Photoelectrode for bidirectional multifunctional nerve regulation and preparation method thereof

By combining microLED and optical waveguide structures on the photoelectrode, the Y-type beam splitter is used to achieve multi-color light source stimulation and bidirectional regulation, which solves the shortcomings of existing photoelectrodes in multi-color light stimulation and bidirectional regulation, and improves nerve cell activity Regulatory accuracy and biocompatibility.

CN119113408APending Publication Date: 2024-12-13HANGZHOU DIANZI UNIV
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Patent Information

Application Number
CN202411176216.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-08-26
Publication Date
2024-12-13

AI Technical Summary

Technical Problem

Existing photoelectrodes have insufficient spatial resolution and biocompatibility problems in the regulation of multicolor photostimulation and bidirectional regulation of nerve cell activity, and bidirectional neural regulation cannot be achieved.

Method used

The combined structure of micro LED and optical waveguide is adopted to improve the spatial resolution of multi-color light source stimulation through the Y-type beam splitter structure, and the optical waveguide is used as a feedback channel for light intensity detection and calcium ion imaging, realizing bidirectional multifunctional neural regulation.

Benefits of technology

Multicolor light stimulation regulation and bidirectional nerve regulation at high spatial resolution are achieved, which improves the regulation accuracy of nerve cell activity and simplifies the preparation process of photoelectrodes.

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Abstract

The invention discloses a photoelectrode for bidirectional multifunctional nerve regulation and a preparation method thereof. Most of the existing neural photoelectrodes can only realize monochromatic light neural regulation and control, and the regulation and control spatial resolution is insufficient. The photoelectrode provided by the invention comprises a plurality of probe handles and an electrode base part, the tip of the probe handle is provided with a micro LED light stimulation site and an optical waveguide stimulation / detection site. The optical waveguide stimulation / detection site is connected to the electrode base through the optical waveguide. A laser diode or a photodiode is mounted on the electrode base part; the optical waveguide stimulation / detection site of each probe handle is connected to the optical coupling port through the optical waveguide of the optical waveguide stimulation / detection site and the one-stage or multi-stage Y-shaped beam splitter structure. The photoelectrode can be controlled to emit light in multiple colors, and the nerve cell activity can be activated and inhibited through light in different colors. In addition, the device can be matched with a photodiode to detect the illumination intensity stimulated by the micro LED and collect fluorescence signals emitted by cells or tissues.
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Description

Technical Field

[0001] The present invention belongs to the technical field of biosensor preparation in the field of brain-computer interface; specifically, it relates to a photoelectrode for bidirectional multifunctional neural regulation and a preparation method thereof. Background Art

[0002] People's exploration of brain science has been a hot topic in scientific research in the past few decades. Among them, rationally stimulating nerve cells to regulate brain neural activity is an important part of promoting the development of brain science. At first, we were able to preliminarily regulate brain neural activity and understand brain function by electrically stimulating the brain. However, in order to study the interaction of group neurons in complex networks, it is sometimes necessary to selectively activate and inhibit single neurons of specific types. Electrical stimulation is difficult to effectively regulate single neurons of specific types. Optogenetics has revolutionized neural circuit analysis by introducing photosensitive proteins into specific cell types, greatly improving the spatiotemporal resolution of stimulation. Optogenetics is a powerful neuromodulatory strategy with spatiotemporal precision, cell type specificity and bidirectionality. In order to take advantage of the advantages of optogenetics in regulating neural activity, some new types of photoelectrodes have gradually been proposed to regulate the neural activity of specific cells, which helps people better understand the mechanism of brain neural activity.

