CN115363591A - Electrode array structure for multi-type neural signal acquisition and preparation method thereof - Google Patents

Abstract

The invention provides an electrode array structure for multi-type neural signal acquisition and a preparation method thereof, wherein the electrode array structure comprises a conducting layer, a first insulating layer positioned above the conducting layer and a second insulating layer positioned below the conducting layer; the conducting layer comprises a Laplace electrode and a single-point electrode, the Laplace electrode is an electrode with a concentric ring structure, and the collection of neuron signals of different types is achieved through the Laplace electrode and the single-point electrode. The invention utilizes the implanted brain-computer interface electrode array with two composite collecting electrode structures to collect in-vivo neuron signals, can realize the synchronous acquisition of various types of neural signals, can select the required neural signals according to the application requirements, and greatly promotes the development of brain science and brain disease research.

Description

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

Technical Field

The invention relates to the technical field of brain-computer interface implanted neural microelectrode devices, in particular to an electrode array structure for multi-type neural signal acquisition and a preparation method thereof.

Background

Bioelectric signals are the cornerstone of human life activities. The human body is a very complex system as an organism, and the bioelectricity is closely related to any vital activity of the human body. The potential of an unstimulated nerve cell is called "resting potential", and conversely, the potential generated when a nerve cell is stimulated is called "action potential". This potential difference is due to the positive charge on the outside of the cell membrane and the negative charge on the inside of the cell membrane.

Because of the relative accuracy and the predictability of the disease judgment of the acquisition and the analysis of the brain nerve electrical signals, the method has great application prospect in the diagnosis and treatment of brain diseases. The conventional point electrode array is mainly used for collecting the current nerve electric signals, the characteristic extraction is realized by combining a clustering analysis algorithm, and electrodes in all forms have selectivity on a signal space, namely when a signal source is far away from the position of the electrode point, due to energy dissipation in the signal transmission process, the signals which can be collected by the electrode point can be reduced along with the continuous distance of the signal source. The suppression of the signal response to a distant source and the enhancement of the signal response to a close source is the spatial selectivity of the electrodes. In order to reduce the interference of signals generated by peripheral irrelevant electroencephalograms, the impedance spectrum of the electroencephalograms is increased by reducing the radius of the electrodes, so that the response amplitude of the near-end and far-end signals is regulated, the response amplitude of the far-end signals is lower than the noise of the collector, the far-end signals are submerged in the noise, and the interference of the signals generated by a remote signal source can be filtered. The method for improving the electrochemical impedance spectrum of the electrode is a method for improving the spatial selectivity of the electrode. However, the method improves the space selectivity and simultaneously reduces the response amplitude of the near-end neural signal, thereby influencing the acquisition and analysis of the neural signal with high signal-to-noise ratio.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide an electrode array structure for multi-type neural signal acquisition and a preparation method thereof.

According to an aspect of the present invention, there is provided an electrode array structure for multi-type neural signal acquisition, the electrode array structure including a conductive layer, a first insulating layer located above the conductive layer, and a second insulating layer located below the conductive layer; the conducting layer comprises a Laplace electrode and a single-point electrode, the Laplace electrode is an electrode with a concentric ring structure, and the collection of neuron signals of different types is achieved through the Laplace electrode and the single-point electrode.

Further, the laplace electrode comprises a laplace outer ring electrode, a laplace inner ring electrode and a laplace electrode lead, the laplace outer ring electrode and the laplace inner ring electrode are concentrically arranged, and the laplace electrode lead is used for leading out the laplace outer ring electrode and the laplace inner ring electrode respectively; the Laplace electrode comprises any one or more of a double-ring concentric electrode structure, a three-ring concentric electrode structure and a multi-ring concentric electrode structure.

Further, the single-point electrode comprises an electrode part and a single-point electrode lead, and the single-point electrode lead is used for leading out the electrode part; the single-point electrode realizes the regulation and control of the impedance value by regulating the diameter of the electrode part, thereby realizing the collection of the discharge of all neurons in different distance ranges.

