Neuromorphic visual interface system for recovering pattern recognition capability of blind animal, preparation method and application

Abstract

The invention relates to the field of damaged vision recovery of artificial retinas, and particularly discloses a preparation method of a neuromorphic visual interface for recovering the pattern recognition capability of a blind animal. The interface is composed of a photo-thermal assembly, a photoelectric assembly and an electrode array. The photo-thermal assembly is dispersed in a continuous medium, can rapidly and transversely transfer a thermal signal, and is used for repairing the rapid extraction process of an animal visual pathway on a graphic contour; the electrode arrays are located on the upper surface and the lower surface of the photoelectric assembly, can vertically transmit electric signals in a delayed mode and correspond to the follow-up pattern detail machining process of a visual path. The interface also reproduces a central-peripheral activation-inhibition effect formed by retinal horizontal / bipolar cell transverse / longitudinal signal transmission, and realizes multi-channel signal connection with a visual center. The technology is mature, processing is simple, an artificial system which is highly matched with animal optic nerve signals and functions is developed, the artificial system is different from existing light magical vision, and recovery of the pattern recognition function is achieved.

Description

Technical Field

[0001] The present invention relates to the technical fields of biomedical engineering and neural interface technology, and particularly relates to the preparation of a neuromorphic highly adaptable optic nerve interface and its application in restoring the graphic recognition function of an animal model with degenerative retinopathy. Background Art

[0002] The research on artificial vision can be traced back to the last century. In 2010, the first artificial retina prosthesis was approved for marketing, and representative products such as Argus II in the United States, AG Alpha AMS in Germany, and II in France, etc. Such prostheses have cumbersome external devices and complex intraocular signal receiving and processing devices, resulting in their being very bulky and the surgery being complex, increasing the possibility of adverse side effects. The retina prostheses disclosed in CN115778630A and CN114028712A have made improvements in aspects such as device structure and signal transmission mode, but essentially still belong to this category. In the latest research, researchers construct a wireless electronic nerve interface through light-responsive materials to avoid the physical connection between the implanted electrodes and external devices, thereby effectively realizing remote control and device simplification, such as the ultrasonic piezoelectric module and optoelectronic gel respectively disclosed in CN115154902A and CN116585534A. This breakthrough has made the artificial retina implantable in a true sense, but its disadvantages are also very obvious, that is, the resolution is extremely low, only forming delocalized phosphenes and unable to complete the process of visual pattern recognition. The main reason for this phenomenon is that the existing nerve interfaces only adopt a simple multi-electrode array structure and cannot achieve multi-channel signal connection and high adaptability with the animal visual center. Such as CN103301576A and CN109350847A, etc. The increase in the number of these electrodes not only cannot improve the visual pixels, but also causes signal crosstalk between the electrodes, prompting the formed phosphenes to fuse together in an unreadable manner. In addition, these electrodes cannot process these signals in the decoding mode of the nervous system and often activate countless neurons without distinction, causing disorders in biological signals. In fact, the graphic clarity is determined by the information processing mode of retinal neurons rather than the electrode pixels. Adding functional components on the basis of the interface electrodes to replicate the signal processing mode of the optic nerve is an inevitable choice for graphic vision restoration. The realization of different visual functions often depends on the formation of visual patterns, and graphic recognition is currently a great obstacle restricting the development of the artificial vision system towards more advanced visual functions. Summary of the Invention

[0003] In view of the dilemmas in the development of existing artificial retina technologies, such as: single structure (simply optimizing the number and size of electrode arrays, lacking functional components for docking with neural signals, resulting in signal crosstalk and phosphene phenomena); single function (only capable of transmitting light intensity signals, lacking the ability to hierarchically process graphic contours and details, and unable to restore advanced visual functions); insufficient signal adaptability (unable to process signals in the decoding manner of the nervous system, unable to form multi-path signal connections with the visual center, activating numerous neurons without discrimination, causing disorders in biological signals); high implantation complexity (the device is bulky and requires complex external equipment, with significant surgical risks and side effects).

[0004] To solve the above problems, the present invention introduces neuromorphic functional components into an electrode array device, designs a visual interface for restoring the graphic recognition ability of blind animals by imitating the dual-path signal processing mechanism of the retina and combining the photothermal-photoelectric synergistic effect. The aim is to provide an artificial retina with spatio-temporal signal separation to achieve the collaborative processing of graphic contours and details; establish highly adaptable multi-path connections with the visual center through three-dimensional bionic design of materials-devices-signals; in addition, the present invention also aims to develop implantable flexible thin-film devices to simplify the process, reduce surgical invasiveness and improve biocompatibility.

[0005] To achieve the above object, according to several aspects of the present invention, the present application provides the following technical solutions:

[0006] The first aspect of the present invention provides a neuromorphic visual interface system for restoring the graphic recognition ability of blind animals, comprising: a photothermal component, dispersed in a continuous medium, capable of generating a primary thermal effect; a photoelectric component, existing in the form of a continuous medium functional thin film, capable of both transmitting thermal signals and delaying the generation of secondary electrical signals; an electrode array, including a light-transmitting electrode and a metal conduction array electrode disposed on the upper and lower surfaces of the photoelectric component. The neural interface is assembled in multiple layers with an electrode-functional layer structure.

[0007] Furthermore, the signal response of the photothermal component is sensitive and has diffusivity. It can repair the fast transmission function of the retina for transmitting high-time-resolution information over a large area through lateral heat diffusion, and is used to simulate the magnocellular pathway of the retina to achieve rapid extraction of graphic contours and distinguish objects from the background. The optoelectronic component and the electrode array structure can vertically transmit the delayed-response electrical signals point-to-point along the upper and lower electrodes to repair the function of the retina for transmitting high-spatial-resolution information with delay, and are used to simulate the parvocellular pathway to transmit fine graphic details. The multi-layer assembled electrode-functional layer structure, in coordination with the light-thermal-electric signals, can also simulate the center-peripheral activation-inhibition formed by the lateral / longitudinal signal transmission of the retinal horizontal / bipolar cells, realizing high-adaptation connection of multi-path signals with the visual center. In addition, the bionic multi-layer structure adapts to the deformation of biological tissues, has small surgical invasiveness and biocompatibility.

