Biological mixed nerve interface

Abstract

The invention relates to the technical field of nerve interfaces, in particular to a biological mixed nerve interface. According to the technical scheme, the device comprises a three-dimensional multi-layer structure electrode, composite conductive hydrogel, a neuron layer and a signal decoding module, the three-dimensional multi-layer structure electrode comprises a three-dimensional cavity multichannel electrode layer, the three-dimensional cavity multichannel electrode layer is provided with a plurality of independent micro cavities, and each micro cavity loads the composite conductive hydrogel and the neurons in an adaptive mode. According to the biological mixed nerve interface, through the three-dimensional cavity multi-channel design of the three-dimensional multi-layer structure electrode, the supporting regulation and control of the methacrylamide esterified gelatin hydrogel and the nerve cell axon extension characteristic, high-precision electric signal collection and single-nerve-cell-level precise electrical stimulation are achieved, nerve cell survival and regulation and control are guaranteed, and the biological mixed nerve interface has the advantages of being simple in structure, convenient to operate and high in reliability. The action potential of neurons in the cortex can be collected only by implanting into the brain surface so as to record high-quality electroencephalogram signals, and meanwhile nerve tissue trauma is reduced and biocompatibility is improved.

Description

Technical Field

[0001] This invention relates to the field of neural interface technology, and more particularly to a bio-hybrid neural interface. Background Technology

[0002] Brain-computer interfaces (BCIs) aim to establish a direct communication and control channel between the brain and the external environment, enabling interaction between the brain and external devices. Based on whether the electrodes are inserted into the cranium, BCIs can be divided into invasive and non-invasive types. Invasive BCIs acquire brain signals by implanting electrodes into brain tissue, providing stable and clear signals, but they suffer from surgical trauma, biocompatibility limitations, and glial scarring. Non-invasive BCIs do not require surgery, but the signal quality is poor, and the electrodes are prone to displacement. Therefore, this application proposes a bio-hybrid neural interface. Summary of the Invention

[0003] The purpose of this invention is to address the problems existing in the background technology by proposing a bio-hybrid neural interface, which aims to solve the technical problems of large trauma from puncture electrodes and difficulty in high-precision acquisition of action potentials of neurons inside the cortex by surface electrodes in existing neural interfaces.

[0004] The technical solution of the present invention: a bio-hybrid neural interface, comprising a three-dimensional multilayer structure electrode, a composite conductive hydrogel, a neuron layer and a signal decoding module; The three-dimensional multilayer structure electrode includes a three-dimensional chamber multichannel electrode layer, which has multiple independent microchambers. Each microchamber is adapted to load the composite conductive hydrogel and the neuron. The three-dimensional multilayer structure electrode is made of a biocompatible conductive material. The composite conductive hydrogel is a methacrylamide esterified gelatin hydrogel, which is filled in the micro cavity; The neuron layer is composed of neurons grown within the composite conductive hydrogel, and the axons of the neurons can extend into the cerebral cortex after the interface is implanted on the brain surface. The signal decoding module is electrically connected to the three-dimensional multilayer structure electrode and is used to receive and decode the electroencephalogram (EEG) signals collected by the three-dimensional multilayer structure electrode.

[0005] Optionally, the electrode tip of the three-dimensional multilayer structure electrode is a micro needle-like structure or a structure with a micro-contact surface, and the electrode tip is in direct contact with the neuron.

[0006] Optionally, the three-dimensional multilayer structure electrode uses a biocompatible conductive material.

[0007] Optionally, it also includes an electrical stimulation device, which is electrically connected to the three-dimensional multilayer structure electrode and can output a 50Hz frequency, 50μA constant current, cathode-guided biphasic square wave stimulation signal, which is transmitted to the neural stem cells in the composite conductive hydrogel through the three-dimensional multilayer structure electrode. The electrical stimulation device includes a stimulation parameter adjustment module.

[0008] Optionally, each micro-cavity of the three-dimensional chamber multi-channel electrode layer is provided with a microfluidic channel, and the channel diameter of the microfluidic channel is adapted to the cavity size of the micro-cavity.

[0009] Optionally, the three-dimensional multilayer structure electrode further includes an embedded signal processing unit, which is electrically connected to the three-dimensional cavity multichannel electrode layer.

[0010] Optionally, the degree of crosslinking of the composite conductive hydrogel can be adjusted.

[0011] Optionally, the signal decoding module includes a signal receiving unit, a signal preprocessing unit, and a decoding algorithm unit; the signal receiving unit is used to receive electrical signals output from the three-dimensional multilayer structure electrodes, the signal preprocessing unit is used to process the received electrical signals, and the decoding algorithm unit has a built-in single-neuron signal decoding algorithm.

[0012] Optionally, the number of micro-chambers in the three-dimensional cavity multi-channel electrode layer is 8-64, arranged in an array, with the spacing between adjacent micro-chambers being 100μm-500μm.

