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

Abstract

The invention provides an optoelectronic integrated stretchable flexible nerve electrode and a preparation method. The flexible nerve electrode comprises a first layer of elastic substrate, a photostimulation electrode, a second layer of elastic substrate and a recording electrode; wherein, the photostimulation electrode and the recording electrode are both A serpentine curved wiring structure is adopted; a first silicon dioxide layer is arranged on the lower surface of the light stimulation electrode, and the strong chemical bond generated by the condensation reaction between the first silicon dioxide layer and the first layer of elastic substrate makes the light stimulation electrode adhere to the first layer of the elastic substrate. A layer of elastic substrate surface; a second layer of elastic substrate is arranged on the upper surface of the light stimulation electrode, and a second silicon dioxide layer is arranged on the lower surface of the recording electrode. The strong chemical bond makes the recording electrode adhere to the surface of the second layer of elastic substrate, so that the recording electrode and the light stimulation electrode are integrated into one structure. The flexible nerve electrode of the present invention can be implanted for a long time, has high flexibility, and can withstand deformation effects such as expansion and contraction of brain tissue.

Description

A kind of optoelectronic integrated stretchable flexible nerve electrode and preparation method

technical field

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

Background technique

With the rapid progress and development of brain-computer interface and neuroscience, in-depth understanding of brain functions and diseases has become one of the frontier directions of research in countries around the world. With the help of flexible electronic science and MEMS micro-nano processing capabilities, flexible neural micro-electrodes are increasingly used to accurately collect high-density, high-information EEG signals for neural circuit function research, brain lesion diagnosis, and neural decoding. etc. provide a brand new tool.

Since the advent of optogenetics, allowing people to precisely stimulate or inhibit certain types of neurons, it has become an indispensable tool for neurological disease models and neural circuit function research. At present, the main way to introduce a light source into the brain is through an optical fiber inserted into the brain tissue for illumination, but the resolution is extremely poor. In recent years, light sources such as optode probes, optical waveguides, and micro-LED arrays with openings have been developed, which are divided into two methods: piercing the light source deep into the brain and light stimulation through the cerebral cortex. The relatively small invasive light stimulation through the surface of the cerebral cortex needs to take into account the volume changes brought about by the expansion and contraction of the brain itself.

After searching the prior art, it is found that no research has proposed a stretchable brain-computer interface device that integrates a micro-LED chip array and a cerebral cortex electrical signal acquisition function. Japan Toyohashi University of Technology Morikawa Y, Yamagiwa S et al. in Advanced healthcare materials, 2018, 7(3): 1701100, in the article "Ultrastretchable kirigami bioprobes", proposed a highly stretchable kirigami structure with a maximum strain of up to 840 %, a flexible neural microelectrode with a Young's modulus of only 3.6 kPa. The device uses 11-micron-thick Parylene-C material as a flexible substrate, and contains a total of 10 platinum electrode points with a diameter of 50 microns. The spacing and position between the electrode points can be adjusted by stretching, which reduces the stress of the device itself and is harmful to the soft brain. Potential damage to tissue. However, the proposed device only has the function of recording the ECoG signal of the cerebral cortex, and does not combine other functions; the entire structure is deformed out of plane after being stretched, and the electrode points are difficult to keep flat and reliably attached to the curved surface; the mechanical strength of the device is low, and it is easy to break and break. Difficult to use for long-term implantation.

It has been reported that flexible neural microelectrodes based on elastic polymer materials (such as PDMS) can stretch and deform by themselves when subjected to brain expansion or extrusion, reducing electrode dislocation and potential mechanical damage to brain tissue. Zhang J, Liu X, et al., Peking University, China, in Nano letters, 2018, 18(5): 2903-2911, "Stretchabletransparent electrode arrays for simultaneous electrical and opticalinterrogation of neural circuits in vivo", in polydimethylsiloxane ( The carbon nanotube electrode is integrated into the PDMS) substrate, which has certain stretchability and transparency. The upper limit of the carbon nanotube electrode can be stretched to 50%, and the cyclic stretching of 20% can still maintain good electrochemical performance for 10,000 times. Finally, combined with Large-scale optical stimulation with laser fiber synchronously collects ECoG cerebral cortex electrical signals. Tybrandt K, Khodagholy D, et al., ETH Zurich, Switzerland, wrote "High-density stretchable electrode grids for chronic neural recording" in Advanced Materials, 2018, 30(15): 1706520, and also integrated gold-coated titanium dioxide nanowires in PDMS substrate to prepare high-density Electrodes, long-term implanted on the rat cerebral cortex for 3 months, can still collect electrical signals in the cerebral cortex. However, since the Young's modulus of brain tissue (~1kPa) is 2-3 orders of magnitude lower than that of PDMS (~1Mpa), a softer elastic base material is more suitable for long-term implantation of brain tissue. In addition, the above two electrodes have a single function , and there is no light stimulation combined with precise positioning, only a large-scale laser irradiation stimulation without resolution.

In addition, Yan Z, Pan T, et al., University of Electronic Science and Technology of China, in Advanced Science, 2017, 4(11): 1700251, wrote the article "Thermal release transfer printing for stretchable conformalbioelectronics" by thermally peeling tape the sandwich-structured polyimide -Metal layer-polyimide serpentine wire structure electrode, transferred to PDMS substrate, can achieve 10.4% stretch, and ECoG cerebral cortical electrical signals were collected in rat cerebral cortex through acute animal experiments. However, due to the weak adhesion between polyimide and PDMS itself, it is difficult to ensure that the device does not delaminate during use, and also only has a single EEG recording function, which is not combined with optical stimulation.

