Method for manufacturing a retinal prosthesis and retinal prosthesis

Abstract

The application provides a preparation method of a retinal prosthesis and the retinal prosthesis, and is applied to the preparation of a retinal prosthesis integrated circuit (IC) chip. The application prepares a light-controlled nanowire array as an electric stimulation signal switch of the IC chip, and integrates the nanowire and the IC chip by using a flexible electrode. When a certain region of the nanowire array is irradiated by a light signal, the impedance of the irradiated region of the nanowire array is significantly reduced, the electric pulse of the connected IC chip is output through the low-impedance region, and then the optic nerve cells on the retina are stimulated, the bottleneck of low photoelectric conversion efficiency is overcome, the difficulty of high channel number electric stimulation needing high-density IC chip pins and packaging is overcome, and the retinal prosthesis pixel and the stimulation effect are greatly improved.

Description

Technical Field

[0001] This application relates to the field of medical implant devices, and in particular to a method for preparing a retinal prosthesis and the retinal prosthesis itself. Background Technology

[0002] Visual reconstruction via implantation of visual prostheses is a cutting-edge, clinically proven solution for long-term, effective restoration of basic vision. It utilizes microelectronic devices as its core, directly stimulating intact parts of the visual pathway (such as residual bipolar cells and ganglion cells) through implanted microelectrode arrays, thereby converting external image information into specific nerve impulses that are transmitted to the visual center. Depending on the implantation location of the stimulating microelectrodes, existing visual prostheses are mainly classified into three types: retinal, optic nerve, and visual cortex prostheses. The implantation location is increasingly closer to the visual center, and the difficulty is also increasing. Retinal prostheses, which use cameras to capture external image signals or directly convert them into electrical pulses using photoelectric chips, stimulate the retina with a microelectrode array, are primarily used for retinitis pigmentosa (RP) and age-related macular degeneration (AMD). This prosthesis technology is the most mainstream, mainly divided into extraretinal and subretinal implantation. To date, approximately 400 implants have been performed in developed countries such as Europe and the United States. Most patients can achieve light perception and judge simple movements, while a small number can recognize large text and simple graphics. However, the resolution is insufficient, and the visual effect is limited, largely due to the current encapsulation and integration technology of the implants. The complexity of electrodes, chips, and integrated packaging in retinal prostheses increases dramatically with pixel counts, leading to enormous power consumption and information processing pressures, poor reliability, and limited practicality. For electrical stimulation of the retina, each electrode requires an independent IC chip with a single output drive. Although some studies have employed 1:4 time-division multiplexing, the reliable connection of numerous pins, power consumption requirements, signal processing, and encoding / decoding pose a significant burden, severely limiting pixel count increases. While subretinal prostheses (photovoltaic type) have a simpler implant structure and can easily achieve over 1000 photosensitive pixels, their drawbacks are also significant. Limited by photoelectric conversion efficiency and the energy supply within the eye, the photocurrent is too weak, and the sensing wavelengths are limited. Ordinary light intensity or wavelengths sensitive to the human eye cannot directly induce photic hallucinations, requiring hundreds of times the amplification of the IC chip or the use of modulated infrared laser pulses, greatly increasing system complexity and power consumption, limiting the expansion of photosensitive pixels, and causing heat dissipation and long-term safety issues.

[0003] Therefore, the current encapsulation and integration technology for retinal prostheses still needs to be improved to enhance performance and reduce costs. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the purpose of this application is to provide a method for preparing a retinal prosthesis and a method for encapsulating and integrating a retinal prosthesis, in order to solve the problem that existing retinal prostheses rely on photocurrent.

[0005] To achieve the above objectives, this application adopts the following technical solution:

[0006] In a first aspect, this application provides a method for fabricating a retinal prosthesis, applied to the fabrication of a retinal prosthesis integrated circuit (IC) chip, the method comprising:

[0007] Fabrication of IC chips;

[0008] Fabrication of flexible electrodes;

[0009] A nanowire array is integrated on the first end face of the IC chip, and each nanowire of the nanowire array is electrically connected to the IC chip on the first end face. When the nanowire array is illuminated by light within a preset frequency range, the impedance of the nanowire array region illuminated by the light signal decreases significantly, thereby increasing the stimulation current of the IC chip output pin in the illuminated nanowire array region. The increased stimulation current is higher than the nerve cell stimulation threshold of the retina. The flexible electrode is electrically connected to the second end face of the IC chip to obtain an integrated chip.

