Million-channel level neural information detection and stimulation dual-mode bidirectional brain-computer interface

Abstract

The application discloses a million-channel-level neural information detection and stimulation dual-mode bidirectional brain-computer interface, and belongs to the technical field of brain-computer interfaces. The brain-computer interface comprises at least two multi-handle bidirectional CMOS probes and a micro interface board which can be used for assembling and integrating multiple multi-handle bidirectional CMOS probes. The multi-handle bidirectional CMOS probe has the functions of dual-mode neural signal detection and electrical stimulation regulation. The multi-handle bidirectional CMOS probe is designed and prepared by using a CMOS process, and the probe adopts a time-division multiplexing signal lead-out strategy. Multiple electrode sites are connected to the same signal lead-out line through controllable switches. By configuring the switch state, only the signal of one site can be transmitted by the lead-out line at the same time. The preparation process with a small line width and the special signal lead-out mode greatly improve the number of electrode sites of the probe. The brain-computer interface realizes the detection of million-channel-level neural electrophysiological signals or electrochemical signals, and meets the demand for precise electrical stimulation regulation.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of brain-computer interface, and particularly relates to a million-channel-level neural information detection and stimulation dual-mode bidirectional brain-computer interface. BACKGROUND

[0002] Brain cognitive function analysis and research on pathogenesis and treatment mechanism of neurological diseases are important scientific problems in the field of brain-computer interface. Understanding the biological basis of brain cognitive functions such as perception, memory, and recognition, especially the specific characteristics at the microscopic neuron level, is of great significance for further understanding brain structure and function, and has a positive driving effect on the development of cognitive science and related disciplines such as artificial intelligence. At the same time, research shows that many neurological diseases such as sleep disorders, insomnia, sleep paralysis, epilepsy, Parkinson's disease, etc. are related to abnormal activities of neurons in the deep brain, and the capture of abnormal activities of neurons can significantly help analyze the causes of diseases and seek treatment methods. The exploration of the above problems cannot be separated from neural information detection tools. Implantable neural probes have been widely used as effective tools for detecting neural signals.

[0003] At present, most neural probes are silicon-based MEMS neural probes with a three-layer structure of an insulating silicon substrate layer, a metal layer, and an insulating layer. In order to improve the biocompatibility and reduce the damage caused during implantation and the serious inflammatory response after implantation, some researchers replace the hard insulating silicon substrate layer with insulating flexible materials such as Parylene, polyimide (PI), etc. to form a flexible neural probe with a three-layer structure of a flexible substrate layer, a metal layer, and a flexible insulating layer. Whether it is a hard silicon-based neural probe or a flexible neural probe, the structure of a single metal layer determines that the number of electrode sites is limited, and the number of electrode sites of a common one will not exceed 128. While the number of neurons in the human brain is estimated to be hundreds of millions, and we also know that whether it is the formation of cognitive function or the induction of disease, it is the huge neuron network that plays a dominant role, not the normal work or abnormal activity of a single neuron, so there is an urgent need for a neural probe with a high number of electrode sites to detect the discharge activities of multiple neurons at the same time.

[0004] For the neural probe, the ways to increase the number of electrode sites include increasing the probe size, reducing the process linewidth, increasing the number of metal layers, using multi-layer metal layer interconnection wiring, or using a time-division multiplexing signal lead-out strategy. By increasing the probe size, the number of electrode sites can be effectively increased, but implantable neural probes must consider the problem of implantation damage, so the probe size is often strictly limited. The process linewidth is largely dependent on the process line hardware equipment, and CMOS process has a clear advantage in linewidth compared to MEMS process. As for multi-layer metal layer interconnection wiring, some researchers have tried it, and this method is suitable for both MEMS process and CMOS process, but is affected by the process linewidth, and the advantage of using CMOS process is more obvious. The time-division multiplexing signal lead-out strategy can only be realized by CMOS process, and its effect on increasing the number of electrode sites is the most obvious. SUMMARY

[0005] To solve the above technical problems, the application provides a million-channel level neural information detection and stimulation dual-mode bidirectional brain-computer interface, which realizes the detection of million-channel level neural electrophysiological signals or electrochemical signals.