To sum up, there is no report on the stretchable brain-computer interface flexible electrode that integrates precise optical stimulation and cerebral cortex electrical signal acquisition functions. The reasons include complex processing technology and high requirements for device integration. Therefore, it is urgent to develop a flexible electrode. It can be implanted for a long time, is highly flexible, can withstand deformation such as expansion and contraction, and integrates flexible neural electrodes with precise light stimulation functions to meet the needs of various brain science and neuroscience research tools.

SUMMARY OF THE INVENTION

In view of the defects in the prior art, the purpose of the present invention is to provide an optoelectronic integrated stretchable flexible nerve electrode and a preparation method.

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

Wherein, both the optical stimulation electrode and the recording electrode adopt a serpentine bending wiring structure to ensure that the metal wire will not reach the critical value of yield strain during the stretching process;

The lower surface of the light stimulation electrode is provided with a first silicon dioxide layer, and the strong chemical bond generated by the condensation reaction between the first silicon dioxide layer and the first layer of elastic substrate makes the light stimulation electrode adhere to the first layer of the elastic substrate. layer elastic substrate surface;

The second layer of elastic substrate is arranged on the upper surface of the light stimulation electrode, and the second layer of silicon dioxide is arranged on the lower surface of the recording electrode, and the second layer of silicon dioxide is formed with the second layer of the elastic substrate. The strong chemical bond produced by the condensation reaction makes the recording electrode adhere to the surface of the second layer of elastic substrate, so that the recording electrode and the photo-stimulation electrode are integrated into an integrated structure.

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

Further, the light stimulation electrode includes a first polyimide substrate layer, a metal wire layer, a first polyimide encapsulation layer and a micro LED chip, wherein the first polyimide substrate layer is located in the light The bottommost layer of the stimulation electrode, the metal wire layer is arranged on the upper surface of the first polyimide substrate layer, the first polyimide encapsulation layer is arranged above the metal wire layer, and the first polyimide encapsulation layer is arranged on the upper surface of the first polyimide substrate layer. The micro LED chip is arranged on the layer; the lower surface of the light stimulation electrode refers to the lower surface of the first polyimide substrate layer; the second layer of elastic substrate is located on the first polyimide encapsulation layer the upper surface.

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

Further, the recording electrode includes a second polyimide substrate layer, a metal shielding layer, a polyimide insulating layer, a metal recording layer and a second polyimide encapsulation layer, wherein the second polyimide The 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, and the polyimide insulating layer is arranged above the second polyimide substrate layer. The metal recording layer is arranged above the layer, and the second polyimide encapsulation layer is arranged above the metal recording layer; the lower surface of the recording electrode refers to the lower surface of the second polyimide substrate layer.

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

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

Preferably, the thickness of the second polyimide encapsulation 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:

Prepare optical stimulation electrodes and recording electrodes respectively, and both the stimulation electrodes and the recording electrodes adopt a circular arc serpentine bending wiring structure to ensure that the metal wires will not reach the critical value of yield strain during the stretching process;

A first silicon dioxide layer is deposited on the lower surface of the photostimulation electrode, and the first silicon dioxide layer on the lower surface of the photostimulation electrode is transferred onto a first layer of elastic substrate. A condensation reaction occurs between the silicon oxide layer and the first layer of elastic substrate to generate strong chemical bonds, so that the photostimulation electrode is adhered to the surface of the first layer of elastic substrate;

A second layer of elastic substrate is prepared on the upper surface of the light stimulation electrode, a second silicon dioxide layer is deposited on the lower surface of the recording electrode, and the second silicon dioxide layer on the lower surface of the recording electrode is transferred to printed on the second layer of elastic substrate, the second silicon dioxide layer and the second layer of elastic substrate undergo condensation reaction to generate strong chemical bonds, so that the recording electrode is adhered to the surface of the second layer of elastic substrate ; Obtain an integrated device integrating the photostimulation electrode and the recording electrode.

Further, follow the steps below:

Step 1: use the first silicon wafer as the supporting substrate for the light stimulation electrode; use the second silicon wafer as the supporting substrate for the recording electrode; clean the first silicon wafer and the second silicon wafer. the first silicon wafer and the second silicon wafer are baked;

Step 2: thermally evaporate or sputter a layer of metal on the first silicon wafer and the second silicon wafer respectively, as the last metal release layer of the superstructure;

Step 3: Spin-coat and pattern polyimide glue on the first silicon wafer, that is, above the metal release layer, to form a first polyimide substrate layer of the light stimulation electrode; On the second silicon wafer, the polyimide adhesive is spin-coated and photolithographically patterned on the metal release layer to form the second polyimide substrate layer of the recording electrode;

Step 4: On the first silicon wafer, that is, above the first polyimide substrate layer, sputter a layer of chromium as a seed layer, and then sputter a layer of gold on the chromium layer as a metal layer. The metal layer is spin-coated and photolithographically patterned with positive photoresist, and the metal wire layer patterning of the photostimulation electrode is completed by ion beam etching; on the second silicon wafer, the second polyimide Above the amine substrate layer, first sputter a layer of chromium as a seed layer, then sputter a layer of gold on the chromium layer as a metal layer, and complete the patterning of the metal shielding layer of the recording electrode by ion beam etching;

Step 5: Spin-coat and pattern polyimide glue on the first silicon wafer, that is, above the metal wire layer, to form the first polyimide encapsulation layer of the photostimulation electrode. On the first silicon wafer, the preparation of the photo-stimulation electrode is completed; on the second silicon wafer, the polyimide glue is spin-coated and photolithographically patterned on the top of the metal shielding layer to form the polyimide of the recording electrode. Amine insulating layer;