[0008] As a further improvement of the above solution, the photothermal component includes a photothermal material that can absorb light energy and efficiently convert it into heat energy.

[0009] Preferably, the core conversion mechanism of the photothermal material includes at least one of local plasma heating, non-radiative relaxation, and molecular thermal vibration, and the materials covered involve metal nanomaterials, semiconductor materials, carbon-based materials, organic materials, and metal derivatives.

[0010] Preferably, the photothermal material is selected from at least one of MXene (transition metal carbides, transition metal sulfides, transition metal nitrides), MOFs, indocyanine green, polypyrrole, polydopamine, fullerenes, carbon black, graphite, graphene, graphene oxide, reduced graphene oxide, carbon nanotubes, black phosphorus, black TiO2, MoO3, MoS2, gold, silver, and copper nanoparticles / wires.

[0011] As some embodiments of the above solution, the photothermal material is MXene, and the lateral heat diffusion coefficient is greater than 0.5 mm 2 / s, the thermal response time is in the millisecond level, and the thermal signal diffusion range can cover 81 pixel points within 142 ms.

[0012] As a further improvement of the above solution, the optoelectronic component includes an organic optoelectronic material that can absorb photons and convert them into electrical energy through a primary or secondary effect. Preferably, the conversion mechanism of the optoelectronic material is selected from at least one of the primary photoelectric effect, the photovoltaic effect, the secondary photothermal-pyroelectric effect, and the photoinduced deformation-flexoelectric effect.

[0013] Preferably, the first-level optoelectronic material is selected from semiconductor conjugated polymers, including at least one of polyacetylene, polythiophene, polypyrrole, polyaniline, polyfluorene, derivatives of the above materials, and perovskite thin film materials; the second-level photo-thermal-electric material is selected from piezoelectric / ferroelectric materials, including one or a composite of several of PVDF, PTFE, P(VDF-TrFE), P(VDF-CFE), P(VDF-CTFE), P(VDF-HFP), P(VDF-TrFE-CFE), P(VDF-TrFE-CTFE), P(VDF-TrFE-HFP), odd nylon, polyacrylonitrile, vinylidene dicyanide and its copolymers, polyurea, polyphenyl cyanate ether, polyvinyl chloride, polyvinyl acetate, polypropylene, polycaprolactone, and small molecule ferroelectrics.

[0014] As some embodiments of the above solution, the photo-thermal-electric material is P(VDF-TrFE), and the delay time of the generated secondary electrical signal ranges from 50 ms to 200 s, and the voltage signal amplitude ranges from 1 mV to 898 mV.

[0015] As a further improvement of the above solution, the material of the array electrode is selected from one or a composite of several of inorganic non-metals, metals, metal oxides, and multiphase material substances; the electrode shape is one or a composite of several of circular, rectangular, triangular, and trapezoidal; the transparent electrode is selected from one or more of ITO, FTO, nanosilver wires, and metal grid conductive films.

[0016] As a further improvement of the above solution, the interface realizes the bionic of the retinal structure through multi-layer assembly and adapts to the deformation of biological tissues. Specifically, the lowermost layer is a flexible transparent polymer substrate; the second-lowermost layer is a transparent electrode; the third-lowermost layer is a functional layer, and the functional layer is a composite film of a photo-thermal material and an optoelectronic material; the uppermost layer is an array electrode.

[0017] Preferably, the flexible transparent polymer substrate is selected from one or more of PET, PI, PC, PMMA, PDMS, and hyperbranched polymers.

[0018] As some embodiments of the above solution, the mass ratio of the photo-thermal component to the optoelectronic component is 0-2 wt.%, and the thickness of the functional layer film is 10 nm-100 μm; the array electrode is gold nanoparticles, the unit size of the electrode is 50 μm-1 cm, the array spacing is 1 / 5-1 / 3 of the unit size, and the shape is circular; the transparent electrode is ITO, the light transmittance is ≥80%, and the film thickness is z185 nm; the flexible transparent polymer substrate is PET, and the film thickness is 100 μm;

[0019] As some embodiments of the above solution, under the synergistic effect of primary photothermal and secondary pyroelectric signals, the neuromorphic interface generates a thermal signal of 0.4 - 67 °C under 808 nm near-infrared light stimulation, and further converts it into an electrical signal after 50 ms. The generated voltage is 1 - 898 mV, stimulating retinal nerve cells or the visual center to restore the graphic recognition function.

[0020] Preferably, the range of the stimulation light intensity is 40 - 1084 mW / cm 2 , and the frequency range is 0.01 - 3.3 Hz.

[0021] The second aspect of the present invention provides a preparation method of a neuromorphic visual interface, and the method includes the following steps:

[0022] Step 1, preparation of the functional layer: Mix the photothermal material (MXene nanosheets) and the photo-thermo-electric material (P(VDF-

[0023] TrFE)) in a proportion of 0 - 2 wt.%, disperse them in a solvent, and prepare a slurry with a concentration of 1 - 50 mg / mL;

[0024] Step 2, assembly of the transparent electrode: Form a film on a flexible substrate through a casting process and dry it at 50 °C for 6 - 24 hours;

[0025] Step 3, processing of the array electrode: Prepare a metal electrode on the surface of the functional layer by using a mask plate in combination with a micro-nano processing technology, with a thickness of 50 - 500 nm;

[0026] Step 4, device cutting: Cut it into a target size according to the requirements of the application scenario.

[0027] Preferably, the dispersion solvent of the functional layer is selected from at least one of N,N-dimethylformamide (DMF), acetone, and 2-butanone; the casting process is selected from at least one of the spin coating method and the casting method; the micro-nano processing technology is selected from at least one of evaporation, photolithography, chemical vapor deposition, and magnetron sputtering; the device size ranges from the millimeter scale to the centimeter scale.

