CN115399777A - Flexible double-sided nerve probe and preparation method thereof - Google Patents

Abstract

The invention provides a flexible double-sided nerve probe and a preparation method thereof, wherein the probe comprises a first insulating layer, a lead layer and a second insulating layer which are sequentially arranged from bottom to top; the brain wave stimulation device is characterized in that the first insulating layer and the second insulating layer are flexible polymer insulating layers, bottom electrode points communicated with the lead layer are arranged on the first insulating layer, top electrode points communicated with the lead layer are arranged on the second insulating layer, the top electrode points and the bottom electrode points are both made of nuclear magnetic compatible materials, and all-dimensional brain wave collection and directional electrical stimulation are achieved through the bottom electrode points and the top electrode points. The probe has a double-sided electrode point structure, can meet the requirement of omnibearing electroencephalogram acquisition and has higher electrode point density; the double-sided structure can perform directional electrical stimulation, so that the accuracy of neural activity intervention can be improved.

Description

Flexible double-sided nerve probe and preparation method thereof

Technical Field

The invention relates to the technical field of brain-computer interface neural microelectrodes, in particular to a flexible double-sided nerve probe and a preparation method thereof.

Background

The implanted brain-computer interface is an important tool for brain science and brain-like research, can be directly contacted with neurons, can acquire and transmit more abundant information with cerebral neurons, and has important significance for brain science research, brain disease diagnosis and treatment and brain-computer interaction research. Implantable brain-computer interfaces can employ electrical power to precisely interact with the brain and diagnose disease by monitoring electrical activity of the brain, bringing a very optimistic prospect. In addition, the brain-computer interface technology can also recover vision and hearing, generate synthesized voice and help to treat diseases such as obsessive-compulsive disorder, addiction and Parkinson's disease.

The interface characteristic of the implant and the neuron is the key of brain-computer interaction, and the essence of electroencephalogram signal acquisition and neuron electrical stimulation is charge transmission and regulation between the electrode and the neuron. The flexible implantable brain-computer interface has unique advantages in the aspect of low injury, but the number of acquisition channels of the traditional flexible electrode array is insufficient, and the number of acquisition neurons cannot meet the requirements of neuroscience research and neural coding and decoding; moreover, the implanted electrode is usually a single-sided electrode, which is not beneficial to all-around acquisition of electroencephalogram signals; implantation of electrode materials can produce artifacts, heating and some displacement in fMRI. By using an electromagnetic compatible material and an advanced micro-nano processing technology, a double-sided electrode structure based on a laser direct writing processing technology is realized, so that the high density and the electromagnetic compatibility of the flexible electrode are improved; the electrode point arrangement density is changed along with the brain area, so that the electrode point arrangement density and the stimulation directionality in different brain areas and different cortex depths are adjustable, and the omnibearing stimulation function of the electrode point is improved.

In view of the prior art, the fraunhhoff biomedical engineering research institute Thomas stieglititz et al, sensor and Actuators a, physics, 2001,90 (3): 203-211, written "Flexible two-dimensional micro devices with double-sided electrodes for neural applications", proposes a Flexible double-sided electrode fabricated by a multi-step spin coating, deposition and etching process using non-photosensitive polyimide as a base material, which is disadvantageous to large-area fabrication due to the use of an aluminum hardmask process requiring multi-step exposure during patterning of the material, and also requires separation and flip-attachment of the Flexible base from the rigid substrate after patterning of the front surface of the electrode, and the process requires extreme care since the thin film must be placed very smoothly on the wafer to ensure proper, uniform and repeatable mass etching. It is difficult to accurately position the film on the wafer during the process and place it without trapping any air bubbles or bending the film, which makes the manufacturing process time consuming and prone to large yield losses.

"Flexible polyimide probes with microelectrodes and embedded microfluidic channels for multiple polyimide drug delivery and multi-channel monitoring of biological activity" by the Federal institute of Federal engineering, switzerland S.Metz et al in biosens, bioelectron.19,1309-1318 (2004) proposes a double-sided polyimide structure manufactured using lamination technology, which also integrates microfluidic channels. The process is relatively simple because only one metallization step is required to create the contacts on both sides. However, this technique cannot be used to create a structure with two electrode points at the same location on both sides. In addition, the electrode points on the top surface of the prepared probe are concave, while the electrode points on the bottom surface are not concave, so that the two surfaces of the probe have different current density distributions, and the acquisition and stimulation effects of neural signals are influenced.