[0003] After searching the existing technical literature, it was found that the current neural photoelectrode stimulation method mainly achieves light output through integrated micro-LED or waveguide structure. In the paper "Monolithically Integrated mLEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals", Wu Fan's research group at the University of Michigan used fine silicon micromachining technology to make InGaN LED photoelectrodes on silicon substrates, and directly integrated the light source at the stimulation point. The photoelectrode has a total of four handles, each with three micro-LEDs, which improves the spatial resolution of stimulation and can achieve a spatial resolution of less than 1 μm. In the paper "In vivo optical modulation of neural signals using monolithically integrated two-dimensional neural probe arrays", Son Yoojin's team at the Center for Bio-Microsystems, Institute of Brain Science, Korea Institute of Science and Technology introduced a Y-beam splitter to design a multi-channel silicon-based optogenetic probe based on SU-8 waveguide, realizing multi-channel light output from the optical waveguide and improving the spatial resolution of light stimulation. In the paper "Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe", the LiZhu LI team of the Center for Flexible Electronics Technology of Tsinghua University developed a neural stimulation probe that emits dual-color (red and blue) light by stacking InGaP micro-LEDs, silicon oxide / titanium oxide optical filter layers, and InGaN micro-LEDs, providing a solution for realizing multifunctional neural regulation (red light inhibition, blue light activation). However, the above three photoelectrode structures still have some shortcomings. Although the spatial resolution of stimulation has been improved in the first two, they are limited to the monochromatic light stimulation regulation of nerve cell activity; and although the latter has achieved multi-color light stimulation, in order to limit the number of micro-LEDs, the spatial resolution that can be regulated is insufficient, mainly because the increase in the number of micro-LEDs will lead to poor biocompatibility of the photoelectrode and greater damage to brain tissue. In addition, during the preparation process, due to the harsh growth conditions of the InGaP micro-LED (red light) epitaxial layer, it is often necessary to integrate it into the photoelectrode by transfer printing, and its processing technology and transfer printing alignment precision are often a great challenge.Finally, the above-mentioned photoelectrodes are unable to detect the intensity of light radiation inside the optical probe body and cannot achieve bidirectional neural regulation, namely active light stimulation and passive light detection. Summary of the invention

[0004] The purpose of the present invention is to address the defects in the prior art and propose an opto-electrode for bidirectional multifunctional neural regulation, which has multi-color bidirectional function. On the one hand, the opto-electrode adopts a combination structure of micro-LED and optical waveguide to realize multi-color light source emission, and the Y-type beam splitter structure of the optical waveguide improves the spatial resolution of multi-color light source stimulation; on the other hand, the optical waveguide can also be used as a feedback channel to detect the light intensity of micro-LED stimulation and collect the fluorescence signal emitted by cells or tissues, and transmit it back to the detection device, thereby realizing calcium ion imaging.

[0005] In a first aspect, the present invention provides an optical electrode for bidirectional multifunctional neural regulation, which includes a plurality of probe handles and an electrode base; each probe handle is arranged side by side, and the inner end is connected to the electrode base. The tip of the probe handle is provided with one or more micro-LED light stimulation sites and an optical waveguide stimulation / detection site. The optical waveguide stimulation / detection site is connected to the electrode base via an optical waveguide.

[0006] A laser diode or a photodiode is installed on the electrode base; the light outlet of the laser diode or the receiving end of the photodiode serves as an optical coupling port. The optical waveguide stimulation / detection site of each probe handle is connected to the optical coupling port through its own optical waveguide and a primary or multi-stage Y-beam splitter structure.

[0007] When a laser diode is installed, the laser diode can transmit a light signal with a wavelength different from that of the micro-LED light stimulation site to the optical waveguide stimulation / detection site, and cooperate with the micro-LED stimulation site to perform multi-color light stimulation.

[0008] When a photodiode is installed, the optical waveguide stimulation / detection site and the Y-beam splitter structure transmit the fluorescent signal emitted by cells or tissues to the photodiode for calcium ion imaging.

[0009] Preferably, the probe handle is provided with a plurality of micro LED light stimulation sites arranged in a matrix.

