CN112450939B - Implantable extensible multi-mode recording and photo-stimulation brain-computer interface device - Google Patents
Implantable extensible multi-mode recording and photo-stimulation brain-computer interface device Download PDFInfo
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- G06F3/01—Input arrangements or combined input and output arrangements for interaction between user and computer
- G06F3/011—Arrangements for interaction with the human body, e.g. for user immersion in virtual reality
- G06F3/015—Input arrangements based on nervous system activity detection, e.g. brain waves [EEG] detection, electromyograms [EMG] detection, electrodermal response detection
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- A61B2562/164—Details of sensor housings or probes; Details of structural supports for sensors the sensor is mounted in or on a conformable substrate or carrier
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Abstract
The invention discloses an implantable ductile multi-mode recording and light-stimulated brain-computer interface device, which comprises a deep penetration electrode part and a surface plane electrode part. The deep penetrating electrode part comprises a deep recording electrode point and a miniature LED chip encapsulated in elastic transparent silica gel, and the surface layer plane electrode part comprises a skin layer recording electrode point. The miniature LED chip emits light to activate neurons to emit electric potential, and the cortex electrode points are recorded through cortex to collect brain cortex electric signals, and the electrode points are recorded deeply to collect single neuron pulse signals; the brain cortex electric signals and the single neuron pulse signals are transmitted to the interface end at the same time. The device has deep brain light stimulation and synchronous multi-spatial-scale nerve signal monitoring capability, has the multi-spatial-scale nerve signal monitoring capability, and simultaneously uses a unified interface end, thereby effectively improving the system integration level and the long-term implantation reliability.
Description
Technical Field
The invention belongs to the technical field of biomedical electricity, and particularly relates to a brain-computer interface device.
Background
In recent years, optogenetics brings revolutionary influence to nerve loop research, and compared with nerve regulation means such as electric stimulation, medicine stimulation and the like, the optical stimulation has millisecond-level time response precision, can selectively regulate and control specific types of neurons, and can accurately explore the causal relationship between specific nerve loops and brain functions by combining electrophysiological records to form a closed-loop system. Compared with optical transmission modes such as optical fibers, optical waveguides and the like, the miniature LED chip is small in size and low in power consumption, and is suitable for in-situ integration to provide high-resolution optical stimulation. Aiming at the characteristic that brain tissues are extremely soft, mechanical wounds or inflammatory reactions of the tissues are easily caused during and after the implantation of the device, and the problem can be effectively solved by developing the soft stretchable material device.
In the aspect of electrophysiological recording function, a probe type electrode which directly penetrates into brain tissue can acquire single neuron pulse signals (spikes) with different depths, a planar electrode which is attached to the cerebral cortex can capture a larger range of neuron group activities with shallower layers, namely cerebral cortex electric signals (Electrocorticography, ECoG), the two electrode recording signals have strong correlation, however, there are few devices which combine the advantages of the two electrodes to synchronously monitor the neural activities of the surface and deep space scales, and the device is important for understanding the relationship between single neurons and a large range of cerebral networks and the relationship between the actions. Therefore, development of an implantable brain-computer interface device with a cortex and deep dual-mode nerve recording function and integrated with a micro-LED chip is needed, and a brand new tool is provided for neuroscience research.
Through the search for the prior art, the university of Texas, amersham, inc. Cao H, gu L et al, IEEE Transactions on Biomedical Engineering,2012,60 (1): 225-229 writing articles "AN INTEGRATED μ LED Optrode for Optogenetic Stimulation AND ELECTRICAL recording", a penetrating probe was prepared based on a Polyimide (PI) flexible substrate 125 microns thick, integrating a single LED chip and 3 recording microelectrodes; kim T, mcCall J G et al in science 2013,340 (6129):211-216 writing articles "Injectable, cellular-scale optoelectronics with applications for wireless optogenetics", U.S. Illinois Champagne division, reported that a penetration probe was prepared based on a 6 micron thick Polyester (PET) flexible substrate, integrating 4 LED chips and a single recording microelectrode; penetration probes were prepared based on 10 micron thick parylene (parylene) flexible substrates, single probes integrating no less than 22 LED chips and 41 recording microelectrodes in situ, as described in Frontiers in neuroscience,2019,13 writing articles "HIGH DENSITY, double-Sided, flexible Optoelectronic Neural Probes With Embedded μleds", U.S. university of california, reddy J W, kimukin I et al. It can be seen that most of the current penetration brain-computer interface devices based on flexible substrate integrated rigid LED chips do not have extensibility, and the extensibility is of great significance for improving the biocompatibility of the device and reducing the long-term implantation immune rejection reaction.
