Rigid-flexible multifunctional optical genetic implantable probe and preparation method thereof

Abstract

The invention provides a rigidity-flexibility variable multifunctional optical genetic implantable probe and a preparation method thereof. The probe comprises a thin film electrode layer and a rigidity-flexibility variable shape memory layer arranged at the bottom of the thin film electrode layer. The micro LED is integrated in the flexible nerve probe through contact type laser transfer printing to serve as a light stimulation light source, the preparation success rate is remarkably increased, heat radiated outwards during light stimulation is reduced, and damage to brain tissue of the brain caused by high-Young-modulus optical fibers is avoided; meanwhile, a rigid-flexible variable shape memory layer is also integrated, so that the Young modulus of the probe is high when the in-vitro temperature is relatively low, fixed-point implantation can be directly carried out without an auxiliary tool, the Young modulus of the probe is reduced along with the rise of the body temperature after the probe is implanted into the body, and the probe finally adapts to the mechanical tissue strength of the brain; therefore, the implantation efficiency and the mechanical adaptability of the probe to brain tissues are improved, and micron-scale accurate implantation of the probe, neuron-scale positioning of electrical stimulation and light stimulation points and long-term stable recording of electrophysiological signals are realized.

Description

TECHNICAL FIELD

[0001] The present application relates to a multi-functional optical genetic implantable nerve probe, in particular to a multi-functional optical genetic implantable probe with variable rigidity and softness and a preparation method thereof. BACKGROUND

[0002] Neuroscience is one of the mainstream disciplines for comprehensive research on human language, memory, thinking and other high-level cognitive functions. The core research goal is to understand the function of neural circuits and organizations composed of many cell types, so as to improve and treat diseases caused by abnormalities in some nerve nuclei. Traditional neural circuit research generally uses electrical stimulation to activate nerve cells, but this activation method cannot accurately control the brain region and range. Therefore, optical genetic technology is developed to achieve precise control and functional testing of brain cells. Optical genetic technology refers to expressing light-sensitive proteins on cells of selected specific parts of nerve tissue or functional nuclei, and then applying light stimulation to the target area to activate the light-sensitive proteins, thereby achieving fine regulation of cell, tissue, organ and animal physiological functions.

[0003] The light stimulation device used in optical genetics can be divided into two categories. One is local light stimulation based on optical fiber, and the light source is a laser diode. The other is light stimulation realized by a light-emitting diode (LED) array, and the light source is a light-emitting diode. The traditional optical fiber electrode has a large Young's modulus, which does not match the Young's modulus of the biological brain tissue, and is only suitable for short-term recording. In long-term recording, it is highly destructive to the structure of the brain. The light-emitting diode (LED) needs to be transferred from the sapphire substrate to a new substrate for subsequent operation. The substrate can be divided into hard substrates such as silicon substrates, or flexible substrates such as polyimide and pdms. The hard substrate also faces the problem of mechanical mismatch with the brain, which damages the main structure of the brain. The flexible substrate also has the problem of difficulty in implantation and precise positioning. At the same time, the transfer technology in the process of transferring the LED is easy to damage the LED or pollute the surface of the target substrate, thereby affecting the yield of device preparation. Although the larger size LED has a higher success rate in the transfer process, it is easy to generate a large amount of heat in the long-term lighting process, thereby damaging the structure of the brain and producing scar tissue. In addition, the lighting of the light-emitting diode needs to be introduced to the power supply line, which is easy to produce electromagnetic interference to the electrophysiological signal recording electrode, so it is difficult to realize the synchronous recording of photoelectric stimulation and brain electrophysiological signals. SUMMARY

[0004] The purpose of the present application is to provide a multi-functional optical genetic implantable probe with variable rigidity and softness and a preparation method thereof, which can realize multi-point light stimulation, electrical stimulation, and synchronous recording of electrophysiological signals.

