: 刘景全; 吉博文; 郭哲俊; 王隆春
Original assignee: Shanghai Jiaotong University
Current assignee: Shanghai Jiaotong University
Priority date: 2019-06-26
Filing date: 2019-06-26
Publication date: 2020-10-30
Anticipated expiration: 2039-06-26
Also published as: CN110367977A

Abstract

The invention provides a photoelectric integrated stretchable flexible nerve electrode and a preparation method thereof, wherein the flexible nerve electrode comprises a first layer of elastic substrate, a light stimulation electrode, a second layer of elastic substrate and a recording electrode; wherein, the optical stimulation electrode and the recording electrode both adopt a snake-shaped bent wiring structure; the lower surface of the photostimulation electrode is provided with a first silicon dioxide layer, and the photostimulation electrode is bonded on the surface of the first layer of elastic substrate through a strong chemical bond generated by condensation reaction between the first silicon dioxide layer and the first layer of elastic substrate; the upper surface of the photostimulation electrode is provided with a second layer of elastic substrate, the lower surface of the recording electrode is provided with a second silicon dioxide layer, and the recording electrode is bonded on the surface of the second layer of elastic substrate through a strong chemical bond generated by condensation reaction between the second silicon dioxide layer and the second layer of elastic substrate, so that the recording electrode and the photostimulation electrode are integrated into an integral structure. The flexible nerve electrode can be implanted for a long time, has high flexibility, and can bear the deformation influence of expansion and contraction of brain tissues and the like.

Description

Photoelectric integrated stretchable flexible nerve electrode and preparation method thereof

Technical Field

The invention belongs to a neural microelectrode in the technical field of biomedical engineering, and particularly relates to a photoelectric integrated stretchable flexible neural electrode and a preparation method thereof.

Background

With the rapid progress and development of brain-computer interfaces and neuroscience, deep understanding of brain function and disease has become one of the leading directions of disputed research in various countries around the world. By means of flexible electronic science and MEMS micro-nano processing capability, the flexible neural microelectrode is increasingly used for accurately acquiring high-density and high-information-content electroencephalogram signals, and a brand-new tool is provided for neural loop function research, brain area focus diagnosis, neural decoding and the like.

Since the advent of optogenetics, the accurate stimulation or inhibition of a specific class of neurons has become an essential tool for the study of neurological disease models and neural circuit function. The current main means of introducing a light source into the brain is to irradiate the brain tissue through an optical fiber, but the resolution is extremely poor. In recent years, light sources such as a probe with a hole, an optical waveguide, and a micro LED array have been developed, and the light sources are classified into two modes, i.e., a mode of penetrating the light source deep into the brain and a mode of performing light stimulation through the cerebral cortex. When the light stimulation is performed through the surface of the cerebral cortex in a relatively small invasive way, the volume change caused by the expansion and contraction of the brain needs to be considered.

The search of the prior art shows that no research is provided for the stretchable brain-computer interface device integrating the micro LED chip array and the function of acquiring the electrical signals of the cerebral cortex at present. Morikawa Y, Yamagiwas et al, university of Toyobo technical science, Advanced healthcare materials,2018,7(3):1701100, written in "ultrastretchableKirigami bioprobes", propose a flexible neuromicroelectrode with a paper-cut structure that is highly stretchable, can withstand a maximum strain of 840%, and has a Young's modulus of only 3.6 kPa. The device adopts 11 micron thick Parylene-C material as flexible substrate, contains 10 platinum electrode points which are directly 50 microns in total, and the distance and position between the electrode points can be adjusted through stretching, so that the potential damage of the stress of the device to soft brain tissue is reduced. The device only has the function of recording the ECoG signals of the cerebral cortex and is not combined with other functions; the whole structure generates out-of-plane deformation after being stretched, and electrode points are difficult to keep flat and reliably attached to the surface of a curved surface; the device has low mechanical strength, is easy to break and fracture and is difficult to be buried for long time.

It has been reported that flexible neural microelectrodes based on elastic polymer materials (e.g., PDMS) can reduce electrode dislocation and potential mechanical damage to brain tissue by self-stretching deformation when subjected to brain swelling or compression. "Stretchabletaspentent electrode arrays for chemical and optical interconnections in vivo" written in 2903 2911 by Zhang J, Liu X et al, Beijing university, China, Nano letters,2018,18 (5). "Stretchabletaspentent electrode arrays for chemical and optical circuits in vivo" in PDMS (polydimethylsiloxane) substrate, has certain stretchability and transparency, can be stretched to 50% at the upper limit, can still maintain good electrochemical performance after 20% cyclic stretching for 10000 times, and finally combines with laser fiber large-range optical stimulation to synchronously acquire ECoG brain cortex electrical signals. The inventor of Khodagholy D et al, Tybrandt K, university of Federal science and technology, Zurich, Switzerland, in Advanced materials,2018,30(15):1706520, writes "High-density stranded electrode grid for neural recording" that High-density electrodes are prepared by integrating gold-plated titanium dioxide nanowires in PDMS substrate, and still can acquire electrical signals of cerebral cortex after being buried on cerebral cortex of rat for 3 months for a long time. But the Young modulus (1 kPa) of the brain tissue is 2-3 orders of magnitude lower than that of PDMS (1 Mpa), so that the softer elastic substrate material is more suitable for long-term implantation matching of the brain tissue, and the two electrodes have single functions, are not combined with accurately positioned light stimulation and only have large-range laser irradiation stimulation without resolution.

In addition, Yan Z, Pan T et al, China university of electronics, Advanced Science,2017,4(11):1700251, written "Thermal release transfer printing for curable resins" transfer polyimide serpentine electrodes in sandwich structure to PDMS substrate by Thermal peeling tape, can achieve 10.4% stretching, and collect ECoG electrical signals in rat cortex by acute animal experiments. But because the adhesion of polyimide and PDMS is weak, the device is difficult to be ensured not to be delaminated and separated in use, and the device also has only a single electroencephalogram recording function and is not combined with optical stimulation.

In summary, at present, there is no report on a stretchable flexible electrode of a brain-computer interface that integrates functions of precise optical stimulation and acquiring electrical signals of a cerebral cortex, because the processing technology is complex, the requirement for device integration is high, and the like, and therefore, there is a need to develop a flexible neural electrode that can be implanted for a long time, has high flexibility, can bear deformation influences such as expansion and contraction, and integrates functions of precise optical stimulation, so as to meet the tool requirements of various brain science and neuroscience researches.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide a photoelectric integrated stretchable flexible nerve electrode and a preparation method thereof.