[0028] Specifically, the MXene nanosheets are prepared by a selective etching method: Mix 2 g of LiF and 40 mL of hydrochloric acid solution in a Teflon beaker and stir for 15 minutes, then slowly add 2 g of MAX phase Ti3AlC2 and stir at 35 °C for 24 hours to remove the Al layer, and then wash and exfoliate by centrifugation until the pH is greater than 6; the P(VDF-TrFE) is prepared by direct purchase or gas-phase free radical copolymerization method; the functional layer is directly formed on the surface of the transparent electrode by the spin coating method, and the spin coating speed is 2000 - 5000 rpm; cover the mask plate, and evaporate gold nanoparticles onto the surface of the functional layer by plasma sputtering to form an array electrode.

[0029] The third aspect of the present invention provides an application system of a neuromorphic vision interface. The application includes parameters and effects.

[0030] As a further improvement of the above application, the application parameters of the light stimulation module are: wavelength 808 nm, light intensity 657 mW / cm 2 , light pulse width 10 s (frequency 0.1 Hz); the application size of the interface is 1 cm * 1 cm (cellular level) or 1 mm * 2 mm (implanted into the subretinal space of animals).

[0031] As a further improvement of the above application, the application effects include adaptability, biological function, and system integration and expansion.

[0032] Furthermore, the surgical invasiveness is reduced through a flexible multi-layer structure design (total thickness < 200 μm), which is suitable for different animal models and does not require external complex equipment.

[0033] Preferably, the animal models are selected from rodents and primates.

[0034] Preferably, the cytotoxicity and biocompatibility of the nerve interface are verified by live / dead cell staining (AO / PI) and MTT method; the implantation adaptability and long-term biological stability of the interface are verified by fundus imaging and optical coherence tomography (OCT).

[0035] Furthermore, the biological function communicates with in vitro nerve cells through the interface, and responds to the contour and detail signals of the light pattern; it is implanted into the subretinal space of animals to verify the light response and the accuracy of pattern recognition.

[0036] Preferably, the constructed nerve cells are mouse neuroblastoma cells (N2A) and fluorescence-enhanced calmodulin N2A cell line (GCaMP6-expressed N2A).

[0037] Preferably, the constructed blind animal models are selected from at least one of hereditary retinal degeneration rats RCS, ABCA4, Tub, RHO, Mertk, Rpgr, Crb1, Rd1 / Rd10 (Pde6b), RP2, Best1, Tyr, and sodium iodate-induced model rats.

[0038] Furthermore, the nerve interface can be integrated into an artificial retina or a brain-machine interface system, and extended for the treatment of degenerative diseases (such as retinitis pigmentosa) or nerve stimulation repair.

[0039] The fourth aspect of the present invention provides a test method for a neuromorphic vision interface, including:

[0040] (1) Electrical signal detection: The response amplitude (1-898 mV) and response time (50 ms-200 s) of the delayed electrical signal are recorded using a semiconductor tester and an electrode array;

[0041] (2) Thermal signal calibration: Use a high-precision infrared thermal imager to monitor the lateral diffusion range of the photothermal component (142ms covers 81 pixels) and the temperature changes of specific pixels;

[0042] (3) Optical-thermal-electrical signal testing: Build an integrated collaborative testing system that combines electrical testing, thermal testing, optical components, timing components, electronic shutters, and probe stations to simultaneously test the response differences of thermal and electrical signals.

[0043] (4) In vitro cell signaling test: The cells are incubated and cultured on the neural interface, and the synaptophysin expression and calcium ion influx of the cells are detected by immunofluorescence staining or calcium ion probe.

[0044] Preferably, a point light source is used to test the signal connection of multiple channels, and an "E"-shaped dot matrix light source is used in combination with calcium imaging to test the pattern outline and detail recognition.

[0045] (5) In vivo behavioral and electrophysiological verification: light-dark box and pupil reflex verification of the restoration of the animal's visual sensitivity; trapezoidal water maze test to evaluate the pattern recognition accuracy and response speed of the implanted animals; electroretinogram (ERG) and visual evoked potential (VEP) to verify the complete restoration of the visual pathway.

[0046] In some in vivo implantation examples, blind mice implanted with the neural interface of the present invention achieved pupil constriction rates exceeding 90%. The water maze test demonstrated recognition accuracy (≥80%) and response speed (seeking time ≤3 seconds) for square / triangular grating pattern outlines and horizontal / vertical striped grating pattern details. The VEP signal amplitude was ≥100 μV and remained stable for three months. This invention achieves breakthrough progress in artificial vision by mimicking the neural encoding of retinal image formation activity. Its beneficial effects are as follows:

[0047] 1. A neuromorphic electronic interface was designed, which was innovatively modeled after the working principles and imaging characteristics of the natural retina. This approach breaks through the limitations of artificial retinal phosphenes and restores the pattern recognition ability of blind animals. Specifically, it simulates the dynamic overall information acquisition of the retinal magnocellular pathway and the static precise information filling of the parvocellular pathway, pioneering a photothermal (lateral rapid thermal diffusion)-photoelectric (longitudinal delayed electrical signal) dual-pathway signal synergy mechanism to achieve spatiotemporal signal separation; it reproduces the retinal "center-peripheral activation-inhibition" mechanism and forms a multi-pathway, highly adaptable signal connection with the visual center. For the first time, hierarchical processing of graphic contours and details is achieved, avoiding the phosphene fusion problem of traditional electrodes.