In conclusion, electrode points are formed on two sides of the nerve probe, so that the density of nerve signal collection can be improved, omnibearing nerve signal collection and stimulation are realized, and the requirements of multiple brain areas and high density in rodent research are further met. Therefore, it is highly desirable to develop a flexible probe electrode with a double-sided electrode structure and good processing characteristics for application to biological tissues.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide a flexible double-sided nerve probe and a preparation method thereof.

According to one aspect of the invention, a flexible double-sided nerve probe is provided, which comprises a first insulating layer, a wire layer and a second insulating layer which are arranged in sequence from bottom to top; the brain wave stimulation device is characterized in that the first insulating layer and the second insulating layer are flexible polymer insulating layers, bottom electrode points communicated with the lead layer are arranged on the first insulating layer, top electrode points communicated with the lead layer are arranged on the second insulating layer, the top electrode points and the bottom electrode points are both made of nuclear magnetic compatible materials, and all-dimensional brain wave collection and directional electrical stimulation are achieved through the bottom electrode points and the top electrode points.

Further, the bottom electrode point is formed by a micro-machining process, and the top electrode point is formed by a micro-machining process.

Furthermore, the geometrical shapes of the top layer electrode points and the bottom layer electrode points are any one or combination of a plurality of circular, rectangular and triangular shapes, and the diameters of the top layer electrode points and the bottom layer electrode points are 10-200 micrometers.

Further, the top layer electrode points and the bottom layer electrode points both comprise collecting points and stimulating points, and the arrangement mode of the collecting points and the stimulating points is set according to brain area distribution.

Further, the flexible polymer insulating layer is made of any one of non-photosensitive polyimide, photosensitive polyimide and parylene; the thickness of the probe is 1-50 microns.

Further, the wire layer includes a conductive layer and an adhesion layer for adhering the conductive layer to the first insulating layer, the conductive layer being located above the adhesion layer; the thickness of the adhesion layer is 10-100 nanometers; the thickness of the conducting layer is 200-500 nanometers.

Furthermore, a tail end connecting port is arranged at the tail end of the probe, a steel needle auxiliary implantation hole is arranged at the implantation end of the probe, the tail end connecting port is used for being electrically connected with an external circuit, and the lead layer is used for transmitting the nerve signals to the tail end connecting port from the top layer electrode points and the bottom layer electrode points; the steel needle auxiliary implantation hole is used for the penetration of a steel needle so as to facilitate the implantation of the probe to a required position.

According to another aspect of the present invention, there is provided a method for preparing the flexible double-sided nerve probe, the method comprising:

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

then spin-coating and patterning the sacrificial layer to obtain a first insulating layer, and forming bottom electrode points at each electrode point of the first insulating layer by adopting a micro-processing technology;

sequentially depositing an adhesion layer and a conducting layer on the first insulating layer, spin-coating a positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking, and performing ion beam etching or wet etching to obtain a conductor layer;

spin-coating and patterning a second insulating layer on the patterned conductor layer, and forming top electrode points at each electrode point of the second insulating layer by adopting a micro-machining process;

corroding or dissolving the sacrificial layer to complete the release of the electrode, and obtaining the flexible double-sided nerve probe.

Further, the providing a substrate and depositing a layer of metal on the substrate to form a sacrificial layer, wherein: the sacrificial layer is made of metal aluminum, and the thickness of the sacrificial layer is larger than 200nm.

According to another aspect of the present invention, there is provided a method for preparing the flexible double-sided nerve probe, the method comprising:

providing a substrate;

forming a first insulating layer on the substrate;

forming a bottom electrode point on the electrode point of the first insulating layer by using a micro-machining process;

sequentially depositing an adhesion layer and a conducting layer on the first insulating layer, throwing positive photoresist on the conducting layer, developing after exposure, post-baking, and then forming a lead layer by wet etching;

forming a second insulating layer on the wire layer;

forming a top electrode point on the second insulating layer by using a micro-processing technology;

throwing positive photoresist on the second insulating layer, developing and baking after photoetching to form a groove around the top layer electrode point and an electrode overall contour line; etching the whole contour of the tail end connecting port and the electrode which are not covered by the positive glue;

and finally tearing off the formed electrode from the substrate to obtain the flexible double-sided nerve probe.