[0010] Alternatively, a substrate with the nanowires can be prepared, and the IC chip, flexible electrode, and nanowire substrate can be sequentially integrated together to obtain the integrated chip; wherein the nanowire micropillar array in the nanowire array can be either thin-film encapsulated or exposed.

[0011] Secondly, this application also provides a retinal prosthesis, manufactured by any of the methods described above, the device comprising:

[0012] Integrated chips, including:

[0013] IC chips;

[0014] A nanowire array is disposed on the first end face of the IC chip and is integrated with the IC chip. Each nanowire of the nanowire array forms a microelectrode on the first end face and is electrically connected to the IC chip. It is used to reduce the impedance of the nanowire array region irradiated by the light signal, so as to enhance the stimulation current of the irradiated nanowire array region.

[0015] A flexible electrode is integrated on the second end face of the IC chip, and the electrodes on the flexible electrode are connected one-to-one with the nanowires on the nanowire array.

[0016] Alternatively, the integrated chip may include:

[0017] The flexible electrode;

[0018] A substrate integrated on the first end face of the flexible electrode, wherein the nanowire array is disposed on the substrate;

[0019] An IC chip integrated on the second end face of the flexible electrode. Attached Figure Description

[0020] Figure 1 A flowchart of one embodiment of the method for preparing a retinal prosthesis provided in this application;

[0021] Figure 2 A flowchart of another embodiment of the method for preparing the retinal prosthesis provided in this application;

[0022] Figure 3 A schematic diagram illustrating the implantation of the retinal prosthesis provided in this application;

[0023] Figure 4 This is a structural schematic diagram of the retinal prosthesis provided in this application;

[0024] Figure 5 A schematic diagram of an integrated chip package provided in this application;

[0025] Figure 6 This is a schematic diagram of another package for the integrated chip provided in this application. Detailed Implementation

[0026] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present application, and not all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present application.

[0027] The terms "first," "second," etc., in the specification, claims, and accompanying drawings of this application are used to distinguish different objects, not to describe a specific order. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or apparatus that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products, or apparatuses.

[0028] In this document, the term "embodiment" means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of this phrase in various places throughout the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0029] In this application, "at least one" refers to one or more, and "multiple" refers to two or more. In this application, "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone, where A and B can be singular or plural. The character " / " generally indicates that the preceding and following related objects are in an "or" relationship. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single or plural items. For example, at least one of a, b, or c can represent: a, b, c, a and b, a and c, b and c, or a, b, and c, where each of a, b, and c can be an element itself or a set containing one or more elements.

[0030] It should be noted that the term "equal to" in the embodiments of this application can be used with "greater than" to apply to technical solutions adopted when "greater than", and can also be used with "less than" to apply to technical solutions adopted when "less than". It should be pointed out that when "equal to" is used with "greater than", it is not used with "less than"; conversely, when "equal to" is used with "less than", it is not used with "greater than". In the embodiments of this application, "of", "corresponding (relevant)", and "corresponding" can sometimes be used interchangeably. It should be noted that when their distinction is not emphasized, their intended meanings are consistent.

[0031] Currently, existing retinal prostheses are generally implanted outside the eyeball. They function by converting photoelectric signals into electrical impulses that stimulate the optic nerve cells in the retina. However, these prostheses are dependent on light intensity, and the limited photocurrent means they cannot provide sufficient electrical energy to the implant, thus limiting the pixel size of the retinal prosthesis.

[0032] For the above issues, please refer to Figures 1-4 This application provides a method for fabricating a retinal prosthesis, applied to the fabrication of a retinal prosthesis integrated circuit IC chip 1002, such as... Figure 1 and Figure 4 As shown, the method includes:

[0033] Step 101: Prepare IC chip 1002.

[0034] For example, the IC chip 1002 is a system-on-chip (SoC), also known as a system-on-a-chip. In this application, it is specifically a highly integrated, low-power mixed-signal system-on-a-chip. This enables the driving of a high number of channels of electrodes under conditions of limited area, poor heat dissipation, and complex electromagnetic environment.

[0035] In some embodiments, the fabrication of the IC chip 1002 includes:

[0036] A radio frequency transceiver circuit, a power management circuit, a controller, a drive circuit, a signal detection circuit, and a sensor circuit are integrated on the first chip; the first chip is thinned to obtain the IC chip 1002.