According to a first aspect of the present invention, there is provided an optoelectronic integrated stretchable flexible neural electrode, comprising a first layer of elastic substrate, a photostimulation electrode, a second layer of elastic substrate and a recording electrode;

the optical stimulation electrode and the recording electrode both adopt a snake-shaped bent wiring structure, so that the metal lead is ensured not to reach a yield strain critical value in the stretching process;

the lower surface of the photostimulation electrode is provided with a first silicon dioxide layer, and the photostimulation electrode is bonded on the surface of the first layer of elastic substrate through a strong chemical bond generated by condensation reaction between the first silicon dioxide layer and the first layer of elastic substrate;

the upper surface of the photostimulation electrode is provided with the second layer of elastic substrate, the lower surface of the recording electrode is provided with the second silicon dioxide layer, and the recording electrode is bonded on the surface of the second layer of elastic substrate through a strong chemical bond generated by condensation reaction between the second silicon dioxide layer and the second layer of elastic substrate, so that the recording electrode and the photostimulation electrode are integrated into an integral structure.

Preferably, the first layer elastic substrate and the second layer elastic substrate adopt platinum-catalyzed silicone rubber Dragonskin or Ecoflex.

Further, the photostimulation electrode comprises a first polyimide substrate layer, a metal wire layer, a first polyimide packaging layer and a micro LED chip, wherein the first polyimide substrate layer is positioned at the bottommost layer of the photostimulation electrode, the metal wire layer is arranged on the upper surface of the first polyimide substrate layer, the first polyimide packaging layer is arranged above the metal wire layer, and the micro LED chip is arranged on the first polyimide packaging layer; the lower surface of the photostimulation electrode refers to the lower surface of the first polyimide substrate layer; the second layer of elastic substrate is positioned on the upper surface of the first polyimide packaging layer.

Preferably, the thickness of the first polyimide substrate layer is 2-10 μm; and/or the thickness of the first polyimide packaging layer is 2-10 mu m.

Further, the recording electrode comprises a second polyimide substrate layer, a metal shielding layer, a polyimide insulating layer, a metal recording layer and a second polyimide packaging layer, wherein the second polyimide substrate layer is located at the bottommost layer of the recording electrode, the metal shielding layer is arranged above the second polyimide substrate layer, the polyimide insulating layer is arranged above the metal shielding layer, the metal recording layer is arranged above the polyimide insulating layer, and the second polyimide packaging layer is arranged above the metal recording layer; the lower surface of the recording electrode means the lower surface of the second polyimide substrate layer.

Preferably, the thickness of the second polyimide substrate layer is 2-10 mu m.

Preferably, the thickness of the polyimide insulating layer is 2-10 μm.

Preferably, the thickness of the second polyimide packaging layer is 2-10 μm.

According to a second aspect of the present invention, there is provided a method for preparing an optoelectronic integrated stretchable flexible neural electrode, comprising:

respectively preparing a light stimulation electrode and a recording electrode, wherein the stimulation electrode and the recording electrode both adopt an arc snake-shaped bending wiring structure, so that the metal lead is ensured not to reach a yield strain critical value in the stretching process;

depositing a first silica layer on the lower surface of the photostimulation electrode, transferring the first silica layer on the lower surface of the photostimulation electrode onto a first layer of elastic substrate, wherein the first silica layer and the first layer of elastic substrate are subjected to condensation reaction to generate strong chemical bonds, so that the photostimulation electrode is bonded on the surface of the first layer of elastic substrate;

preparing a second layer of elastic substrate on the upper surface of the photostimulation electrode, depositing a second silicon dioxide layer on the lower surface of the recording electrode, transferring the second silicon dioxide layer on the lower surface of the recording electrode onto the second layer of elastic substrate, and enabling the second silicon dioxide layer and the second layer of elastic substrate to generate strong chemical bonds through condensation reaction so that the recording electrode is adhered to the surface of the second layer of elastic substrate; and obtaining an integrated device integrating the optical stimulation electrode and the recording electrode.

Further, the method comprises the following steps:

step 1: using a first silicon chip as a supporting substrate of a photostimulation electrode; using a second silicon wafer as a supporting substrate of the recording electrode; cleaning the first silicon wafer and the second silicon wafer, and baking the first silicon wafer and the second silicon wafer after cleaning;

step 2: respectively thermally evaporating or sputtering a layer of metal on the first silicon chip and the second silicon chip to be used as a final metal release layer of the upper layer structure;

and 3, step 3: spin-coating and photo-etching patterned polyimide glue on the first silicon chip, namely above the metal release layer, so as to form a first polyimide substrate layer of the photostimulation electrode; spin-coating and photo-etching patterned polyimide glue on the second silicon chip, namely above the metal release layer, so as to form a second polyimide substrate layer of the recording electrode;

and 4, step 4: sputtering a layer of chromium as a seed layer on the first silicon chip, namely above the first polyimide substrate layer, sputtering a layer of gold as a metal layer on the chromium layer, spin-coating and photoetching the metal layer to form a patterned positive photoresist, and completing the patterning of the metal wire layer of the photostimulation electrode through ion beam etching; sputtering a layer of chromium on the second silicon chip, namely above the second polyimide substrate layer, as a seed layer, sputtering a layer of gold on the chromium layer as a metal layer, and completing the patterning of the metal shielding layer of the recording electrode through ion beam etching;

and 5, step 5: spin-coating and photo-etching patterned polyimide glue on the first silicon chip, namely above the metal wire layer to form a first polyimide packaging layer of the photostimulation electrode, and completing the preparation of the photostimulation electrode on the first silicon chip; spin-coating and photoetching patterned polyimide glue on the second silicon chip, namely above the metal shielding layer, so as to form a polyimide insulating layer of the recording electrode;

and 6, step 6: sputtering a layer of chromium on the second silicon chip, namely above the polyimide insulating layer, sputtering a layer of gold on the chromium layer to form a metal recording layer, spin-coating and photoetching the metal recording layer to form a patterned positive photoresist, and finally completing the patterning of the metal recording layer of the recording electrode through ion beam etching;

and 7, step 7: spin-coating and photo-etching patterned polyimide glue on the second silicon chip, namely above the metal recording layer, to form a second polyimide packaging layer of the recording electrode, and completing the preparation of the recording electrode on the second silicon chip;

and 8, step 8: covering the first silicon wafer and the second silicon wafer with dust-free paper or dust-free cloth, completely covering the first silicon wafer and the second silicon wafer with glass sheets with the same diameter and size as the first silicon wafer and the second silicon wafer, and then soaking the first silicon wafer and the glass sheets, the second silicon wafer and the glass sheets which are stacked together in a hydrochloric acid solution to sacrifice a metal release layer on the first silicon wafer and the second silicon wafer;

step 9: then, the first silicon wafer and the glass sheet, and the second silicon wafer and the glass sheet which are overlapped together are placed into deionized water for soaking, washing and drying, and the release of the photostimulation electrode and the recording electrode is completed;

step 10: sticking the photostimulation electrode from the first silicon chip by using a water-soluble adhesive tape to separate the first silicon chip from the photostimulation electrode, fixing the lower surface of the photostimulation electrode on a substrate in an upward manner, sputtering a layer of titanium on the lower surface of the photostimulation electrode, and sputtering a first silicon dioxide layer on the titanium layer;