[0013] Compared with the prior art, this application includes at least one of the following beneficial technical effects: 1. High-precision signal acquisition and stimulation: The three-dimensional multi-layer structure electrode's three-dimensional chamber multi-channel design enables high-precision electrical signal acquisition and precise electrical stimulation at the single neuron level. Combined with signal decoding algorithms, it can achieve cortical signal decoding at the single neuron level.

[0014] 2. Neuronal survival and regulation: Methacrylamide-esterified gelatin hydrogel can provide a suitable microenvironment for neuronal growth and maintain neuronal activity. The electrical stimulation device can both induce neural stem cell differentiation and achieve precise functional regulation of mature neurons. 3. Low trauma and structural compatibility: This invention significantly reduces trauma to nerve tissue by implanting the interface on the brain surface rather than piercing the cerebral cortex; the axons of the neuronal layer can extend into the cerebral cortex to achieve structural fusion, reducing glial scarring.

[0015] 4. High-quality EEG signal recording: With the help of the neuronal axonal conduction mechanism, it can collect the action potentials of neurons in the cortex that can only be obtained by traditional puncture electrodes. It has the characteristics of high spatiotemporal resolution, high signal specificity, high signal-to-noise ratio, coexistence of low-frequency and high-frequency electrical activity, and excellent biocompatibility. Attached Figure Description

[0016] Figure 1 A schematic diagram of a bio-hybrid neural interface; Figure 2 This is a schematic diagram of a three-dimensional multilayer electrode structure; Figure 3 This is a schematic diagram of electrodes and conductive hydrogel-loaded neurons. Figure 4 A schematic diagram (left) and a staining diagram (right) showing the extension of neuronal axons into the cerebral cortex; Figure 5 A schematic diagram of recording electroencephalogram (EEG) signals using a neural interface.

[0017] Figure labels: 1. Electrode; 2. Composite conductive hydrogel; 3. Neuron. Detailed Implementation

[0018] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that, unless otherwise specified, the following embodiments and features described therein can be combined with each other.

[0019] Example Examples, such as Figures 1 to 2 As shown, this invention proposes a bio-hybrid neural interface, comprising a three-dimensional multilayer structure electrode 1. The electrode 1 includes a three-dimensional chambered multichannel electrode layer with multiple independent micro-chambers. Each chamber can load a composite conductive hydrogel 2 and a neuron 3. The three-dimensional multilayer structure combined with the independent micro-chambers provides a dedicated growth space for the neuron 3 and enables high-precision electrical signal acquisition. Each chamber's growth environment is precisely controlled using microfluidic technology, promoting stable growth of the neuron 3 while avoiding signal interference and stimulation crosstalk between chambers. The multichannel parallel design allows the electrode 1 to simultaneously acquire the electrical activity of different neurons 3 or apply electrical stimulation to specific neurons. An embedded signal processing module optimizes signal quality and stimulation accuracy in real time, meeting the high spatiotemporal resolution and precise control requirements of brain-computer interfaces. Furthermore, electrode 1 is made of biocompatible material, possessing high conductivity and corrosion resistance, enabling long-term stable implantation. The tip of electrode 1 is designed as a micro-needle structure or with a micro-contact surface to ensure direct contact with neuron 3, minimizing signal attenuation and ensuring efficient electrical stimulation transmission.

[0020] like Figure 3 As shown, this embodiment includes a composite conductive hydrogel 2 and an electrical stimulation device. The composite conductive hydrogel 2 is a methacrylamide esterified gelatin (GelMA) hydrogel, which not only provides structural support and a biocompatible growth microenvironment for neural stem cells but also maintains neuronal activity. During hydrogel preparation, the mechanical properties and biocompatibility of the material are optimized by adjusting the degree of cross-linking. During culture, the differentiation effect is evaluated through immunofluorescence labeling of neuron-specific proteins (such as NeuN and MAP2), morphological observation, and electrophysiological testing.

[0021] like Figure 4 As shown, after this bio-hybrid neural interface is implanted on the surface of the host brain, the axons of neurons in the neuronal layer can naturally extend into the cerebral cortex, achieving structural fusion with the host neurons. Glial response was assessed using GFAP and Iba1 labeling, and the results showed no significant glial scarring, indicating excellent compatibility between the interface and the host brain tissue.

[0022] It should be noted that after implanting the bio-hybrid neural interface onto the brain surface of an animal model, immunofluorescence staining confirmed that the axon of neuron 3 extended into the cerebral cortex and formed a functional connection with the host neuron. Electrophysiological tests, using a multi-electrode array (MEA), recorded bidirectional electrical signal transmission, verifying that electrode 1 could accurately acquire action potentials of neurons within the host cortex and simultaneously modulate host neuronal activity through stimulation. Specifically, utilizing the independent micro-chamber structure of electrode layer 1, stimulation signals generated by an electrical stimulation device (such as 50Hz, 50μA constant current, cathode guidance, biphasic square wave) can be applied to neurons 3 within specific chambers, achieving precise localization stimulation at the single-neuron level. Histological examination and behavioral evaluation showed that the transplanted neuron 3 effectively integrated into the host neural network, improving motor coordination.