Further, the diameter of the electrode part is 10 to 500 μm.

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

Further, the number of the laplace electrodes and the number of the single-point electrodes are set according to the requirement of acquiring signals respectively.

Furthermore, the arrangement density degree of the laplace electrode and the single-point electrode at different depths is set according to the characteristic that the number of neurons in different brain areas in a body is different.

Furthermore, an electrode point windowing exposure area used for exposing the electrode point structure is formed in the first insulating layer.

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

According to another aspect of the present invention, there is provided a method for preparing the electrode array structure for multi-type neural signal acquisition, the method comprising:

providing a substrate, and depositing a metal layer on the substrate to form a sacrificial layer;

spin-coating and patterning the sacrificial layer to obtain a second insulating layer;

sputtering or evaporating an adhesion layer and a conducting layer on the second insulating layer, spin-coating a positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking and dry etching or wet etching to obtain a conducting layer pattern containing the Laplace electrode and the single-point electrode;

spin-coating and patterning a first insulating layer on the patterned conductive layer, wherein the laplace electrode and the single-point electrode are exposed out of an opening pattern of the first insulating layer;

and after corroding or dissolving the sacrificial layer, releasing the electrode array to obtain the electrode array structure for collecting the multi-type neural signals.

Compared with the prior art, the invention has the following beneficial effects:

the electrode array structure comprises a Laplace electrode structure for collecting high-resolution single neuron action potential signals and a single-point electrode for collecting local field potential signals, and the Laplace concentric ring structure is utilized to overcome the defects that the signal-to-noise ratio of current nerve signal collection is low and different neurons discharge crosstalk mutually, so that the space selectivity of an electrode point is improved, and single neuron signal discharge collection is realized; the discharge of all neurons in different distance ranges is collected by utilizing a single-point electrode structure; the electrode array with the two combined collecting electrode structures is used for collecting in-vivo neuron signals, so that the synchronous acquisition of various types of nerve signals can be realized, the required nerve signals can be selected according to application requirements, and the progress of brain science and brain disease research is greatly promoted.

Drawings

Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:

FIG. 1 is a schematic diagram of a layer structure of an electrode array according to an embodiment of the present invention;

FIG. 2 is a schematic flow chart of a method for manufacturing an electrode array according to an embodiment of the invention;

fig. 3 is a schematic diagram of a dual-ring laplace electrode for signal acquisition to achieve single neuron signal acquisition according to an embodiment of the present invention;

FIG. 4 is a schematic diagram illustrating a single-point electrode acquiring signals to achieve local field potential signal acquisition according to an embodiment of the present invention;

fig. 5 is a schematic diagram illustrating the number and density arrangement of different types of electrodes in the electrode array according to an embodiment of the invention.

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 windowing exposed region.

Detailed Description

The present invention will be described in detail with reference to specific examples. The following examples will aid those skilled in the art in further understanding the present invention, but are not intended to limit the invention in any manner. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.

To address the limitations of the signal acquisition electrodes described above, bin He et al, at chicago, proposed to improve the spatial selectivity of the electrodes using the principle of surface laplacian estimation, the core of which is the laplacian:

the acquired signals are subjected to weighted addition processing through a Laplace operator through calculation, the obtained Laplace potential is in inverse proportion to the fourth power of the distance from the electric dipole to the observation point, namely the Laplace potential response power is reduced by the fourth power of the distance, compared with the situation that the potential response power is reduced by the first power of the distance, the Laplace potential response power is sensitive to the distance, the signal far away from the observation point of a signal source has strong inhibition effect, and the inhibition effect on the signal near the signal source is small or even has no influence. Therefore, the acquired potential is changed into the acquired Laplace potential, so that the space selectivity of the electrode is remarkably improved, and the quality of the acquired signal is improved. However, the structure of the Laplace operator combined with a double-ring or multi-ring Laplace electrode is not applied to the acquisition of implanted electroencephalogram signals at present.