[0048] 2. It has excellent material device functions and expandable manufacturing processes. First, the lateral thermal diffusion rate of MXene (covering 81 pixel points in 142 ms) far exceeds that of traditional electrodes, supporting fast signal acquisition; combined with P(VDF-TrFE) and array electrodes, it endows the device with wireless near-infrared regulation and high-spatial-resolution signal transduction capabilities, enabling precise nerve activation. Second, the signals of the device are adjustable. By adjusting the ratio of photothermal / photoelectric materials (0 - 2 wt.%), near-infrared light parameters (light intensity, frequency), it can adapt to the requirements of different pathological models and application scenarios. In addition, using standardized micro-nano processing technologies such as spin coating and magnetron sputtering, the yield is high, the cost is controllable, and the cost can be reduced by up to 90% compared with traditional prostheses (the cost of a single piece is less than 100 yuan). The single-piece size supports customization from millimeter level (1 mm 2 ) to meter level (1 m 2 ), and the electrode size supports customization from micron level (50 μm) to centimeter level (1 cm), with arbitrary variable shapes.

[0049] 3. The three-dimensional biocompatible structure can reduce invasion and surgical risks. The total thickness of the flexible multi-layer architecture (PET / ITO / functional layer / gold electrode) is <200 μm, which is close to the multi-layer structure and mechanical properties of the natural retina; the size can be adjusted arbitrarily, the implantation incision is as low as 1 mm, the operation is simple, and the implantation time is less than 30 min; fundus imaging and OCT show that it can be closely attached to the upper and lower layer structures of the subretinal space, and the implantation stability is >3 months, without adverse symptoms such as dislocation, folding, and inflammation; MTT / AO-PI verification shows that the cell survival rate >95%, with almost no cytotoxicity.

[0050] 4. Combining the above advantages, the present invention can simplify the clinical translation path: a. It can restore the complex and advanced functions of vision. In animal model experiments, the pupil reflex recovery rate ≥90%, and the graphic recognition accuracy rate ≥80%, reaching the clinically acceptable threshold; b. Wireless near-infrared regulation, without external equipment, has great advantages in surgical adaptability and maturity compared with traditional prostheses, the operation is simple, and the risk is greatly reduced; c. High implantation stability and good biocompatibility, greatly reducing implantation risks; d. The preparation process of the interface is mature, with high yield, low cost, and can be customized, which is conducive to clinical adoption and translation.

[0051] 5. Have the potential for good multi-scenario application expansion: Compatible with rodent / primate models, adaptable to various retinal diseases such as RP and AMD, applicable to the functional repair of degenerative retinal diseases; By replacing the photothermal material (such as black phosphorus), full-spectrum response from 400 - 1550 nm can be achieved, which can enhance and improve human vision; The multi-path signal adaptation mechanism provides a new paradigm for visual-neural interaction, can be integrated into the brain-computer interface system to improve the decoding efficiency of neural signals; Provide a tool platform for neural stimulation and repair in visual signal encoding and neural plasticity research; The establishment of this bionic vision principle model also opens up an idea for the application of neural networks in electronic information, machine vision algorithms, digital analog circuits, etc.

[0052] The present invention realizes the leap from light intensity perception to pattern recognition for the first time, provides a transformative solution for the treatment of degenerative retinal diseases, and the relevant technical indicators meet the requirements for clinical transformation (ISO13485 standard), promoting the development of artificial retinas and contributing to the development of artificial vision systems with more advanced visual functions. Brief Description of the Drawings

[0053] Figure 1 It is a schematic diagram of the design idea of the present invention and the principle of the neuromorphic interface for repairing graphic visual function;

[0054] Figure 2 It is the working principle of the electronic device in the neuromorphic interface, the device structure, and the physical diagrams of a series of devices with different resolutions and dot matrix electrode sizes prepared by micro-nano processing technology;

[0055] Figure 3 It is the result diagram of contour extraction and detail supplementation of the two modes of thermal signal and electrical signal in the neuromorphic interface during pattern recognition;

[0056] Figure 4 It is the signal transduction between the neuromorphic interface and nerve cells and the recognition effect diagram of the pattern "E" during their co-culture period;

[0057] Figure 5 It is a schematic diagram of the visual water maze for training and testing the pattern recognition effect of rats after implanting the neuromorphic interface. Detailed Description of the Invention

[0058] In order to deepen the understanding of the present invention, the implementation methods of the present application will be further described in detail below in conjunction with the drawings and examples. Obviously, the drawings and examples described are only partial displays of the present application and are only used to further illustrate the present invention. They cannot limit the scope of protection required by the present invention. Based on the drawings and examples in this application, non-essential changes and adjustments obtained by those skilled in the art without making creative work, as well as equivalent changes or substitutions made based on the technical solution of the present invention, all fall within the scope of protection required by this application. Figure 1 As shown, given the extremely low resolution of existing visual neural interfaces, which can only produce delocalized phosphenes and are unable to perform visual pattern recognition, the present invention designs a neuromorphic visual interface that restores pattern recognition capabilities in blind animals, modeled on the principles of natural retinal imaging. A photothermal component generates a sensitive, laterally diffusive primary thermal effect to simulate the retinal magnocellular pathway, restoring the ability to transmit high-temporal-resolution information over a large area from photoreceptors to neural circuits, enabling instant contour extraction and distinguishing objects from background. The optoelectronic component, in the form of a continuous dielectric functional film, transmits thermal signals and delays the generation of secondary electrical signals. Transparent electrodes and metal conductive array electrodes, arranged on the upper and lower surfaces of the optoelectronic component, transmit slow-response electrical signals vertically from point to point along the upper and lower electrodes, simulating the parvocellular pathway, restoring the animal retina's ability to transmit high-spatial-resolution information with time delay, and supplementing the details of interest. This multi-layer assembly, combining multiple array electrodes with a functional layer structure, also synergizes the central-peripheral activation-inhibition mechanism of lateral / vertical signal transmission from horizontal / bipolar cells in the retina, achieving highly adaptable multi-pathway signal connections with the visual center. The present invention addresses the issues of topological signal connection and functional matching between the electronic system and the nervous system. It adds functional components to the interface electrodes to replicate the signal processing mode of the optic nerve, giving the artificial retina pattern recognition capabilities.