[0005] The first aspect of this invention provides a variable stiffness multifunctional optogenetic implantable probe, comprising a thin-film electrode layer and a rigid-flexible shape memory layer disposed at the bottom of the thin-film electrode layer; the thin-film electrode layer comprises, from bottom to top, a polymer substrate layer, a metal recording contact layer, an intermediate polymer isolation layer, a metal electrical signal shielding layer, an LED polymer transfer layer, an LED chip layer, an LED polymer encapsulation layer, a metal stimulation contact layer, and a polymer outline layer; the rigid-flexible shape memory layer is disposed at the bottom of the polymer substrate layer; the polymer substrate layer provides a substrate for the metal recording contact layer; the metal recording contact layer is used to collect brain electrophysiological data. The signal processing mechanism includes: an intermediate polymer isolation layer for isolating the metal recording contact layer and the metal electrical signal shielding layer; a metal electrical signal shielding layer for isolating the metal recording contact layer and the LED chip layer, thereby avoiding electromagnetic interference from the LED chip layer; an LED polymer transfer layer for providing a transfer substrate for the LED chip layer; an LED polymer encapsulation layer for encapsulating the LED chip layer; a metal stimulation contact layer for interconnecting with the wires of the LED chip layer to apply electrical and optical stimulation; and a polymer outline layer for defining the electrode outline and creating windows in the metal recording contact layer, the metal electrical signal shielding layer, and the metal stimulation contact layer to achieve signal acquisition, signal shielding, and stimulation application.

[0006] The variable stiffness flexible implantable probe of this invention specifically uses a shape memory polymer with temperature-sensitive properties (specifically, it can be selected from acrylate copolymers, polynorbornene, trans-polyisoprene, styrene-butadiene copolymers, polyurethane, etc.) as a rigid-flexible variable shape memory layer. This allows the probe to be rigid at room temperature before implantation, enabling precise positioning in the brain region. After implantation, as the brain temperature rises, the Young's modulus of the probe gradually decreases, thereby solving the stress mismatch problem between the probe and brain tissue and achieving the long-term recording function of the flexible probe.

[0007] Preferably, the polymer substrate layer, intermediate polymer isolation layer, LED polymer transfer layer, LED polymer encapsulation layer, and polymer outline layer are all made of biocompatible polymer materials with a thickness of 2-5 μm. The external shape of the LED polymer encapsulation layer is the same as that of the polymer substrate layer, with windows at the positive and negative electrodes of the LED; the external shape of the polymer outline layer is the same as that of the polymer substrate layer, with windows at the electrodes of the metal recording contact layer and the metal stimulation contact layer. The specific size and position of the windows can be determined according to testing requirements. The LEDs in the LED chip layer are micro LEDs.

[0008] More preferably, the biocompatible flexible polymer material is selected from either polyimide or parylene.

[0009] Preferably, the bonding of the rigid-flexible shape memory layer and the thin-film electrode layer requires the use of a specially made polydimethylsiloxane mold. The method for obtaining the specially made polydimethylsiloxane mold is as follows: an SU8 mold larger than the shape of the thin-film electrode layer is prepared using SU8-type negative photoresist; the SU8 mold is placed on the surface of uncured polydimethylsiloxane and dried to obtain the specially made polydimethylsiloxane mold; wherein, in the polydimethylsiloxane, the mass ratio of PDMS basic component to curing agent is 20:1.

[0010] Preferably, the overall thickness of the flexible implantation probe is 15μm-150μm.

[0011] Preferably, the metal recording contact layer, the metal electrical signal shielding layer, and the metal stimulation contact layer all include a microelectrode array (electrode size on the micrometer scale). The microelectrode array is a patterned metal conductor or a patterned conductive polymer. The metal is any one of chromium-gold, chromium-gold-chromium, titanium-gold, titanium-gold-titanium, titanium-platinum, or titanium-platinum-titanium, where gold and platinum are used for conductivity, and chromium and titanium are used to improve the adhesion between the metal and the polymer. The conductive polymer includes nano-silver paste conductive materials, carbon nanofilms, and metal nanowires. The number of electrode channels and the electrode arrangement are selectable and can be determined according to testing requirements. To accommodate the tiny size of EEG data, the electrode size is on the micrometer scale. Based on electrical performance requirements, the electrodes are electroplated using chloroplatinic acid as the electroplating solution and a three-electrode system of an electrochemical workstation to reduce electrode impedance and improve the resolution of the acquired signal.