[0006] To achieve the above purpose, the technical scheme adopted by the application is as follows:

[0007] A million-channel level neural information detection and stimulation dual-mode bidirectional brain-computer interface, the brain-computer interface comprising at least two multi-shaft bidirectional CMOS probes and a micro interface board that can be used for integration of multiple multi-shaft bidirectional CMOS probes;

[0008] The multi-shaft bidirectional CMOS probe comprises a probe base connected in the axial direction and at least two probe shafts, the probe shafts are provided with electrode site regions, and signal detection sites, electrical stimulation sites and reference electrodes are arranged in the electrode site regions; the multi-shaft bidirectional CMOS probe comprises a plurality of layered structures in the longitudinal axis direction, from bottom to top, the layered structures are a base device layer, at least two intermediate insulating layers, at least one intermediate metal layer, an uppermost metal layer and a surface insulating layer;

[0009] The signal detection sites are connected to the transmission gate switch input contact holes on the base device layer through the metal through holes in the intermediate insulating layer, the metal through hole contact points on the intermediate metal layer, the transmission gate switch output contact holes are connected to the probe pad sites of the multi-shaft bidirectional CMOS probe base through the metal through holes in the intermediate insulating layer, the metal through hole contact points on the intermediate metal layer, the metal through hole contact points on the uppermost metal layer, and the conductive wires of the intermediate metal layer and the uppermost metal layer; the electrical stimulation sites and the reference electrodes are directly connected to the probe pad sites of the multi-shaft bidirectional CMOS probe base through the conductive wires;

[0010] The micro interface board is provided with at least one probe integrated welding area for multi-handle bidirectional CMOS probe integration on the front and back surfaces; the probe pad sites of the probe base are welded with the pad sites in the probe integrated welding area on the micro interface board to realize the integration of the multi-handle bidirectional CMOS probe and the micro interface board.

[0011] Further, the micro interface board is a double-layer circuit structure circuit board, the pad sites in the probe integrated welding area on the circuit board are square with a side length of 100 μm to 200 μm; and the pad sites on the circuit board for connecting with external devices are rectangular with a width of 300 μm to 400 μm and a length of 600 μm to 800 μm.

[0012] Further, the width of the probe handle of the multi-handle bidirectional CMOS probe is 100 μm to 300 μm, and the length is 6 mm to 15 mm; and the number of signal detection sites arranged on each probe handle is at least 1024.

[0013] Further, the signal detection sites are circular with a diameter of 0.5 μm to 15 μm; the electric stimulation sites are rectangular with a length of 50 μm and a width of 20 μm; and the reference electrodes are rectangular with a length of 100 μm and a width of 30 μm.

[0014] Further, when the signal detection sites are used as the electric physiological signal detection sites, the signal detection sites are modified by platinum nanoparticles, carbon nanotubes or gold nanoparticles; and when the signal detection sites are used as the electric chemical signal detection sites, the signal detection sites are modified by platinum nanoparticles, carbon nanotubes or gold nanoparticles and Nafion film or glutamate oxidase, for detecting dopamine and glutamate neurotransmitters.

[0015] Further, the substrate device layer is provided with a transmission gate state storage D flip-flop and a transmission gate switch composed of MOS tubes.

[0016] Further, the intermediate insulating layer is inlaid with metal vias for interconnecting the upper layer signals and the lower layer signals; the metal vias are square vias with a side length of 100 μm to 200 μm, or circular vias with a diameter of 0.5 μm to 15 μm.

[0017] Further, the intermediate metal layer is provided with a plurality of wires, and the two ends of the wires and the positions needing to form effective connections with the metal via contact points of the intermediate insulating layer are provided with metal via contact points.