[0037] The controller comprises two parts: a global controller and a local controller. The global controller is used for command parsing and execution, while the local controller primarily receives and stores stimulus information and controls the output of the stimulus current. The drive circuit primarily outputs a specified stimulus current according to a specific digital timing sequence. The signal detection circuit primarily performs temperature and power detection. The sensor circuit includes a temperature sensor and a power sensor. The temperature sensing module primarily monitors on-chip temperature information and provides timely overheating alarms. The power detection module primarily monitors the chip's energy consumption.

[0038] For example, the IC chip 1002 integrates a controller, a drive circuit, a signal detection circuit, and a sensor circuit, enabling the IC chip 1002 to perform corresponding circuit control to achieve full control of the high-channel-count flexible electrode. The IC chip 1002 performs functions including stimulation signal output (e.g., outputting 9 voltage waveforms to 9 zones of the nanoarray, each with adjustable voltage), data acquisition (temperature, power, impedance, etc.), and corresponding digital functions (control, data encoding / decoding).

[0039] Understandably, the output of the stimulation signal is not limited to 9 channels and can be adjusted according to actual needs, such as 4 channels, 16 channels, 25 channels, etc.

[0040] For example, the IC chip 1002 is polished using mature industrial technologies such as chemical mechanical polishing (CMP), which can reduce its thickness to more than one hundred micrometers or even tens of micrometers, at which point the silicon wafer will have a certain degree of flexibility.

[0041] As can be seen, in this embodiment, the integration of the corresponding circuit functions on the IC chip 1002 is achieved.

[0042] In some embodiments, please refer to Figure 4After the IC chip 1002 is fabricated, the method includes:

[0043] A metal interconnect 200 is prepared, wherein the metal interconnect 200 is a flexible printed interconnect, one end of the metal interconnect 200 is connected to the output pin of the IC chip 1002, and can be connected to discrete components such as resistors, capacitors, and diodes or communication antennas on the IC chip 1002 substrate.

[0044] As can be seen, in this embodiment, the driving circuit of the 9 partitions is partitioned and set on the IC chip 1002. The IC chip 1002 is connected to the antenna 400 and discrete components. There are only a dozen or so connection lines in total, and the integration complexity is low. It can be optimized by drawing on industrial experience to improve reliability.

[0045] In some embodiments, please continue reading Figure 4 After obtaining the integrated chip 100, the method further includes:

[0046] The antenna 400 is fabricated, and multiple discrete components are integrated on the antenna 400, wherein the antenna 400 is connected to the multiple discrete components, and the multiple discrete components are used for filtering and data transmission and reception; the multiple discrete components are connected to the metal connection line 200.

[0047] For example, the antenna 400 is a coil with a certain curvature, which can be arranged around the lens 20 to conform to the internal curvature of the eyeball 10 and improve biocompatibility.

[0048] For example, the antenna 400 coil is equipped with corresponding wireless power supply (rectification and filtering, voltage regulation, biasing, clock signal recovery, etc.) and data transceiver circuits.

[0049] As can be seen, in this embodiment, energy reception and data transmission and reception are achieved through antenna 400.

[0050] Step 102: Prepare flexible electrodes.

[0051] For example, the flexible electrode has a certain degree of flexibility and can be bent accordingly according to the shape of the retina to adapt to the shape of the retina and enhance biocompatibility.

[0052] In some embodiments, the fabrication of the flexible electrode includes:

[0053] A flat, flexible PCB substrate is obtained through processing. The flexible PCB substrate is either a polyimide substrate or Parylene (Parylene is a protective polymer material that can be vapor-deposited under vacuum. It has good penetration and can form a transparent, uniform, and pinhole-free insulating coating inside, under, and around components, providing a complete and high-quality protective coating. It is a waterproof, mildew-proof, and salt spray-proof material). Pads and patterned metal conductors are printed on both sides of the flexible PCB substrate.

[0054] The flexible electrode is based on flexible microelectromechanical systems (MEMS) electrode technology. It utilizes a self-fabricated flat medical-grade polyimide (PI) substrate on a flexible PCB, employing techniques such as screen printing and micro-contact printing to fabricate patterned metal interconnects and pads on both sides. Its advantages include flexible customization and the ability to further reduce thickness, typically to tens of micrometers, or even below 50 micrometers.