[0012] In another aspect, this invention provides a method for preparing the aforementioned flexible and multifunctional optogenetic implantable probe, the specific preparation process of which includes: S1: Prepare a clean substrate for later use. The specific method is to perform electron beam evaporation or magnetron sputtering on a clean silicon wafer to deposit a layer of aluminum with a thickness of 500μm for later use. S2: A 2.5 μm thick polyimide film is spin-coated on the substrate and dried by step heating to obtain a polymer substrate layer; S3: Spin-coating, pre-baking, photolithography, and development of forward photoresist are performed on the polymer substrate layer obtained in step S2 to obtain a patterned photoresist layer. Electron beam evaporation or magnetron sputtering is performed on the patterned photoresist layer and the photoresist is stripped off to obtain a metal recording contact layer. S4: Spin-coating and drying a polyimide film on the metal recording contact layer to obtain an intermediate polymer isolation layer; S5: A second photoresist spin coating, pre-baking, photolithography, and development are performed on the polymer isolation layer to obtain a patterned photoresist layer. An electron beam evaporation coating is then performed on the patterned photoresist layer to obtain a chromium-gold metal layer, and the photoresist is stripped off to obtain a metal electrical signal shielding layer. S6: Spin-coating and pre-drying of a biocompatible flexible polymer material are performed on the metal electrical signal shielding layer to obtain an LED polymer transfer layer. S7: Micro LEDs are transferred to the target positions of the LED polymer transfer layer by contact laser transfer to obtain the LED chip layer; the LED polymer transfer layer is then thoroughly cured by step heating. S8: A third spin coating, pre-baking, photolithography, and development of SU8 negative photoresist are performed on the LED polymer transfer layer to obtain a patterned photoresist layer, and windows are opened at the positive and negative electrodes of the LED to obtain an LED polymer encapsulation layer. S9: Perform a fourth spin coating, pre-baking, photolithography, and development of photoresist on the LED polymer encapsulation layer to obtain a patterned photoresist layer. Perform electron beam evaporation or magnetron sputtering on the patterned photoresist layer and then peel off the photoresist to obtain a metal stimulation contact layer. S10: Spin-coating and drying of a biocompatible flexible polymer material on the metal stimulation contact layer to obtain a polymer outer layer. S11: Perform a fifth photolithography on the polymer outer layer, and use electron beam evaporation or magnetron sputtering to deposit an aluminum metal sacrificial layer onto the polymer encapsulation layer, exposing the aluminum metal sacrificial layer and the area where the electrode is located. S12: Perform plasma etching on the aluminum metal sacrificial layer and the area where the electrode is located to create windows in the metal recording contact layer, the metal electrical signal shielding layer and the metal stimulation contact layer. S13: Dissolve the aluminum metal sacrificial layer and peel it off to obtain the thin film electrode layer; S14: Prepare a clean substrate for later use; S15: Using photolithography and SU8 negative photoresist on the substrate prepared in step S14, prepare an SU8 mold with a larger shape than the thin film electrode layer. S16: Prepare uncured polydimethylsiloxane for later use; S17: Place the SU8 mold on the uncured polydimethylsiloxane, and after drying, obtain a PDMS mold with a thin film electrode layer shape; S18: Prepare a temperature-controlled shape memory polymer (SMP) solution; S19: Place the thin film electrode layer obtained in step S13 into the PDMS mold, then pour the prepared SMP solution into the PDMS mold and smooth it out. After photocuring the SMP with ultraviolet light with a wavelength of 365 nanometers, remove it to obtain a flexible implantation probe with variable stiffness at different temperatures.

[0013] This invention can adjust the stimulation mode to perform light stimulation, electrical stimulation or combined stimulation on target neural tissue of organisms according to different needs. Different styles of devices can be prepared according to different stimulation areas. At the same time, it integrates an electrical signal shielding layer to realize the synchronous recording of multimodal stimulation and neurophysiological signals.