[0010] Preferably, the electrode base is provided with a plurality of power supply pads and two contact point pads. The laser diode or the photodiode is integrated on the two contact point pads. Each micro-LED light stimulation site corresponds to a power supply pad. The mutually corresponding micro-LED light stimulation sites are connected to the power supply pads through a micro-LED signal line. The two contact point pads are connected to the two power supply pads through signal lines respectively. One of the contact point pads is connected to the power supply pad as a ground wire interface, and is simultaneously connected to the ground terminals of all micro-LED light stimulation sites.

[0011] Preferably, the micro-LED light stimulation site and the optical waveguide on the probe handle are both prepared by a monolithic integration process using a silicon-based or sapphire-based gallium nitride wafer.

[0012] Preferably, the core material of the optical waveguide is silicon nitride or SU-8 photoresist.

[0013] In a second aspect, the present invention provides a method for preparing an optical electrode for bidirectional multifunctional neural regulation, wherein the prepared optical electrode comprises a plurality of probe handles and an electrode base; the tip of the probe handle has one or more micro-LED light stimulation sites and an optical waveguide stimulation / detection site. The optical waveguide stimulation / detection site on each probe handle is connected to the same optical coupling port on the electrode base through an optical waveguide structure; the optical waveguide structure comprises an optical waveguide on the probe handle, and a primary or multi-stage Y-beam splitter structure on the electrode base. A laser diode or a photodiode is installed at the optical coupling port.

[0014] The preparation method comprises the following steps: Step 1: Use gallium nitride wafer as substrate and sputter ohmic contact diffusion layer on the substrate Step 2: deposit a layer of SiO2 on the ohmic contact diffusion layer; and etch the SiO2 after spinning and patterning to form an outer convex structure of the micro-LED light stimulation site and a lower cladding of the optical waveguide.

[0015] Step 3: Use ion beam to etch the ohmic contact diffusion layer.

[0016] Step 4: Etching the GaN epitaxial layer of the substrate.

[0017] Step 5: After debonding, deposit a layer of silicon nitride; after spinning and patterning, etch the silicon nitride; passivate the micro-LED light stimulation site with silicon nitride; and simultaneously etch to form two contact windows on the micro-LED light stimulation site; thus forming the core material of the optical waveguide structure.

[0018] Step 6: After debonding, a conductive layer is formed by electron beam evaporation; after spinning and patterning, the conductive layer is wet-etched to form a signal line.

[0019] Step 7: After debonding, deposit a layer of SiO2; after spinning and patterning, etch SiO2 to form an insulating layer for the signal line and an upper cladding layer for the optical waveguide, obtain a complete optical waveguide structure, and expose the pad.

[0020] Step 8: After debonding, release the photoelectrode on the substrate by laser cutting; install and weld a laser diode or photodiode on the photoelectrode.

[0021] Preferably, the silicon nitride on the lower cladding of the optical waveguide is retained during the etching in step five, so that the silicon nitride is directly used as the core material of the optical waveguide structure; the optical waveguide structure is automatically formed in the process of forming the micro-LED light stimulation site without the need for additional steps.

[0022] Preferably, the silicon nitride on the lower cladding of the optical waveguide is removed in the etching of step five; after the silicon nitride etching is completed, SU-8 photoresist is spin-coated and patterned, so that the SU-8 photoresist serves as the core material of the optical waveguide structure.

[0023] Preferably, in step 1, the material of the ohmic contact diffusion layer is Ni / Au / Ni; the thickness of the Ni / Au / Ni layer is 10 / 20 / 10 nm.

[0024] Preferably, the gallium nitride wafer in step 1 is ultrasonically cleaned and dried in acetone, ethanol and deionized water respectively.

[0025] The present invention has the following beneficial effects: 1. The present invention utilizes the micro-LED array and optical waveguide structure integrated simultaneously on the photoelectrode, which can control the multi-color light emission of the photoelectrode and has the ability to activate and inhibit the activity of nerve cells through different colors of light. In addition, the present invention introduces the photoelectrode into the optical waveguide structure of the Y-beam splitter, which can perform multi-color light stimulation and regulation on the activity of nerve cells at high spatial resolution.