sticking the recording electrode from the second silicon wafer by using a water-soluble adhesive tape to separate the second silicon wafer from the recording electrode; fixing the lower surface of the recording electrode on a substrate in an upward manner, sputtering a layer of titanium on the lower surface of the recording electrode, and sputtering a second silicon dioxide layer on the titanium layer;

step 11, selecting a glass sheet, covering a layer of PI adhesive tape on the glass sheet, fixing a glass slide with a layer of parylene deposited on the surface on the glass sheet by using the PI adhesive tape, spraying a layer of release agent on the glass slide, namely the parylene, and then spinning a layer of hyperelastic silicon rubber on the release agent to serve as a first layer of elastic substrate;

step 12: irradiating the first layer of elastic substrate by using UV ultraviolet light, then transferring the water-soluble adhesive tape adhered with the photostimulation electrode to the surface of the first layer of elastic substrate, enabling the surface of the photostimulation electrode sputtered with the first silicon dioxide layer to be in contact with the surface of the first layer of elastic substrate, placing the surface in a baking oven under certain pressure, and then dissolving the water-soluble adhesive tape by using hot water;

step 13: aligning and attaching a mask to the photo-stimulation electrode, namely the upper surface of the first polyimide packaging layer, brushing conductive silver paste on the metal bonding pad exposed through the mask, and finishing solder patterning on the photo-stimulation electrode;

step 14: utilizing a graphical die to reverse the die to obtain a female die seal, fixing the micro LED chips in the pits of the seal to finish the transfer printing of the plurality of micro LED chips to form a micro LED chip array, and putting the micro LED chip array into an oven to completely cure and conduct the conductive silver paste on the photostimulation electrode;

step 15: brushing conductive silver paste on the tail end of the photostimulation electrode by using a mask to form a photostimulation electrode interface, selecting a PI (polyimide) flexible flat cable, aligning the PI flexible flat cable to the photostimulation electrode interface under the pressing action of a cover glass, connecting the photostimulation electrode interface and the front end of the PI flexible flat cable into an integrated device, and putting the integrated device into an oven under the action of keeping the upper pressure;

step 16: coating sealant on the photostimulation electrode interface and the PI flexible flat cable connecting area, performing oxygen plasma pretreatment on the whole device surface, covering a polyethylene glycol terephthalate film on the rear end of the PI flexible flat cable, spin-coating a layer of superelastic silicon rubber on the whole first silicon chip to serve as a second layer of elastic substrate, and immediately uncovering the polyethylene glycol terephthalate film after spin-coating to expose the rear end of the PI flexible flat cable;

step 17: irradiating the second layer elastic substrate by using UV ultraviolet light, aligning the water-soluble adhesive tape adhered with the recording electrode prepared in the step 10 with the position, transferring the surface of the recording electrode sputtered with the second silicon dioxide layer to the surface of the second layer elastic substrate, placing the surface in an oven under certain pressure, and then placing the surface in hot water to dissolve the water-soluble adhesive tape;

step 18: brushing conductive silver paste on a local area at the rear end of the recording electrode by using a mask to form a recording electrode interface, selecting a PI (polyimide) flexible flat cable, aligning the PI flexible flat cable to the recording electrode interface under the pressing action of a cover glass, and putting the PI flexible flat cable into an oven under the action of keeping the upper pressure;

step 19: coating silicone sealant on the recording electrode interface and the PI flexible flat cable connection area, and cutting the first layer of elastic substrate and the second layer of elastic substrate by laser to obtain the outline of an integrated device;

step 20: the entire integrated device is released from the slide and the electrode points of the integrated device are electrochemically modified.

Preferably, in the step 2, the metal of the release layer of the first silicon wafer and/or the second silicon wafer is aluminum or copper, and the thickness of the metal release layer of the first silicon wafer and/or the second silicon wafer is 200-1000 nm.

Preferably, in the-4 th step, the thickness of the seed layer of the first silicon wafer and the second silicon wafer is 10-50 nm; the thicknesses of the metal layers of the first silicon wafer and the second silicon wafer are 100-500 nm;

in the 6 th step, firstly sputtering a layer of chromium on the second silicon chip, namely above the polyimide insulating layer, and then sputtering a layer of gold on the chromium layer to form a metal recording layer, wherein the thickness of the chromium is 10-50 nm; the thickness of the gold is 100-500 nm.

In the 10 th step, firstly sputtering a layer of titanium on the lower surface of the photostimulation electrode, and then sputtering a layer of silicon dioxide on the titanium layer, wherein the thickness of the titanium is 3-10 nm; the thickness of the silicon dioxide is 30-100 nm;

sputtering a layer of titanium on the lower surface of the recording electrode, and then sputtering a layer of silicon dioxide on the titanium layer, wherein the thickness of the titanium is 3-10 nm; the thickness of the silicon dioxide is 30-100 nm.

Compared with the prior art, the invention has at least one of the following beneficial effects:

1. in the structure, the precise optical stimulation function is combined into the stretchable flexible nerve electrode for the first time, so that the relative positions of an optical stimulation site and a recording electrode point cannot be changed even under a deformation condition, and the reliability of the stimulation and recording positions is ensured; the flexible nerve electrode fills the blank of stretchable photoelectric integrated brain-computer interface devices at home and abroad, and has the potential of providing a powerful support tool for the research of neuroscience and brain science. In the structure, the photostimulation electrode and the recording electrode adopt a snake-shaped wiring structure, have certain stretchability, can deform along with a hyperelastic silicon rubber substrate, can be implanted for a long time, are highly flexible, and can bear deformation influences such as expansion and contraction of brain tissues;

2. furthermore, the structure of the invention adopts the superelasticity platinum catalysis silicon rubber Dragonskin or Ecoflex series with Young modulus lower than that of the most common PDMS as the electrode substrate, which is helpful to improve the stretchability of the electrode and is easier to form a conformal attaching state with cerebral cortex.

3. In the preparation method, the light stimulation electrode integrated with the micro LED chip and the recording electrode are integrated into a whole by a transfer printing method, the flexible nerve electrode has high integration level and low MEMS processing technology difficulty, and the high flexibility can deform along with the expansion and contraction of brain tissues, so that the flexible nerve electrode is more suitable for being implanted into a mouse body for a long time and researching long-term nerve loops and nervous system disease models based on optogenetics.

4. Based on the structure and the preparation method, different elastic bases and electrode substrate materials can be replaced according to the needs, and the integration process flow of the electrode does not need to be changed.