[0014] The beneficial effects of this invention are as follows: 1. This invention integrates a micro LED as a light stimulation source, which reduces the heat radiated outward during light stimulation, while avoiding damage to brain tissue caused by high Young's modulus optical fibers, thus reducing the possibility of brain scarring. 2. The micro-LED of this invention is transferred from a sapphire substrate to a target biocompatible polymer material via contact laser. A pre-curing method is used to initially cure the surface, and the surface temperature is maintained at 110°C during the transfer. The laser energy used is 4.88 × 10⁻⁶. 5 W / cm 2 With a duration of 1ms, it overcomes the problems of low precision and high failure rate in general transfer processes, and can efficiently transfer micro LEDs to the substrate surface, effectively improving the cleanliness of the micro LED transfer process and reducing damage to the transfer substrate, thus significantly improving the success rate of preparation. 3. The present invention prepares a metal electrical signal shielding layer between the metal recording contact layer and the metal stimulation contact layer to reduce the electromagnetic interference generated on the recording electrode when the metal stimulation contact applies voltage, thereby realizing the synchronous recording of electrophysiological signals during photoelectric stimulation; 4. This invention utilizes temperature-sensitive shape memory materials to achieve implantation without auxiliary devices. After implantation, as the temperature rises, the Young's modulus of the electrode material in the brain of the organism rapidly decreases, achieving Young's modulus matching between the electrode and the soft brain tissue, and ultimately achieving stable long-term recording of electrode signals. 5. The present invention provides a neural electrode that can realize multi-point optical stimulation and electrical stimulation, and realize the recording of synchronous electrophysiological signals. Attached Figure Description

[0015] Figure 1 A top view of a flexible and multifunctional optogenetic implantable probe according to a preferred embodiment of the present invention; Figure 2This is a longitudinal cross-sectional view of a flexible and rigid multifunctional optogenetic implantable probe according to a preferred embodiment of the present invention, wherein 1 is a flexible and rigid shape memory layer, 2 is a polymer substrate layer, 3 is a metal recording contact layer, 4 is an intermediate polymer isolation layer, 5 is a metal electrical signal shielding layer, 6 is an LED polymer transfer layer, 7 is an LED chip layer, 8 is an LED polymer encapsulation layer, 9 is a metal stimulation contact layer, and 10 is a polymer outline layer, wherein 2, 3, 4, 5, 6, 7, 8, 9, and 10 together constitute a thin film electrode layer; Figure 3 This is a flowchart of a preferred embodiment of the preparation method of the present invention. Detailed Implementation

[0016] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments. It is to be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the invention.

[0017] like Figure 1 and Figure 2 The present invention discloses a flexible and multifunctional optogenetic implantable probe comprising: a thin-film electrode layer and a flexible and variable shape memory layer 1, wherein the flexible and variable shape memory layer 1 is disposed at the bottom of the polymer substrate layer. The thin-film electrode layer comprises, from bottom to top, a polymer substrate layer 2, a metal recording contact layer 3, an intermediate polymer isolation layer 4, a metal electrical signal shielding layer 5, an LED polymer transfer layer 6, an LED chip layer 7, an LED polymer encapsulation layer 8, a metal stimulation contact layer 9, and a polymer outline layer 10. The flexible and variable shape memory layer 1 is disposed at the bottom of the polymer substrate layer 2.

[0018] The flexible implantable probe with variable stiffness features a rigid-flexible shape memory layer made of a temperature-sensitive shape memory polymer, specifically an acrylate copolymer, polynorbornene, trans-polyisoprene, styrene-butadiene copolymer, or polyurethane, with a thickness of 2-5 μm. This rigid-flexible shape memory layer is biocompatible. The polymer base layer, intermediate polymer isolation layer, LED polymer transfer layer, LED polymer encapsulation layer, and polymer outline layer are all made of biocompatible polymer materials. The biocompatible flexible polymer material is selected from either polyimide or parylene.