Until now, neural activity, which is a range of dimensions of a single neuron or a larger neural network, has a greater impact on understanding and restoring neural function, and there is still a lack of deep research, and as spikes and ECoG reflect different aspects of neural function, the relationship between these measured signals is getting research attention. In the aspect of synchronous recording of surface and deep nerve signals, most of the current researches adopt a surface plane electrode and deep penetrating electrode to be independently processed and separately implanted, and the separate implantation mode not only can influence the relative position precision between the two electrodes, but also needs to be connected with the outside through respective interfaces, so that certain difficulty is caused for electrode implantation and connection. The university of san diego state Goshi N, castagnola E et al, journal of Micromechanics and Microengineering,2018,28.6:065009 writing articles "Glassy carbon MEMS for novel origami-styled 3D integrated intracortical and epicortical neural probes",, based on Polyimide (PI) flexible substrates, prepared brain-computer interface devices that can record simultaneously the surface and deep nerve electrical signals of the cerebral cortex, which is significant for understanding complex nerve responses and analyzing the nerve signal relationships of different brain regions. However, no implantable extensible brain-computer interface device with synchronous multimode recording and deep brain light stimulation function integration and good mechanical matching with brain soft tissues exists at present, and the device has important use value for neuroscience research.
Disclosure of Invention
In order to overcome the deficiencies of the prior art, the present invention provides an implantable ductile multi-mode recording and light-stimulated brain-computer interface device comprising a deep penetrating electrode portion and a superficial planar electrode portion. The deep penetrating electrode part comprises a deep recording electrode point and a miniature LED chip encapsulated in elastic transparent silica gel, and the surface layer plane electrode part comprises a skin layer recording electrode point. The miniature LED chip emits light to activate neurons to emit electric potential, and the cortex electrode points are recorded through cortex to collect brain cortex electric signals, and the electrode points are recorded deeply to collect single neuron pulse signals; the brain cortex electric signals and the single neuron pulse signals are transmitted to the interface end at the same time. The device has deep brain light stimulation and synchronous multi-spatial-scale nerve signal monitoring capability, has the multi-spatial-scale nerve signal monitoring capability, and simultaneously uses a unified interface end, thereby effectively improving the system integration level and the long-term implantation reliability.
The technical scheme adopted for solving the technical problems is as follows:
An implantable extensible multi-mode recording and optical stimulation brain-computer interface device comprises a deep penetrating electrode part, a surface plane electrode part and an interface end, wherein the deep penetrating electrode part is embedded in a deep brain region, the surface plane electrode part is attached to a surface brain region, and the interface end is used for transmitting an electrode recording signal to the outside of the brain-computer interface device and transmitting electric energy of an external power supply to the brain-computer interface device;
the deep penetrating electrode part comprises a deep recording electrode point array, a miniature LED chip array, a plurality of recording serpentine leads and a plurality of power supply serpentine leads; the deep recording electrode point array comprises a plurality of deep recording electrode points, and the micro LED chip array comprises a plurality of micro LED chips; the deep recording electrode points are connected to the interface end through recording serpentine leads, and electrode recording signals are transmitted from the deep recording electrode points to the interface end; the miniature LED chip is connected to the interface end through a power supply serpentine wire, and is powered by an external power supply through the interface end;
The surface layer plane electrode part comprises a surface layer recording electrode point array and a plurality of recording serpentine wires, and the surface layer recording electrode point array comprises a plurality of surface layer recording electrode points; the cortex recording electrode points are connected to the interface end through recording serpentine leads, and electrode recording signals are transmitted from the cortex recording electrode points to the interface end;
The micro LED chip emits light in brain tissue areas with different depths, neurons with different depths are activated to emit electric potentials, cortex recording electrode points collect brain cortex electric signals induced by the micro LED chip, and meanwhile, deep recording electrode points collect single neuron pulse signals induced by the micro LED chip; the brain cortex electric signals and the single neuron pulse signals are transmitted to the interface end at the same time.