Step 6: Sputter a layer of chromium on the second silicon wafer, that is, above the polyimide insulating layer, and then sputter a layer of gold on the chromium layer to form a metal recording layer. Spin coating on the layer and pattern positive photoresist by photolithography, and finally complete the patterning of the metal recording layer of the recording electrode by ion beam etching;

Step 7: Spin-coat and pattern polyimide glue on the second silicon wafer, that is, above the metal recording layer, to form a second polyimide encapsulation layer for the recording electrode. The preparation of the recording electrode is completed on the silicon wafer;

Step 8: Cover the top of the first silicon wafer and the second silicon wafer with clean paper or a clean cloth respectively, and then use the same diameter as the first silicon wafer and the second silicon wafer respectively. The size of the glass sheet is completely covered, and then the superimposed first silicon wafer and glass sheet, the second silicon wafer and glass sheet are immersed in hydrochloric acid solution, sacrificing the first silicon wafer and the second Metal release layer on silicon wafer;

Step 9: After that, put the superimposed first silicon wafer and glass wafer, and the second silicon wafer and glass wafer into deionized water to soak, rinse and dry to complete the photostimulation electrode and the the release of the recording electrode;

Step 10: Adhere the photostimulation electrode from the first silicon wafer with water-soluble tape, separate the first silicon wafer from the photostimulation electrode, and turn the lower surface of the photostimulation electrode upward It is fixed on the substrate, and then a layer of titanium is first sputtered on the lower surface of the light stimulation electrode, and then a first silicon dioxide layer is sputtered on the titanium layer;

Adhere the recording electrode from the second silicon wafer with a water-soluble tape to separate the second silicon wafer from the recording electrode; fix the recording electrode on the substrate with the lower surface facing up, and then place the recording electrode on the substrate. A layer of titanium is first sputtered on the lower surface of the recording electrode, and then a second silicon dioxide layer is sputtered on the titanium layer;

Step 11: Select a glass sheet, cover the top of the glass sheet with a layer of PI tape, and then fix the glass slide with a layer of parylene on the surface on the glass sheet with the PI tape. A layer of release agent is sprayed on the parylene, and then a layer of superelastic silicone rubber is spin-coated on the release agent as the first layer of elastic substrate;

Step 12: irradiate the first layer of elastic substrate with UV light, and then transfer the water-soluble tape with the photostimulation electrodes to the surface of the first layer of elastic substrate, so that the photostimulation electrodes splash The surface on which the first silicon dioxide layer is sprayed is in contact with the surface of the first layer of elastic substrate, and is placed in an oven under a certain pressure, and then the water-soluble adhesive tape is dissolved in hot water;

Step 13: Align and attach a mask on the photostimulation electrode, that is, the upper surface of the first polyimide encapsulation layer, and the metal pads exposed through the mask are used for brushing conductive silver paste, and solder patterning is completed on the photo-stimulation electrode;

Step 14: Using a patterned mold, reverse the mold to obtain a concave mold stamp, fix the micro LED chips in the pits of the stamp, and complete the transfer of multiple micro LED chips to form a micro LED chip array, put it into an oven, and make the The conductive silver paste on the photostimulation electrode is completely cured and conducts electricity;

Step 15: Use a mask to brush conductive silver paste on the tail end of the photostimulation electrode to form a photostimulation electrode interface, select a PI flexible cable, and align the PI flexible cable under the cover glass. The optical stimulation electrode interface is connected with the front end of the PI flexible cable to form an integrated device, and is placed in an oven under the action of the upper pressure;

Step 16: Apply sealant to the connection area of the optical stimulation electrode interface and the PI flexible cable, perform oxygen plasma pretreatment on the entire surface of the device, and apply polyethylene terephthalate film Cover the back end of the PI flexible cable, spin-coat a layer of super-elastic silicone rubber on the entire first silicon wafer as the second layer of elastic substrate, and uncover the polyethylene terephthalate immediately after spin-coating Ester film to expose the rear end of the PI flexible cable;

Step 17: irradiate the second layer of elastic substrate with UV light, align the water-soluble tape with the recording electrode prepared in step 10 to the position, and sputter the recording electrode with a second dioxide One side of the silicon layer is transferred to the surface of the second layer of elastic substrate, and placed in an oven under a certain pressure, and then placed in hot water to dissolve the water-soluble adhesive tape;

Step 18: Use a mask to brush conductive silver paste on the local area of the rear end of the recording electrode to form a recording electrode interface, then select a PI flexible cable, and connect the PI flexible cable to the PI flexible cable under the cover glass. Align to the recording electrode interface, keep the pressure above, and put it into the oven;

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

Step 20: Release the entire integrated device from the glass slide and electrochemically modify the electrode sites of the integrated device.

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

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

- In step 6, a layer of chromium is first sputtered on the second silicon wafer, that is, above the polyimide insulating layer, and then a layer of gold is sputtered on the chromium layer to form a metal recording layer, wherein the chromium The thickness of the gold is 10-50 nm; the thickness of the gold is 100-500 nm.