In conclusion, the double-ring or multi-ring laplace electrode structure is combined with the operation of the laplace operator, so that the spatial resolution of neural signal acquisition can be remarkably improved, and the acquisition of single neuron signals is further realized. The electrode array for collecting the multi-type neural signals by further matching the single-point electrode structure combination greatly promotes the progress in the field of the neuroelectrophysiological recording.

To this end, an embodiment of the present invention provides an electrode array structure for multi-type neural signal acquisition, referring to fig. 1, the electrode array structure is a sandwich structure, and includes 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 conducting layer includes Laplace electrode 3 and single-point electrode 2, and Laplace electrode 3 is for having the electrode of concentric circles ring structure, can gather local field potential signal through single-point electrode 2, and local field potential signal is the stack of many neuron discharge signals, can gather neuron action potential signal through Laplace electrode 3, realizes the collection at the neuron signal of the different type of reality jointly through Laplace electrode 3 and single-point electrode 2. The electrode array structure comprises a Laplace electrode 3 for collecting high-resolution single neuron action potential signals and a single-point electrode 2 for collecting local field potential signals, and the Laplace concentric ring structure is utilized to overcome the defects that the current nerve signal collection signal-to-noise ratio is low and different neurons discharge crosstalk mutually, so that the space selectivity of electrode points is improved, and single neuron signal discharge collection is realized; the discharge of all neurons in different distance ranges is collected by using a single-point electrode structure; the electrode array with two combined collecting electrode structures can be used for collecting in-vivo neuron signals, so that the synchronous acquisition of multiple types of nerve signals can be realized, the required nerve signals can be selected according to application requirements, and the progress of brain science and brain disease research is greatly promoted.

In some embodiments, the laplace electrode 3 includes 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 disposed, and the laplace electrode lead 33 is used for leading out the laplace outer ring electrode 31 and the laplace inner ring electrode 32 respectively; the Laplace electrode 3 comprises any one or more of a double-ring concentric electrode structure and a three-ring concentric electrode structure to a multi-ring concentric electrode structure, different ring numbers are analyzed corresponding to different Laplace algorithms, the more the ring numbers are, the higher the precision is, the larger the occupied area is, the difference signal acquisition is carried out by utilizing the Laplace electrode 3, the weighted phase processing (weighted potential analysis) is carried out on signals on different rings through a Laplace operator, the space selectivity of an electrode point is improved, and the single neuron signal discharge acquisition is realized.

In some embodiments, the single-point electrode 2 includes an electrode portion 22 and a single-point electrode lead 21, and the single-point electrode lead 21 is used for leading out the electrode portion 22; the single-point electrode 2 adjusts and controls the impedance value by adjusting the diameter of the electrode part 22, so that the discharge of all neurons in different distance ranges is collected. The larger the diameter of the electrode part 22 of the single-point electrode 2 is, the smaller the electrochemical impedance is, and the local field potential signal in a wider range can be collected, preferably, the diameter of the electrode part 22 is 10-500 μm, and the size of the internal body area can be adjusted and controlled through the adjustment of the impedance.

In some embodiments, the conductive layer is made of a conductive layer material, the conductive layer is formed by a metal film growth method including, but not limited to, multi-target magnetron sputtering, electrochemical plating, electron beam evaporation, ion beam sputtering, etc., the conductive layer material includes, but not limited to, gold, platinum, silver, etc., and the conductive layer thickness is preferably 100-1000nm, considering the overall thickness and conductive effect of the implanted electrode.

In some embodiments, the number of laplace electrodes 3 and single-point electrodes 2 is set according to the requirement of acquiring signals. The arrangement density degree of the Laplace electrode 3 and the single-point electrode 2 at different depths is set according to the characteristic that the number of neurons in different brain areas in a body is different. Specifically, the cerebral cortex can be classified into 6-layer structures according to functions and nerve cell types, wherein the number of nerve cells is larger in the second layer (about 500 μm in depth) and the fourth layer (about 1500 μm in depth), and the number of nerve cells is smallest in the third layer and the fifth layer, and the first layer and the sixth layer. Therefore, to maximize the implantable neural electrode acquisition efficiency, the number of laplace electrodes and single electrodes is the greatest at the second and fourth layers, the second to the first and sixth layers.