Drawings

Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:

FIG. 1a is a schematic structural diagram of a photoelectric integrated stretchable flexible neural electrode according to a preferred embodiment of the present invention;

FIG. 1b is a schematic diagram of a partially enlarged structure of the photostimulation electrode in FIG. 1 a;

FIG. 1c is a schematic view of a partially enlarged structure of the recording electrode in FIG. 1 a;

FIG. 2 is a flow chart of an integrated process for electro-optically integrating stretchable flexible neural electrodes in an embodiment of the present invention;

FIG. 3 is a schematic diagram showing the relative positions and sizes of the recording electrode dots and the micro LED chips in an embodiment of the present invention;

FIG. 4 is a schematic cross-sectional structure and dimensions of an electro-optically integrated stretchable flexible neural electrode in an embodiment of the present invention;

FIG. 5a is a serpentine configuration design of an opto-electronic integrated stretchable flexible neural electrode in an embodiment of the present invention;

FIG. 5b is a schematic representation of the unidirectional stretched serpentine structure of FIG. 5a before and after deformation;

FIG. 5c is a parameter diagram of the serpentine structure of FIG. 5 a;

FIG. 6 is a photograph of an opto-electronic integrated stretchable flexible neural electrode device in an embodiment of the present invention;

FIG. 7 is a schematic diagram of the operation of performing simultaneous optical stimulation and electrical recording on the cerebral cortex of a mouse by the optoelectronic integrated stretchable flexible neural electrode in the embodiment of the present invention;

the scores in the figure are indicated as: the device comprises a first elastic substrate 1, a first silica layer 2, a first polyimide substrate layer 3, a metal conducting wire layer 4, a first polyimide packaging layer 5, a micro LED chip 6, a second elastic substrate 7, a second silica layer 8, a second polyimide substrate layer 9, a metal shielding layer 10, a polyimide insulating layer 11, a metal recording layer 12, a second polyimide packaging layer 13, a recording electrode point 14, a reference electrode point 15, a snake-shaped bent wiring structure 16, 470nm blue light 17, an electroencephalogram signal acquisition site 18, an LED power supply flat cable 19 and an electroencephalogram signal acquisition flat cable 20.

Detailed Description

The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention. The present invention can be implemented by using the prior art for the parts which are not described in detail in the following examples.

Referring to fig. 1a, 1b and 1c, which are schematic structural views of a preferred embodiment of an optoelectronic integrated stretchable flexible neural electrode, the flexible neural electrode includes a first layer of elastic substrate 1, a photostimulation electrode, a second layer of elastic substrate 7 and a recording electrode; the optical stimulation electrode and the recording electrode both adopt an arc snake-shaped bent wiring structure 16; the lower surface of the photostimulation electrode is provided with a first silicon dioxide layer 2, and the photostimulation electrode is bonded on the surface of the first layer of elastic substrate 1 through a strong chemical bond generated by condensation reaction between the first silicon dioxide layer 2 and the first layer of elastic substrate 1; the other side (upper surface) of the photostimulation electrode is provided with a second layer of elastic substrate 7, the lower surface of the recording electrode is provided with a second silicon dioxide layer 8, and the recording electrode is bonded on the surface of the second layer of elastic substrate 7 through a strong chemical bond generated by condensation reaction between the second silicon dioxide layer 8 and the second layer of elastic substrate 7, so that the recording electrode and the photostimulation electrode are integrated into an integral structure.

In other preferred embodiments, the first layer elastic substrate 1 and the second layer elastic substrate 7 are made of Dragnkin or Ecoflex series using super elastic platinum catalyzed silicone rubber with Young's modulus lower than that of the most commonly used PDMS. Specifically, a platinum-catalyzed silicone rubber Dragonskin manufactured by Smooth-on company of America can be selected. The Young modulus of the platinum catalytic silicone rubber Dragnkin is 166kPa, the Young modulus of the Ecoflex is 60kPa, Polydimethylsiloxane (PDMS) is usually adopted as an elastic substrate in the prior art, the Young modulus of the PDMS is in the range of 0.5-1.8 MPa, and the Young modulus of the superelasticity platinum catalytic silicone rubber Dragnkin or Ecoflex series is lower than that of the most common PDMS. The super-elastic material is used as the substrate, so that the flexibility of the electrode can be improved.

In other preferred embodiments, the photostimulation electrode comprises a first polyimide substrate layer 3, a metal wire layer 4, a first polyimide packaging layer 5 and a micro LED chip 6, wherein the first polyimide substrate layer 3 is positioned at the bottommost layer of the photostimulation electrode, the metal wire layer 4 is arranged on the upper surface of the first polyimide substrate layer 3, the first polyimide packaging layer 5 is arranged above the metal wire layer 4, and the micro LED chip 6 is arranged on the first polyimide packaging layer 5; the lower surface of the photostimulation electrode refers to the lower surface of the first polyimide substrate layer 3; the second layer of elastic substrate is located on the upper surface of the first polyimide encapsulation layer 5.

In some embodiments, the micro LED chip 6 may be a gan LED bare chip with a thickness of 50 μm, model TR2227 or TR1823, Cree, usa. The height of the corresponding SU-8 negative photoresist mold is 20-30 μm, and the length and width dimensions are 5-10 μm larger than the dimensions of the micro LED chip 6, so that the micro LED chip 6 can be positioned and separated conveniently.

In other embodiments, the thickness of the first polyimide substrate layer 3 is 2-10 μm; the thickness of the first polyimide packaging layer 5 is 2-10 μm.

In other embodiments, the recording electrode includes a second polyimide substrate layer 9, a metal shielding layer 10, a polyimide insulating layer 11, a metal recording layer 12, and a second polyimide encapsulation layer 13, where the second polyimide substrate layer 9 is located at the lowermost layer of the recording electrode, the metal shielding layer 10 is disposed above the second polyimide substrate layer 9, the polyimide insulating layer 11 is disposed above the metal shielding layer 10, the metal recording layer 12 is disposed above the polyimide insulating layer 11, and the second polyimide encapsulation layer 13 is disposed above the metal recording layer 12; the lower surface of the recording electrode means the lower surface of the second polyimide substrate layer 9.

In other embodiments, the thickness of the second polyimide substrate layer 9 is 2-10 μm; the thickness of the polyimide insulating layer 11 is 2-10 μm; the thickness of the second polyimide packaging layer 13 is 2-10 μm.

In a specific embodiment, the flexible neural electrode comprises 9 recording electrode points 14, 1

reference electrode point

15 and 4 micro LED chips 6, and the size of the recording electrode points 14, the number and the distribution positions of the recording electrode points 14 and the micro LED chips 6, and the like can be adjusted according to the target animal tissue.

Based on the structural features of the flexible neural electrode of the above embodiment, an embodiment of a method for manufacturing an optoelectronic integrated stretchable flexible neural electrode is provided, the method comprising:

and respectively preparing a light stimulation electrode and a recording electrode, wherein the stimulation electrode and the recording electrode both adopt an arc snake-shaped bending wiring structure 16, so that the metal lead is ensured not to reach a yield strain critical value in the stretching process.