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

1. according to the flexible double-sided nerve probe, the electrode points are uniformly distributed on the front side and the back side of the probe, and compared with a single-sided nerve probe, the flexible double-sided nerve probe has higher electrode point density, so that nerve electrical stimulation and signal recording spatial resolution of double electrode points can be provided under the condition of the same implantation injury; meanwhile, a double-sided electrode structure is adopted, electrode points are distributed on two sides of the probe, and compared with a single-sided electrode structure, the brain-electrical signal acquisition and stimulation probe can simultaneously acquire and stimulate neurons in the same region in different directions, so that all-dimensional brain electrical signal acquisition and stimulation can be realized.

2. The conductive material formed by the micromachining process cannot generate artifacts, heat and displacement in fMRI, so that the high density and the electromagnetic compatibility of the flexible electrode are improved.

3. PSS and other electrode materials are used for reducing detection impedance and noise, meanwhile, the electrodes have the capacity of detecting various signals, the layout and the structure of electrode points are customized according to brain area distribution, the functions of electroencephalogram signal detection, chemical signal detection and electric pulse stimulation on nerves in a specific area are realized, the flexible double-sided nerve probe has stronger robustness in the practical application of nerve electrical stimulation, and the flexible double-sided nerve probe has wide application value in the aspect of intervention and treatment of nerve diseases; meanwhile, the probe type structure has the advantages of small size, low damage caused by invasion into a body and the like.

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 structural diagram of a flexible double-sided nerve probe according to an embodiment of the present invention;

FIG. 2 is a process flow diagram of a flexible bi-facial nerve probe according to an embodiment of the present invention;

FIG. 3 is a schematic diagram of the distribution of the front and back side electrode points of the flexible double-sided nerve probe according to an embodiment of the present invention;

fig. 4 is a schematic diagram showing the comparison of the nerve signal acquisition capacity of the flexible double-sided nerve probe and the single-sided electrode in the brain of the living body according to the embodiment of the invention, wherein (a) represents the single-sided electrode, and (b) represents the flexible double-sided nerve probe.

In the figure: 1 is a substrate, 2 is a sacrificial layer, 3 is a first insulating layer, 4 is a conducting wire layer, 5 is a second insulating layer, 6 is a bottom electrode point, 7 is a top electrode point, 8 is a tail end connecting port, and 9 is a steel needle auxiliary implantation hole.

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 concept of the invention. All falling within the scope of the present invention.

In the description of the present invention, it is to be understood that the terms "upper", "lower", "left", "right", "top", "bottom", and the like, indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience in describing the present invention and simplifying the description, but do not indicate or imply that the device or element referred to must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present invention.

The embodiment of the invention provides a flexible double-sided nerve probe, and referring to fig. 1, the flexible double-sided nerve probe is of a sandwich structure and comprises a first insulating layer 3, a lead layer 4 and a second insulating layer 5 which are sequentially arranged from bottom to top; first insulating layer 3 and second insulating layer 5 are flexible polymer insulating layer, be equipped with the bottom electrode point 6 with wire layer 4 intercommunication on the first insulating layer 3, be equipped with the top layer electrode point 7 with wire layer 4 intercommunication on the second insulating layer 5, top layer electrode point 7 and bottom electrode point 6 are all adopting the compatible material of nuclear magnetism to form two-sided electrode point in upper and lower two-layer flexible polymer insulating layer, realize all-round brain electricity collection and directional electro photoluminescence through bottom electrode point 6 and top layer electrode point 7. According to the embodiment of the invention, the electrode points are uniformly distributed on the front side and the back side of the probe, and compared with a single-side nerve probe, the electrode point density is higher, so that the nerve electrical stimulation and signal recording spatial resolution of double electrode points can be provided under the condition of the same implantation injury; meanwhile, a double-sided electrode structure is adopted, electrode points are distributed on two sides of the probe, and compared with a single-sided electrode structure, the brain-electrical signal acquisition and stimulation probe can simultaneously acquire and stimulate neurons in the same region in different directions in the brain, so that the all-dimensional brain-electrical signal acquisition and stimulation can be realized.