- In step 10, a layer of titanium is first sputtered on the lower surface of the light stimulation electrode, and then a layer of silicon dioxide is sputtered on the titanium layer, wherein the thickness of titanium is 3-10 nm; the thickness of silicon dioxide is 30～100nm;

A layer of titanium is first sputtered on the lower surface of the recording electrode, and then a layer of silicon dioxide is sputtered on the titanium layer. 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 present invention has at least one of the following beneficial effects:

1. For the first time in the above structure of the present invention, the precise optical stimulation function is integrated into the stretchable flexible nerve electrode. Even under deformation conditions, the relative position of the optical stimulation site and the recording electrode point will not change, ensuring stimulation and recording. Position reliability; this flexible neural electrode fills the gap of stretchable optoelectronic integrated brain-computer interface devices at home and abroad, and has the potential to provide a powerful support tool for neuroscience and brain research. In the above structure, the light stimulation electrode and the recording electrode adopt a serpentine wiring structure, which has a certain stretchability, can follow the deformation of the superelastic silicone rubber substrate, can be implanted for a long time, is highly flexible, and can withstand deformation effects such as brain tissue expansion and contraction;

2. Further, in the above structure of the present invention, the superelastic platinum-catalyzed silicone rubber Dragonskin or Ecoflex series with a Young's modulus lower than the most commonly used PDMS is used as the electrode substrate, which helps to improve the stretchability of the electrode and the connection between the electrode and the cerebral cortex. It is easier to form a conformal attachment state.

3. In the above preparation method of the present invention, the photostimulation electrode and the recording electrode integrated with the micro LED chip are integrated by the transfer printing method. Due to the expansion and contraction of brain tissue, it is more suitable for long-term implantation in mice for the study of long-term neural circuits and neurological disease models based on optogenetics.

4. Based on the above structure and preparation method of the present invention, different elastic substrates and electrode substrate materials can be replaced as required, without changing the integrated process flow of the electrodes.

Description of drawings

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

FIG. 1a is a schematic structural diagram of an optoelectronic 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. 1a;

Fig. 1c is a partial enlarged structural schematic diagram of the recording electrode in Fig. 1a;

FIG. 2 is a flow chart of an integration process of an optoelectronic integrated stretchable flexible neural electrode in an embodiment of the present invention;

3 is a schematic diagram of the relative position and size of the recording electrode point and the micro LED chip in the embodiment of the present invention;

4 is a schematic diagram of the cross-sectional structure and size of the optoelectronic integrated stretchable flexible neural electrode in an embodiment of the present invention;

5a is a schematic diagram of a serpentine structure design of an optoelectronic integrated stretchable flexible neural electrode according to an embodiment of the present invention;

Figure 5b is a schematic diagram before and after deformation of the uniaxially stretched serpentine wire structure in Figure 5a;

Fig. 5c is a schematic diagram of the structure parameters of the serpentine line in Fig. 5a;

FIG. 6 is a photo of an optoelectronic integrated stretchable flexible neural electrode device in an embodiment of the present invention;

7 is a schematic diagram of the photoelectric integrated stretchable flexible neural electrode in the embodiment of the present invention for synchronous optical stimulation and electrical recording in the mouse cerebral cortex;

The symbols in the figure are respectively: the first layer of elastic substrate 1, the first silicon dioxide layer 2, the first polyimide substrate layer 3, the metal wire layer 4, the first polyimide encapsulation layer 5, the micro LED chip 6. The second layer of elastic substrate 7, the second silicon dioxide layer 8, the second polyimide substrate layer 9, the metal shielding layer 10, the polyimide insulating layer 11, the metal recording layer 12, the second polyimide Amine encapsulation layer 13 , recording electrode point 14 , reference electrode point 15 , serpentine curved wiring structure 16 , 470nm blue light 17 , EEG signal collection site 18 , LED power supply cable 19 , EEG signal collection cable 20 .

Detailed ways

The present invention will be described in detail below with reference to specific embodiments. The following examples will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that, for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention. The parts that are not described in detail in the following embodiments of the present invention can all be implemented by using the prior art.

Referring to Figures 1a, 1b, and 1c, it is a schematic structural diagram of a preferred embodiment of an optoelectronic integrated stretchable flexible nerve electrode. The flexible nerve electrode includes a first layer of elastic substrate 1, photostimulation electrodes, and a second layer of elastic substrate 7. And the recording electrode; the light stimulation electrode and the recording electrode all adopt the arc serpentine curved wiring structure 16; the lower surface of the light stimulation electrode is provided with the first silicon dioxide layer 2, the first silicon dioxide layer 2 and the first layer of elastic substrate 1 The strong chemical bond generated by the condensation reaction makes the photo-stimulation electrode adhere to the surface of the first layer of elastic substrate 1; the other side (upper surface) of the photo-stimulation electrode is provided with a second layer of elastic substrate 7, and the lower surface of the recording electrode is provided with a second layer of elastic substrate 7. The silicon oxide layer 8, the strong chemical bond generated by the condensation reaction between the second silicon dioxide layer 8 and the second layer of elastic substrate 7 makes the recording electrode adhere to the surface of the second layer of elastic substrate 7, so that the recording electrode and the light stimulation electrode are integrated into one structure .

In other preferred embodiments, the first layer of elastic substrate 1 and the second layer of elastic substrate 7 are selected from Dragonskin or Ecoflex series of superelastic platinum-catalyzed silicone rubber with Young's modulus lower than the most commonly used PDMS. Specifically, the platinum-catalyzed silicone rubber Dragonskin produced by Smooth-on Company in the United States can be selected. Platinum-catalyzed silicone rubber Dragonskin Young's modulus is 166kPa, Ecoflex Young's modulus is 60kPa, polydimethylsiloxane (PDMS) is usually used as the elastic substrate in the prior art, and the Young's modulus of PDMS is in the range of 0.5 ~1.8MPa, the Young's modulus of the superelastic platinum-catalyzed silicone rubber Dragonskin or Ecoflex series is lower than the most commonly used PDMS. Using superelastic materials as substrates can improve electrode flexibility.