Depositing a first silicon dioxide layer 2 on the lower surface of the photostimulation electrode, transferring the first silicon dioxide layer 2 on the lower surface of the photostimulation electrode onto the first layer of elastic substrate 1, and carrying out a reaction condensation reaction between the first silicon dioxide layer 2 and the first layer of elastic substrate 1 to generate a strong chemical bond so that the photostimulation electrode is adhered to the surface of the first layer of elastic substrate 1; preparing a second layer of elastic substrate 7 on the other surface (upper surface) of the photostimulation electrode, depositing a second silicon dioxide layer 8 on the lower surface of the recording electrode, transferring the second silicon dioxide layer 8 on the lower surface of the recording electrode onto the second layer of elastic substrate, and carrying out a condensation reaction between the second silicon dioxide layer 8 and the second layer of elastic substrate 7 to generate a strong chemical bond so that the recording electrode is adhered to the surface of the second layer of elastic substrate 7, thereby obtaining the integrated photostimulation electrode and recording electrode integrated device.

In a preferred embodiment, the preparation method of the photoelectric integrated stretchable flexible nerve electrode is implemented by the following steps:

step 1: using a first silicon chip as a supporting substrate of a photostimulation electrode; using a second silicon wafer as a supporting substrate of the recording electrode; and cleaning the first silicon wafer and the second silicon wafer, and baking the first silicon wafer and the second silicon wafer after cleaning.

Step 2: and respectively thermally evaporating or sputtering a layer of metal on the first silicon chip and the second silicon chip to be used as a final metal release layer of the upper layer structure.

The metal of the release layer of the first silicon chip and/or the second silicon chip is aluminum or copper, and the thickness of the metal release layer of the first silicon chip and/or the second silicon chip is 200-1000 nm.

And 3, step 3: spin-coating and photo-etching patterned polyimide glue on a first silicon chip, namely above the metal release layer to form a first polyimide substrate layer 3 of the photostimulation electrode; a second polyimide substrate layer 9 for the recording electrode is formed on the second silicon wafer, i.e. above the metal release layer, by spin coating and photo-etching a patterned polyimide glue.

And 4, step 4: firstly sputtering a layer of chromium (Cr) on a first silicon chip, namely above a first polyimide substrate layer 3, then sputtering a layer of gold (Au) on the chromium layer to be used as a metal layer, spin-coating and photoetching a patterned positive photoresist on the metal layer, and completing the patterning of a metal wire layer 4 of a photostimulation electrode through ion beam etching; a layer of chromium (Cr) is sputtered on the second silicon wafer, i.e. above the second polyimide substrate layer 9, a layer of gold (Au) is sputtered on the chromium layer as a metal layer, and patterning of the metal shielding layer 10 of the recording electrode is completed by ion beam etching.

Sputtering a chromium (Cr) layer on the first silicon chip, namely on the polyimide substrate layer, wherein the thickness of the chromium (Cr) layer is 10-50 nm; the thickness of the gold (Au) layer sputtered on the chromium (Cr) layer is 100-500 nm.

Sputtering a chromium layer on a second silicon chip, namely the polyimide substrate layer, wherein the thickness of the chromium layer is 10-50 nm; the thickness of the gold (Au) layer sputtered on the chromium (Cr) layer is 100-500 nm.

And 5, step 5: spin-coating and photo-etching patterned polyimide glue on a first silicon chip, namely above the metal wire layer 4 to form a first polyimide packaging layer 5 of the photostimulation electrode, and completing the preparation of the photostimulation electrode on the first silicon chip; a polyimide paste is spin-coated and photo-lithographically patterned on the second silicon wafer, i.e., above the metal shielding layer 10, to form a polyimide insulating layer 11 for the recording electrode.

And 6, step 6: sputtering a layer of chromium (Cr) on a second silicon chip, namely above the polyimide insulating layer 11, sputtering a layer of gold (Au) on the chromium layer to form a metal recording layer 12, spin-coating and photoetching the metal recording layer 12 to form a patterned positive photoresist, and finally completing the patterning of the metal recording layer 12 of the recording electrode through ion beam etching; wherein the thickness of the chromium (Cr) layer is 10-50 nm; the thickness of the gold (Au) layer is 100-500 nm.

And 7, step 7: and spin-coating and photo-etching the patterned polyimide glue on a second silicon chip, namely above the metal recording layer 12 to form a second polyimide packaging layer 13 of the recording electrode, and completing the preparation of the recording electrode on the second silicon chip.

And 8, step 8: and covering the first silicon wafer and the second silicon wafer with dust-free paper or dust-free cloth respectively, then completely covering the first silicon wafer and the second silicon wafer with glass sheets with the same diameters and sizes as the first silicon wafer and the second silicon wafer respectively, and then soaking the first silicon wafer and the glass sheets, the second silicon wafer and the glass sheets which are stacked together in a hydrochloric acid solution to sacrifice the metal release layers on the first silicon wafer and the second silicon wafer.

Adopting dust-free paper or dust-free cloth, which mainly has the function of ensuring that the hydrochloric acid solution can permeate into contact with the metal release layer of the electrode; the recording electrode and the light stimulation electrode are laminated between the silicon chip and the glass sheet, and the metal release layer is slowly contacted and reacted with the hydrochloric acid solution, so that the soaking time needs to be properly prolonged to 1-2 days to ensure that the metal release layer on the lower layer of the polyimide is completely etched and completely reacted.

Step 9: and then, putting the first silicon wafer and the glass sheet which are overlapped together, and the second silicon wafer and the glass sheet into deionized water for soaking, washing and drying to complete the release of the photostimulation electrode and the recording electrode.

Step 10: sticking a photostimulation electrode from a first silicon chip by using a water-soluble adhesive tape, separating the first silicon chip from the photostimulation electrode, fixing the photostimulation electrode on a substrate with the lower surface facing upwards, sputtering a layer of titanium (Ti) on the lower surface of the photostimulation electrode, and sputtering first silicon dioxide (SiO) on the titanium layer₂) A layer; the thickness of the titanium (Ti) layer is 3-10 nm, and the titanium (Ti) layer is used as an adhesion layer, so that the bonding force between the first silicon dioxide layer 2 and the first polyimide substrate is improved. The first silicon dioxide layer 2 has a thickness of 30-100 nm and is made of first silicon dioxide (SiO)₂) The layer will chemically react with the silicone rubber substrate.

Sticking the recording electrode from the second silicon wafer by using a water-soluble adhesive tape to separate the second silicon wafer from the recording electrode; fixing the lower surface of the recording electrode on the substrate, sputtering a layer of titanium (Ti) on the lower surface of the recording electrode, and sputtering a second silicon dioxide (SiO) on the titanium layer₂) A layer 8, the thickness of the titanium (Ti) layer being 3-10 nm; titanium (IV)The (Ti) layer serves as an adhesion layer to improve the bonding force between the second silica layer 8 and the second polyimide substrate layer 9. The second silicon dioxide layer 8 has a thickness of 30-100 nm and is made of a second silicon dioxide (SiO)₂) The layer 8 will react chemically with the silicone rubber substrate.