[0023] like Figure 5 As shown, after long-term implantation, neuron 3 establishes a stable connection with the host brain. Based on the neuronal axonal conduction mechanism, the acquired cortical EEG signals have the characteristics of high spatiotemporal resolution, high signal specificity, high signal-to-noise ratio, and the coexistence of low-frequency and high-frequency electrical activity. A dedicated signal decoding algorithm can achieve cortical signal decoding at the single neuron 3 level, accurately analyzing complex EEG signals. Simultaneously, the electrical stimulation device can apply stimulation signals to specific target neurons using the independent chamber structure of electrode layer 1, achieving closed-loop feedback regulation. The bio-hybrid neural interface of this invention employs a three-dimensional, multi-layered structure, including a three-dimensional chambered multi-channel electrode layer, a hydrogel layer, and a neuron layer. The three-dimensional chambered multi-channel electrode layer contains multiple independent micro-chambers with excellent conductivity to achieve high-precision electrical signal acquisition and precise electrical stimulation at the single-neuron level. The hydrogel layer uses methacrylamide-esterified gelatin hydrogel to load neural stem cells and provide a growth microenvironment, maintaining neuronal activity. The neuronal axons in the neuron layer can extend into the cerebral cortex after the interface is implanted on the brain surface, thereby transmitting cortical neuronal action potentials. Through this structural design, this invention can accurately acquire intracortical neuronal action potentials, which are typically only obtainable with traditional invasive electrodes, by implanting the interface only on the brain surface rather than penetrating the cerebral cortex, and achieve precise electrical stimulation at the single-neuron level. It features high signal quality, high stimulation accuracy, minimal trauma to neural tissue, and excellent biocompatibility.

[0024] The above specific embodiments are merely several optional embodiments of the present invention. Based on the technical solutions of the present invention and the relevant teachings of the above embodiments, those skilled in the art can make various alternative improvements and combinations to the above specific embodiments.

Claims

1. A bio-hybrid neural interface, characterized in that, It includes a three-dimensional multilayer structure electrode (1), a composite conductive hydrogel (2), a neuron layer, and a signal decoding module; The three-dimensional multilayer structure electrode (1) includes a three-dimensional chamber multichannel electrode layer, which has multiple independent micro-chambers. Each micro-chamber is adapted to load the composite conductive hydrogel (2) and the neuron (3). The three-dimensional multilayer structure electrode (1) is made of biocompatible conductive material. The composite conductive hydrogel (2) is a methacrylamide esterified gelatin hydrogel, which is filled in the micro cavity; The neuron layer is composed of neurons (3) growing in the composite conductive hydrogel (2), and the axons of the neurons (3) can extend into the cerebral cortex after the interface is implanted on the brain surface. The signal decoding module is electrically connected to the three-dimensional multilayer structure electrode (1) and is used to receive and decode the electroencephalogram (EEG) signals collected by the three-dimensional multilayer structure electrode (1).

2. The bio-hybrid neural interface according to claim 1, characterized in that, The electrode tip of the three-dimensional multilayer structure electrode (1) is a micro needle-like structure or a structure with a micro-contact surface, and the electrode tip is in direct contact with the neuron (3).

3. The bio-hybrid neural interface according to claim 1, characterized in that, The three-dimensional multilayer structure electrode (1) uses a biocompatible conductive material.

4. The bio-hybrid neural interface according to claim 1, characterized in that, It also includes an electrical stimulation device, which is electrically connected to the three-dimensional multilayer structure electrode (1) and can output a biphasic square wave stimulation signal with a frequency of 50Hz, a constant current of 50μA, and a cathode-guided structure, and transmit it to the neural stem cells in the composite conductive hydrogel (2) through the three-dimensional multilayer structure electrode (1). The electrical stimulation device includes a stimulation parameter adjustment module.

5. A bio-hybrid neural interface according to claim 1, characterized in that, Each micro-cavity of the three-dimensional chamber multi-channel electrode layer is provided with a microfluidic channel, and the channel diameter of the microfluidic channel is adapted to the cavity size of the micro-cavity.

6. A bio-hybrid neural interface according to claim 1, characterized in that, The three-dimensional multilayer structure electrode (1) also includes an embedded signal processing unit, which is electrically connected to the three-dimensional cavity multichannel electrode layer.

7. A bio-hybrid neural interface according to claim 1, characterized in that, The degree of crosslinking of the composite conductive hydrogel (2) can be adjusted.

8. A bio-hybrid neural interface according to claim 1, characterized in that, The signal decoding module includes a signal receiving unit, a signal preprocessing unit, and a decoding algorithm unit; the signal receiving unit is used to receive the electrical signal output by the three-dimensional multilayer structure electrode (1), the signal preprocessing unit is used to process the received electrical signal, and the decoding algorithm unit has a built-in single neuron signal decoding algorithm.

9. A bio-hybrid neural interface according to claim 1, characterized in that, The three-dimensional multi-channel electrode layer has 8-64 micro-chambers arranged in an array, with a spacing of 100μm-500μm between adjacent micro-chambers.

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