[0055] Step 103: Generate a nanowire array 1001 on the first end face of the IC chip 1002.

[0056] Each nanowire of the nanowire array 1001 is electrically connected to the IC chip 1002 on the first end face. When the nanowire array 1001 is irradiated with light within a preset frequency range, the impedance of the area of ​​the nanowire array 1001 irradiated by the light signal decreases significantly, thereby increasing the stimulation current of the output pin of the IC chip 1002 in the irradiated area of ​​the nanowire array 1001. The increased stimulation current is higher than the nerve cell stimulation threshold of the retina.

[0057] It is understandable that the IC chip 1002 can determine the region of the irradiated nanowire array 1001 by detecting the impedance value, so as to supply power to the corresponding region.

[0058] For example, the nanowire can be a nanowire unit, which may include multiple nanowires or only a single nanowire.

[0059] For example, when the nanowire array 1001 is irradiated by the light signal, the impedance value is significantly reduced, basically reaching 2-3 orders of magnitude, which enhances the conductivity of the irradiated nanowire array 1001 region, realizing the switching function, so that the IC chip 1002 and the electrode between the irradiated nanowire array 1001 regions are connected, thereby generating electrical pulses to stimulate the optic nerve cells, so as to image on the retina and restore some vision to the patient.

[0060] In some embodiments, generating a nanowire array 1001 on the first end face of the IC chip 1002 includes:

[0061] A nano-matrix mask is deposited on the IC chip 1002, and then a nanopillar array is obtained by silicon etching of the nano-matrix mask. A nanowire array 1001 is obtained by ion doping or by modifying the surface of the nanopillars with photoelectric response materials. Alternatively, a nanowire template is prepared, which includes a nanowire substrate and a hole model region disposed on the nanowire substrate. The hole model region includes multiple holes. The nanowire array 1001 is grown on the nanowire substrate through the multiple holes of the nanowire template.

[0062] For example, since the nanowire array 1001 is obtained through masking and etching, the nanowire array 1001 is integral with the IC chip 1002 and cannot be separated. The masking process also involves sequentially forming microelectrodes, depositing a second metal, reacting with cesium salt vapor to form a top electrode, and finally etching to obtain the corresponding shape of the nanowire array 1001.

[0063] As can be seen, in this embodiment, the nanowire array 1001 was obtained through processes such as masking and etching.

[0064] For example, a nanowire template is prepared by chemical vapor deposition, wherein the nanowire template is a porous alumina nanowire template, the porous alumina nanowire template includes a substrate and a pore pattern region disposed on the substrate, the pore pattern region including a plurality of pores; a nanowire array 1001 is grown on the substrate of the nanowire template through the plurality of pores of the nanowire template.

[0065] For example, multiple pores on the pore model region are arranged in an array for growing a nanowire array 1001.

[0066] For example, the plurality of holes are through holes, meaning that the substrate is penetrated by the plurality of holes.

[0067] As can be seen, in this embodiment, the goal of obtaining the nanowire array 1001 through the template is achieved, which is faster than the process of mask re-etching.

[0068] In some embodiments, growing a nanowire array 1001 on the substrate of the nanowire template through a plurality of holes in the nanowire template includes:

[0069] A first metal is deposited on the substrate at the bottom of each hole of the nanowire template as a microelectrode; a second metal is electrodeposited on the microelectrode; the nanowire template after the second metal deposition is placed in a tube furnace and a nanowire array 1001 template with photoelectric response characteristics is generated by chemical vapor deposition; a metal layer is sputtered on the nanowire array 1001 template to form a top electrode, so as to form a nanowire array 1001 on the nanowire template.

[0070] For example, since the substrate is penetrated by the plurality of holes, the microelectrode is parallel to the bottom of the substrate during the formation of the microelectrode, thereby enabling the microelectrode to be electrically connected to the IC chip 1002 and the flexible electrode.

[0071] For example, the nanowires are grown by CVD (template-assisted chemical vapor deposition); the nanowire template is removed by dry or wet etching to form a nanowire array 1001.

[0072] For example, the substrate has the same curvature as the IC chip 1002, and an ultrathin nanowire array 1001 with a certain curvature (only tens of micrometers thick) can be fabricated based on a 3D template to suit a specific retinal shape.

[0073] For example, the material of the microelectrode is gold or platinum; the material of the second metal is tin or bismuth; and the metal layer is indium tin or other metals or metal compounds, without being limited to a single material.