11, selecting a glass sheet, covering a layer of PI adhesive tape on the glass sheet, fixing a glass slide with a layer of parylene deposited on the surface on the glass sheet by using the PI adhesive tape, spraying a layer of release agent on the glass slide, namely the parylene, and then spinning a layer of hyperelastic silicon rubber on the release agent to serve as a first layer of elastic substrate 1; the spin-coated super-elastic silicone rubber is made of platinum-catalyzed silicone rubber Dragonskin or Ecoflex series manufactured by Smooth-on company of America.

Step 12: the first layer of elastic substrate 1 is irradiated by UV ultraviolet light, then the water-soluble adhesive tape adhered with the photostimulation electrode is transferred to the surface of the first layer of elastic substrate 1, the surface of the photostimulation electrode sputtered with the first silicon dioxide layer 2 is in contact with the surface of the first layer of elastic substrate 1, the water-soluble adhesive tape is placed in an oven under the action of certain pressure, and then the water-soluble adhesive tape is dissolved by hot water.

Step 13: aligning and attaching a mask on the photostimulation electrode, brushing conductive silver paste on a metal bonding pad exposed through the mask, and finishing solder imaging on the photostimulation electrode; in the specific embodiment, the mask is PET, the thickness of the PET mask is 12.5-25 μm, and small holes with the diameter of 75-80 μm are etched through laser cutting, so that the metal bonding pads of the photostimulation electrode are exposed during alignment, and the patterned conductive silver paste is conveniently brushed to obtain the patterned conductive silver paste for connecting and fixing the micro LED chip 6.

Step 14: and (3) utilizing a graphical die to reverse the die to obtain a female die seal, fixing the micro LED chips 6 in the pits of the seal to finish the transfer printing of the plurality of micro LED chips 6 to form a micro LED chip 6 array, and putting the array into an oven to completely cure and conduct the conductive silver paste on the photostimulation electrode.

Step 15: brushing conductive silver paste on the tail end of the photostimulation electrode by using a mask to form a photostimulation electrode interface, selecting a PI (polyimide) flexible flat cable, aligning the PI flexible flat cable with the photostimulation electrode interface under the pressing action of a cover glass, connecting the photostimulation electrode interface and the front end of the PI flexible flat cable into an integrated device, and putting the integrated device into an oven under the action of keeping the upper pressure; the mask material used when the conductive silver paste is brushed is a stainless steel sheet with the thickness of 15-25 microns, and an opening with the size smaller than that of the rectangular pad of the electrode interface is cut out through laser, so that the conductive silver paste is prevented from diffusing to the adjacent pad area in the pressing process.

Step 16: coating sealant on a photostimulation electrode interface and a PI flexible flat cable connecting area, performing oxygen plasma pretreatment on the surface of the whole device, covering a polyethylene terephthalate film on the rear end of the PI flexible flat cable, spin-coating a layer of hyperelastic silicon rubber on the whole glass sheet to serve as a second layer of elastic substrate 7, and immediately uncovering the polyethylene terephthalate film after spin-coating to expose the rear end of the PI flexible flat cable; in the specific implementation: the oxygen plasma pretreatment time is 30-120 seconds, and the main purpose is to ensure the firm combination and the sealing effect between the elastic silicon rubber packaging layer and the silicon rubber substrate layer.

Step 17: irradiating the second layer elastic substrate 7 by using UV ultraviolet light, aligning the water-soluble adhesive tape adhered with the recording electrode prepared in the step 10 with the position, transferring the side of the recording electrode sputtered with the second silicon dioxide layer 8 to the surface of the second layer elastic substrate 7, placing the side in an oven under certain pressure, and then placing the side in hot water to dissolve the water-soluble adhesive tape.

Step 18: and brushing conductive silver paste on the recording electrode interface by using a mask, aligning the PI flexible flat cable to the recording electrode interface under the pressing action of a cover glass, and putting the PI flexible flat cable into an oven under the action of keeping the upper pressure.

Step 19: and coating silicone sealant on the connection area of the recording electrode interface and the PI flexible flat cable, and cutting the silicone rubber elastic substrate layer and the silicone rubber elastic packaging layer by laser to obtain the profile of the integrated device.

Step 20: the entire integrated device is released from the slide and the electrode sites of the integrated device are electrochemically modified.

In other preferred embodiments, the electrode modification material may be iridium oxide (IrOx), polyethylenedioxythiophene (PEDOT: PSS), platinum black (Pt-black), etc. for reducing the electrochemical impedance of the electrode point, improving the signal-to-noise ratio, and ensuring good signal pickup capability.

In one embodiment, referring to fig. 2, an integrated process flow diagram of a method for manufacturing an electro-optically integrated stretchable flexible neural electrode includes the following steps:

the first step is as follows: a 3-inch transparent glass plate was covered with a Polyimide (PI) tape, and then a transparent glass slide having a Parylene-C (Parylene-C) deposited on the surface thereof was fixed to the glass plate with both ends of the Polyimide (PI) tape, and a release agent was sprayed, and then a Dragonskin superelastic silicone rubber having a thickness of 100 μm was spin-coated as the first elastic substrate 1.

The second step is that: and aligning and attaching a polyethylene terephthalate (PET) mask with the thickness of 12.5 mu m on the photo-stimulation electrode on a triaxial mobile station, wherein the diameter size of a circular opening is 80 mu m, brushing conductive silver paste on a metal bonding pad aligned with the photo-stimulation electrode, and uncovering the PET mask to finish the patterning of the conductive silver paste.

The third step: UV ultraviolet light irradiates the first layer of elastic substrate for 110 minutes, the American AQUASOL water-soluble adhesive tape adhered with the light stimulation electrode is transferred to the surface of the first layer of elastic substrate 1, and is placed in an 80-degree oven for 10 minutes under certain pressure, and then is stirred in 50-degree hot water to dissolve the water-soluble adhesive tape.

The fourth step: and photoetching an SU-8 male die structure with the patterning thickness of 25 mu m, spin-coating liquid PDMS, curing and reversing the die to obtain a PDMS female die stamp, fixing the micro LED chip 6 in a stamp pit, completing the transfer printing of the array of the micro LED chip 6 on a three-axis moving table, and then placing in a 100-degree oven for 6 hours.

The fifth step: the photostimulation electrode interface is coated with conductive silver paste by using a stainless steel mask with the thickness of 20 mu m, a PI flexible flat cable with the length of 35mm is selected, the photostimulation electrode interface is aligned under the pressing of a cover glass, and the photostimulation electrode interface is placed into a 100-DEG oven for 6 hours to complete the full curing of the conductive silver paste under the action of the upper pressure.

