Electrode array structure for multi-type neural signal acquisition and preparation method thereof

Abstract

The application provides an electrode array structure for multi-type neural signal collection and a preparation method thereof. The electrode array structure comprises a conductive layer, a first insulating layer above the conductive layer and a second insulating layer below the conductive layer. The conductive layer comprises a Laplace electrode and a single-point electrode. The Laplace electrode is an electrode with a concentric circular ring structure. The Laplace electrode and the single-point electrode are used together to collect different types of in-vivo neuron signals. The application uses an implanted brain-machine interface electrode array with two types of electrode structures to collect in-vivo neuron signals. The electrode array can realize the synchronous acquisition of multi-type neural signals, so that the required neural signals can be selected according to the application requirements, and the progress of brain science and brain disease research is greatly promoted.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of implanting brain-computer interface neural microelectrode devices, in particular to an electrode array structure for multi-type neural signal collection and a preparation method thereof. BACKGROUND

[0002] Bioelectric signal is the cornerstone of human life activities. The human body as an organism is a very complex system, and bioelectricity is closely related to any life activities of the human body. The electric potential of unstimulated nerve cells is called "resting potential", and the electric potential generated by nerve cells when stimulated is called "action potential". This potential difference is formed by the positive charge outside the cell membrane and the negative charge inside the cell membrane.

[0003] Due to the relative accuracy and pre-emptiveness of the collection and analysis of brain neural electrical signals in the judgment of the disease, it has a great application prospect in the diagnosis and treatment of brain diseases. The current neural electrical signal collection uses a conventional point electrode array as the main part, and a clustering analysis algorithm is used to realize feature extraction. All types of electrodes have selectivity in the signal space, that is, when the signal source is far away from the position of the electrode point, due to the energy dissipation in the signal transmission process, the signal that the electrode point can collect will decrease with the continuous distance of the signal source. This signal response inhibition of the distant signal source and the signal response enhancement of the close signal source is the spatial selectivity of the electrode. In order to reduce the interference of irrelevant brain electrical signals in the surrounding, the radius of the electrode is reduced, thereby increasing the impedance spectrum of the brain electrode, so as to control the response amplitude of the near-end and far-end signals. The signal response of the far-end will be submerged in the noise because the response amplitude is lower than the noise of the collector, so as to filter out the interference of the signal generated by the distant signal source. This method of increasing the electrochemical impedance spectrum of the electrode is a method of improving the spatial selectivity of the electrode. However, this method reduces the response amplitude of the near-end neural signal while improving the spatial selectivity, which affects the collection and analysis of the high signal-to-noise ratio neural signal. SUMMARY

[0004] In view of the defects in the prior art, the purpose of the present application is to provide an electrode array structure for multi-type neural signal collection and a preparation method thereof.

[0005] According to one aspect of the present application, an electrode array structure for multi-type neural signal collection is provided, which comprises a conductive layer, a first insulating layer located above the conductive layer, and a second insulating layer located below the conductive layer; wherein the conductive layer comprises a Laplace electrode and a single-point electrode, the Laplace electrode is an electrode with a concentric circular ring structure, and the collection of different types of neuron signals in the body is realized by the Laplace electrode and the single-point electrode.

[0006] Further, the Laplace electrode comprises a Laplace outer ring electrode, a Laplace inner ring electrode and a Laplace electrode lead wire, the Laplace outer ring electrode is concentrically arranged with the Laplace inner ring electrode, and the Laplace electrode lead wire is used to lead out the Laplace outer ring electrode and the Laplace inner ring electrode respectively; the Laplace electrode comprises any one or several of a double-ring concentric electrode structure, a three-ring concentric electrode structure to a multi-ring concentric electrode structure.

[0007] Further, the single-point electrode comprises an electrode part and a single-point electrode lead wire, the single-point electrode lead wire is used to lead out the electrode part; the single-point electrode realizes the regulation of the impedance value by adjusting the diameter of the electrode part, so as to realize the collection of all neuron discharges in different distance ranges.

[0008] Further, the diameter of the electrode part is 10-500 μm.

[0009] Further, the thickness of the conductive layer is 100-1000 nm.

[0010] Further, the number of the Laplace electrode and the single-point electrode is set according to the demand of the acquired signal respectively.

[0011] Further, the arrangement density of the Laplace electrode and the single-point electrode at different depths is set according to the characteristics that the number of neurons in different brain areas in the body is different.

[0012] Further, the first insulating layer is provided with an electrode point windowed exposure area for exposing the electrode point structure.