[0074] In the specific implementation, metallic gold is first deposited on the nanowire template as a microelectrode. Then, metallic tin reactant is used as a precursor and reacted with cesium salt vapor in the tube furnace, so that a perovskite nanowire array 1001 is deposited on the metallic tin to obtain the nanowire array 1001 template. Then, an indium tin oxide layer is sputtered on the perovskite nanowire array 1001 to form a top electrode. Finally, the hole model area on the nanowire array 1001 template is etched away to obtain the substrate on which the nanowire array 1001 is disposed.

[0075] Step 104: Electrically connect the flexible electrode to the second end face of the IC chip 1002 to obtain the integrated chip 100.

[0076] For example, the flexible electrode and the IC chip 1002 are integrated by soldering.

[0077] As can be seen, in this embodiment, the integrated structure of IC chip 1002 + nanowire array 1001 and the two-layer structure of flexible electrode are realized.

[0078] In some embodiments, please refer to Figure 2and Figure 4 The method further includes:

[0079] Step 105: Prepare a substrate with the nanowires, and integrate the IC chip 1002, flexible electrode and nanowire substrate together in sequence to obtain the integrated chip 100.

[0080] Among them, the nanowire micropillar array in the nanowire array 1001 can be either thin-film encapsulated or exposed.

[0081] For example, the substrate of the nanowire array 1001, the flexible electrode, and the IC chip 1002 can be integrated by soldering.

[0082] For example, the positional relationship of the substrate of the nanowire array 1001, the flexible electrode and the IC chip 1002 is as follows: the substrate of the nanowire array 1001 is on top (i.e., facing the lens), the flexible electrode is in the middle, and the IC chip 1002 is on the bottom (i.e., facing the retina).

[0083] As can be seen, this embodiment achieves the integration of the substrate with the nanowire array 1001, the flexible electrode, and the IC chip 1002.

[0084] In some embodiments, after obtaining the integrated chip 100, the method further includes:

[0085] The retinal prosthesis is obtained by sequentially encapsulating at least one organic thin film layer 500 and at least one inorganic thin film layer 600 on the integrated chip 100.

[0086] For example, the encapsulation may be a full cover, exposing only the corresponding electrodes to achieve electrical stimulation.

[0087] In specific implementation, such as Figure 5 As shown, for ultra-thin retinal prostheses, the integrated chip 100 is encapsulated using an organic / inorganic composite multilayer thin film (e.g., Figure 5 The nanowire array 1001, IC chip 1002, and flexible electrode 1003 shown, for example, are composed of a total of 5 layers of organic and inorganic thin films, which can be co-deposited under vacuum at room temperature with a thickness of <5μm, achieving at least 5 years of life (after immersion in physiological saline and accelerated aging test at 87℃). The biocompatibility of the device after flexible encapsulation meets the implantation requirements; the specific method is existing technology and will not be further elaborated here.

[0088] In some embodiments, please refer to Figure 6 ,and Figure 5The difference is that the nanowire array 1001 is exposed outside the organic thin film layer 500 and the inorganic thin film layer 600 and is not wrapped by the organic thin film layer 500 and the inorganic thin film layer 600. This ensures that the impedance of the irradiated area of ​​the nanowire array 1001 is smaller when it is irradiated by light, while the IC chip 1002 and the flexible electrode 1003 are wrapped in the organic thin film layer 500 and the inorganic thin film layer 600.

[0089] For example, the inorganic thin film is biocompatible, specifically including Al2O3 thin film, SiO2 thin film, SiC chip 1002 thin film, TiO2 thin film or SiN thin film, etc., without being limited to a single type. The inorganic thin film not only has good biocompatibility, but also has good ability to isolate water and oxygen.

[0090] For example, the thickness of the organic thin film layer 500 is 0.5-60 μm, and further, the thickness of the organic thin film layer 500 can be 1-25 μm, 5-20 μm, or 30-55 μm; the thickness of the inorganic thin film layer 600 is 20-100 nm, and further, the thickness of the inorganic thin film layer 600 can be 30-90 nm, 50-70 nm, or 60-80 nm. Suitable thickness settings not only ensure good bonding between the layers but also achieve better water and oxygen isolation capabilities. The biocompatible pyreline film of the organic thin film layer 500 can be a pyreline with an N-type, C-type, D-type, or HT-type structure.