And a sixth step: the interface packaging is completed by coating elastic transparent silicone sealant 705 on the connection area of the photostimulation electrode interface and the PI flexible flat cable, then the surface of the whole device is pretreated by oxygen plasma for 60 seconds, and the rear end of the short PI flexible flat cable is covered by a PET film. A layer of Dragonskin superelastic silicon rubber with the thickness of 100 mu m is coated on the surface of the whole device in a spinning mode to serve as a second elastic substrate 7, and the PET film is removed immediately after the coating in the spinning mode, so that the rear end of the short PI flexible flat cable is exposed.

The seventh step: the second layer elastic substrate was irradiated with UV ultraviolet light for 710 minutes, and the AQUASOL water-soluble tape having the recording electrode adhered thereto was transferred to the surface of the second layer elastic substrate 7 in alignment, and placed in an 80-degree oven under a certain pressure for 10 minutes, followed by stirring in hot water of 50 degrees to dissolve the water-soluble tape.

Eighth step: and brushing conductive silver paste on the recording electrode interface by using a stainless steel mask with the thickness of 20 mu m, aligning the PI flexible flat cable to the recording electrode interface under the pressing action of a cover glass, and putting the recording electrode interface into a 100-DEG oven for 6 hours to complete full curing of the conductive silver paste under the action of the upper pressure.

The ninth step: and coating an elastic transparent silicone sealant 705 on the connection area of the recording electrode interface and the PI flexible flat cable to complete interface packaging, and cutting the silicone rubber elastic substrate layer and the silicone rubber elastic packaging layer by adopting laser with the power of 400W to obtain an accurate electrode profile.

The tenth step: and slightly picking up the glass slide by using a pair of tweezers, releasing the whole integrated device, and ultrasonically electroplating platinum black in a chloroplatinic acid solution to complete electrode point modification.

Referring to fig. 3, which is a diagram showing relative positions and sizes of the recording electrode dots 14 and the micro LED chips 6, the diameter of the recording electrode dots 14 in a 3 × 3 recording electrode array is 100 μm, the center-to-center distance is 700 μm, the diameter of the reference electrode is 250 μm, 4 recording electrode dots 14 are distributed around each LED in a 2 × 2 micro LED chip 6 array, the size of the micro LED chip 6 is 180 × 230 μm, and the center-to-center distance between adjacent micro LED chips 6 is also 700 μm.

Referring to fig. 4, which is a schematic view of the cross-sectional structure and size of the optoelectronic integrated stretchable flexible neural electrode, it can be seen that the micro LED chip 6 can emit blue light 17 with a dominant wavelength of about 470nm through almost transparent Dragonskin silicone rubber, and is kept at a certain distance from the recording electrode point 14 in the horizontal direction; the thickness of the photostimulation electrode is 10 mu m, the thickness of the recording electrode is 7.5 mu m, the thickness of the micro LED is 50 mu m, and the thickness of the elastic basal layer and the thickness of the elastic packaging layer are both 100 mu m.

Referring to fig. 5a and 5b, as shown in the drawings, in order to design the serpentine structure of the flexible photoelectric integrated stretchable neural electrode, it can be seen that, as the elastic substrate is stretched, the serpentine lead of the electrode can undergo a certain degree of deformation, the designed stretchable flexible neural electrode faces the mouse cerebral cortex model, the serpentine wiring occupies a larger planar space than a straight line, and therefore the line width needs to be reduced as much as possible, but at the same time, the reliability of the device needs to be considered, and the metal lead is too thin and is more prone to failure in the manufacturing and using processes, therefore, referring to fig. 5c, the following design parameters are adopted in the serpentine structure design: center angle theta is 225 degrees, and width W of metal wire_metal25 μm, wire width W_PI50 μm, and the radius of the arc inner corner R is 50 μm.

Referring to fig. 6, which is a photo of the photo-electric integrated stretchable flexible neural electrode device, the relative positions of the integrated recording electrode points 14 and the micro LED chip 6 can be seen through the partial enlargement of the front end of the electrode, and the reflective texture on the upper surface of the second layer elastic substrate 7 is the SiO deposited on the surface of the water-soluble adhesive tape during the process of transferring the recording electrode₂The film belongs to a transparent film and does not influence the penetrating irradiation of LED light.

Referring to fig. 7, the diagram is that the photoelectric integrated stretchable flexible nerve electrode performs synchronous optical stimulation and electrical recording work on the cerebral cortex of a mouse, a device can be attached to a unilateral cerebral region of the cerebral cortex of the mouse for use, the recording electrode and the optical stimulation electrode work simultaneously, and electroencephalogram signal acquisition sites 18 are acquired and powered by an LED through an electroencephalogram signal acquisition flat cable 20 and an LED power supply flat cable 19.

In specific implementation, Dragonskin silicone rubber with the Young modulus of 160kPa can be replaced by Ecoflex silicone rubber with the Young modulus of 60 kPa. The softer elastic substrate is helpful to improve the stretchability of the electrode and is easier to form a conformal attaching state with the cerebral cortex. Meanwhile, the first polyimide substrate layer 3 of the recording electrode and the second polyimide substrate layer 9 of the optical stimulation electrode can be replaced by transparent Parylene-C, and the front metal layer of the recording electrode, i.e. the front recording electrode point 14 of the metal recording layer 12 and the nearby connecting lines, can be replaced by transparent conductive materials, such as: indium tin oxide, graphene or silver nanowires are adopted, so that the transparency is improved to facilitate optical microscopic observation, and meanwhile, photoelectric artifacts caused by illumination on the metal recording electrode points 14 can be reduced, and interference on nerve signals is avoided. The flexible nerve electrode can be replaced by different elastic substrates and electrode substrate materials according to the needs without changing the integration process flow of the electrode.

In another embodiment, the method for manufacturing the optoelectronic integrated stretchable flexible neural electrode has the same steps as the above embodiments, and the changes are mainly in the selection of the electrode thickness of the recording electrode and the optical stimulation electrode in the schematic diagram of the cross-sectional structure and the size of the optoelectronic integrated stretchable flexible neural electrode. Because the photostimulation electrode needs to be coated with conductive silver paste and transferred with the micro LED chip 6 and needs a harder substrate, especially when extrusion transfer printing is carried out on a softer elastic substrate layer, a thicker PI electrode substrate can provide harder support, the thickness of the first polyimide substrate layer 3 and the first polyimide packaging layer 5 of the photostimulation electrode can be increased to 10 micrometers, and the total thickness of the photostimulation electrode reaches 20 micrometers.