[0019] The external shape of the LED polymer encapsulation layer is the same as that of the polymer substrate layer, with windows at the positive and negative electrodes of the LED. The external shape of the polymer outer layer is the same as that of the polymer substrate layer, with windows at the electrodes of the metal recording contact layer and the metal stimulation contact layer. The specific size and position of the windows can be determined according to the testing requirements. The LED in the LED chip layer is a micro LED.

[0020] The overall thickness of the flexible implantation probe is 15μm-150μm.

[0021] Both the metal recording contact layer and the metal stimulation contact layer include microelectrode arrays (electrode sizes on the micrometer scale). The microelectrode arrays are patterned metal conductors or patterned conductive polymers. The metal can be any one of chromium-gold, chromium-gold-chromium, titanium-gold, titanium-gold-titanium, titanium-platinum, or titanium-platinum-titanium. Gold and platinum are used for conductivity, while chromium and titanium are used to improve the adhesion between the metal and the polymer. The conductive polymers include nano-silver paste conductive materials, carbon nanofilms, and metal nanowires. The number of electrode channels and the electrode arrangement are selectable and can be determined according to testing requirements. To accommodate the tiny size of EEG signals, the electrode size is on the micrometer scale. Based on electrical performance requirements, the electrodes are electroplated using chloroplatinic acid as the electroplating solution and a three-electrode system of an electrochemical workstation to reduce electrode impedance and improve the resolution of the acquired signal.

[0022] Reference Figure 3 This embodiment provides a process for preparing a flexible and multifunctional optogenetic implantable probe.