Further, the deep penetrating electrode part and the surface plane electrode part are integrally formed based on the same micro-nano technology, and an included angle is formed between the deep penetrating electrode part and the surface plane electrode part by bending the deep penetrating electrode part, so that the deep penetrating electrode part and the surface plane electrode part are synchronously implanted into different parts of a brain tissue region.
Further, the diameter of the electrode point of the deep recording is 10-40 micrometers, and the electrode point is used for collecting single neuron pulse signals with different depths; the diameter of the cortex recording electrode point is 50-200 microns, and the cortex recording electrode point is attached to the surface of the cerebral cortex and is used for collecting the cerebral cortex electric signals.
Further, cathode bonding pads of all micro LED chips in the micro LED chip array are mutually communicated through the same power supply serpentine wire and then connected to the interface end, and anode bonding pads of all micro LED chips are independently connected to the interface end through different power supply serpentine wires, so that the ductility of the brain-computer interface device is ensured.
Further, the micro LED chip is encapsulated inside an elastic transparent silica gel;
Further, the micro LED chip has a length of not more than 270 micrometers and a width of not more than 220 micrometers for providing deep brain light stimulation.
Further, the implantable malleable brain-computer interface device that synchronizes multi-mode recording with deep brain light stimulation includes a plurality of deep penetrating electrode portions and a plurality of surface plane electrode portions.
Further, the conductive materials of the recording serpentine wire and the power supply serpentine wire are metal film materials.
Further, the metal film material of the inner package of the recording serpentine wire and the power supply serpentine wire is gold or platinum or copper.
The implantable extensible multi-mode recording and light-stimulated brain-computer interface device has the following beneficial effects:
1. the interface device is bent and deeply penetrated into the electrode part in a plane state, so that the interface device and the surface plane electrode part are combined to form a space three-dimensional structure, thereby having the nerve signal monitoring capability of multiple space scales, and simultaneously, the unified interface end is used, so that the system integration level and the long-term implantation reliability are effectively improved.
2. The elastic substrate material is used for packaging the rigid micro LED chip, so that potential damage to brain tissues in the implantation penetration process is reduced.
3. The use of malleable materials and structures significantly improves the mechanical matching of the device to brain soft tissue and is significant in reducing implant immune rejection.
4. Compared with the existing method for independently processing and separating the implanted surface plane electrode and the deep penetrating electrode, the method realizes multi-mode recording and deep brain light stimulation through the unified interface and external connection, can effectively solve the problems of poor mechanical hardness matching of an optogenetic brain-computer interface device and brain soft tissues, single nerve recording mode and the like, and has important significance for long-term monitoring and understanding of how the brain coordinates.
Drawings
Fig. 1 is a schematic side view of a device of the present invention.
FIG. 2 is a schematic view of the front and partial enlarged structure of the device of the present invention when the deep penetrating electrode portion is not bent.
Fig. 3 is a schematic plan view of a device according to the invention.
FIG. 4 is a schematic diagram of the device of the present invention implanted in a brain region of a mouse for simultaneous multi-mode recording.
In the figure: the electrode comprises a 1-deep penetrating electrode part, a 2-surface plane electrode part, a 3-cortex recording electrode point, a 4-deep recording electrode point, a 5-micro LED chip, a 6-cerebral cortex area, a 7-cerebral deep area, an 8-recording serpentine wire, a 9-power supply serpentine wire, a 10-LED cathode pad and an 11-LED anode pad.