[0091] For example, the organic film and the inorganic film can be stacked alternately, or one or more organic films can be set first, followed by one or more inorganic films; no unique limitation is made here.

[0092] As can be seen, in this embodiment, the enhanced biocompatibility through encapsulation and the formation of a multi-layered dense structure by stacking with the organic thin film layer 500 can significantly extend the water and oxygen permeation path, effectively protecting the device body. By setting the inorganic thin film, a better ability to isolate water and oxygen can be obtained.

[0093] In summary, the method for fabricating a retinal prosthesis in this application uses a nanowire array 1001 as a switch between the IC chip 1002 and the flexible electrode. When a certain area of ​​the nanowire array 1001 is irradiated by a light signal, it is equivalent to closing the switch between the integrated chip 100 corresponding to the irradiated area of ​​the nanowire array 1001 and the upper electrode of the flexible electrode, thereby forming an electrical circuit and generating an electrical pulse to stimulate the optic nerve cells on the retina. This completely eliminates the dependence on photocurrent and is beneficial for pixel amplification.

[0094] In some embodiments, this application also provides a retinal prosthesis, manufactured by any of the above-described methods, the device comprising:

[0095] The integrated chip 100 includes: an IC chip 1002; a nanowire array 1001 disposed on the first end face of the IC chip 1002 and integral with the IC chip 1002, wherein each nanowire of the nanowire array 1001 forms a microelectrode on the first end face and is electrically connected to the IC chip 1002, and is used to reduce the impedance of the area of ​​the nanowire array 1001 irradiated by the light signal, so as to enhance the stimulation current of the irradiated area of ​​the nanowire array 1001; and a flexible electrode integrated on the second end face of the IC chip 1002, wherein the electrode on the flexible electrode is connected to the nanowire on the nanowire array 1001 in a one-to-one correspondence.

[0096] Alternatively, the integrated chip 100 may include: the flexible electrode; a substrate integrated on the first end face of the flexible electrode, on which the nanowire array 1001 is disposed; and an IC chip 1002 integrated on the second end face of the flexible electrode.

[0097] As can be seen, in this embodiment, the nanowire array 1001 acts as a switch between the IC chip 1002 and the flexible electrode. When a certain area of ​​the nanowire array 1001 is irradiated by a light signal, it is equivalent to closing the switch between the integrated chip 100 corresponding to the irradiated area of ​​the nanowire array 1001 and the upper electrode of the flexible electrode, thereby forming an electrical circuit and generating an electrical pulse to stimulate the optic nerve cells on the retina. This completely eliminates the dependence on photocurrent and is beneficial for pixel amplification.

[0098] In some embodiments, the IC chip 1002 also integrates a controller, a drive circuit, a signal detection circuit, and a sensor circuit.

[0099] For example, the controller comprises two parts: a global controller and a local controller. The global controller is used for command parsing and execution, while the local controller's main function is to receive and store stimulus information and control the output of the stimulus current. The drive circuit's main function is to output a specified stimulus current according to a specific digital timing sequence. The signal detection circuit mainly performs temperature and power detection. The sensor circuit includes a temperature sensor and a power sensor. The temperature sensing module's main function is to monitor on-chip temperature information and promptly issue an overheating alarm. The power detection module's main function is to monitor the chip's energy consumption.

[0100] For example, the controller includes control of the control function drive circuit and reception of data detected by the signal detection circuit, as well as data transmission function.

[0101] For example, the driving circuit is used to drive the electrodes on the flexible electrode.

[0102] For example, the signal detection circuit is used to detect the impedance of the nanowires, as well as the power and charge balance of the entire system.

[0103] For example, the sensor circuit includes a temperature sensor for detecting the temperature of the implant and transmitting the data to the signal detection circuit for analog-to-digital conversion. The signal detection circuit then sends the data to the controller, which transmits it to the antenna 400 via the metal connection line 200, and finally transmits it to an external device via the antenna 400.

[0104] As can be seen, in this embodiment, the integration of the corresponding circuit functions on the IC chip 1002 is achieved.

[0105] In some embodiments, please continue reading Figure 4 The device also includes a metal connecting wire 200, one end of which is connected to the controller and the drive circuit.

[0106] For example, the metal connecting line 200 is a flexible PCB, which enables data transmission between the receiving circuit 300 in the antenna 400 coil and the controller on the IC chip 1002.