[0018] Further, the uppermost metal layer is provided with wires, signal detection sites, electric stimulation sites, reference electrodes, probe pad sites and metal via contact points.

[0019] Further, the surface insulation layer covers the uppermost metal layer, and the surface insulation layer at the corresponding positions above the signal detection sites, the electrical stimulation sites, the probe pad sites, and the reference electrodes in the uppermost metal layer is selectively etched to form windows.

[0020] Further, the width of the wire is 0.18 μm~5 μm.

[0021] Further, the metal via contact point is a square contact point with a side length of 100 μm~200 μm or a circular contact point with a diameter of 0.5 μm~15 μm.

[0022] Further, the probe pad site of the multi-shaft bidirectional CMOS probe base is a square with a side length of 100 μm~200 μm.

[0023] Further, the number of signal detection sites connected to the same signal lead wire and probe pad site on the probe shaft is at least two.

[0024] Further, the material of the intermediate insulation layer and the surface insulation layer is one of silicon dioxide, silicon nitride, and silicon oxynitride; the material of the wire, the metal via, the metal via contact point, and the probe pad site of the multi-shaft bidirectional CMOS probe base is copper; the material of the signal detection site, the electrical stimulation site, and the reference electrode is titanium nitride, copper, and a surface modification material, and the surface modification material includes one or more of platinum nanoparticles, carbon nanotubes, gold nanoparticles, Nafion, and glutamic acid oxidase.

[0025] The beneficial effects of the present application are:

[0026] The multi-shaft bidirectional CMOS probe adopts a multi-layer interconnection wiring method and a time-division multiplexing lead-out strategy, and the line width advantage of the CMOS manufacturing process, so that the probe has a high number of electrode sites; the multi-shaft bidirectional CMOS probe integrates neural electrophysiological signal detection and neural electrochemical signal detection, and the probe has a dual-mode detection capability; the multi-shaft bidirectional CMOS probe integrates neural information detection and electrical stimulation regulation function, and can judge the probe implantation position by the detected neural signal to realize precise electrical stimulation regulation; the brain-computer interface can realize million-channel level neural electrophysiological signal or electrochemical signal detection by integrating multiple high-electrode-site-number CMOS probes; the diversification integration of probes with different numbers and different numbers of probe shafts makes the brain-computer interface widely applicable to different animals. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 It is a whole structure schematic diagram of the million-channel level neural information detection and stimulation dual-mode bidirectional brain-computer interface.

[0028] Figure 2 This is a schematic diagram of a multi-layer stack of a multi-handled bidirectional CMOS probe.

[0029] Figure 3 A schematic diagram of the electrode site arrangement on a multi-handled bidirectional CMOS probe;

[0030] Figure 4 A schematic diagram of the gating control circuit for signal detection sites on a multi-handled bidirectional CMOS probe;

[0031] Figure 5 This is a schematic diagram of the cross-section of a multi-handled bidirectional CMOS probe.

[0032] Reference numerals: 1-Miniature interface board, 2-Multi-handled bidirectional CMOS probe, 3-Probe base, 4-Probe handle, 5-Probe pad site, 6-Probe electrode site area, 7-Probe integration soldering area, 8-Pad site on the miniature interface board for integrating probes, 9-Pad site on the miniature interface board for connecting external devices, 10-Base device layer, 11-Intermediate insulating layer, 12-Intermediate metal layer, 13-Top metal layer, 14-Surface insulating layer, 15-Metal via, 16-Wire, 17-Signal detection site, 18-Metal via contact point, 19-Transmission gate state storage D flip-flop, 20-Transmission gate switch, 21-Electrical stimulation site, 22-Reference electrode. Detailed Implementation

[0033] Embodiments of the present invention will now be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the invention. In the following detailed description, numerous specific details are set forth to provide a thorough understanding of the embodiments of the invention for ease of explanation. However, it will be apparent that one or more embodiments may be practiced without these specific details. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concept of the invention.