In some embodiments, the bottom electrode point 6 and the top electrode point 7 are formed by micromachining processes such as laser direct writing, for example, when both the bottom electrode point 6 and the top electrode point 7 are carbon electrode points, the bottom electrode point 6 is formed by laser direct writing carbonization of the first insulating layer 3, the top electrode point 7 is formed by laser direct writing carbonization of the second insulating layer 5, and the electrode points are regions where the bottom polymer film or the top polymer film is carbonized by laser and are communicated with the middle conducting wire layer 4 for conduction. The position of the flexible probe where the electrode points are located and the number of the electrode points can be adjusted according to actual needs, the electrode points are processed in two steps in the processing process, and the bottom layer electrode points 6 are processed first and then the top layer electrode points 7 are processed.

In some embodiments, the top electrode point and the bottom electrode point both comprise collection points and stimulation points, and the arrangement of the collection points and the stimulation points is set according to the distribution of the brain area. The geometrical shapes of the top layer electrode points and the bottom layer electrode points are any one or the combination of any more of circles, rectangles and triangles, the diameters of the top layer electrode points and the bottom layer electrode points are matched with the size of the neuron and the brain area, and the diameter is preferably 10-200 micrometers.

The flexible polymer insulating layer is formed by a biocompatible flexible polymer material, in some embodiments, the material of the flexible polymer insulating layer is selected from any one of non-photosensitive polyimide, photosensitive polyimide and colorless transparent parylene, and in other embodiments, a person skilled in the art may also perform any appropriate adjustment on the material of the flexible polymer insulating layer and select another insulating polymer film material to form the flexible polymer insulating layer; the polymer film is processed in two steps in the processing process, wherein the bottom polymer film is processed firstly, and then the top polymer film is processed, and the thickness of the probe is 1-50 micrometers.

The wire layer 4 is located between the second insulating layer 5 and the first insulating layer 3 after the first insulating layer 3 is processed in the order of the processing. In some embodiments, the wire layer 4 includes a conductive layer and an adhesion layer for adhering the conductive layer to the first insulating layer 3, the conductive layer being located above the adhesion layer; the material of the adhesion layer comprises but is not limited to conductive materials with good bonding force of insulating layers such as titanium, chromium, nickel or titanium-tungsten alloy, and the thickness of the adhesion layer is 10-100 nanometers; the material of the conducting layer includes, but is not limited to, high conductivity and high biocompatibility materials such as gold, platinum, titanium, etc., and the thickness of the conducting layer is 200-500 nanometers.

In some embodiments, the tail end of the probe is provided with a tail end connecting port 8, the implanting end of the probe is provided with a steel needle auxiliary implanting hole 9, the tail end connecting port 8 is used for being electrically connected with an external circuit, electrode points formed by nuclear magnetic compatible materials enable the electrode points to have good biocompatibility and electromagnetic compatibility after implantation, and the lead layer 4 is used for conducting nerve signals from the top electrode point 7 and the bottom electrode point 6 to the tail end connecting port 8; the steel needle auxiliary implantation hole 9 is used for the penetration of a steel needle so as to facilitate the implantation of the probe to a required position, and has the advantages of small size, low injury invasion in vivo and the like.

It should be noted that in other embodiments, the top electrode point 7 and the bottom electrode point 6 may be formed of other nuclear magnetic compatible materials besides carbon electrode points, the artifact of the metal implant is influenced by the magnetic susceptibility (χ), and the volume of the metal artifact is equal to | χ under the same other conditions _v -χ _water L is proportional, wherein χ _v Is the volume magnetic susceptibility, χ, of the metal _water Is the bulk magnetic susceptibility of water, and thus, in order to develop low artifact magnetically compatible alloys, for paramagnetic alloys, the bulk magnetic susceptibility is reduced as much as possible to approach that of water; for diamagnetic alloy, the volume magnetic susceptibility of the diamagnetic alloy is basically the same as that of water by adjusting the alloy components; therefore, phenomena such as artifacts and the like cannot be generated in fMRI, and the electromagnetic compatibility of the flexible electrode is improved.

The embodiment of the invention also provides a preparation method of the flexible double-sided nerve probe, and referring to fig. 2, the method comprises the following steps:

s1, providing a substrate 1, and depositing a layer of metal on the substrate 1 to form a sacrificial layer 2;

in some embodiments, a substrate 1 is provided, and a layer of metal is deposited on the substrate 1 to form a sacrificial layer 2, wherein: the sacrificial layer 2 is made of metal aluminum, and the thickness of the sacrificial layer 2 is larger than 200nm.