[0026] 2. The present invention designs an optical electrode for bidirectional multifunctional neural regulation, which is bidirectional in function. Its bidirectionality is reflected in active light stimulation and passive light detection. When the optical waveguide structure is combined with a laser diode, the optical electrode can realize multi-color light source emission; when the optical waveguide structure is combined with a photodiode, the optical waveguide channel serves as a feedback channel to detect the light intensity stimulated by the micro-LED and collect the fluorescence signals emitted by cells or tissues, and transmit them back to the detection device, thereby realizing calcium ion imaging.

[0027] 3. The present invention uses silicon nitride to passivate the micro-LED light stimulation site and etch a contact window, and also uses silicon nitride to form the core material of the optical waveguide structure, thereby simplifying the production process of the micro-LED and optical waveguide combined structure. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a schematic diagram of the overall structure of the photoelectrode provided in Example 1 of the present invention.

[0029] Figure 2 The process flow chart of the preparation method in Example 1 of the present invention.

[0030] Figure 3 This is a process flow chart of the preparation method in Example 2 of the present invention. DETAILED DESCRIPTION

[0031] The present invention will be further described below in conjunction with the accompanying drawings.

[0032] Example 1 like Figure 1 As shown, an optical electrode for bidirectional multifunctional neural regulation includes a plurality of probe handles 1 and an electrode base 2; each probe handle 1 is arranged side by side, and the inner ends are connected to the electrode base 2.

[0033] The tip of the probe handle 1 is provided with a plurality of micro-LED light stimulation sites 1-1 arranged in a matrix, and an optical waveguide stimulation / detection site 1-2. The optical waveguide stimulation / detection site 1-2 is the tip portion of the optical waveguide arranged on the probe handle 1. In this embodiment, the tip of the probe handle 1 has a total of four micro-LED light stimulation sites 1-1, arranged in a 2×2 matrix.

[0034] The electrode base 2 is provided with a plurality of power supply pads 2-1 and two contact point pads 2-2. An external stimulation / detection installation area is provided on the electrode base 2. Two contact point pads 2-2 are provided in the external stimulation / detection installation area. A laser diode or a photodiode is installed on the external stimulation / detection installation area. Two interfaces of the laser diode or the photodiode of the two contact point pads 2-2 are connected respectively.

[0035] The micro-LED light stimulation sites 1-1 on each probe handle 1 correspond to a power supply pad 2-1. The corresponding micro-LED light stimulation sites 1-1 are connected to the power supply pad 2-1 through the micro-LED signal line 1-3. The two contact point pads 2-2 are connected to the two power supply pads 2-1 through signal lines. One of the contact point pads 2-2 is connected to the power supply pad 2-1 as a ground line interface, and is also connected to the ground terminals of all micro-LED light stimulation sites 1-1.

[0036] The light outlet of the laser diode or the receiving end of the photodiode serves as the optical coupling port of the optical electrode. In this embodiment, the number of probe handles 1 is four; a two-stage Y-type beam splitter structure 2-3 is provided on the electrode base 2; the two-stage Y-type beam splitter structure 2-3 includes a first-stage Y-type beam splitter structure 2-3 and a second-stage two Y-type beam splitter structures 2-3. The first-stage one Y-type beam splitter structure 2-3 is used to split the optical signal into two; the first-stage two Y-type beam splitter structures 2-3 are used to split the optical signal into four.

[0037] The optical waveguide stimulation / detection site 1-2 at the tip of each probe handle 1 is connected to the optical coupling port of the photoelectrode through the optical waveguide on each probe handle 1 and the two-stage Y-type beam splitter structure 2-3.

[0038] During operation, the power supply pad 2-1 is used to provide a driving signal to the micro LED, control the brightness and light frequency of the light stimulation site, and power the laser diode or transmit a signal to the photodiode. The optical coupling port is used to couple an external light source or receive an optical signal transmitted from the tip of the probe handle through the optical waveguide structure.