Detailed Description
The invention will be further described with reference to the drawings and examples.
As shown in fig. 1, an implantable ductile multimode recording and optical stimulation brain-computer interface device comprises a deep penetrating electrode part 1, a surface plane electrode part 2 and an interface end, wherein the deep penetrating electrode part 1 is embedded in a deep brain region 7, the surface plane electrode part 2 is attached to a surface brain region 6, and the interface end is used for transmitting an electrode recording signal to the outside of the brain-computer interface device and transmitting electric energy of an external power supply to the brain-computer interface device;
The deep penetrating electrode part 1 comprises a deep recording electrode point array, a miniature LED chip array, a plurality of recording serpentine leads 8 and a plurality of power supply serpentine leads 9; the deep recording electrode point array comprises a plurality of deep recording electrode points 3, and the micro LED chip array comprises a plurality of micro LED chips 5; the deep recording electrode point 4 is connected to the interface end through a recording serpentine lead 8, and electrode recording signals are transmitted from the deep recording electrode point 4 to the interface end; the micro LED chip 5 is connected to the interface end through a power supply serpentine wire 9, and an external power supply supplies power to the micro LED chip 5 through the interface end;
The surface plane electrode part 2 comprises a surface layer recording electrode point array and a plurality of recording serpentine wires 8, wherein the surface layer recording electrode point array comprises a plurality of surface layer recording electrode points 3; the cortex recording electrode point 3 is connected to the interface end through a recording serpentine wire 8, and an electrode recording signal is transmitted from the cortex recording electrode point 3 to the interface end;
The micro LED chip 5 emits light in brain tissue areas with different depths, neurons with different depths are activated to emit electric potentials, the cortex recording electrode point 3 collects brain cortex electric signals induced by the micro LED chip 5, and the deep recording electrode point 4 collects single neuron pulse signals induced by the micro LED chip 5; the brain cortex electric signals and the single neuron pulse signals are transmitted to the interface end at the same time.
Further, the deep penetrating electrode part 1 and the surface plane electrode part 2 are integrally formed based on the same micro-nano technology, and an included angle is formed between the deep penetrating electrode part 1 and the surface plane electrode part 2 by bending, so that the deep penetrating electrode part and the surface plane electrode part 2 are synchronously implanted into different parts of a brain tissue region.
Further, the diameter size of the deep recording electrode point 4 is 10-40 micrometers, and the deep recording electrode point is used for collecting single neuron pulse signals with different depths; the diameter of the cortex recording electrode point 3 is 50-200 microns, and the cortex recording electrode point is attached to the surface of the cerebral cortex and is used for collecting cerebral cortex electric signals.
Further, the cathode pads of all the micro LED chips 5 in the micro LED chip array are mutually communicated through the same power supply serpentine wire 9 and then connected to the interface end, and the anode pads of all the micro LED chips 5 are independently connected to the interface end through different power supply serpentine wires 9, so that the ductility of the brain-computer interface device is ensured.
Further, the micro LED chip 5 is encapsulated inside an elastic transparent silica gel;
further, the micro LED chip 5 has a length of not more than 270 micrometers and a width of not more than 220 micrometers, for providing deep brain light stimulation.
Further, the implantable ductile brain-computer interface device for simultaneous multi-mode recording and deep brain light stimulation comprises a plurality of deep penetrating electrode portions 1 and a plurality of surface plane electrode portions 2.
Further, the conductive materials of the inner package of the recording serpentine wire 8 and the power supply serpentine wire 9 are metal film materials.
Further, the metal film material of the inner package of the recording serpentine wire 8 and the power supply serpentine wire 9 is gold or platinum or copper.
Specific examples:
Referring to fig. 1, an implantable ductile multi-mode recording and photo-stimulation brain-computer interface device of the present invention includes a deep penetrating electrode portion 1 and a superficial planar electrode portion 2. Wherein the surface plane electrode part 2 mainly comprises an array formed by cortex recording electrode points 3, and the attaching position is a cerebral cortex area 6; the deep penetrating electrode part 1 mainly comprises an array of deep recording electrode points 4 and micro LED chips 5, and the implantation position is a deep brain region 7. In the deep penetration electrode part 1 and the surface plane electrode part 2, the number and the size of all the recording electrode points and the micro LED chips 5 can be designed according to actual needs, and the embodiment is mainly directed to rodent mice.