[0013] Further, the thickness of the first insulating layer and the second insulating layer is 100-2000 nm.

[0014] According to another aspect of the present application, a preparation method of the above-mentioned electrode array structure for multi-type neural signal collection is provided, and the method comprises the following steps:

[0015] A substrate is provided, and a layer of metal is deposited on the substrate to form a sacrificial layer;

[0016] A second insulating layer is spin-coated and patterned on the sacrificial layer;

[0017] An adhesion layer and a conductive layer are sputtered or evaporated on the second insulating layer, a positive photoresist is spin-coated as a mask, and after pre-baking, exposure, development and post-baking, dry etching or wet etching is adopted to obtain a conductive layer pattern containing a Laplace electrode and a single-point electrode;

[0018] A first insulating layer is spin-coated and patterned on the patterned conductive layer, and the aperture pattern of the first insulating layer exposes the Laplace electrode and the single-point electrode.

[0019] After the sacrifice layer is corroded or dissolved, the release of the electrode array is completed, and an electrode array structure for collecting multiple types of neural signals is obtained.

[0020] Compared with the prior art, the present application has at least one of the following beneficial effects:

[0021] The electrode array structure of the present application includes a Laplace electrode structure for high-resolution single neuron action potential signal collection and a single-point electrode for local field potential signal collection. The Laplace concentric ring structure solves the problems of low signal-to-noise ratio and mutual interference of different neuron discharges in current neural signal collection, improves the spatial selectivity of the electrode points, and realizes single neuron signal discharge collection. The single-point electrode structure realizes the collection of all neuron discharges within different distance ranges. The in-vivo neuron signal collection by the electrode array composed of the two types of collection electrode structures can realize the synchronous acquisition of multiple types of neural signals, so that the required neural signals can be selected according to the application needs, greatly promoting the progress of brain science and brain disease research. BRIEF DESCRIPTION OF DRAWINGS

[0022] Other features, objects and advantages of the present application will become more apparent from the following detailed description of non-limiting embodiments, made with reference to the accompanying drawings:

[0023] Figure 1 Figure 1 is a layered schematic diagram of the electrode array structure in an embodiment of the present application;

[0024] Figure 2 Figure 1 is a layered schematic diagram of the electrode array structure in an embodiment of the present application;

[0025] Figure 3 Figure 1 is a layered schematic diagram of the electrode array structure in an embodiment of the present application;

[0026] Figure 4 Figure 1 is a layered schematic diagram of the electrode array structure in an embodiment of the present application;

[0027] Figure 5 Figure 1 is a layered schematic diagram of the electrode array structure in an embodiment of the present application;

[0028] In the figure: 1 is a second insulating layer, 2 is a single-point electrode, 21 is a single-point electrode lead, 22 is an electrode part, 3 is a Laplace electrode, 31 is a Laplace outer ring electrode, 32 is a Laplace inner ring electrode, 33 is a Laplace electrode lead, 4 is a first insulating layer, and 5 is an electrode point windowed exposed area. DETAILED DESCRIPTION

[0029] The application will be described in detail below with reference to specific embodiments. The following embodiments will help those skilled in the art to further understand the application, but do not limit the application in any form. It should be pointed out that, for those skilled in the art, without departing from the concept of the application, several modifications and improvements can be made. These all belong to the protection scope of the application.

[0030] In order to solve the limitations of the above-mentioned signal acquisition electrode, Bin He of the University of Chicago proposed to use the surface Laplace estimation principle to improve the spatial selectivity of the electrode, and the core of the estimation principle is the Laplace operator:

[0031]

[0032] By calculating the acquired signal through the Laplace operator for weighted addition processing, the obtained Laplace potential is inversely proportional to the fourth power of the distance of the electric dipole to the observation point, that is, the response power of the Laplace potential decreases with the fourth power of the distance, compared with the electric potential response power decreasing with the first power of the distance, the response power of the Laplace potential is much more sensitive to the distance, and has a strong inhibitory effect on the signal source far away from the observation point, and has little or even no effect on the signal source close to the observation point. Therefore, replacing the acquisition potential with the acquisition of the Laplace potential can significantly improve the spatial selectivity of the electrode and thus improve the quality of the acquired signal. However, the Laplace operator combined with the double-ring or multi-ring Laplace electrode structure has not been applied to the implanted brain electrical signal acquisition.

[0033] In summary, the double-ring or multi-ring Laplace electrode structure combined with the operation of the Laplace operator can significantly improve the spatial resolution of neural signal acquisition, and further realize the acquisition of single neuron signals. Further matching single-point electrode structure to form a multi-type neural signal acquisition electrode array will greatly promote the progress in the field of neural electrophysiological recording.