[0039] The micro LED light stimulation site 1-1 and the optical waveguide on the probe handle 1 are both prepared by a monolithic integration process of a silicon-based / sapphire-based gallium nitride wafer. The main material of the optical waveguide is silicon nitride or SU-8 photoresist.

[0040] When a laser diode is installed, the Y-shaped beam splitter structure can guide the optical waveguide into multiple probe handle tips, transmit optical signals with wavelengths different from the micro-LED light stimulation site 1-1 to the tip of each probe handle 1, and cooperate with the micro-LED stimulation site 1-1 to achieve multi-color light output with high spatial resolution, thereby realizing multi-color light stimulation.

[0041] When a photodiode is installed, the optical waveguide stimulation / detection site 1-2 can detect the light intensity stimulated by the micro-LED and collect the fluorescent signal emitted by the cells or tissues and transmit it to the photodiode, thereby realizing calcium ion imaging.

[0042] In some embodiments, the luminescent color of the micro-LED light stimulation site 1-1 is blue, with a wavelength of 400nm to 500nm, preferably 470nm.

[0043] In some embodiments, the light emission color of the laser diode is selected according to the actual needs of light stimulation.

[0044] The method for preparing the aforementioned photoelectrode for bidirectional multifunctional neural regulation comprises the following steps: Step 1: Figure 2 As shown in (1), a gallium nitride wafer is used as the substrate of the photoelectrode. Before the process starts, the substrate is first ultrasonically cleaned in acetone, ethanol, and deionized water for 5 minutes respectively, then blown dry with nitrogen and baked in an oven at 180°C for more than 15 minutes. The gallium nitride wafer includes a base layer, an N-type gallium nitride layer, a quantum well layer, and a P-type gallium nitride layer stacked in sequence from bottom to top. The N-type gallium nitride layer, the quantum well layer, and the P-type gallium nitride layer are the gallium nitride epitaxial layers of the gallium nitride wafer.

[0045] Step 2: Figure 2 As shown in (2), Ni / Au / Ni is sputtered on the substrate as an ohmic contact diffusion layer, and the thickness of the Ni / Au / Ni layer is 10 / 20 / 10 nm, respectively.

[0046] Step 3: Figure 2As shown in (3), a 200 nm thick SiO2 layer is deposited on the ohmic contact diffusion layer by PECVD (plasma enhanced chemical vapor deposition).

[0047] Step 4: Figure 2 As shown in (4), after spinning, the photoresist is patterned using planar photolithography technology. The photoresist is a positive photoresist with a thickness of 5 μm.

[0048] Step 5: Figure 2 As shown in (5), SiO2 is etched by RIE (reactive ion etching technology) to form the outer convex structure of the LED and the lower cladding of the optical waveguide.

[0049] Step 6: Figure 2 As shown in (6), the ohmic contact diffusion layer is etched using an ion beam.

[0050] Step 7: Figure 2 As shown in (7), ICP (inductively coupled plasma etching technology) is used to etch the gallium nitride epitaxial layer on the substrate to form the micro-LED light stimulation site 1-1 and the optical waveguide bottom structure.

[0051] Step 8: Figure 2 As shown in (8), after debonding in acetone, drying and further processing with a debonding machine, a layer of silicon nitride is deposited by PECVD to passivate the micro-LED photostimulation site 1-1 and as an optical waveguide core material.

[0052] Step 9: Figure 2 As shown in (9), after spinning, the photoresist is patterned using planar photolithography technology. The photoresist is a positive photoresist with a thickness of 5 μm.

[0053] Step 10: Figure 2 As shown in (10), silicon nitride and silicon oxide are etched by RIE (reactive ion etching technology) to form contact windows of the N-type gallium nitride layer and the P-type gallium nitride layer on the micro-LED light stimulation site 1-1, and to form an optical waveguide structure.

[0054] Step 11: Figure 2 As shown in (11), after debonding in acetone, Ti / Al was evaporated using electron beam; the thickness of the Ti / Al layers were 20 / 500 nm, respectively.