In other preferred embodiments, the light stimulation electrode includes a first polyimide substrate layer 3, a metal wire layer 4, a first polyimide encapsulation layer 5 and a micro LED chip 6, wherein the first polyimide substrate The bottom layer 3 is located at the bottommost layer of the light stimulation electrode, a metal wire layer 4 is arranged on the upper surface of the first polyimide substrate layer 3, a first polyimide encapsulation layer 5 is arranged above the metal wire layer 4, and the first polyimide encapsulation layer Micro LED chips 6 are arranged on the layer 5 ; the lower surface of the light stimulation electrode refers to the lower surface of the first polyimide substrate layer 3 ; the second elastic substrate is located on the upper surface of the first polyimide encapsulation layer 5 .

In some specific embodiments, the micro LED chip 6 may be a gallium nitride LED bare chip with a model number of TR2227 or TR1823 from Cree in the United States, and the thickness is 50 μm. The height of the corresponding SU-8 negative photoresist mold is 20-30 μm, and the length and width are 5-10 μm larger than the size of the micro LED chip 6 , so as to facilitate the positioning and separation of the micro LED chip 6 .

In other embodiments, the thickness of the first polyimide substrate layer 3 is 2-10 μm; the thickness of the first polyimide encapsulation 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, wherein the first The two polyimide substrate layer 9 is located at the bottommost layer of the recording electrode, a metal shielding layer 10 is arranged above the second polyimide substrate layer 9, a polyimide insulating layer 11 is arranged above the metal shielding layer 10, and the polyimide insulating layer A metal recording layer 12 is arranged above the layer 11 , and a second polyimide encapsulation layer 13 is arranged above the metal recording layer 12 ; the lower surface of the recording electrode refers to 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 encapsulation layer 13 is 2-10 μm 10μm.

In a specific embodiment, the flexible neural electrode includes 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 and the recording electrode points 14 can be adjusted according to the target animal tissue. and the number and distribution position of the micro LED chips 6, etc.

Based on the structural features of the flexible nerve electrodes in the above embodiments, an embodiment of a method for preparing a stretchable flexible nerve electrode with optoelectronic integration is provided, and the preparation method includes:

Optical stimulation electrodes and recording electrodes are prepared respectively, and both the stimulation electrodes and the recording electrodes adopt a circular arc serpentine bending wiring structure 16 to ensure that the metal wires will not reach the critical value of yield strain during the stretching process.

A first silicon dioxide layer 2 is deposited on the lower surface of the light stimulation electrode, and the first silicon dioxide layer 2 on the lower surface of the light stimulation electrode is transferred to the first layer of elastic substrate 1. The first silicon dioxide layer 2 and the The first layer of elastic substrate 1 generates strong chemical bonds through the reverse condensation reaction, so that the photostimulation electrode is bonded to the surface of the first layer of elastic substrate 1; a second layer of elastic substrate is prepared on the other side (upper surface) of the photostimulation electrode 7. Deposit the second silicon dioxide layer 8 on the lower surface of the recording electrode, transfer the second silicon dioxide layer 8 on the lower surface of the recording electrode to the second elastic substrate, the second silicon dioxide layer 8 and the second layer The elastic substrate 7 undergoes a condensation reaction to generate strong chemical bonds, so that the recording electrode is bonded to the surface of the second layer of the elastic substrate 7, and an integrated device of the integrated light stimulation electrode and the recording electrode is obtained.

In a preferred embodiment, a method for preparing an optoelectronic integrated stretchable flexible neural electrode is performed according to the following steps:

Step 1: Use the first silicon wafer as the support substrate for the light stimulation electrode; use the second silicon wafer as the support substrate for the recording electrode; clean the first silicon wafer and the second silicon wafer, and clean the first silicon wafer after cleaning. Bake with the second silicon wafer.

Step 2: A layer of metal is thermally evaporated or sputtered on the first silicon wafer and the second silicon wafer, respectively, as the last metal release layer of the superstructure.

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.

Step 3: Spin-coat and pattern polyimide glue on the first silicon wafer, that is, above the metal release layer, to form the first polyimide substrate layer 3 of the photo-stimulating electrode; The polyimide paste is spin-coated and photolithographically patterned on the metal release layer to form the second polyimide substrate layer 9 of the recording electrode.

Step 4: Sputter a layer of chromium (Cr) on the first silicon wafer, that is, above the first polyimide substrate layer 3, and then sputter a layer of gold (Au) on the chromium layer as a metal layer. The metal layer is spin-coated and photolithographically patterned with positive photoresist, and the patterning of the metal wire layer 4 of the light-stimulated electrode is completed by ion beam etching; A layer of chromium (Cr) is sputtered, and then a layer of gold (Au) is sputtered on the chromium layer as a metal layer, and the metal shielding layer 10 of the recording electrode is patterned by ion beam etching.

The thickness of sputtering a chromium (Cr) layer on the first silicon wafer, that is, above the polyimide substrate layer, is 10-50 nm; the thickness of sputtering a gold (Au) layer on the chromium (Cr) layer is 100-500 nm.

The thickness of the chromium layer sputtered on the second silicon wafer, that is, above the polyimide substrate layer, is 10-50 nm; the thickness of the gold (Au) layer sputtered on the chromium (Cr) layer is 100-500 nm.

Step 5: Spin-coating and photolithography patterning polyimide glue on the first silicon wafer, that is, above the metal wire layer 4, to form the first polyimide encapsulation layer 5 of the light stimulation electrode, on the first silicon wafer The preparation of the optical stimulation electrode is completed; the polyimide glue is spin-coated and photolithographically patterned on the second silicon wafer, that is, above the metal shielding layer 10 , to form the polyimide insulating layer 11 of the recording electrode.