The in-vivo neuron signals are acquired by using the implanted brain-computer interface electrode array with the two combined acquisition electrode structures, so that the synchronous acquisition of multiple types of neural signals can be realized, the required neural signals can be selected according to application requirements, and the progress of brain science and brain disease research is greatly promoted.

In some embodiments, the first insulating layer 4 is provided with an electrode point opening window exposure region 5 for exposing the electrode point structure including the laplace electrode 3 and the single-point electrode 2. The insulating layer is formed by a film growth process including, but not limited to, thermal oxidation growth, multi-target magnetron sputtering, plasma enhanced chemical vapor deposition, low pressure chemical vapor deposition, and the like. Insulating layer materials include, but are not limited to, polyimide, SU-8, parylene, polydimethylsiloxane, silicon oxide, silicon nitride, silicon oxynitride, silicon oxide/silicon nitride composite films, and the like. The thicker the insulating layer, the better the insulating effect and the stability of the insulating layer, but too thick the insulating layer increases the size of the implant electrode, causing more implant damage, and preferably the thickness of the first insulating layer 4 and the second insulating layer 1 is 100-2000nm.

The embodiment of the invention also provides a preparation method of the electrode array structure for multi-type neural signal acquisition, which comprises the following steps:

s1, providing a substrate, and depositing a layer of metal on the substrate to form a sacrificial layer;

s2, spin-coating and patterning the sacrificial layer to obtain a second insulating layer 1;

s3, sputtering or evaporating an adhesion layer and a conducting layer on the second insulating layer 1, spin-coating a positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking and dry etching or wet etching to obtain a conducting layer pattern containing the Laplace electrode 3 and the single-point electrode 2;

s4, spin-coating and patterning a first insulating layer 4 on the patterned conducting layer, wherein an opening pattern of the first insulating layer 4, namely an electrode point windowing exposed region 5, exposes the Laplace electrode 3 and the single-point electrode 2;

and S5, using a reagent for corroding or dissolving the sacrificial layer to complete the release of the electrode array after corroding or dissolving the sacrificial layer, thereby obtaining the electrode array structure for collecting the multi-type neural signals.

The electrode array structure for multi-type neural signal acquisition and the preparation method thereof in the embodiment of the invention are described in more detail with an embodiment.

Example 1

The embodiment provides an electrode array structure facing multi-type neural signal acquisition, in particular to an electrode array facing multi-type neural signal acquisition and made of flexible polyimide, and with reference to fig. 2, the preparation method includes:

s1, using a common silicon wafer as a substrate material of an electrode, respectively putting the silicon wafer into acetone, ethanol and deionized water, ultrasonically cleaning for 5 minutes, and then drying by using nitrogen;

evaporating a layer of aluminum with the thickness of 300nm on the cleaned silicon wafer as sacrificial layer metal, as shown in FIG. 2 (1);

s2, spin-coating photosensitive polyimide Durimide 7505 on the sacrificial layer metal, and obtaining a lower electrode insulating layer with the thickness of 2 microns, namely a second insulating layer after exposure, development and curing, as shown in figure 2 (2);

s3, sputtering 30nm titanium and 300nm gold above the bottom layer of polyimide, as shown in a figure 2 (3);

s4, spin-coating a positive photoresist with the thickness of 5 microns on the metal layer, carrying out pre-baking, photoetching, developing and post-baking to obtain a patterned photoresist mask, then patterning the metal layer by using ion beam etching or wet etching, and removing the positive photoresist by using acetone to obtain an electrode point and a lead-out wire pattern, wherein the electrode point and the lead-out wire pattern are shown in a figure 2 (4);

s5, spin-coating polyimide on the patterned conductive layer, exposing, developing and curing to obtain an upper insulating layer (a first insulating layer) with the thickness of 2 microns, wherein compared with the lower insulating layer, the upper insulating layer is provided with an opening area for exposing electrode points, as shown in a figure 2 (5);

and S6, finally, corroding the aluminum metal sacrificial layer through dilute hydrochloric acid to release the electrode array with the flexible polyimide base facing to the multi-type neural signal acquisition, as shown in fig. 2 (6).