[0107] In some embodiments, the device further includes:

[0108] Antenna 400 is used to receive external alternating electromagnetic fields to generate an induced electric field;

[0109] Multiple discrete components mounted on the antenna 400 are connected to the other end of the metal connection line 200 for filtering and data transmission and reception.

[0110] For example, the antenna 400 is a coil, and the coil is provided with a receiving circuit 300 composed of multiple discrete components. The receiving circuit 300 is used for filtering and data transmission and reception.

[0111] For example, the receiving circuit 300 includes a filtering circuit, a data transceiver circuit, etc. The filtering circuit filters the electrical energy received and converted by the antenna 400 coil to obtain a stable current to power the IC chip 1002; the data transceiver circuit enables the IC chip 1002 to communicate with the outside.

[0112] As can be seen, energy transmission has been achieved, meeting the power supply requirements of the retinal prosthesis. At the same time, data transmission and reception have been achieved, enabling the implant to communicate with the outside world for implant status monitoring, current regulation, and other purposes.

[0113] In some embodiments, the device further includes a packaging layer for encapsulating the integrated chip 100.

[0114] As can be seen, in this embodiment, the encapsulation layer prevents harmful or easily corrosive or oxidizing materials from coming into contact with the human body, water, and air in the environment.

[0115] In some embodiments, please refer to Figure 5 The encapsulation layer includes at least one organic thin film layer 500 and at least one inorganic thin film layer 600.

[0116] For example, the organic film and the inorganic film can be stacked alternately, or one or more organic films can be set first, followed by one or more inorganic films; no unique limitation is made here.

[0117] As can be seen, in this embodiment, by stacking with the organic thin film layer 500 to form a multi-layered dense structure, the water and oxygen permeation path can be extended to a great extent, effectively protecting the main body of the device. By setting the inorganic thin film, a better ability to isolate water and oxygen can be obtained.

[0118] In some embodiments, please refer to Figure 6 ,and Figure 5 The difference is that the nanowire array 1001 is exposed outside the organic thin film layer 500 and the inorganic thin film layer 600 and is not wrapped by the organic thin film layer 500 and the inorganic thin film layer 600. This ensures that the impedance of the irradiated area of ​​the nanowire array is smaller when it is irradiated by light, while the IC chip 1002 and the flexible electrode 1003 are wrapped in the organic thin film layer 500 and the inorganic thin film layer 600.

[0119] For example, perovskite materials can improve the performance of various optoelectronic devices due to their excellent performance and simple processing. However, their application in biomedicine is limited by their own material defects, mainly lead toxicity and poor long-term stability. However, these defects can be solved by encapsulating perovskite nanowires, thereby enhancing biocompatibility.

[0120] For example, the perovskite nanowires can receive both visible and infrared light, exhibiting low dependence on the type of light, which is beneficial for the daily use of retinal prostheses.

[0121] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application.

Claims

1. A method for preparing a retinal prosthesis, characterized in that, The method for fabricating an integrated circuit (IC) chip for use in retinal prostheses includes: Fabrication of IC chips; Fabrication of flexible electrodes; A nanowire array is integrated on the first end face of the IC chip, with each nanowire of the array electrically connected to the IC chip on the first end face. When the nanowire array is illuminated by light within a preset frequency range, the impedance of the illuminated area of ​​the nanowire array decreases significantly, thereby increasing the stimulation current of the IC chip output pin in the illuminated area. The increased stimulation current is higher than the nerve cell stimulation threshold of the retina. The flexible electrode is electrically connected to the second end face of the IC chip to obtain an integrated chip. Alternatively, a substrate with the nanowires is prepared, and the IC chip, flexible electrode, and nanowire substrate are sequentially integrated together to obtain the integrated chip. The nanowire micropillar array in the nanowire array can be either thin-film encapsulated or exposed. The retinal prosthesis is obtained by sequentially encapsulating at least one organic thin film layer and at least one inorganic thin film layer on the integrated chip; wherein, for the ultrathin retinal prosthesis, the integrated chip is encapsulated by a composite multilayer film composed of organic and inorganic thin film layers; the nanowire array is exposed outside the composite multilayer film, and the irradiated area has lower impedance; the IC chip and the flexible electrode are encapsulated within the composite multilayer film; the thickness of the organic thin film layer is 0.5-60 μm, and the thickness of the inorganic thin film layer is 20-100 nm; the biocompatible phenelzine film of the organic thin film layer includes N-type, C-type, D-type, or HT-type.