Meanwhile, the recording electrode is attached to the upper surface of the second layer of elastic substrate 7, compared with the optical stimulation electrode packaged in the two layers of elastic substrate and elastic packaging layer, the metal recording layer 12 is subjected to a greater strain during stretching and is more susceptible to failure, whereas by increasing the overall thickness of the second polyimide substrate layer 9, the polyimide insulating layer 11 and the second polyimide encapsulating layer 13, the influence of the stretching process of the second layer elastic substrate 7 on the metal layer in the recording electrode can be effectively reduced, therefore, the thicknesses of the polyimide substrate layer (namely the second polyimide substrate layer 9) of the recording electrode and the polyimide packaging layer (namely the second polyimide packaging layer 13) of the recording electrode can be increased to 5 μm, the thickness of the polyimide insulating layer 11 of the recording electrode is kept unchanged, the electromagnetic shielding capability of the metal shielding layer 10 of the recording electrode is favorably exerted, and the total thickness of the recording electrode reaches 12.5 μm.

The integration method of the flexible nerve electrode can expand and integrate more flexible biological signal sensors and actuators of different types into the flexible nerve electrode, and provides possibility for the invention of a high-integration brain-computer interface with complex functions.

While particular embodiments of the present invention have been described, it is to be understood that the invention is not limited to the precise embodiments described above, and that various changes and modifications may be effected therein by one skilled in the art without departing from the scope or spirit of the invention as defined in the appended claims.

Claims

1. The flexible nerve electrode is characterized by comprising a first layer of elastic substrate, a light stimulation electrode, a second layer of elastic substrate and a recording electrode; wherein the content of the first and second substances,

the optical stimulation electrode and the recording electrode both adopt a snake-shaped bending wiring structure, so that the metal lead is ensured not to reach a yield strain critical value in the stretching process;

2. The electro-optically integrated stretchable flexible nerve electrode according to claim 1, wherein the first layer of elastic substrate and the second layer of elastic substrate are made of platinum-catalyzed silicone rubber Dragonskin or Ecoflex.

3. The optoelectronic integrated stretchable flexible nerve electrode according to claim 1, wherein the optical stimulation electrode comprises a first polyimide substrate layer, a metal wire layer, a first polyimide packaging layer and a micro LED chip, wherein the first polyimide substrate layer is located at the bottommost layer of the optical stimulation electrode, the metal wire layer is arranged on the upper surface of the first polyimide substrate layer, the first polyimide packaging layer is arranged above the metal wire layer, and the micro LED chip is arranged on the first polyimide packaging layer; the lower surface of the photostimulation electrode is the lower surface of the first polyimide substrate layer; the second layer of elastic substrate is positioned on the upper surface of the first polyimide packaging layer.

4. The electro-optically integrated stretchable flexible nerve electrode according to claim 3, wherein: the thickness of the first polyimide substrate layer is 2-10 mu m; the thickness of the first polyimide packaging layer is 2-10 mu m.

5. The optoelectronic integrated stretchable flexible neural electrode according to claim 1, wherein the recording electrode comprises a second polyimide substrate layer, a metal shielding layer, a polyimide insulating layer, a metal recording layer and a second polyimide packaging layer, wherein the second polyimide substrate layer is located at the bottommost layer of the recording electrode, the metal shielding layer is arranged above the second polyimide substrate layer, the polyimide insulating layer is arranged above the metal shielding layer, the metal recording layer is arranged above the polyimide insulating layer, and the second polyimide packaging layer is arranged above the metal recording layer; the lower surface of the recording electrode means the lower surface of the second polyimide substrate layer.

6. The electro-optically integrated stretchable flexible nerve electrode according to claim 5, wherein:

the thickness of the second polyimide substrate layer is 2-10 mu m;

the thickness of the polyimide insulating layer is 2-10 mu m;

the thickness of the second polyimide packaging layer is 2-10 mu m.

7. A method for preparing the optoelectronic integrated stretchable flexible neural electrode as claimed in any one of claims 1 to 6, comprising:

respectively preparing a light stimulation electrode and a recording electrode, wherein the stimulation electrode and the recording electrode both adopt a snake-shaped bending wiring structure, so that the metal lead is ensured not to reach a yield strain critical value in the stretching process;

8. The method for preparing the optoelectronic integrated stretchable flexible nerve electrode as claimed in claim 7, which is characterized by comprising the following steps:

step 1: using a first silicon chip as a supporting substrate of the photostimulation electrode; using a second silicon wafer as a supporting substrate of the recording electrode; cleaning the first silicon wafer and the second silicon wafer, and baking the first silicon wafer and the second silicon wafer after cleaning;

and 8, step 8: covering the first silicon wafer and the second silicon wafer with dust-free paper or dust-free cloth, completely covering the first silicon wafer and the second silicon wafer with glass sheets with the same diameter and size as the first silicon wafer and the second silicon wafer, and then soaking the first silicon wafer and the glass sheets, the second silicon wafer and the glass sheets which are stacked together in a hydrochloric acid solution to sacrifice the metal release layers on the first silicon wafer and the second silicon wafer;

step 12: irradiating the first layer of elastic substrate by using UV ultraviolet light, then transferring the water-soluble adhesive tape adhered with the photostimulation electrode to the surface of the first layer of elastic substrate, enabling the surface of the photostimulation electrode sputtered with the first silicon dioxide layer to be in contact with the surface of the first layer of elastic substrate, placing the surface in a baking oven under the action of certain pressure, and then dissolving the water-soluble adhesive tape by using hot water;

step 16: coating sealant on the photostimulation electrode interface and the PI flexible flat cable connecting area, performing oxygen plasma pretreatment on the whole device surface, covering a polyethylene glycol terephthalate film on the rear end of the PI flexible flat cable, spin-coating a layer of hyperelastic silicon rubber on the whole glass sheet to serve as a second layer of elastic substrate, and immediately uncovering the polyethylene glycol terephthalate film after spin-coating to expose the rear end of the PI flexible flat cable;

9. The method for preparing a photoelectric integrated stretchable flexible nerve electrode according to claim 8, wherein in the step 2, the metal of the metal release layer of the first silicon wafer and/or the second silicon wafer is aluminum or copper, and the thickness of the metal release layer of the first silicon wafer and/or the second silicon wafer is 200-1000 nm.

10. The method for preparing the optoelectronic integrated stretchable flexible nerve electrode according to claim 8, characterized by comprising one or more of the following features:

in the 4 th step, the thickness of the seed layer of the first silicon wafer and the second silicon wafer is 10-50 nm; the thicknesses of the metal layers of the first silicon wafer and the second silicon wafer are 100-500 nm;

in the 6 th step, firstly sputtering a layer of chromium on the second silicon chip, namely above the polyimide insulating layer, and then sputtering a layer of gold on the chromium layer to form a metal recording layer, wherein the thickness of the chromium is 10-50 nm; the thickness of the gold is 100-500 nm;

firstly sputtering a layer of titanium on the lower surface of the recording electrode, and then sputtering a layer of silicon dioxide on the titanium layer, wherein the thickness of the titanium is 3-10 nm; the thickness of the silicon dioxide is 30-100 nm.