[0034] As shown in Figure 1 - Figure 2As shown, a million-channel level neural information detection and stimulation double-mode bidirectional brain-computer interface can realize million-channel level neural electrophysiological signal or electrochemical signal detection, and at the same time meet the demand for precise electrical stimulation regulation. The brain-computer interface comprises a micro interface board 1 which can be used for integration of multiple multi-shaft bidirectional CMOS probes, and at least two multi-shaft bidirectional CMOS probes 2. The micro interface board 1 has at least one probe integration welding area 7 for integration of the multi-shaft bidirectional CMOS probes on the front and back surfaces. The probe integration welding area 7 is usually square. The number of pad sites 8 for integrated probes on the micro interface board is consistent with the number of probe pad sites 5 provided on the base of the integrated probe. The multi-shaft bidirectional CMOS probe 2 comprises a probe base 3 and at least two probe shafts 4. The probe pad sites 5 are provided on the probe base 3, and the probe electrode site area 6 is provided on the probe shaft 4. The multi-shaft bidirectional CMOS probe 2 can be integrated on the micro interface board 1 by welding the probe pad sites 5 of the probe base 3 with the pad sites 8 for integrated probes on the micro interface board. The micro interface board 1 can integrate multiple multi-shaft bidirectional CMOS probes 2. The probe electrode site area 6 is provided with a signal detection site 17, an electrical stimulation site 21 and a reference electrode 22. The front and back surfaces of the micro interface board 1 are provided with pad sites 9 on the micro interface board for connecting external devices. The neural signals detected by the signal detection site 17 can be led out to the acquisition device, and the voltage or current generated by the electrical stimulation device can be transmitted to the electrical stimulation site 21, realizing the detection and regulation bidirectional function of the probe.

[0035] The pad sites 8 for integrated probes on the micro interface board are square with a side length of 100 μm to 200 μm. The pad sites 9 on the micro interface board for connecting external devices are rectangular with a width of 300 μm to 400 μm and a length of 600 μm to 800 μm.

[0036] Preferably, the micro interface board 1 is provided with 100 probe integration welding areas 7. The number of probe shafts 4 of the multi-shaft bidirectional CMOS probe 2 is 10, and each probe shaft 4 is provided with 1024 signal detection sites 17. The brain-computer interface has a total of 1024000 signal detection sites 17, which can realize million-channel level neural information detection.

[0037] Figure 2 schematically shows the multi-layer stacked structure of the multi-shaft bidirectional CMOS probe 2.

[0038] The multi-lead bidirectional CMOS probe 2 has high electrode site quantity by using multi-layer interconnection wiring and time division multiplexing, and the probe composition comprises a substrate device layer 10, at least two intermediate insulating layers 11, at least one intermediate metal layer 12, an uppermost metal layer 13, and a surface insulating layer 14; the substrate device layer 10 is provided with a transmission gate state storage D flip-flop 19 and a transmission gate switch 20 composed of MOS tubes; the intermediate insulating layer 11 is arranged between the substrate device layer 10 and the intermediate metal layer 12, between the two intermediate metal layers 12, and between the uppermost metal layer 13 and the intermediate metal layer 12, and the intermediate insulating layer 11 is inlaid with metal vias 15 for signal interconnection of the upper and lower two layers; the intermediate metal layer 12 is located between the two intermediate insulating layers 11, and the intermediate metal layer 12 is provided with a plurality of wires 16, and the two ends of the wire 16 and other positions needing effective connection with the metal vias of the upper and lower intermediate insulating layers are provided with metal via contact points 18, the metal via contact points 18 can form electrical connection with the metal vias 15 in the intermediate insulating layer 11 of the upper or lower layer; the uppermost metal layer 13 is located between the surface insulating layer 14 and the intermediate insulating layer 11, and the uppermost metal layer 13 is provided with the wire 16, a signal detection site 17, an electrical stimulation site 21, a reference electrode 22, a probe pad site 5, and the metal via contact point 18; the surface insulating layer 14 covers the uppermost metal layer 13, and the surface insulating layer 14 at the corresponding positions above the signal detection site 17, the electrical stimulation site 21, the probe pad site 5, and the reference electrode 22 of the uppermost metal layer 13 is selectively etched to form a window.