[0059] Example 1:

[0060] This embodiment provides a solution for realizing the graphic recognition function of an artificial vision system.

[0061] To achieve the above functions, the electronic interface involved is required to have at least two characteristics: one is to be able to transmit information both horizontally and vertically, and the other is to be able to identify and output two differential signals, fast and slow. Therefore, this embodiment designs a photothermal-pyroelectric device, which has a photothermal primary effect and a photo-thermal-electric secondary effect, in which the thermal signal and the electrical signal can be transmitted horizontally and vertically respectively. The secondary effect is always triggered when the primary effect has been completed, forming a time difference between the fast and slow signals, such as Figure 1As shown, the optic nerve interface designed in this embodiment replaces the functions of the outer retinal cells and the optic nerve pathway.

[0062] Example 2:

[0063] This embodiment provides a preparation method of the light-responsive material.

[0064] In a possible embodiment, photothermal signal conversion is carried out by MXene (a class of two-dimensional transition metal carbides, nitrides or carbonitrides). The MXene nanosheets are prepared by a selective etching method. Specifically, 2 g of LiF and 40 mL of hydrochloric acid solution are mixed and stirred in a Teflon beaker for 15 minutes, then 2 g of MAX phase Ti3AlC2 is slowly added, and the Al layer is removed by stirring at 35 °C for 24 hours. After that, washing and exfoliation are carried out by centrifugation until the pH is greater than 6.

[0065] In a possible embodiment, photothermal signal conversion is carried out by graphene oxide (GO). The GO nanosheets are obtained by commercial purchase or prepared by the improved Hummer's method. The preparation process can be roughly divided into three processes: pre-oxidation, re-oxidation, and cleaning and exfoliation.

[0066] In a possible embodiment, pyroelectric signal conversion is carried out by P(VDF-TrFE). P(VDF-TrFE) is prepared by direct purchase or gas-phase free radical copolymerization.

[0067] In a possible embodiment, pyroelectric signal conversion is carried out by P(VDF-HFP). The used P(VDF-HFP) is prepared by suspension polymerization or emulsion polymerization. Specifically: first, the reaction kettle is evacuated and replaced with an inert gas (such as nitrogen) 3 times to remove oxygen; then the monomer mixture of VDF and HFP, solvent (water or N-methylpyrrolidone), emulsifier (ammonium perfluorooctanoate) or initiator (ammonium persulfate or benzoyl peroxide) are added. After that, the temperature is raised to 60–80 °C, the pressure is maintained, and the reaction is carried out for 6-24 hours. After the reaction is completed, it is first cooled to room temperature, the residual gas is released, and then the polymer is separated by precipitation (such as adding methanol), filtered and washed with solvent (such as water / methanol) for many times, and vacuum dried (60–80 °C, 24 hours) to obtain a white solid product.

[0068] For the convenience of understanding this application and shortening the length, in the subsequent examples, MXene and P(VDF-TrFE) are used as representatives to show the properties and functions of the photothermal material and the pyroelectric material.

[0069] Example 3:

[0070] This embodiment provides a structural design and a preparation method of the electronic device in the neuromorphic interface.

[0071] The device structure is as follows Figure 2 shown. A transparent electrode and an array of metal electrodes are respectively constructed on the upper and lower surfaces of the photo-thermal-electric functional thin film. Preparation of the functional layer thin film: First, the photo-thermal MXene and the pyroelectric P(VDF-TrFE) powder are mixed evenly, and then formulated into a solution, stirred at room temperature for 24 hours, spread evenly on the substrate, and dried at 50 °C for 6 hours.

[0072] In a possible embodiment, the photo-thermal-pyroelectric thin film device is prepared by a spin coating process. The mixed powder is dispersed in 2-butanone to formulate a solution of 2 mg mL -1 . It is coated on a flexible indium tin oxide (ITO) substrate at 3000 rpm by a spin coater. After drying to form a film, a gold electrode array is evaporated on its surface through a mask plate. The typical thickness of the functional thin film is nanoscale.

[0073] In a possible embodiment, the photo-thermal-pyroelectric thin film device is prepared by a casting process. The mixed powder is dispersed in DMF to formulate a solution of 50 mg mL -1 . It is coated on a flexible ITO substrate by drop casting. After drying to form a film, a gold electrode array is evaporated on its surface through a mask plate. The typical thickness of the functional thin film is micron scale.

[0074] The size and shape of the gold electrode array evaporated on the thin film surface through the mask plate are not specifically limited. In a possible embodiment (such as Figure 2 ), the array electrodes are circular or square, and the array size can be 1 cm, 2 mm, 500 μm, 250 μm, 50 μm, etc.

[0075] Example 4

[0076] This example provides the performance parameters of the output electrical signal and thermal signal of the bionic optic nerve interface.

[0077] In this example, the light source used is 808 nm near-infrared light, and the selectable input light intensities are 40, 247, 463, 657, 874, and 1084 mW cm -2 . The light stimulation frequencies are 0.01, 0.02, 0.03, 0.1, 0.2, 0.3, 1.0, 2.0, and 3.3 Hz. The test results show that as the light intensity gradually increases and the stimulation frequency decreases, the output voltage and temperature gradually increase.

[0078] In a possible embodiment, the MXene and P(VDF-TrFE) powders are mixed at a mass ratio of 1 wt.%, and the light intensity is 1084 mW cm -2, when the optical frequency is 0.01 Hz, the maximum output voltage can reach 508 mV, and the maximum temperature change is 60 °C; the lower limit of the response at the fastest frequency of 3.3 Hz is 247 mW cm -2 , and the corresponding output voltage is 1.2 mV, and the temperature change is 0.4 °C.

[0079] In a possible embodiment, MXene and P(VDF-TrFE) powders are mixed at a mass ratio of 2 wt.%, and the light intensity is 1084 mW cm -2 , when the optical frequency is 0.01 Hz, the maximum output voltage can reach 898 mV, and the maximum temperature change is 67 °C; the lower limit of the response at the fastest frequency of 3.3 Hz is 247 mW cm -2 , and the corresponding output voltage is 3 mV, and the temperature change is 0.7 °C.