S2, cleaning the sacrificial layer 2, then spin-coating and patterning the sacrificial layer 2 to obtain a first insulating layer 3, and forming bottom electrode points 6 on each electrode point of the first insulating layer 3, namely the electrode points distributed on the corresponding probe by adopting a micromachining process such as laser direct writing of the first insulating layer 3;

in some embodiments, if the laser direct write carbonization of the first insulating layer 3 is used to form the bottom electrode point 6, wherein: the laser wavelength is 500-2000 nm, and the laser power is 0.1-10W.

S3, sequentially depositing an adhesion layer and a conducting layer on the first insulating layer 3, spin-coating a positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking, and performing ion beam etching or wet etching to obtain a wire layer 4;

s4, spin-coating and patterning a second insulating layer 5 on the patterned lead layer 4, and forming a top electrode point 7 at each electrode point of the second insulating layer 5 by directly writing the second insulating layer 5 by a micro-processing technology such as laser;

in some embodiments, the top electrode point 7 is formed if the second insulating layer 5 is carbonized by laser direct writing, wherein: the laser wavelength is 500-2000 nm, and the laser power is 0.1-10W.

And S5, corroding or dissolving the sacrificial layer 2 to complete the release of the electrode, so as to obtain the flexible double-sided nerve probe.

The preparation method of the flexible double-sided nerve probe provided by the other embodiment of the invention comprises the following steps:

s1, providing a substrate;

s2, forming a first insulating layer on the substrate;

s3, forming a bottom layer electrode point on the electrode point of the first insulating layer by using a micro-machining process;

s4, sequentially depositing an adhesion layer and a conductive layer on the first insulating layer, throwing positive photoresist on the conductive layer, developing after exposure, post-baking, and then forming a lead layer by wet etching;

s5, forming a second insulating layer on the wire layer;

s6, forming a top layer electrode point on the electrode point of the second insulating layer by using a micro-machining process;

s7, throwing positive photoresist on the second insulating layer, developing and baking after photoetching to form a groove around the top-layer electrode point and an electrode overall contour line; etching the whole outlines of the tail end connecting port and the electrode which are not covered by the positive glue;

and S8, finally tearing off the formed electrode from the substrate to obtain the flexible double-sided nerve probe.

The flexible double-sided nerve probe provided by the embodiment of the invention has the electrode point structures arranged on two sides, can meet the requirements of all-dimensional electroencephalogram acquisition, has higher electrode point density, and can perform directional electrical stimulation on the double-sided structure, so that the accuracy of nerve activity intervention is improved. In addition, PSS (patterned sapphire substrate) and other electrode modification materials such as platinum black, iridium oxide and PEDOT (PEDOT-substrate gold nanoparticles) are used for reducing detection impedance and noise, meanwhile, the electrode has the capability of detecting various signals, the layout and the structure of electrode points are customized according to brain area distribution, the functions of electroencephalogram signal detection, chemical signal detection and electric pulse stimulation on nerves in a specific area can be realized, the robustness is higher in the practical application of nerve electrical stimulation, and the application value is wide in the aspect of nerve disease intervention and treatment; meanwhile, the probe type structure has the advantages of small size, low damage caused by invasion into a body and the like.

The flexible double-sided nerve probe and the preparation method thereof in the embodiment of the invention are further explained by taking the preparation of the flexible double-sided nerve probe by two different polymer films as an example.

Example 1

The embodiment provides a photosensitive polyimide flexible double-sided nerve probe and a preparation method thereof, and the preparation method specifically comprises the following steps:

s100: referring to (1) in fig. 2, a substrate 1 with a common single-side polished silicon wafer as an electrode is put into acetone, ethanol and deionized water respectively for ultrasonic cleaning for 5 minutes, then dried by blowing with nitrogen and then baked in an oven at 180 ℃ for 3 hours.

S200: referring to (2) in FIG. 2, a 400nm thick layer of aluminum is evaporated as a sacrificial layer 2 on the cleaned silicon wafer.

S300: referring to fig. 2 (3), photosensitive polyimide Durimide 7505 was spin-coated on the sacrificial layer 2, and exposed, developed, and cured to obtain an electrode underlayer polymer layer having a thickness of 2.5 μm, i.e., the first insulating layer 3.