[0055] Step 12: Figure 2 As shown in (12), after spinning, the photoresist is patterned using planar photolithography technology. The photoresist is a positive photoresist with a thickness of 5 μm.

[0056] Step 13: Figure 2As shown in (13), the Ti / Al layer is wet-etched, and the color of the substrate is observed to change from metallic color to substrate color, forming a signal line, and the contact windows of the N-type gallium nitride layer and the P-type gallium nitride layer on the micro-LED light stimulation site 1-1 are led out to the corresponding power supply pad.

[0057] Step 14: Figure 2 As shown in (14), after debonding in acetone, a layer of SiO2 is deposited by PECVD as the insulating layer of the signal line and the upper cladding of the waveguide.

[0058] Step 15: Figure 2 As shown in (15), after spinning, the photoresist is patterned using planar photolithography technology. The photoresist is a positive photoresist with a thickness of 5 μm.

[0059] Step 16: Figure 2 As shown in (16), SiO2 is etched by RIE to form a complete optical waveguide structure and expose the pad at the electrode base.

[0060] Step 17: Figure 2 As shown in (17), the adhesive is removed in acetone.

[0061] Step 18: Use a laser cutting machine to cut out the outline of each photoelectrode and release the photoelectrode from the wafer.

[0062] Step 19: Solder the laser diode or photodiode to the contact pad of the released photoelectrode.

[0063] Example 2 A photoelectrode for bidirectional multifunctional neural regulation, the difference between this embodiment and embodiment 1 is that the material of the optical waveguide is different; in this embodiment, the optical waveguide uses SU-8 photoresist. Silicon oxide / silicon nitride is only used as an insulating layer.

[0064] The specific steps of setting the LED light stimulation sites in this embodiment are the same as those in Embodiment 1.

[0065] The specific steps for setting up the optical waveguide stimulation / probe sites are modified as follows: like Figure 3 As shown in (14), Figure 2 Based on (13), after stripping in acetone, SU-8 photoresist is re-spin-coated as the insulating layer on the wire and the optical waveguide core.

[0066] like Figure 3 As shown in (15), the photoresist is patterned using planar photolithography technology to define the optical waveguide structure and expose the pads at the electrode base.

[0067] Finally, a laser cutter is used to cut out the outline of each photoelectrode and release the photoelectrodes from the wafer.

Claims

1. A method for preparing a photoelectrode for bidirectional multifunctional neural regulation, wherein the prepared photoelectrode comprises a plurality of probe handles (1) and an electrode base (2); Features: The tip of the probe handle (1) has one or more micro-LED light stimulation sites (1-1) and optical waveguide stimulation / detection sites (1-2); the optical waveguide stimulation / detection sites (1-2) on each probe handle (1) are connected to the same optical coupling port on the electrode base (2) via an optical waveguide structure; the optical waveguide structure comprises an optical waveguide on the probe handle (1) and a primary or multi-stage Y-beam splitter structure (2-3) on the electrode base (2); a laser diode or a photodiode is installed at the optical coupling port; The preparation method comprises the following steps: Step 1: Use gallium nitride wafer as substrate and sputter ohmic contact diffusion layer on the substrate Step 2: Deposit a layer of SiO on the ohmic contact diffusion layer 2 ; Spinning, patterning and etching SiO 2 , forming an outer convex structure of the micro-LED light stimulation site (1-1) and a lower cladding of the optical waveguide; Step 3, etching the ohmic contact diffusion layer using an ion beam; Step 4, etching the GaN epitaxial layer of the substrate; Step 5: After debonding, deposit a layer of silicon nitride; after spinning and patterning, etch the silicon nitride; passivate the micro-LED light stimulation site (1-1) with silicon nitride; and simultaneously etch to form two contact windows on the micro-LED light stimulation site (1-1); and form the core material of the optical waveguide structure; Step 6: After stripping, a conductive layer is formed by electron beam evaporation; after spinning and patterning, the conductive layer is wet-etched to form a signal line; Step 7: After degumming, deposit a layer of SiO 2 ; Spinning, patterning and etching SiO 2 , forming an insulating layer of the signal line and an upper cladding layer of the optical waveguide, obtaining a complete optical waveguide structure, and exposing the pad; Step 8: After debonding, release the photoelectrode on the substrate by laser cutting; install and weld a laser diode or photodiode on the photoelectrode.