Step 6: Sputter a layer of chromium (Cr) on the second silicon wafer, that is, above the polyimide insulating layer 11, and then sputter a layer of gold (Au) on the chromium layer to form a metal recording layer 12, The positive photoresist is spin-coated and photolithographically patterned on the metal recording layer 12, and finally the metal recording layer 12 of the recording electrode is patterned by ion beam etching; wherein, the thickness of the chromium (Cr) layer is 10-50 nm; The thickness of the Au) layer is 100 to 500 nm.

Step 7: Spin-coat and pattern polyimide glue on the second silicon wafer, that is, above the metal recording layer 12, to form the second polyimide encapsulation layer 13 of the recording electrode, and complete the recording electrode on the second silicon wafer preparation.

Step 8: Cover the tops of the first silicon wafer and the second silicon wafer with clean paper or clean cloth, and then cover them completely with glass pieces of the same diameter as the first silicon wafer and the second silicon wafer, and then The superposed first silicon wafer and glass wafer, and the second silicon wafer and glass wafer are soaked in a hydrochloric acid solution, and the metal release layers on the first silicon wafer and the second silicon wafer are sacrificed.

Using clean paper or clean cloth, the main function is to ensure that the hydrochloric acid solution can penetrate and contact the metal release layer of the electrode; since the recording electrode and the photostimulation electrode are stacked between the silicon wafer and the glass wafer, the metal release layer is in contact with the hydrochloric acid solution. The reaction is slow, so the soaking time needs to be appropriately extended to 1-2 days to ensure that the metal release layer under the polyimide is completely etched and reacted cleanly.

Step 9: After that, put the superimposed first silicon wafer and glass wafer, and the second silicon wafer and glass wafer into deionized water to soak, rinse and dry to complete the release of the photostimulation electrode and the recording electrode.

Step 10: Use water-soluble tape to stick the photostimulation electrode from the first silicon wafer, separate the first silicon wafer from the photostimulation electrode, fix the lower surface of the photostimulation electrode on the substrate, and then place the photostimulation electrode on the substrate. First, sputter a layer of titanium (Ti) on the lower surface of the titanium layer, and then sputter a first silicon dioxide (SiO ₂ ) layer on the titanium layer; wherein, the thickness of the titanium (Ti) layer is 3-10 nm, and the titanium (Ti) is used as The adhesion layer improves the bonding force between the first silicon dioxide layer 2 and the first polyimide substrate. The thickness of the first silicon dioxide layer 2 is 30-100 nm, and the first silicon dioxide (SiO ₂ ) layer will chemically react with the silicone rubber substrate.

Use water-soluble tape to stick the recording electrode from the second silicon wafer to separate the second silicon wafer from the recording electrode; fix the lower surface of the recording electrode on the substrate, and then sputter a layer on the lower surface of the recording electrode Titanium (Ti), and then sputtering a second silicon dioxide (SiO ₂ ) layer 8 on the titanium layer, the thickness of the titanium (Ti) layer is 3-10 nm; The bonding force between the silicon oxide layer 8 and the second polyimide substrate layer 9 . The thickness of the second silicon dioxide layer 8 is 30-100 nm, and the second silicon dioxide (SiO ₂ ) layer 8 will chemically react with the silicone rubber substrate.

Step 11: Select a glass slide, cover the top of the glass slide with a layer of PI tape, and then fix the glass slide with a layer of parylene on the surface with PI tape, and place the glass slide on the glass slide. A layer of release agent was sprayed on toluene, and then a layer of superelastic silicone rubber was spin-coated on the release agent as the first layer of elastic substrate 1; Dragonskin or Ecoflex series.

Step 12: Irradiate the first layer of elastic substrate 1 with UV ultraviolet light, and then transfer the water-soluble tape with the photostimulation electrodes to the surface of the first layer of elastic substrate 1, so that the photostimulation electrodes are sputtered with the first dioxide One side of the silicon layer 2 is in contact with the surface of the first layer of the elastic substrate 1, and is placed in an oven under a certain pressure, and then the water-soluble adhesive tape is dissolved in hot water.

Step 13: Align the mask on the photo-stimulation electrode, brush the conductive silver paste through the metal pads exposed by the mask, and complete the solder patterning on the photo-stimulation electrode; in the specific embodiment, the mask is PET, PET mask thickness is 12.5~25μm, through laser cutting, etch small holes with a diameter of 75~80μm to ensure that the metal pad of the light stimulation electrode is exposed during alignment, so as to facilitate brushing to obtain patterned conductive silver paste, Used to connect and fix the micro LED chip 6 .

Step 14: Using the patterned mold, reverse the mold to obtain the concave mold seal, fix the micro LED chips 6 in the pits of the seal, complete the transfer of multiple micro LED chips 6, form an array of micro LED chips 6, put them in an oven, The conductive silver paste on the photostimulation electrode is fully cured and conductive.

Step 15: Use the mask to brush conductive silver paste on the end of the photostimulation electrode to form the photostimulation electrode interface, select the PI flexible cable, and align the PI flexible cable with the cover glass to the photostimulation electrode interface. , so that the optical stimulation electrode interface and the front end of the PI flexible cable are connected into an integrated device, and under the action of the upper pressure, it is placed in the oven; the mask material used when brushing the conductive silver paste is stainless steel with a thickness of 15-25 μm. Through laser cutting the openings smaller than the rectangular pads of the electrode interface, the conductive silver paste can be prevented from diffusing to the adjacent pad area during the pressing process.