S400: referring to (4) in fig. 2, the primer polymer layer is carbonized at the electrode points of the primer polymer layer by direct laser writing, and carbonized primer electrode points 6 concentric with the electrode points are formed.

S500: referring to (5) in fig. 2, 30nm chromium and 300nm gold are sputtered on the bottom polyimide to form a metal layer, i.e., a wire layer 4, a positive photoresist AZ4620 with a thickness of 5 μm is spin-coated on the metal layer, a patterned photoresist mask is obtained through pre-baking, photolithography, development and post-baking, the patterned metal layer is patterned by ion beam etching or wet etching, and the positive photoresist mask is removed by acetone. This step forms the intermediate wiring layer 4, the tail end connection port 8 and the electrode points.

S600: referring to (6) in fig. 2, photosensitive polyimide is further spin-coated on the patterned metal layer, and the top polyimide layer, i.e. the second insulating layer 5, with a thickness of 2.5 μm is obtained after exposure, development and curing.

S700: referring to (7) in fig. 2, at the electrode point of the top polymer layer, the bottom polymer layer is carbonized by direct laser writing to form a carbonized top electrode point 7 concentric with the electrode point.

S800: referring to (8) in fig. 2, the electrodes are released by corroding the sacrificial layer 2 of aluminum with electrochemical or dilute hydrochloric acid to obtain the flexible double-sided nerve probe.

Example 2

The embodiment provides a parylene flexible stretchable probe electrode and a preparation method thereof, which specifically comprise the following steps:

using a common 4-inch round glass sheet as a substrate of an electrode, respectively putting the glass sheet into acetone, ethanol and 1 deionized water for ultrasonic cleaning for 5 minutes, then blowing to dry by using nitrogen, and then putting into an oven at 180 ℃ for baking for 3 hours;

depositing 5 μm Parylene C as a bottom insulating layer of the electrode, i.e., a first insulating layer, on the glass sheet using a chemical vapor deposition system (CVD);

carbonizing Parylene C at the electrode point of the bottom layer insulating layer in a laser direct writing mode to form a carbonized bottom layer electrode point concentric with the electrode point;

sputtering a Cr metal layer as an adhesion layer on the bottom insulating layer, wherein the thickness of the Cr metal layer is 30nm; sputtering an Au metal layer as a conducting layer, wherein the thickness of the Au metal layer is 300nm, and forming a conducting layer;

throwing positive glue (AZ 4620) 5 microns on the metal layer, developing after exposure, post-baking, and then forming a metal wire and an electrode point, namely a wire layer, by wet etching;

depositing 5 mu m Parylene C on the lead layer as a top insulating layer of the electrode, namely a second insulating layer, by using a chemical vapor deposition system (CVD) again;

carbonizing Parylene C at the electrode point of the top insulating layer in a laser direct writing mode to form a carbonized top electrode point concentric with the electrode point;

throwing positive photoresist (AZ 4620) with the thickness of 10 mu m on the top insulating layer, developing after photoetching and baking on a hot plate with the temperature of 60 ℃ for 30 minutes to form a groove around an electrode point and an integral contour line of the electrode;

etching the metal tail end connecting part (tail end connecting port) which is not covered by the positive glue and the whole outline of the electrode by adopting oxygen plasma etching equipment, wherein the etching time and power are controlled during the etching, if the etching is insufficient, the electrode is not conducted, and the electrode is not shaped; if the etching is over-etched, the top insulating layer is etched, and the insulating effect is not achieved;

and finally, slowly tearing off the formed electrode from the glass substrate by using forceps to obtain the flexible double-sided nerve probe.

For the two different process modes, the flexible double-sided nerve probe has the same structure and similar functions, and in order to further illustrate the advantages of the flexible double-sided nerve probe in the embodiment of the invention compared with the traditional single-sided flexible probe, a customizable electrode point distribution design and a schematic diagram for comparing the collection stimulation conditions with the single-sided nerve probe are shown. As shown in fig. 3, the collection and stimulation electrode sizes can be optimized, the arrangement intervals of the collection electrodes are reasonably arranged, dense arrangement of key brain areas such as visual cortex, motor cortex and the like is realized, the arrangement of sparse arrangement of other brain areas is realized, the high resolution of neurons in the same depth is realized, and the cooperative interaction of different brain areas is explored at the same time.