2. The preparation method according to claim 1, Features: In the etching of step five, the silicon nitride on the lower cladding of the optical waveguide is retained, so that the silicon nitride is directly used as the core material of the optical waveguide structure; the optical waveguide structure is automatically formed in the process of forming the micro-LED light stimulation site (1-1) without the need for additional steps.

3. The preparation method according to claim 1, Features: In step five, the silicon nitride on the lower cladding of the optical waveguide is removed by etching; after the silicon nitride etching is completed, SU-8 photoresist is spin-coated and patterned, so that the SU-8 photoresist serves as the core material of the optical waveguide structure.

4. The preparation method according to claim 1, Features: In step 1, the material of the ohmic contact diffusion layer is Ni / Au / Ni; the thickness of the Ni / Au / Ni layer is 10 / 20 / 10 nm.

5. The preparation method according to claim 1, Features: The gallium nitride wafer described in step 1 is ultrasonically cleaned and dried in acetone, ethanol and deionized water respectively.

6. An optical electrode for bidirectional multifunctional neural regulation, comprising a plurality of probe handles (1) and an electrode base (2); Features: Each probe handle (1) is arranged side by side, and the inner end is connected to the electrode base (2); the tip of the probe handle (1) is provided with one or more micro-LED light stimulation sites (1-1) and optical waveguide stimulation / detection sites (1-2); the optical waveguide stimulation / detection sites (1-2) are connected to the electrode base (2) via an optical waveguide; A laser diode or a photodiode is mounted on the electrode base (2); the light outlet of the laser diode or the receiving end of the photodiode serves as an optical coupling port; the optical waveguide stimulation / detection site (1-2) of each probe handle (1) is connected to the optical coupling port via its own optical waveguide and a primary or multi-stage Y-beam splitter structure (2-3); When a laser diode is installed, the laser diode can transmit a light signal having a wavelength different from that of the micro-LED light stimulation site (1-1) to the light waveguide stimulation / detection site (1-2), and cooperate with the micro-LED stimulation site (1-1) to perform multi-color light stimulation; When a photodiode is installed, the optical waveguide stimulation / detection site (1-2) and the Y-beam splitter structure (2-3) transmit the fluorescent signal emitted by cells or tissues to the photodiode for calcium ion imaging.

7. The photoelectrode for bidirectional multifunctional neural regulation according to claim 6, Features: The probe handle (1) is provided with a plurality of micro LED light stimulation sites (1-1) arranged in a matrix shape.

8. The photoelectrode for bidirectional multifunctional neural regulation according to claim 6, Features: The electrode base (2) is provided with a plurality of power supply pads (2-1) and two contact point pads (2-2); a laser diode or a photodiode is integrated on the two contact point pads (2-2); each micro-LED light stimulation site (1-1) corresponds to a power supply pad (2-1); mutually corresponding micro-LED light stimulation sites (1-1) are connected to the power supply pads (2-1) via micro-LED signal lines (1-3); the two contact point pads (2-2) are connected to the two power supply pads (2-1) via signal lines respectively; one of the contact point pads (2-2) is connected to the power supply pad (2-1) as a ground line interface, and is simultaneously connected to the grounding terminals of all micro-LED light stimulation sites (1-1).

9. The photoelectrode for bidirectional multifunctional neural regulation according to claim 6, Features: The micro LED light stimulation site (1-1) and the optical waveguide on the probe handle (1) are both prepared by a monolithic integration process using a silicon-based or sapphire-based gallium nitride wafer.

10. The photoelectrode for bidirectional multifunctional neural regulation according to claim 6, Features: The core material of the optical waveguide is silicon nitride or SU-8 photoresist.