Referring to fig. 2, the deep recording electrode point 1 is connected to the interface end through a recording serpentine wire 8, the micro LED chip 5 is connected with the interface end through a power supply serpentine wire 9, all LED cathode pads 10 are interconnected, all LED anode pads 11 are independently powered, and the whole ductility of the device is effectively ensured. The cortex recording electrode point 3 is also connected to the same interface end through a recording serpentine wire 8 which is positioned on the same plane when the deep recording electrode point 4 is processed.
Referring to fig. 3, the device substrate layer and the packaging layer of the micro LED chip 5 use flexible elastic silica gel with good transparency, metal thin film wires (such as chromium/gold) are deposited and packaged in a transparent polymer thin film, namely parylene, by sequentially depositing titanium and silicon dioxide on the bottom surface of parylene, reliable bonding between the functional thin film device and the elastic silica gel substrate is realized, and finally all recording electrode points of the integrated packaging device are subjected to electrochemical modification, such as by electrochemical deposition of conductive polymer poly (3, 4-dioxyethylthiophene) doped poly p-styrenesulfonic acid PEDOT: PSS and the like, so that the electrochemical impedance of all recording electrode points is reduced, and the signal to noise ratio of recording signals is improved.
Referring to fig. 4, the micro LED chip 5 is implanted into brain region of a mouse to emit light in brain tissue regions with different depths, neurons with different depths can be activated to emit electric potential, induced ECoG signals can be collected through the cortical recording electrode point 3, and corresponding induced Spike signals can be collected through the deep recording electrode point 4. The two types of synchronously recorded signals can reflect different aspects of nerve functions, and the two types of signals crossing the cortex are subjected to correlation analysis, so that the method can be used for solving the complex action potential transmission process of neurons, and can be used for more comprehensively and effectively supporting the research of nerve loop functions and pathogenesis of brain diseases.
In the second embodiment, the number of probes of the deep penetration electrode part 1 can be increased according to the requirement of animal model test, so as to realize optical stimulation and electrical recording of any combination of multiple brain regions, and further complete deep exploration of the working mechanism of a nerve loop in a larger range. For example, animal models with larger brain tissue volume structures, such as pigs, monkeys, etc., can simultaneously embed multiple probes in the device into different functional areas of the left brain and the right brain or the same side brain so as to expand the research target range of central nervous tissue.
In the third embodiment, the conductive material is replaced, and the conductive material most commonly used for the internal package of the recording serpentine wire 8 and the power supply serpentine wire 9 is a metal film material, such as gold, platinum or copper, however, when the micro LED chip 5 is powered on or off, significant electromagnetic interference is brought, and due to the existence of the photoelectric effect, noise components in the recording signal are further aggravated, and even the amplitude change of the neural signal caused by submerged light activation is further aggravated. In addition, the metal film material is not light-permeable, and may block light generated by the micro LED chip 5 to some extent. Therefore, the replaceable conductive material is a highly transparent material such as graphene, silver nanowire, indium tin oxide and the like, so that the noise interference resistance of the recording electrode point under the light-emitting working condition of the micro LED chip 5 is improved, and a cleaner nerve signal is obtained.