[0039] Preferably, the electrical stimulation site 21 and the reference electrode 22 are directly connected with the probe pad site 5 through the wire 16; preferably, the signal detection site 17 needs to be connected with the transmission gate switch 20 input contact hole on the substrate device layer 10 through the metal via 15 in the intermediate insulating layer 11 and the metal via contact point 18 on the intermediate metal layer 12 first, and then the transmission gate switch 20 output contact hole is connected with the probe pad site 5 through the metal via 15 in the intermediate insulating layer 11, the metal via contact point 18 on the intermediate metal layer 12, the metal via contact point 18 on the uppermost metal layer 13, and the wire 16 of the intermediate metal layer 12 and the uppermost metal layer 13.

[0040] The number of probe stems 4 of the multi-stem bidirectional CMOS probe 2 is at least two, the width of the probe stem 4 is 100 μm-300 μm, the length is 6 mm-15 mm, and the number of signal detection sites 17 arranged on each probe stem 4 is at least 1024. The length, width, size and number of electrode sites arranged on different probe stems 4 can be designed according to the requirements of the target brain region. The multi-stem bidirectional CMOS probe 2 has signal detection sites 17 and electrical stimulation sites 21 at the same time, and can realize detection and regulation functions at the same time. The probe has bidirectional nature. The signal detection sites 17 on the multi-stem bidirectional CMOS probe 2 can be used as neural electrophysiological signal detection sites or neural electrochemical signal detection sites, and the probe has dual-mode detection capability. The width of the wire 16 is 0.18 μm-5 μm, and the wire 16 is distributed in the middle metal layer 12 and the uppermost metal layer 13. The metal via contact point 18 is a square contact point with a side length of 100 μm-200 μm or a circular contact point with a diameter of 0.5 μm-15 μm, and the metal via contact point 18 is distributed in the middle metal layer 12 and the uppermost metal layer 13. The metal via 15 is a square via with a side length of 100 μm-200 μm or a circular via with a diameter of 0.5 μm-15 μm, and the metal via 15 is distributed in the middle insulating layer 11. The probe pad site 5 is a square with a side length of 100 μm-200 μm.

[0041] The material of the middle insulating layer 11 and the surface insulating layer 14 is one of silicon dioxide, silicon nitride and silicon oxynitride. The material of the wire 16, the metal via 15, the metal via contact point 18 and the probe pad site 5 is copper. The material of the signal detection site 17, the electrical stimulation site 21 and the reference electrode 22 is titanium nitride, copper and surface modification material. The surface material includes platinum nanoparticles, carbon nanotubes, gold nanoparticles, Nafion and glutamate oxidase.

[0042] Figure 3 schematically shows the arrangement of electrode sites on the multi-stem bidirectional CMOS probe 2. Taking a probe stem 4 with 1024 signal detection sites 17 as an example.

[0043] The signal detection sites 17 are circular with a diameter of 0.5 μm to 15 μm. The probe handle 4 has 1024 signal detection sites 17 arranged in 256 rows along the length of the probe handle 4 and 4 columns along the width of the probe handle 4. The electrical stimulation sites 21 are rectangles 50 μm long and 20 μm wide. The probe handle 4 has 64 electrical stimulation sites 21. The reference electrodes 22 are rectangles 100 μm long and 30 μm wide. The probe handle 4 has 32 reference electrodes 22. The probe handle 4 also has 1024 transmission gate switches 20 and 1024 transmission gate state storage D flip-flops 19.