Step 16: Apply sealant to the connection area of the optical stimulation electrode interface and the PI flexible cable, perform oxygen plasma pretreatment on the entire surface of the device, and cover the polyethylene terephthalate film on the PI flexible cable On the rear end of the glass sheet, spin-coat a layer of superelastic silicone rubber as the second elastic substrate The end is exposed; in the specific implementation: the oxygen plasma pretreatment time is 30 to 120 seconds, the main purpose is to ensure the firm bonding and sealing effect between the elastic silicone rubber encapsulation layer and the silicone rubber substrate layer.

Step 17: Irradiate the second layer of elastic substrate 7 with UV light, align the water-soluble tape with the recording electrode prepared in step 10 to the position, and sputter the side of the recording electrode with the second silicon dioxide layer 8 Transferred to the surface of the second layer of elastic substrate 7, and placed in an oven under a certain pressure, and then placed in hot water to dissolve the water-soluble adhesive tape.

Step 18: Use the mask to brush the conductive silver paste on the recording electrode interface, align the PI flexible cable to the recording electrode interface under the pressure of the cover glass, keep the pressure above, and put it into the oven.

Step 19: Coat the silicone sealant on the recording electrode interface and the connection area of the PI flexible cable, and obtain the outline of the integrated device by laser cutting the silicone rubber elastic base layer and the silicone rubber elastic encapsulation layer.

Step 20: Release the entire integrated device from the glass slide and electrochemically modify the electrode points of the integrated device.

In other preferred embodiments, the electrode modification materials can be selected from iridium oxide (IrOx), polyethylenedioxythiophene (PEDOT:PSS), platinum black (Pt-black), etc., to reduce the electrochemical impedance of the electrode point, improve the Signal-to-noise ratio to ensure good signal pickup capability.

In a specific embodiment, referring to FIG. 2 , the integrated process flow chart of the method for preparing a stretchable flexible neural electrode with optoelectronic integration includes the following steps:

Step 1: Cover a layer of polyimide (PI) tape on a 3-inch transparent glass slide, and then deposit a layer of parylene-C on the surface of a transparent glass slide with polyimide (PI) tape. ) The two ends of the tape were fixed on the glass sheet, and the release agent was sprayed, and then a layer of Dragonskin superelastic silicone rubber with a thickness of 100 μm was spin-coated as the first layer of elastic substrate 1 .

The second step: Align and stick a polyethylene terephthalate (PET) mask with a thickness of 12.5 μm on the photo-stimulation electrode on the three-axis moving stage. The diameter of the circular opening is 80 μm. The metal pad of the quasi-photostimulation electrode is brushed with conductive silver paste, and the PET mask is uncovered to complete the patterning of the conductive silver paste.

Step 3: Irradiate the first layer of elastic substrate with UV light for 110 minutes, transfer the American AQUASOL water-soluble tape with light stimulation electrodes to the surface of the first layer of elastic substrate 1, and place it at 80 degrees under certain pressure. 10 minutes in the oven followed by stirring in 50 degree hot water to dissolve the water-soluble tape.

The fourth step: lithography patterning a SU-8 punch structure with a thickness of 25 μm, spin coating liquid PDMS, curing the inverted mould to obtain a PDMS concave stamp, and fix the micro LED chip 6 in the stamp pit, on the three-axis mobile stage The transfer of the micro-LED chip 6 array was completed, and then placed in a 100-degree oven for 6 hours.

Step 5: Use a stainless steel mask with a thickness of 20 μm to apply conductive silver paste to the optical stimulation electrode interface, select a PI flexible cable with a length of 35 mm, and align the optical stimulation electrode interface under the cover glass to maintain the pressure above. Under the action, put it into a 100-degree oven for 6 hours to complete the full curing of the conductive silver paste.

Step 6: Apply elastic transparent silicone sealant 705 to the connection area between the optical stimulation electrode interface and the PI flexible cable to complete the interface packaging, then perform oxygen plasma pretreatment on the entire surface of the device for 60 seconds, and cover the short PI flexible cable with PET film line back end. A layer of Dragonskin superelastic silicone rubber with a thickness of 100 μm was spin-coated on the entire device surface as the second layer of elastic substrate 7, and the PET film was removed immediately after spin-coating to ensure that the back end of the short PI flexible cable was exposed.

Step 7: Irradiate the second layer of elastic substrate with UV light for 710 minutes, align the AQUASOL water-soluble tape with the recording electrode in place, transfer it to the surface of the second layer of elastic substrate 7, and place it under a certain pressure for 80 In the oven for 10 minutes, then stir in 50 degree hot water to dissolve the water-soluble tape.

Step 8: The recording electrode interface is brushed with conductive silver paste with a stainless steel mask with a thickness of 20 μm, and the PI flexible cable is aligned to the recording electrode interface under the pressure of the cover glass. The conductive silver paste is fully cured in the oven for 6 hours.

Step 9: Apply elastic transparent silicone sealant 705 to the connection area of the recording electrode interface and the PI flexible cable to complete the interface packaging. Use a laser with a power of 400W to cut the silicone rubber elastic base layer and the silicone rubber elastic packaging layer to obtain precise electrodes. contour.

Step 10: Gently lift from the glass slide with tweezers to release the entire integrated device, and ultrasonically electroplate platinum black in a chloroplatinic acid solution to complete the electrode point modification.