[0080] Example 5:

[0081] In this example, the imaging characteristics of the photothermal signal and pyroelectric signal of the neural interface, as well as the contour extraction and detail supplementation of the two modes during the pattern recognition process, were demonstrated (as Figure 3 ), all tests were performed using a 1 wt.% sample, and unless otherwise stated, the test conditions were a light intensity of 657 mW cm -2 , and a frequency of 0.1 Hz.

[0082] In a possible embodiment, a semiconductor tester and an infrared thermal imager were used in combination to synchronously collect the photothermal signal and pyroelectric signal of the electronic interface. The results showed that the electrical signal response would appear several seconds after the thermal signal response, and this delay was always maintained during continuous switching, indicating that the thermal and electrical signals in the electronic interface exhibited fast and slow characteristics respectively.

[0083] In a possible embodiment, in order to simulate the continuous change recognition of light from dark to bright by the visual system, the continuous change response of the electronic interface to light intensities ranging from 0, 40, 247, 463, 657, 874 to 1084 mW cm -2 was characterized. The results showed that at a time interval of 2 s, the photothermal response could clearly distinguish the light intensity change from 0 to 40 mW cm -2 , while when the stimulation time interval was extended to 15 s, the optoelectronic response could only distinguish light changes greater than 247 mW cm -2 , indicating that the thermal response had higher sensitivity (faster response) compared to the electrical response.

[0084] In a possible embodiment, the light source was quickly moved and scribed on the surface of the electronic interface, and the thermal imager was used to capture its trajectory, showing that the response sensitivity of the photothermal signal could reach the millisecond level.

[0085] In a possible embodiment, the diffusion paths of the optothermal signal and pyroelectric signal of the electronic interface are characterized by a semiconductor tester and infrared thermal imaging. A point light source with a diameter of 2 mm is used as the signal input source. In the central region of the optothermal response, 10 pixel points are simultaneously activated, and within a very short time of 142 ms, the signal diffuses from the center to 81 pixel points around. For the pyroelectric (second-order opto-thermal-electric) response, except for the weak signals at the edges, basically only 2-3 pixel points are activated and there is no change over time. This shows that the thermal signal undergoes lateral diffusion and has a low imaging resolution, while the electrical signal only conducts vertical signal transmission and has a high imaging resolution.

[0086] In summary, the characteristics of the thermal signal are fast response speed (high time resolution), high sensitivity, and can be transmitted laterally, but the imaging spatial resolution is low; the characteristics of the electrical signal are slow response speed (low time resolution), low sensitivity, but can perform accurate point-to-point transmission for high-spatial-resolution imaging.

[0087] In a possible embodiment, combining the characteristics of the above two signals in the electronic device, the image recognition process of the electronic interface is demonstrated through a panda pattern (as Figure 3 shown). It can be seen that the optothermal response can successfully extract the overall blurred contour of the panda, while the electrical response can perform high-resolution imaging of the details of the panda. Combining the two, only a very small number of electrodes are needed to supplement the details, and the overall imaging only depends on the thermal effect of the optothermal material.

[0088] Example 6:

[0089] In this embodiment, the signal transduction between the neuromorphic interface and nerve cells and the corresponding graphic signal transmission effect are verified (as Figure 4 shown). The constructed nerve cells are mouse neuroblastoma cells (N2A) and a fluorescent enhanced calmodulin N2A cell line (GCaMP6-expressed N2A). The culture medium is DMEM containing 10% fetal bovine serum and 1% penicillin / streptomycin, and the culture environment is a 5% CO2 atmosphere and a 37°C water circulation constant temperature and humidity incubator. The culture medium is changed daily during the culture period, and subculture is carried out when the cells grow and fuse to 80%-90%.

[0090] In a possible embodiment, N2A cells were seeded on the surface of a thin-film electronic interface and cultured for 5 days, with light stimulation for 30 seconds every day. Then, the cells were fixed with 4% paraformaldehyde. The cells were stained with a rabbit synaptophysin monoclonal antibody and a FITC (fluorescein isothiocyanate)-labeled goat anti-rabbit IgG antibody. Immunofluorescence images were taken with a confocal laser scanning microscope. The experimental results showed that, compared with the control group, the expression of synaptophysin in the cells cultured on the neuromorphic interface was significantly increased. Synaptophysin is an indispensable membrane protein in synaptic vesicles and is closely related to the formation of synapses and the transmission of nerve signals during the development of the nervous system. The increase in its expression indicates that the electronic interface has a significant impact on the transmission of nerve signals. Obviously, there is a signal transduction process between the two.

[0091] In a possible embodiment, GCaMP6-N2A cells were seeded on the surface of a neuromorphic interface and cultured in a confocal dish for 24 hours. Then, the change in the intracellular calcium fluorescence intensity of the cells was detected under light stimulation. The results showed that, compared with the pure cell control group, the intracellular calcium fluorescence intensity of the cells co-cultured with the nerve interface increased significantly under light irradiation stimulation, that is, the phenomenon of calcium ion influx occurred. Calcium ions, as neurotransmitters for information exchange between cells, the change in their fluorescence intensity directly indicates that the neuromorphic interface has successfully transduced the light signal to nerve cells, forming the exchange and flow of information.

[0092] In a possible embodiment, an electronic interface was co-cultured with GCaMP6-N2A cells, and then the signal transduction study between graphic information and nerve cells was carried out under the coverage of a dot matrix photomask plate with an "E" pattern ( Figure 4 ). The results showed that the pure photothermal response speed in the electrode-free area was faster. Except for the cells in the "E" pattern light stimulation area, the cells in the other non-illuminated areas also had obvious signal responses, which was mainly caused by the lateral diffusion of heat. And as the stimulation time prolonged, the photothermal response of the cells gradually decayed to 0, which was due to the conversion of heat to electricity and the dissipation of heat. For the optoelectronic signals in the electrode area, the light stimulation area showed an increasing signal response over time. Combining the two, the intracellular calcium response along the "E" pattern was finally shown. This is completely consistent with the center-periphery activation-inhibition formed by the horizontal / bipolar cell lateral / longitudinal signal transmission at the retinal level.