[0044] The 1024 signal detection sites 17 on the probe handle 4 are divided into 32 electrode blocks. Figure 3 (Represented by B1-B32 respectively), every 32 signal detection points 17 along the length of the probe handle 4 constitute an electrode block. Each electrode block also contains 2 electrical stimulation points 21 and 1 reference electrode 22. The 1024 transmission gate state storage D flip-flops 19 on the probe handle 4 are arranged in 256 rows along the length of the probe handle 4 and in 4 columns along the width of the probe handle 4. The 256 transmission gate state storage D flip-flops 19 in each column are cascaded into a 256-bit shift register. Each shift register shares a clock signal. There are a total of 4 256-bit shift registers on the probe handle 4. Figure 3 (Represented as SR1-SR4 respectively).

[0045] Figure 4 schematically illustrates the gating control circuit connection of the signal detection sites 17 on the multi-handle bidirectional CMOS probe 2. For the probe handle 4 shown in Figure 3, the 32 signal detection sites 17 within each electrode block are divided into 4 groups. Each group of 8 signal detection sites 17 shares the same signal lead-out wire 16. That is, the 32 signal detection sites 17 within one electrode block use 4 signal lead-out wires 16 for signal lead-out. The probe handle 4 uses a total of 128 signal lead-out wires 16. Specifically, whether the neural signal detected by the signal detection site 17 is transmitted via the shared lead-out wire 16 depends on the on / off state of the connected transmission gate switch 20. When the transmission gate switch 20 is on, the signal can be transmitted normally; when the transmission gate switch 20 is off, the signal is shielded and cannot be transmitted. The on / off state of the transmission gate switch 20 is controlled by the transmission gate state storage D flip-flop 19.

[0046] Figure 4Taking the electrode site block B1 on the probe handle as an example, the control circuit connection is explained. The four groups of signal detection sites 17 in the electrode block B1 are distinguished by different filling patterns. The eight signal detection sites 17 in the first group are connected to eight transmission gate switches 20. Figure 4 (Represented by TG1, TG5...TG29 respectively) are connected to the same signal lead wire 16, i.e., channel 1 shown in the figure. The output of the D flip-flop 19 stores the state of the 8 transmission gates in the 256-bit shift register SR1. Figure 4 The signals (represented by Q1, Q5...Q29) are connected to the control ports of eight transmission gate switches 20 for control, ensuring that only one transmission gate switch 20 is in the conducting state at any given time, while the other seven transmission gate switches 20 are in the off state. At this time, the neural signal on the signal detection point 17 connected to the transmission gate switch 20 in the conducting state is transmitted to the probe pad point 5 by the signal lead-out wire 16, while the other seven signal detection points 17 are effectively shielded. By configuring the stored state value of the transmission gate state storage D flip-flop 19 in the shift register, the eight signal detection points 17 in the group can be led out in turn.

[0047] Similarly, each 256-bit shift register can control 256 transmission gate switches 20, thereby controlling whether 256 signal detection points 17 are connected to the common signal lead wire 16. The four 256-bit shift registers can control the selection of 1024 signal detection points 17 on the probe handle 4. Specifically, the 256-bit shift register formed by cascading 256 transmission gate state storage D flip-flops 19 along the width direction of the probe handle 4 controls the selection of 256 signal detection points 17 in each column along the width direction of the probe handle 4.

[0048] Figure 5 schematically shows the cross-sectional structure of the multi-shaft bidirectional CMOS probe 2. The substrate device layer 10 is formed by processes such as active region patterning, STI shallow trench isolation, well implantation, stack gate, source-drain implantation, metal pre-intermediate deposition, opening contact hole, etc. on a P-type epitaxial silicon substrate. After the above processes, the required transmission gate switch 20 composed of MOS tubes and the transmission gate state storage D flip-flop 19 are formed in the substrate device layer 10. The source-drain-gate of the MOS tube is interconnected by contacting the metal via hole 15 in the upper intermediate insulating layer 11. The multi-layer intermediate metal layer 12 and the uppermost metal layer 13 form a global interconnection network through the metal via hole 15. The signal detection site 17, the electrical stimulation site 21, and the reference electrode 22 on the uppermost metal layer 13 are all in a double-layer structure of upper titanium nitride and lower copper to reduce the contact impedance between the electrode site and the neuron. The surface insulating layer 14 is formed on the uppermost metal layer 13. The surface insulating layer 14 above the probe pad site 5, the signal detection site 17, the electrical stimulation site 21, and the reference electrode 22 is selectively removed to form a window.