Claims (8)
1. An implantable extensible multi-mode recording and optical stimulation brain-computer interface device is characterized by comprising a deep penetrating electrode part, a surface plane electrode part and an interface end, wherein the deep penetrating electrode part is embedded in a deep brain region, the surface plane electrode part is attached to a surface brain region, and the interface end is used for transmitting an electrode recording signal to the outside of the brain-computer interface device and transmitting electric energy of an external power supply to the brain-computer interface device;
the deep penetrating electrode part comprises a deep recording electrode point array, a miniature LED chip array, a plurality of recording serpentine leads and a plurality of power supply serpentine leads; the deep recording electrode point array comprises a plurality of deep recording electrode points, and the micro LED chip array comprises a plurality of micro LED chips; the deep recording electrode points are connected to the interface end through recording serpentine leads, and electrode recording signals are transmitted from the deep recording electrode points to the interface end; the miniature LED chip is connected to the interface end through a power supply serpentine wire, and is powered by an external power supply through the interface end;
The surface layer plane electrode part comprises a surface layer recording electrode point array and a plurality of recording serpentine wires, and the surface layer recording electrode point array comprises a plurality of surface layer recording electrode points; the cortex recording electrode points are connected to the interface end through recording serpentine leads, and electrode recording signals are transmitted from the cortex recording electrode points to the interface end;
The micro LED chip emits light in brain tissue areas with different depths, neurons with different depths are activated to emit electric potentials, cortex recording electrode points collect brain cortex electric signals induced by the micro LED chip, and meanwhile, deep recording electrode points collect single neuron pulse signals induced by the micro LED chip; simultaneously transmitting the brain cortex electric signals and the single neuron pulse signals to an interface end;
The deep penetrating electrode part and the surface plane electrode part are integrally processed and molded based on the same micro-nano technology, and an included angle is formed between the deep penetrating electrode part and the surface plane electrode part by bending, so that the deep penetrating electrode part and the surface plane electrode part are synchronously implanted into different parts of a brain tissue region.
2. An implantable ductile multi-mode recording and photostimulation brain-computer interface device according to claim 1 wherein said deep recording electrode point diameter is 10-40 microns in size for collecting individual neuron pulse signals of different depths; the diameter of the cortex recording electrode point is 50-200 microns, and the cortex recording electrode point is attached to the surface of the cerebral cortex and is used for collecting the cerebral cortex electric signals.
3. The implantable ductile multimode recording and light stimulating brain-computer interface device according to claim 1 wherein cathode pads of all micro LED chips in the array of micro LED chips are interconnected by a common power supply serpentine wire and then connected to the interface terminal, and anode pads of all micro LED chips are independently connected to the interface terminal by different power supply serpentine wires, thereby ensuring ductility of the brain-computer interface device.
4. An implantable ductile multi-mode recording and photo-stimulating brain-computer interface device according to claim 1 wherein said micro LED chip is encapsulated inside an elastic transparent silicone.
5. An implantable ductile multi-mode recording and light stimulating brain-computer interface device according to claim 1 wherein said micro LED chip is no greater than 270 microns in length and no greater than 220 microns in width for providing deep brain light stimulation.
6. An implantable ductile multi-mode recording and photo-stimulating brain-computer interface device according to claim 1 wherein said synchronous multi-mode recording and deep brain photo-stimulating implantable ductile brain-computer interface device comprises a plurality of deep penetrating electrode portions and a plurality of surface plane electrode portions.
7. The implantable ductile multi-mode recording and photostimulation brain-computer interface device according to claim 1 wherein said recording serpentine conductor and conductive material encapsulated inside the powering serpentine conductor are metallic film materials.
8. An implantable ductile multi-mode recording and photo-stimulation brain-computer interface device according to claim 1, wherein the metallic film material of the recording serpentine wire and the inner encapsulation of the power supply serpentine wire is gold or platinum or copper.
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| CN113712575B (en) * | 2021-07-16 | 2023-01-10 | 清华大学 | Whole brain multi-modal neural activity detection photoelectric brain-computer interface system |
| CN113925518B (en) * | 2021-09-23 | 2022-09-13 | 中国科学院深圳先进技术研究院 | Minimally invasive neural interface generated in situ by jetting and preparation method and application thereof |
| CN114949618B (en) * | 2022-05-19 | 2023-02-21 | 中国科学院半导体研究所 | Photoelectric integrated module for nerve regulation |
| CN115054257A (en) * | 2022-06-17 | 2022-09-16 | 中国科学院脑科学与智能技术卓越创新中心 | Flexible electrode for brain and manufacturing method thereof |
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