2. The method according to claim 1, characterized in that, The preparation of the IC chip includes: Radio frequency transceiver circuits, power management circuits, controllers, drive circuits, signal detection circuits, and sensor circuits are integrated on the IC chip substrate. The IC chip substrate is thinned to obtain the IC chip.

3. The method according to claim 2, characterized in that, After the IC chip is fabricated, the method includes: Prepare a metal interconnect, wherein the metal interconnect is a flexible printed interconnect, one end of the metal interconnect is connected to the output pin of the IC chip, and is also connected to a resistor, capacitor, diode or communication antenna on the IC chip substrate.

4. The method according to claim 3, characterized in that, After obtaining the integrated chip, the method further includes: An antenna is fabricated and multiple discrete components are integrated into the antenna, wherein the multiple discrete components and the antenna are all connected to the other end of the metal connecting wire, and the multiple discrete components are used for filtering and data transmission and reception; Connect the discrete component to the other end of the metal connecting wire.

5. The method according to claim 1 or 2, characterized in that, The first end face of the IC chip integrates a nanowire array, including: A nano-matrix mask is set on the IC chip, and then a nano-pillar array is obtained by silicon etching of the nano-matrix mask. A nano-wire array integrated with the IC chip is obtained by ion doping or by modifying the nano-pillar surface with photoelectric response material. or, A nanowire template is prepared, the nanowire template comprising a nanowire substrate and a hole model region disposed on the nanowire substrate, the hole model region comprising a plurality of holes; A nanowire array is grown on the nanowire substrate through multiple pores in the nanowire template.

6. The method according to claim 5, characterized in that, The process of growing a nanowire array on the substrate of the nanowire template through multiple holes includes: A first metal is deposited as a microelectrode on the substrate at the bottom of each hole of the nanowire template; A second metal is electrodeposited on the microelectrode; The nanowire template after the second metal is deposited is placed in a tube furnace, and a nanowire array template with photoelectric response characteristics is generated by chemical vapor deposition. A metal layer is sputtered onto the nanowire array template to form a top electrode, thereby forming a nanowire array on the nanowire template.

7. The method according to claim 1, characterized in that, The preparation of the flexible electrode includes: A flexible PCB substrate is obtained through processing, wherein the flexible PCB substrate is a polymer material, and the polymer material includes polyimide or Parylene; Pads and patterned metal wires are printed on both sides of the flexible PCB substrate.

8. A retinal prosthesis, characterized in that, The device is manufactured by the preparation method according to any one of claims 1-7, and comprises: Integrated chips, including: IC chips; A nanowire array is disposed on the first end face of the IC chip and is integrated with the IC chip. Each nanowire of the nanowire array forms a microelectrode on the first end face and is electrically connected to the IC chip. It is used to reduce the impedance of the nanowire array region irradiated by the light signal, so as to enhance the stimulation current of the irradiated nanowire array region. A flexible electrode is integrated on the second end face of the IC chip, and the electrodes on the flexible electrode are connected one-to-one with the nanowires on the nanowire array. Alternatively, the integrated chip may include: The flexible electrode; A substrate integrated on the first end face of the flexible electrode, wherein the nanowire array is disposed on the substrate; An IC chip integrated on the second end face of the flexible electrode; The device further includes: a packaging layer for encapsulating the integrated chip; the packaging layer includes at least one organic thin film layer and at least one inorganic thin film layer; The nanowire array is exposed outside the organic thin film layer and the inorganic thin film layer, while the IC chip and flexible electrode are encapsulated within the organic thin film layer and the inorganic thin film layer; The organic thin film layer 500 has a thickness of 0.5-60 μm, and the inorganic thin film layer has a thickness of 20-100 nm; the biocompatible pyreline film of the organic thin film layer includes N-type, C-type, D-type or HT-type.

9. The retinal prosthesis according to claim 8, characterized in that, The IC chip includes: IC chip substrate; Controllers, drive circuits, signal detection circuits, and sensor circuits integrated on an IC chip substrate; The device also includes a metal connecting wire, one end of which is connected to the controller and the drive circuit. Antennas are used to receive external alternating electromagnetic fields and generate induced electric fields. The receiving circuit, mounted on the antenna, is connected to the other end of the metal connecting wire and is used for filtering and data transmission and reception.

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