[0023] S1: Prepare a clean substrate for use: Use a low-resistivity, single-sided polished 4-inch silicon wafer as the substrate material for the electrodes. Place the silicon wafer in acetone for ultrasonic cleaning for 5 minutes, then use isopropanol for ultrasonic cleaning for 5 minutes, and then dry it with nitrogen gas. Place it on a hot plate at 105°C and bake it for 5 minutes to obtain a clean silicon wafer as the substrate material. Use an electron beam evaporation deposition system to deposit an aluminum metal film with a thickness of about 500nm on the substrate material as a sacrificial layer metal. S2: A polyimide precursor solution was spin-coated onto the sacrificial metal at a speed of 500 r / min for 15 s and then gradually accelerated to 2000 r / min for 45 s. The solution was then kept at 120℃ for 1 h, 200℃ for 2.5 h, and 250℃ for 2.5 h to obtain a polymer substrate layer. S3: Spin-coating positive photoresist AZ5214 onto the obtained polymer substrate layer (500 rpm for 15 seconds, 800 rpm for 30 seconds), followed by 1 minute of pre-baking, 27 seconds of photolithography, and 1 minute of development to obtain a patterned photoresist layer. Then, using an electron beam evaporation deposition system, 5 nm of metallic chromium and 100 nm of metallic gold are deposited onto the obtained photoresist layer. Finally, acetone is used to remove the positive photoresist to obtain a metal recording contact layer. S4: The polyimide precursor solution is spin-coated on the metal recording contact layer obtained in step S3 at a speed of 500 r / min for 15 s and then gradually accelerated to 2000 r / min for 45 s. Then, the intermediate polymer isolation layer is obtained by holding at 120℃ for 1 h, 200℃ for 2.5 h, and 250℃ for 2.5 h. S5: In step S4, positive photoresist AZ5214 is spin-coated on the intermediate polymer isolation layer (500 rpm for 15 seconds, 800 rpm for 30 seconds), pre-baked for 1 minute, photolithographically processed for 27 seconds, and developed for 1 minute to obtain a patterned photoresist layer. 5 nm of metallic chromium and 100 nm of metallic gold are deposited on the obtained photoresist layer using an electron beam evaporation deposition system. The positive photoresist is then removed using acetone to obtain a metal electrical signal shielding layer. S6: The polyimide precursor solution is spin-coated on the metal electrical signal shielding layer obtained in step S5 at a speed of 500 r / min for 15 s and then gradually accelerated to 2000 r / min for 45 s. Then, the LED polymer transfer layer is obtained by preheating at 110℃ for 5 mins to obtain an LED polymer transfer layer with high adhesion performance, thereby improving the LED transfer success rate. S7: In step S6, the LED grown on the sapphire substrate is attached to the surface of the polymer transfer layer and laser transfer is performed at the target location. The surface temperature during transfer is 110℃, and the laser energy is 4.88 × 10⁻⁶. 5 W / cm 2 The duration is 1ms. After the transfer is completed, the LED chip layer is obtained, and the LED polymer transfer layer is thoroughly cured by holding at 120℃ for 1 hour, 200℃ for 2.5 hours, and 250℃ for 2.5 hours. S8: Spin-coating SU8 photoresist of the 2000 series onto the LED polymer transfer layer obtained in step S7 (500 rpm for 15 seconds, 3000 rpm for 30 seconds), followed by pre-baking at 65°C for 10 minutes and 95°C for 15 minutes, then exposure for 10 seconds, followed by post-baking at 65°C for 10 minutes and 95°C for 15 minutes, and then developing in SU8 matching developer for 30 seconds to obtain a patterned photoresist layer, and opening windows at the positive and negative electrodes of the LED to obtain the LED polymer encapsulation layer; S9: In step S8, positive photoresist AZ5214 is spin-coated onto the LED polymer encapsulation layer (500 rpm for 15 seconds, 800 rpm for 30 seconds), pre-baked for 1 minute, photolithographically processed for 27 seconds, and developed for 1 minute to obtain a patterned photoresist layer. On the obtained patterned photoresist layer, 5nm of metallic chromium and 100nm of metallic gold are deposited using an electron beam evaporation deposition system. The positive photoresist is then removed using acetone to obtain a metal-stimulated contact layer. S10: The polyimide precursor solution is spin-coated on the metal stimulation contact layer obtained in step S9 at a speed of 500 r / min for 15 s and then gradually accelerated to 2000 r / min for 45 s. Then, the polymer outline layer is obtained by holding at 120℃ for 1 h, 200℃ for 2.5 h, and 250℃ for 2.5 h. S11: In step S10, positive photoresist AZ5214 is spin-coated onto the LED polymer encapsulation layer (500 rpm for 15 seconds, 800 rpm for 30 seconds), followed by 1 minute of pre-baking, 27 seconds of photolithography, and 1 minute of development to obtain a patterned photoresist layer. 500 nm of metallic aluminum is deposited on the obtained photoresist layer using an electron beam evaporation deposition system, and the positive photoresist is removed using acetone to expose the aluminum metal sacrificial layer and the electrode area. S12: The device obtained in step S11 is surface treated using an plasma etching machine (ICP) to etch the polyimide layer that is not covered by metal, thereby creating windows in the metal recording contact layer, the metal electrical signal shielding layer, and the metal stimulation contact layer. S13: Prepare a sodium chloride / hydrochloric acid electrolytic solution. Use electrolysis to peel off the aluminum sacrificial layer on the device obtained in step S12 to obtain a thin film electrode layer. Use chloroplatinic acid as the electroplating solution and use the three-electrode system of the electrochemical workstation to electroplat the electrode to reduce the electrode impedance and improve the resolution of the acquired signal. S14: First, place the low-resistivity single-sided polished 4-inch silicon wafer in acetone for ultrasonic cleaning for 5 minutes, then use isopropanol for ultrasonic cleaning for 5 minutes, then use nitrogen to dry it and place it on a hot plate at 105°C to bake and dry for 5 minutes to obtain a clean silicon wafer as a substrate material. S15: Using photolithography and SU8 negative photoresist on the substrate prepared in step S14, prepare an SU8 mold that is slightly larger than the obtained thin film electrode layer. S16: Prepare polydimethylsiloxane (PDMS) with a mass ratio of basic components to curing agent of 20:1 for later use; at this ratio, the viscosity of the PDMS mold can ensure that the surface of the thin film electrode layer is tightly bonded to the PDMS mold, preventing uncured shape memory polymer from penetrating to the electrode surface of the thin film electrode layer, which would prevent the electrode from being properly encapsulated.