Referring to FIG. 3 , which is a diagram of the relative position and size of the recording electrode dots 14 and the micro LED chip 6 , the recording electrode dots 14 in the 3×3 recording electrode array have a diameter of 100 μm, a center-to-center spacing of 700 μm, and a reference electrode diameter of 250 μm. In the 2×2 micro-LED chip 6 array, four recording electrode points 14 are distributed around each LED, the size of the micro-LED chips 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 diagram of the cross-sectional structure and size of the stretchable flexible neural electrode for optoelectronic integration, it can be seen that the micro LED chip 6 can emit blue light with a dominant wavelength of about 470 nm through the almost transparent Dragonskin silicone rubber, and The recording electrode points 14 are kept at a certain distance in the horizontal direction; the thickness of the light stimulation electrode is 10 μm, the thickness of the recording electrode is 7.5 μm, the thickness of the micro LED is 50 μm, and the thickness of the elastic base layer and the elastic encapsulation layer are both 100 μm.

Referring to Figures 5a and 5b, which are the design diagrams of the serpentine wire structure of the optoelectronic integrated stretchable flexible neural electrode, it can be seen that with the stretching of the elastic substrate, the serpentine wire of the electrode can withstand a certain degree of deformation. The stretchable flexible neural electrode is oriented towards the mouse cerebral cortex model. The serpentine wiring will take up more plane space than the straight line, so it is necessary to reduce the line width as much as possible, but at the same time, the reliability of the device must be taken into account, and the metal wire is too thin. It is more likely to fail during preparation and use. Therefore, as shown in Figure 5c, the serpentine structure design adopts the following design parameters: the central angle θ=225 degrees, the metal wire width W _metal = 25 μm, the wire width W _PI = 50 μm, the circle The arc inner corner radius R = 50 μm.

Referring to FIG. 6 , which is a photo of the optoelectronic integrated stretchable flexible neural electrode device, the relative position of the integrated recording electrode point 14 and the micro LED chip 6 can be seen by partially magnifying the front end of the electrode, and the second layer of elastic substrate 7 The reflective pattern on the surface is the SiO ₂ film deposited on the surface of the water-soluble tape during the process of transferring the recording electrode. It is a transparent film and does not affect the penetration of LED light.

Referring to Figure 7, it is a schematic diagram of the photoelectric integrated stretchable flexible neural electrodes for simultaneous optical stimulation and electrical recording in the mouse cerebral cortex. The device can be attached to the unilateral brain area of the mouse cerebral cortex. Working at the same time, through the EEG signal collection cable 20 and the LED power supply cable 19, the EEG signal collection site 18 is collected and the LED is powered.

In specific implementation, Dragonskin silicone rubber with a Young's modulus of 160 kPa can also be replaced with Ecoflex silicone rubber with a Young's modulus of 60 kPa. The softer elastic substrate helps to improve the stretchability of the electrode, and it is easier to form a conformal attachment state with the cerebral cortex. At the same time, the first polyimide substrate layer 3 of the recording electrode and the second polyimide substrate layer 9 of the photostimulation electrode can be replaced with transparent Parylene-C, and the front end metal layer of the recording electrode, that is, the front end of the metal recording layer 12, records the The electrode points 14 and the nearby wiring are replaced with transparent conductive materials, such as indium tin oxide, graphene or silver nanowires, etc., to improve the transparency for optical microscopic observation, and at the same time, it can reduce the light on the metal recording electrode points 14. The resulting photoelectric artifacts avoid interference with neural signals. Flexible neural electrodes can be replaced with different elastic substrates and electrode substrate materials as needed, without changing the electrode integration process.

In another specific embodiment, the preparation method of the optoelectronically integrated stretchable flexible neural electrode, the relevant steps are the same as the above-mentioned specific embodiment, and the changes are mainly in the cross-sectional structure and size schematic diagram of the optoelectronically integrated stretchable flexible neural electrode recording electrode and the electrode thickness selection of the photostimulation electrodes. Since the photo-stimulation electrodes need to be brushed with conductive silver paste and transferred to the micro LED chips 6, a harder substrate is required, especially when extrusion transfer is performed on a softer elastic base layer, a thicker PI electrode substrate can To provide a harder support, therefore, the thickness of the first polyimide substrate layer 3 and the first polyimide encapsulation layer 5 of the photostimulation electrode can be increased to 10 μm, and the total thickness of the photostimulation electrode reaches 20 μm.

At the same time, the recording electrode is attached to the upper surface of the second layer of elastic substrate 7. Compared with the optical stimulation electrode encapsulated in the two layers of elastic substrate layer and the elastic encapsulation layer, the metal recording layer 12 bears more during the stretching process. The strain is more likely to fail, and by increasing the overall thickness of the second polyimide substrate layer 9, the polyimide insulating layer 11 and the second polyimide encapsulation layer 13, the second elastic substrate 7 can be effectively reduced. The effect of the stretching process on the metal layer in the recording electrode, therefore, the recording electrode polyimide substrate layer (ie the second polyimide substrate layer 9) and the polyimide encapsulation layer of the recording electrode (ie the second polyimide The thickness of the imine encapsulation layer 13) can be increased to 5 μm, and the thickness of the polyimide insulating layer 11 of the recording electrode remains unchanged, which is beneficial to exert the electromagnetic shielding ability of the metal shielding layer 10 of the recording electrode, and the total thickness of the recording electrode reaches 12.5 μm.

The integration method of flexible neural electrodes can expand and integrate more different types of flexible biosignal sensors and actuators into flexible neural electrodes, providing the possibility for the invention of highly integrated brain-computer interfaces with complex functions.

The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the above-mentioned specific embodiments, and those skilled in the art can make various deformations or modifications within the scope of the claims, which does not affect the the essence of the present invention.

Claims (10)

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 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;

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.

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;

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.

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;

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 the metal release layers 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 the action of 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 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;

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.

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;

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;

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.

Images