[0034] Therefore, the embodiment of the application provides a multi-type neural signal acquisition electrode array structure, which is referred to Figure 1The electrode array structure is a sandwich structure, comprising a conductive layer, a first insulating layer 4 located above the conductive layer, and a second insulating layer 1 located below the conductive layer; wherein the conductive layer comprises a Laplace electrode 3 and a single-point electrode 2, the Laplace electrode 3 is an electrode with a concentric circular ring structure, the local field potential signal can be collected through the single-point electrode 2, the local field potential signal is the superposition of many neuron discharge signals, the neuron action potential signal can be collected through the Laplace electrode 3, and the collection of different types of neuron signals in the body is realized through the Laplace electrode 3 and the single-point electrode 2. The electrode array structure of the embodiment of the present application comprises the Laplace electrode 3 for high-resolution single neuron action potential signal collection and the single-point electrode 2 for local field potential signal collection, the concentric circular ring structure of the Laplace electrode 3 is used to solve the problems of low signal-to-noise ratio and mutual interference of different neuron discharges in current neural signal collection, improve the spatial selectivity of the electrode point, realize single neuron signal discharge collection, and realize the collection of all neuron discharges in different distance ranges through the single-point electrode structure; the collection of in-vivo neuron signals through the electrode array composed of the two types of collection electrode structures can realize the synchronous acquisition of multiple types of neural signals, so that the required neural signal can be selected according to the application requirement, and the progress of brain science and brain disease research is greatly promoted.

[0035] In some embodiments, the Laplace electrode 3 comprises a Laplace outer ring electrode 31, a Laplace inner ring electrode 32, and a Laplace electrode lead 33, the Laplace outer ring electrode 31 and the Laplace inner ring electrode 32 are concentrically arranged, and the Laplace electrode lead 33 is used to lead out the Laplace outer ring electrode 31 and the Laplace inner ring electrode 32 respectively; the Laplace electrode 3 comprises any one or several of a double-ring concentric electrode structure, a three-ring concentric electrode structure, and a multi-ring concentric electrode structure, different ring numbers correspond to different Laplace algorithms for analysis, the more the ring numbers, the higher the precision, and the larger the occupied area, the differential signal is collected by using the Laplace electrode 3, and the signals on different rings are subjected to weighted phase processing (weighted potential analysis) through a Laplace operator, the spatial selectivity of the electrode point is improved, and single neuron signal discharge collection is realized.

[0036] In some embodiments, the single-point electrode 2 comprises an electrode part 22 and a single-point electrode lead 21, the single-point electrode lead 21 is used to lead out the electrode part 22; the single-point electrode 2 realizes the regulation of the impedance value by adjusting the diameter of the electrode part 22, so as to realize the collection of all neuron discharges in different distance ranges. The larger the diameter of the electrode part 22 of the single-point electrode 2, the smaller the electrochemical impedance, and the local field potential signal in a larger range can be collected, preferably, the diameter of the electrode part 22 is 10-500 μm, and the size of the in-vivo region is regulated through the adjustment of the impedance.

[0037] In some embodiments, the wire layer is composed of a conductive layer material, and the forming method of the conductive layer includes but is not limited to multi-target magnetron sputtering, electrochemical plating, electron beam evaporation, ion beam sputtering and other metal thin film growth methods, and the conductive layer material includes but is not limited to gold, platinum, silver and the like. Considering the overall thickness of the implanted electrode and the conductive effect, preferably, the thickness of the conductive layer is 100-1000 nm.

[0038] In some embodiments, the number of Laplace electrodes 3 and single-point electrodes 2 is set according to the demand for acquiring signals. The arrangement density of the Laplace electrodes 3 and single-point electrodes 2 at different depths is set according to the characteristics of different numbers of neurons in different brain regions in the body. Specifically, the cerebral cortex can be divided into a 6-layer structure according to function and neural cell type, among which the number of neurons in the second layer (about 500 μm in depth) and the fourth layer (about 1500 μm in depth) is relatively large, the number of neurons in the third layer and the fifth layer is the second, and the number of neurons in the first layer and the sixth layer is the smallest. Therefore, in order to maximize the acquisition efficiency of the implanted neural electrode, the number of Laplace electrodes and single electrodes at the depth of the second layer and the fourth layer is the largest, the number of Laplace electrodes and single electrodes at the depth of the third layer and the fifth layer is the second, and the number of electrodes at the depth of the first layer and the sixth layer is the smallest.