[0049] Embodiment

[0050] The specific experimental steps of using the above-mentioned million-channel level neural information detection and stimulation dual-mode bidirectional brain-computer interface to realize high-throughput neural information detection and precise electrical stimulation regulation of specific brain regions of mice are as follows:

[0051] Select the target brain region planned to be studied, such as the lateral hypothalamus and the ventral preoptic area, etc. The specific location information of the target brain region is determined through brain mapping;

[0052] Select the signal detection site 17 to be used during the detection process. The relevant signal detection site 17 is selected by configuring the storage values of multiple shift registers in the brain-computer interface;

[0053] Place the mouse in the isoflurane anesthesia equipment for anesthesia. After anesthesia, the mouse is placed on the stereotaxic instrument for in-vitro surgery. The skull above the target brain region is selectively removed by a skull drill. After the dura mater on the surface of the brain region is removed, the multi-shaft bidirectional CMOS probe 2 in the brain-computer interface can be implanted;

[0054] Place the brain-computer interface on the micro-propulsion equipment. The multi-shaft bidirectional CMOS probe 2 is implanted into the target brain region through the micro-propulsion equipment;

[0055] High-throughput neural information detection and precise electrical stimulation regulation of the target brain region can be realized by connecting the brain-computer interface with the detection equipment and the electrical stimulation equipment;

[0056] During the detection, the selection of the signal detection sites 17 can be adjusted by reconfiguring the storage values of the plurality of shift registers in the brain-computer interface, so as to record the neural signals detected by each signal detection site 17, or the signal detection site 17 with more detected neural signals can be selected for long-term detection;

[0057] So far, the brain-computer interface described above has realized the high-throughput neural information detection and electrical stimulation regulation of specific brain regions of mice.

[0058] The above-described specific embodiments further illustrate the purposes, technical solutions and beneficial effects of the present application. It should be understood that the above-described specific embodiments are merely examples of the present application and are not intended to limit the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A million-channel level neural information detection and stimulation dual-mode bidirectional brain-computer interface, characterized in that, The brain-computer interface comprises at least two multi-shaft bidirectional CMOS probes and a micro interface board for integration of the multi-shaft bidirectional CMOS probes. The multi-shaft bidirectional CMOS probe comprises an axially connected probe base and at least two probe shafts, and electrode site areas are arranged on the probe shafts, and signal detection sites, electrical stimulation sites and reference electrodes are arranged in the electrode site areas; the multi-shaft bidirectional CMOS probe comprises a plurality of layered structures in the longitudinal axis direction, from bottom to top, a base device layer, at least two intermediate insulating layers, at least one intermediate metal layer, an uppermost metal layer and a surface insulating layer. The signal detection sites are connected to the transmission gate switch input contact holes on the base device layer through the metal through holes in the intermediate insulating layer, the metal through hole contact points on the intermediate metal layer, the transmission gate switch output contact holes are connected to the probe pad site of the multi-shaft bidirectional CMOS probe base through the metal through holes in the intermediate insulating layer, the metal through hole contact points on the intermediate metal layer, the metal through hole contact points on the uppermost metal layer and the wires of the intermediate metal layer and the uppermost metal layer; the electrical stimulation sites and the reference electrodes are directly connected to the probe pad site of the multi-shaft bidirectional CMOS probe base through the wires. The micro interface board is a double-layer circuit structure circuit board, and the pad sites in the probe integration welding area on the circuit board are square with a side length of 100 μm~200 μm; the pad sites on the circuit board for connecting with external devices are rectangular with a width of 300 μm~400 μm and a length of 600 μm~800 μm.