[0024] S17: Place the SU8 mold obtained in step S15 onto the uncured polydimethylsiloxane (PDMS) prepared in step S16, and dry it in an oven to obtain a PDMS mold with a thin film electrode layer shape. S18: Prepare a fixed-ratio SMP solution for later use. The SMP solution is specifically composed of tricyclo[5.2.1.02,6]decanediethanolacrylic acid, triallyl isocyanurate, tri[2-(3-mercaptopropionyloxy)ethyl isocyanurate] and dimethyl benzoate in a mass ratio of 260.88:237.76:501.36:1. S19: Place the thin film electrode layer obtained in step S13 into the PDMS mold prepared in step S17, then pour the prepared SMP solution into the PDMS mold and smooth it out. After photocuring the SMP with ultraviolet light at a wavelength of 365 nm for 15 minutes, remove it to obtain a flexible implantation probe with variable stiffness at different temperatures.

[0025] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention. All such equivalent modifications or substitutions are included within the scope of the claims of this application.

Claims

1. A flexible and multifunctional optogenetic implantable probe, characterized in that: The system includes a thin-film electrode layer and a rigid-flexible shape memory layer disposed at the bottom of the thin-film electrode layer. From bottom to top, the thin-film electrode layer comprises a polymer substrate layer, a metal recording contact layer, an intermediate polymer isolation layer, a metal electrical signal shielding layer, an LED polymer transfer layer, an LED chip layer, an LED polymer encapsulation layer, a metal stimulation contact layer, and a polymer outline layer. The rigid-flexible shape memory layer is disposed at the bottom of the polymer substrate layer. The polymer substrate layer provides a substrate for the metal recording contact layer. The metal recording contact layer is used to acquire electrophysiological signals from the brain. The intermediate polymer isolation layer isolates the metal recording contact layer from the electrophysiological signals from the brain. The system comprises a recording contact layer and a metal electrical signal shielding layer; the metal electrical signal shielding layer is used to isolate the metal recording contact layer and the LED chip layer, thereby avoiding electromagnetic interference from the LED chip layer; the LED polymer transfer layer is used to provide a transfer substrate for the LED chip layer; the LED polymer encapsulation layer is used to encapsulate the LED chip layer; the metal stimulation contact layer is used to interconnect with the wires of the LED chip layer, thereby applying electrical and optical stimulation; the polymer outline layer is used to determine the electrode outline and to open windows on the metal recording contact layer, the metal electrical signal shielding layer, and the metal stimulation contact layer, thereby realizing signal acquisition, signal shielding, and stimulation application.

2. The flexible and adaptable multifunctional optogenetic implantable probe according to claim 1, characterized in that, The polymer base layer, intermediate polymer isolation layer, LED polymer transfer layer, LED polymer encapsulation layer, and polymer outer layer are made of biocompatible flexible polymer materials with a thickness of 2-5 μm.

3. The flexible and adaptable multifunctional optogenetic implantable probe according to claim 1, characterized in that, The metal recording contact layer and the metal stimulating contact layer are patterned metal conductors or patterned conductive polymers; the electrode sizes in the metal recording contact layer and the metal stimulating contact layer are on the order of micrometers.

4. The flexible and multifunctional optogenetic implantable probe according to claim 1, characterized in that, The outer shape of the LED polymer encapsulation layer is the same as that of the polymer substrate layer, with windows at the positive and negative electrodes of the LED; the outer shape of the polymer outer layer is the same as that of the polymer substrate layer, with windows at the electrodes of the metal recording contact layer and the metal stimulating contact layer.

5. The flexible and adaptable multifunctional optogenetic implantable probe according to claim 1, characterized in that, The rigid-flexible shape memory layer is made of temperature-controlled shape memory polymer material. At room temperature, the rigid-flexible shape memory layer is rigid; after implantation, as the temperature of the brain tissue rises, the rigid-flexible shape memory layer becomes flexible.

6. The flexible and adaptable multifunctional optogenetic implantable probe according to claim 5, characterized in that, The temperature-controlled shape memory polymer material is any one of acrylate copolymers, polynorbornene, trans-polyisoprene, styrene-butadiene copolymers, and polyurethane.