To further illustrate the working process of the multi-type neural signal acquisition-oriented electrode array provided by the embodiment of the present invention, fig. 3 shows that the double-ring laplacian electrode performs signal acquisition, and performs data analysis by combining with a laplacian operator, so as to implement a schematic diagram of acquiring a single neural signal, specifically, the double-ring laplacian electrode 3 performs signal differential acquisition on the laplacian outer ring electrode 31 and the laplacian inner ring electrode 32 during neural signal acquisition, and analyzes a signal by using the laplacian operator after acquisition, so as to implement acquisition of a single neural signal in a near region, where laplacian potential response power is reduced by the fourth power of distance, and compared with the reduction of the potential response power by the first power of distance, the response power of laplacian potential is much sensitive to distance, and has a strong inhibitory effect on a signal farther from a signal source to an observation point, and at the same time, the inhibitory effect on a signal closer to the signal source is little or even has no influence. Fig. 4 is a schematic diagram of a single-point electrode for obtaining a local field potential signal by adjusting and controlling the diameter and impedance of the electrode, wherein the larger the diameter of the single-point electrode is, the smaller the impedance is; conversely, the smaller the diameter of the single-point electrode, the greater the impedance. Fig. 5 is a schematic diagram of arrangement of two electrode structures of a neural signal collecting electrode array matching with the neuron density in different layers of the cerebral cortex, and the arrangement of the number arrangement of the sparse and dense electrodes can reasonably utilize the space and maximize the acquisition of neuron information.

The foregoing description has described specific embodiments of the present invention. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention. The above-described preferred features may be used in any combination without conflict with each other.

Claims (10)

1. An electrode array structure facing multi-type neural signal acquisition is characterized by comprising a conducting layer, a first insulating layer located above the conducting layer and a second insulating layer located below the conducting layer; the conducting layer comprises a Laplace electrode and a single-point electrode, the Laplace electrode is an electrode with a concentric ring structure, and the collection of neuron signals of different types is achieved 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 electrodes comprise laplace outer ring electrodes, laplace inner ring electrodes and laplace electrode leads, the laplace outer ring electrodes and the laplace inner ring electrodes are arranged concentrically, and the laplace electrode leads are used for leading out the laplace outer ring electrodes and the laplace inner ring electrodes respectively; the Laplace electrode comprises any one or more 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 of claim 1, wherein the single-point electrode comprises an electrode portion and a single-point electrode lead, and the single-point electrode lead is used for leading out the electrode portion; the single-point electrode realizes the regulation and control of the impedance value by regulating the diameter of the electrode part, thereby realizing the collection of the discharge of all neurons in different distance ranges.

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

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

6. The electrode array structure for multi-type neural signal acquisition of claim 1, wherein the number of the laplace electrodes and the number of the single-point electrodes are respectively set according to the requirement of acquiring signals.

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

8. The electrode array structure for multi-type neural signal acquisition of claim 1, wherein an electrode point windowing exposure region for exposing the electrode point structure is opened on the first insulating layer.

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

10. A method for preparing an electrode array structure for multi-type neural signal acquisition according to any one of claims 1-9, comprising:

providing a substrate, and depositing a layer of metal on the substrate to form a sacrificial layer;

spin-coating and patterning the sacrificial layer to obtain a second insulating layer;

sputtering or evaporating an adhesion layer and a conducting layer on the second insulating layer, spin-coating a positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking and dry etching or wet etching to obtain a conducting layer pattern containing the Laplace electrode and the single-point electrode;

spin-coating and patterning a first insulating layer on the patterned conductive layer, wherein the laplace electrode and the single-point electrode are exposed out of an opening pattern of the first insulating layer;

and after corroding or dissolving the sacrificial layer, releasing the electrode array to obtain the electrode array structure for collecting the multi-type neural signals.

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