[0093] The above results indicate that the neuromorphic interface can successfully conduct signal transduction with nerve cells and is consistent with the previous bionic design results, enabling high-resolution graphic information recognition.

[0094] Example 7:

[0095] The implantation effect of the optic nerve interface was evaluated in this embodiment. Five SD rats (Sprague-Dawley rats, a species from the United States) were prepared for each of the normal group, the model group, and the implantation group. The rats were blinded by sodium iodate.

[0096] The optic nerve interface designed in this embodiment replaces the Figure 1 function of the outer retinal cells. Therefore, the subretinal space was selected as the implantation site. All operations were carried out under an ophthalmic surgical microscope in a sterile room. First, the rats were anesthetized by intraperitoneal injection of pentobarbital sodium. Then, an incision was made 2 mm behind the corneal limbus of the rats to expose the sclera. An incision of about 1 mm was made at the sclera, and 1-2 μL of normal saline was quickly and carefully injected through a microinjector to leave enough space for the implantation of the nerve morphology interface. The flexible optic nerve interface was cut into a size of 1*2 mm, disinfected, and then implanted.

[0097] In a possible embodiment, the implantation position and implantation safety of the optic nerve interface were observed by fundus imaging and optical coherence tomography (OCT). The results showed that the optic nerve interface was located in the subretinal space, and 3 months after implantation, the thin-film optic nerve interface did not show symptoms such as shrinkage, wrinkling, inflammation, and other retinal abnormalities.

[0098] In a possible embodiment, the signal transmission of the optic nerve interface in the visual nervous system was characterized by visual evoked potential (VEP). After anesthesia, the rats were craniotomized, and recording electrodes and reference electrodes were implanted in their visual cerebral cortex. The ground electrode was placed subcutaneously at the tail. Statistical analysis of the potential amplitude of VEP showed that the evoked potential of the rats in the normal group was about 25 μV, and that of the rats in the implantation group was about 100 μV. This indicates that the signal generated by the bionic optic nerve interface can be transmitted through retinal ganglion cells to the visual cortex of the brain, causing corresponding visual evoked potentials.

[0099] In a possible embodiment, the photosensitive effect and signal transmission of the optic nerve interface were characterized by a pupil reflex experiment. Before the experiment, the rats needed to be dark adapted in a dark environment for more than 2 hours, and the whole process was recorded by an infrared camera. Normal rats showed almost no response under near-infrared light stimulation because rats cannot recognize near-infrared light; the pupil contraction rate of the model rats increased slightly, which may be due to the destruction of the retina by sodium iodate, causing oxidation; different from the above two, the rats implanted with the optic nerve interface showed very obvious pupil contraction, with a contraction rate as high as 90%. This shows that our artificial visual system has near-infrared light responsiveness, and the signal it generates can be perfectly received by the nervous system, providing direct evidence for repairing the optic nerve signal transduction pathway.

[0100] In a possible embodiment, through a trapezoidal water maze behavioral experiment (such as Figure 5As shown in [figure], the visual pattern recognition effect of the optic nerve interface at the in vivo level was tested. The graphic outline was represented by triangular and square graphic gratings, and the graphic details were represented by horizontal and vertical square stripes. The water maze training lasted for 7 days, with 4 tasks per day and 10 trials per task. Different patterns were trained alternately on the left and right. Under white light stimulation, normal rats showed excellent recognition effects, with the graphic recognition rate and the success rate of finding the platform approaching 100%. They could quickly find the dark platform within about 3 seconds. For blind rats, the corresponding indicators decreased significantly, the probability of not being able to find the platform increased, the time to find the platform increased to 10 seconds, and the selection of patterns was random and almost indistinguishable. Under near-infrared light, normal rats and blinded rats could hardly recognize near-infrared light, while implanted rats showed good near-infrared light responses. Whether it was for the differences in graphic outlines or local details, they could be well recognized. This shows that through our design, the graphic recognition ability of rats was effectively restored.

Claims

1. A neuromorphic vision interface system for restoring the graphic recognition ability of blind animals, characterized in that, The system includes: A photothermal component, dispersed in a continuous medium, generating a primary thermal effect, with sensitive signal response and lateral diffusivity, used to simulate the magnocellular pathway of the retina, repair the function of animals to transmit high-time-resolution information over a large area from photoreceptor cells to neural circuits, achieve instant contour extraction, and distinguish an object from the background; An optoelectronic component, existing in the form of a continuous medium functional thin film, capable of both transmitting thermal signals and delaying the generation of secondary electrical signals; An electrode array, including a transparent electrode and a metal conduction array electrode disposed on the upper and lower surfaces of the optoelectronic component, vertically transmitting the delayed electrical signals point-to-point along the upper and lower electrodes, used to simulate the parvocellular pathway, repair the function of animals' retinas to transmit high-spatial-resolution information with a time delay, and supplement graphic details of interest; Multilayer assembled in an electrode-functional layer structure, and under the synergistic action, it can simulate the center-periphery activation-inhibition formed by the horizontal / bipolar cell lateral / longitudinal signal transmission of the retina, and achieve a highly adaptable connection of multi-path signals with the visual center.

2. The neuromorphic vision interface system for restoring the graphic recognition ability of blind animals according to claim 1, wherein: The photothermal component includes a photothermal conversion material, which is selected from one or a combination of several of MXene (transition metal carbides, transition metal sulfides, and transition metal nitrides), metal-organic framework compounds (MOFs), indocyanine green, polypyrrole, polydopamine, fullerenes, carbon black, graphite, graphene, graphene oxide, reduced graphene oxide, carbon nanotubes, black phosphorus, black titanium dioxide (TiO2), molybdenum trioxide (MoO3), molybdenum disulfide (MoS2), gold, silver, copper nanoparticles / wires, and derivatives of the above materials, and its transverse thermal diffusion coefficient is greater than 0.5 mm 2 / s, the thermal response time is in the millisecond level, and the thermal signal diffusion range can cover 81 pixel points within 142 ms.