[0039] The in-vivo neuron signal acquisition using the implanted brain-computer interface electrode array composed of two types of acquisition electrode structures can realize the synchronous acquisition of multiple types of neural signals, so as to select the required neural signals according to the application needs, and greatly promote the progress of brain science and brain disease research.

[0040] In some embodiments, the first insulating layer 4 is provided with an electrode point windowed exposure area 5 for exposing the electrode point structure including the Laplace electrodes 3 and the single-point electrodes 2. The forming method of the insulating layer includes but is not limited to thermal oxidation growth, multi-target magnetron sputtering, plasma enhanced chemical vapor deposition, low pressure chemical vapor deposition and other thin film growth processes. The insulating layer material includes but is not limited to polyimide, SU-8, parylene, polydimethylsiloxane, silicon oxide, silicon nitride, silicon oxynitride, silicon oxide / silicon nitride composite thin film and the like. The thicker the insulating layer is, the better the insulating effect and the stability of the insulating layer are, but too thick insulating layer will increase the size of the implanted electrode, causing greater implantation damage. Preferably, the thickness of the first insulating layer 4 and the second insulating layer 1 is 100-2000 nm.

[0041] The embodiment of the present application also provides a preparation method of the electrode array structure for multiple types of neural signal acquisition.

[0042] S1, providing a substrate, depositing a layer of metal on the substrate to form a sacrificial layer;

[0043] S2, spin coating and patterning the second insulating layer 1 on the sacrificial layer;

[0044] S3. Sputter or evaporate an adhesion layer and a conductive layer on the second insulating layer 1, spin-coat a positive photoresist as a mask, and after pre-baking, exposure, development and post-baking, use dry etching or wet etching to obtain a conductive layer pattern containing the Laplace electrode 3 and the single-point electrode 2.

[0045] S4. Spin-coat and pattern the first insulating layer 4 on the patterned conductive layer. The opening pattern of the first insulating layer 4, namely the electrode point window exposure area 5, exposes the Laplace electrode 3 and the single-point electrode 2.

[0046] S5. Using a reagent to corrode or dissolve the sacrificial layer, after corroding or dissolving the sacrificial layer, the electrode array is released, resulting in an electrode array structure for acquiring multiple types of neural signals.

[0047] The electrode array structure for acquiring multiple types of neural signals and its preparation method in this invention will be described in more detail with a specific embodiment.

[0048] Example 1

[0049] This embodiment provides an electrode array structure for acquiring multiple types of neural signals, specifically a flexible polyimide-based electrode array for acquiring multiple types of neural signals, as described above. Figure 2 Its preparation method includes:

[0050] S1. Using ordinary silicon wafers as the substrate material for electrodes, the silicon wafers are ultrasonically cleaned in acetone, ethanol and deionized water for 5 minutes respectively, and then dried with nitrogen.

[0051] A 300nm thick layer of aluminum is evaporated onto the cleaned silicon wafer as a sacrificial metal layer, such as... Figure 2 As shown in (1);

[0052] S2. Photosensitive polyimide Durimide 7505 is spin-coated onto the sacrificial metal layer. After exposure, development, and curing, a 2μm thick lower electrode insulating layer, i.e., the second insulating layer, is obtained. Figure 2 As shown in (2),

[0053] S3, Sputter 30nm titanium and 300nm gold over the bottom polyimide layer, such as Figure 2 (3) is shown;

[0054] S4. Spin-coat a 5μm thick positive photoresist onto the metal layer. After pre-baking, photolithography, development, and post-baking, a patterned photoresist mask is obtained. Then, ion beam etching or wet etching is used to pattern the metal layer, and the positive photoresist is removed with acetone to obtain the electrode points and lead wire patterns, such as... Figure 2 (4) is shown;

[0055] S5. After spin-coating polyimide onto the patterned conductive layer and exposing, developing, and curing it, a 2μm thick upper insulating layer, i.e., the first insulating layer, is obtained. Compared with the lower insulating layer, the upper insulating layer increases the open area for exposing electrode points, such as... Figure 2 (5) is shown;

[0056] S6. Finally, the flexible polyimide-based electrode array for acquiring multiple types of neural signals is released by etching the aluminum metal sacrificial layer with dilute hydrochloric acid, such as... Figure 2 As shown in (6).