2. The dual-mode bidirectional brain-machine interface of claim 1, wherein, The width of the probe shaft of the multi-shaft bidirectional CMOS probe is 100 μm~300 μm, and the length is 6 mm~15 mm, and the number of signal detection sites arranged on each probe shaft is at least 1024.

3. The dual-mode bidirectional brain-machine interface of claim 1, wherein, The signal detection sites are circular with a diameter of 0.5 μm~15 μm; the electrical stimulation sites are rectangular with a length of 50 μm and a width of 20 μm; and the reference electrodes are rectangular with a length of 100 μm and a width of 30 μm.

4. The dual-mode bidirectional brain-machine interface of claim 1, wherein, When the signal detection sites are used as electrophysiological signal detection sites, the signal detection sites are modified by platinum nanoparticles, carbon nanotubes or gold nanoparticles, and when the signal detection sites are used as electrochemical signal detection sites, the signal detection sites are modified by platinum nanoparticles, carbon nanotubes or gold nanoparticles and Nafion film or glutamate oxidase, for detecting dopamine and glutamate neurotransmitters.

5. The dual-mode bidirectional brain-machine interface of claim 4, wherein, The base device layer is provided with a transmission gate state storage D flip-flop and a transmission gate switch composed of MOS tubes.

6. The dual-mode bidirectional brain-machine interface of claim 1, wherein, ​ 7. The dual-mode bidirectional brain-machine interface of claim 1, wherein, The intermediate insulating layer is inlaid with metal vias for interconnection of upper and lower layer signals; the metal vias are square vias with a side length of 100-200 μm or circular vias with a diameter of 0.5-15 μm.

8. The dual-mode bidirectional brain-machine interface of claim 1, wherein, The intermediate metal layer is provided with a plurality of wires, and the two ends of the wires and positions that need to be effectively connected to the metal vias of the intermediate insulating layer are provided with metal via contact points.

9. The dual-mode bidirectional brain-machine interface of claim 1, wherein, The uppermost metal layer is provided with wires, signal detection sites, electrical stimulation sites, reference electrodes, probe pad sites and metal via contact points.

10. The dual-mode bidirectional brain-machine interface of claim 1, wherein, The surface insulating layer covers the uppermost metal layer, and the surface insulating layer at corresponding positions above the signal detection sites, electrical stimulation sites, probe pad sites and reference electrodes in the uppermost metal layer is selectively etched to form windows.

11. The dual-mode bidirectional brain-machine interface according to claim 8 or 9, characterized in that, The width of the wires is 0.18-5 μm.

12. The dual-mode bidirectional brain-machine interface of claim 8 or 9, wherein, The metal via contact points are square contact points with a side length of 100-200 μm or circular contact points with a diameter of 0.5-15 μm.

13. The dual-mode bidirectional brain-machine interface of claim 9, wherein, The probe pad sites of the multi-pronged bidirectional CMOS probe base are squares with a side length of 100-200 μm.

14. The dual-mode bidirectional brain-machine interface of claim 1, wherein, The number of signal detection sites on the probe prongs that are connected to the same signal lead wire and probe pad site is at least two.

15. The dual-mode bidirectional brain-machine interface of any one of claims 1-14, wherein The materials of the intermediate insulating layer and the surface insulating layer are one of silicon dioxide, silicon nitride and silicon oxynitride; the materials of the wires, metal vias, metal via contact points and probe pad sites of the multi-pronged bidirectional CMOS probe base are all copper; the materials of the signal detection sites, electrical stimulation sites and reference electrodes are titanium nitride, copper and surface modification materials, and the surface modification materials include one or more of platinum nanoparticles, carbon nanotubes, gold nanoparticles, Nafion and glutamate oxidase.

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