3. The neuromorphic vision interface system for restoring the graphic recognition ability of blind animals according to claim 1, wherein: The optoelectronic component contains organic optoelectronic conversion materials, including primary optoelectronic conversion materials: polyacetylene, perovskite, polythiophene, polypyrrole, polyaniline, polyfluorene, and derivatives of the above materials; secondary photo-thermal-electric conversion materials: poly(vinylidene fluoride) [PVDF], poly(tetrafluoroethylene) [PTFE], poly(vinylidene fluoride-trifluoroethylene) copolymer [P(VDF-TrFE)], poly(vinylidene fluoride-chlorofluoroethylene) copolymer [P(VDF-CFE)], poly(vinylidene fluoride-chlorotrifluoroethylene) copolymer [P(VDF-CTFE)], poly(vinylidene fluoride-hexafluoropropylene) copolymer [P(VDF-HFP)], poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) terpolymer [P(VDF-TrFE-CFE)], poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) terpolymer [P(VDF-TrFE-CTFE)], poly(vinylidene fluoride-trifluoroethylene-hexafluoropropylene) terpolymer [P(VDF-TrFE-HFP)], odd nylon, polyacrylonitrile, vinylidene dicyanide and its copolymers, polyurea, polyphenyl cyanate ether, polyvinyl chloride, polyvinyl acetate, polypropylene, polycaprolactone, a small molecule ferroelectric, or a composite of several of them. The delay time of the generated electrical signal ranges from 50 ms to 200 s, and the voltage signal amplitude ranges from 1 mV to 1000 mV.

4. The neuromorphic vision interface system for restoring the graphic recognition ability of blind animals according to claim 1, wherein: The material of the array electrode is selected from one or a composite of several of inorganic non-metals, metals, metal oxides, and multiphase materials; the unit size of the electrode is 50 μm - 1 cm, the array pitch is 1 / 5 - 1 / 3 of the unit size, the electrode shape is one or a composite of several of circular, rectangular, triangular, and trapezoidal, the transparent electrode is selected from one or several of indium tin oxide (ITO), fluorine-doped tin oxide (FTO), nanosilver wires, and metal grid conductive films, the light transmittance is ≥80%, and the film thickness is in the micro-nano scale.

5. The neuromorphic vision interface system for restoring the graphic recognition ability of blind animals according to claim 1, wherein: Multilayer assembly structure, the bottom layer is a flexible transparent polymer substrate, selected from one or more of polyethylene terephthalate (PET), polyimide (PI), polycarbonate (PC), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), hyperbranched polymer; the second last layer is a light-transmitting electrode; the third last layer is a functional layer, and the functional layer is a composite film of a photothermal material and a photoelectric material, and the composite ratio of the two is 0-2 wt.%, and the film thickness is 10 nm-100 μm; the top layer is an array electrode.

6. A method for preparing a neuromorphic visual interface for restoring the pattern recognition ability of blind animals, characterized in that: For preparing the visual interface system according to any one of claims 1-5, the method comprises the following steps: Step 1: Preparation of the functional layer, mixing the photothermal material (MXene nanosheets) and the photo-thermo-electric material (P(VDF-TrFE)) in a ratio of 0-2 wt.%, dispersing in a solvent, and preparing a slurry with a concentration of 1-50 mg / mL. Step 2: Assembly of the light-transmitting electrode, forming a film on the flexible substrate by a casting process, and drying at 50 °C for 6-24 hours. Step 3: Processing of the array electrode, preparing a metal electrode with a thickness of 50-500 nm on the surface of the functional layer by using a mask plate in combination with a micro-nano processing process. Step 4: Device cutting, cutting into a target size according to the requirements of the application scenario.

7. The preparation method of a neuromorphic vision interface for restoring the graphic recognition ability of blind animals according to claim 6, characterized in that: The photothermal material is MXene nanosheets, prepared by etching Ti3AlC2 with lithium fluoride (LiF) / hydrochloric acid (HCl); the secondary conversion photo-thermo-electric material is P(VDF-TrFE), and the crystallinity is ≥60%; the casting process is selected from at least one of spin coating and casting; the micro-nano processing method is selected from at least one of evaporation, photolithography, chemical vapor deposition, and magnetron sputtering.

8. Application of a neuromorphic vision interface for restoring the pattern recognition ability of blind animals, characterized in that: Using the visual interface described in any one of claims 1-5, signal output is achieved by stimulating with 808nm near-infrared light, and the light intensity range is 40-1084mW / cm 2 , the stimulation frequency is 0.01-3.3Hz, generating a voltage signal of 1-898mV and a temperature change of 0.4-67°C.

9. The application of a neuromorphic visual interface for restoring the pattern recognition ability of blind animals according to claim 8, characterized in that: (1) Significantly increasing the expression of synaptophysin in cells, promoting the calcium ion influx of GCaMP6-N2A cells, and enabling the pattern "E" to cause a response of cells in the form of calcium current under the synergistic action of thermal signals and electrical signals. (2) After implantation into the subretinal cavity of rats, through high-adaptation connection with multi-channel signals in the visual center: inducing the amplitude of visual evoked potential (VEP) ≥100 μV; the pupil contraction rate under near-infrared light stimulation ≥90%; in the trapezoidal water maze behavioral test, the pattern recognition accuracy rate ≥80%, and the platform searching time ≤3 seconds.

10. An electronic system for restoring the graphic recognition ability of blind animals, characterized in that, The application of the visual interface with pattern recognition function according to any one of claims 1-5 in artificial retina, brain-computer interface, neurodegenerative diseases, nerve stimulation and repair.

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