[0057] To further illustrate the working process of the electrode array for acquiring multiple types of neural signals proposed in this embodiment of the invention... Figure 3 This diagram illustrates the acquisition of single-neuron signals using a dual-loop Laplace electrode and the subsequent data analysis using the Laplace operator. Specifically, the dual-loop Laplace electrode 3 acquires neural signals through differential acquisition of signals from the outer Laplace electrode 31 and the inner Laplace electrode 32. After acquisition, the Laplace operator is used to analyze the signals, enabling the acquisition of single-neuron signals in the near region. The Laplace potential response power decreases with the fourth power of distance, compared to the potential response power decreasing with the first power of distance. The Laplace potential response power is much more sensitive to distance, exhibiting a strong suppression effect on signals from sources far from the observation point, while having little or no suppression effect on signals from sources close to the observation point. Figure 4 This diagram illustrates how a single-point electrode acquires a local field potential signal by adjusting its diameter and impedance. The larger the diameter of the single-point electrode, the smaller the impedance; conversely, the smaller the diameter of the single-point electrode, the larger the impedance. Figure 5 The diagram shows the arrangement of two electrode structures for neural signal acquisition electrode arrays to match the neuron density in different layers of the cerebral cortex. The arrangement of the sparse and dense electrodes can make reasonable use of space and maximize the acquisition of neuronal information.

[0058] Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention. The above preferred features can be used in any combination without conflict.

Claims

1. An electrode array structure for multi-type neural signal acquisition, characterized by, The electrode array comprises a conductive layer, a first insulating layer above the conductive layer, and a second insulating layer below the conductive layer; wherein the conductive layer comprises a Laplace electrode and a single-point electrode, the Laplace electrode is an electrode with a concentric circular ring structure, the Laplace electrode is used for single neuron action potential signal acquisition, and the single-point electrode is used for local field potential signal acquisition, so that the acquisition of different types of neuron signals in vivo is realized through the Laplace electrode and the single-point electrode.

2. The electrode array structure for multi-type neural signal acquisition according to claim 1, wherein, The Laplace electrode comprises a Laplace outer ring electrode, a Laplace inner ring electrode, and a Laplace electrode lead wire, the Laplace outer ring electrode and the Laplace inner ring electrode are concentrically arranged, and the Laplace electrode lead wire is used to lead out the Laplace outer ring electrode and the Laplace inner ring electrode respectively; the Laplace electrode comprises any one or several of a double-ring concentric electrode structure, a three-ring concentric electrode structure, and a multi-ring concentric electrode structure.

3. The electrode array structure for multi-type neural signal acquisition according to claim 1, wherein, The single-point electrode comprises an electrode part and a single-point electrode lead wire, the single-point electrode lead wire is used to lead out the electrode part; the single-point electrode adjusts the impedance value by adjusting the diameter of the electrode part, so that all neuron discharges in different distance ranges are collected.

4. The electrode array structure for multi-type neural signal acquisition according to claim 3, wherein, The diameter of the electrode part is 10-500 μm.

5. The electrode array structure for multi-type neural signal acquisition according to claim 1, wherein, The thickness of the conductive layer is 100-1000 nm.

6. The electrode array structure for multi-type neural signal acquisition according to claim 1, wherein, The number of the Laplace electrode and the single-point electrode is set according to the demand for signal acquisition.

7. The electrode array structure for multi-type neural signal acquisition according to claim 1, wherein, The arrangement density of the Laplace electrode and the single-point electrode at different depths is set according to the characteristics of different numbers of neurons in different brain regions in vivo.

8. The electrode array structure for multi-type neural signal acquisition according to claim 1, wherein, An electrode point window exposure area for exposing the electrode point structure is formed on the first insulating layer.

9. The electrode array structure for multi-type neural signal acquisition according to claim 1, wherein, The thickness of the first insulating layer and the second insulating layer is 100-2000 nm.

10. A method of producing an electrode array structure for multi-type neural signal acquisition according to any one of claims 1 to 9, characterized by, The method comprises: A substrate is provided, and a metal layer is deposited on the substrate to form a sacrificial layer; A second insulating layer is obtained by spin coating and patterning on the sacrificial layer; An adhesion layer and a conductive layer are sputtered or evaporated on the second insulating layer, positive photoresist is spin coated as a mask, and after front baking, exposure, development and post baking, dry etching or wet etching is adopted to obtain a conductive layer pattern containing a Laplace electrode and a single-point electrode; The first insulating layer is spin coated and patterned on the patterned conductive layer, and the opening pattern of the first insulating layer exposes the Laplace electrode and the single-point electrode; After etching or dissolving the sacrificial layer, the release of the electrode array is completed, and an electrode array structure for multi-type neural signal acquisition is obtained.

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