7. The flexible and adaptable multifunctional optogenetic implantable probe according to claim 1, characterized in that, The LEDs in the LED chip layer are micro LEDs.

8. A method for preparing a flexible and multifunctional optogenetic implantable probe as described in any one of claims 1-7, characterized in that, Includes the following steps: S1: Prepare a clean substrate for later use; S2: Prepare a polymer substrate layer on the substrate; S3: Spin-coating, pre-baking, photolithography, and development of photoresist are performed on the polymer substrate to obtain a patterned photoresist layer. Electron beam evaporation or magnetron sputtering is performed on the patterned photoresist layer, and the photoresist is stripped off to obtain a metal recording contact layer. S4: Spin-coating and drying of a biocompatible flexible polymer material on the metal recording contact layer to obtain an intermediate polymer isolation layer; S5: A second photoresist spin coating, pre-baking, photolithography, and development are performed on the polymer isolation layer to obtain a patterned photoresist layer. Electron beam evaporation or magnetron sputtering is performed on the patterned photoresist layer, and the photoresist is stripped off to obtain a metal electrical signal shielding layer. S6: Spin-coating and pre-drying of a biocompatible flexible polymer material are performed on the metal electrical signal shielding layer to obtain an LED polymer transfer layer. S7: The micro-LED is transferred to the target position of the LED polymer transfer layer by contact laser transfer to obtain the LED chip layer. S8: A third spin coating, pre-baking, photolithography, and development of SU8 negative photoresist are performed on the LED polymer transfer layer to obtain a patterned photoresist layer, and windows are opened at the positive and negative electrodes of the LED to obtain an LED polymer encapsulation layer. S9: Perform a fourth spin coating, pre-baking, photolithography, and development of photoresist on the LED polymer encapsulation layer to obtain a patterned photoresist layer. Perform electron beam evaporation or magnetron sputtering on the patterned photoresist layer and then peel off the photoresist to obtain a metal stimulation contact layer. S10: Spin-coating and drying of a biocompatible flexible polymer material on the metal stimulation contact layer to obtain a polymer outer layer. S11: Perform a fifth photolithography on the polymer outer layer, and use electron beam evaporation or magnetron sputtering to deposit an aluminum metal sacrificial layer onto the polymer encapsulation layer, exposing the aluminum metal sacrificial layer and the area where the electrode is located. S12: Perform plasma etching on the aluminum metal sacrificial layer and the area where the electrode is located to create windows in the metal recording contact layer, the metal electrical signal shielding layer and the metal stimulation contact layer. S13: Dissolve the aluminum metal sacrificial layer and peel it off to obtain the thin film electrode layer; S14: Prepare a clean substrate for later use; S15: Using photolithography and SU8 negative photoresist on the substrate prepared in step S14, prepare an SU8 mold with a larger shape than the thin film electrode layer. S16: Prepare polydimethylsiloxane for later use; S17: Place the SU8 mold on the uncured polydimethylsiloxane, and after drying, obtain a PDMS mold with a thin film electrode layer shape; S18: Prepare a temperature-controlled shape memory polymer (SMP) solution; S19: Place the thin film electrode layer obtained in step S13 into the PDMS mold, then pour the prepared SMP solution into the PDMS mold and smooth it out. After photocuring the SMP with ultraviolet light with a wavelength of 365 nanometers, remove it to obtain a flexible implantation probe with variable rigidity and flexibility at different temperatures.

9. The method for preparing the rigid-flexible, multifunctional optogenetic implantable probe according to claim 8, characterized in that, Step S7 is as follows: In step S6, micro-LEDs grown on a sapphire substrate are attached to the surface of the LED polymer transfer layer, and laser transfer is performed at the target location. The surface temperature during transfer is 110℃, and the laser energy is 4.88 × 10⁻⁶. 5 W / cm 2 The duration is 1ms. After the transfer is completed, the LED chip layer is obtained, and the LED polymer transfer layer is completely cured by step heating.

10. A multifunctional optogenetic implantable electrode, characterized in that: Including one or more flexible, multifunctional optogenetic implantable probes as described in any one of claims 1-8.

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