Referring to fig. 4, electrode points are distributed on only one side of a probe of a traditional single-sided electrode, only the neural signals near one side of the electrode points can be collected and stimulated, the two sides of a flexible double-sided neural probe can collect and stimulate the neural signals, neurons are located in the same area, the collection density can be further improved, the stimulation capability in different directions is achieved, and the intervention effect on neural activities can be remarkably improved.

Therefore, the flexible double-sided nerve probe provided by the embodiment of the invention has the electrode point structure with double-sided arrangement, compared with the traditional single-sided electrode, the flexible double-sided nerve probe meets the requirement of omnibearing electroencephalogram acquisition, has higher electrode point density, and directional electrical stimulation can improve the intervention accuracy of nerve activity.

The foregoing description of specific embodiments of the present invention has been presented. 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. A flexible double-sided nerve probe is characterized by comprising a first insulating layer, a wire layer and a second insulating layer which are sequentially arranged from bottom to top;

the brain wave stimulation device is characterized in that the first insulating layer and the second insulating layer are flexible polymer insulating layers, bottom electrode points communicated with the lead layer are arranged on the first insulating layer, top electrode points communicated with the lead layer are arranged on the second insulating layer, the top electrode points and the bottom electrode points are both made of nuclear magnetic compatible materials, and all-dimensional brain wave collection and directional electrical stimulation are achieved through the bottom electrode points and the top electrode points.

2. The flexible bi-planar nerve probe of claim 1, wherein the bottom layer electrode points and the top layer electrode points are formed by a micro-machining process.

3. The flexible double-sided nerve probe of claim 1, wherein the top layer electrode point and the bottom layer electrode point have any one or a combination of a circle, a rectangle and a triangle in geometric shape, and the diameter of the top layer electrode point and the bottom layer electrode point is 10-200 microns.

4. The flexible double-sided nerve probe of claim 1, wherein the top layer electrode points and the bottom layer electrode points each comprise a collection point and a stimulation point, and the collection points and the stimulation points are arranged according to brain region distribution.

5. The flexible double-sided nerve probe as claimed in claim 1, wherein the flexible polymer insulating layer is made of any one of non-photosensitive polyimide, photosensitive polyimide and parylene; the thickness of the probe is 1-50 microns.

6. The flexible double-sided nerve probe of claim 1, wherein the wire layer comprises a conductive layer and an adhesion layer for adhering the conductive layer to the first insulating layer, the conductive layer being located above the adhesion layer; the thickness of the adhesion layer is 10-100 nanometers; the thickness of the conducting layer is 200-500 nanometers.

7. The flexible double-sided nerve probe according to claim 1, wherein a tail end connecting port is arranged at the tail end of the probe, a steel needle auxiliary implantation hole is arranged at the implantation end of the probe, the tail end connecting port is used for being electrically connected with an external circuit, and the lead layer is used for conducting nerve signals from the top layer electrode point and the bottom layer electrode point to the tail end connecting port; the steel needle auxiliary implantation hole is used for the penetration of a steel needle so as to facilitate the implantation of the probe to a required position.

8. A method of making a flexible, bifacial nerve probe according to any one of claims 1-7, 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 first insulating layer, and forming bottom electrode points at each electrode point of the first insulating layer by adopting a micro-processing technology;

depositing an adhesion layer and a conducting layer on the first insulating layer in sequence, spin-coating a positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking by adopting ion beam etching or wet etching to obtain a wire layer;

spin-coating and patterning a second insulating layer on the patterned conductor layer, and forming top electrode points at each electrode point of the second insulating layer by adopting a micro-machining process;

corroding or dissolving the sacrificial layer to complete the release of the electrode, and obtaining the flexible double-sided nerve probe.

9. The method for preparing a flexible double-sided nerve probe according to claim 8, wherein a substrate is provided, and a metal layer is deposited on the substrate to form a sacrificial layer, wherein: the sacrificial layer is made of metal aluminum, and the thickness of the sacrificial layer is larger than 200nm.

10. A method of making a flexible, bifacial neural probe of any of claims 1-7, comprising:

providing a substrate;

forming a first insulating layer on the substrate;

forming a bottom electrode point on the electrode point of the first insulating layer by using a micro-processing technology;

sequentially depositing an adhesion layer and a conductive layer on the first insulating layer, throwing positive photoresist on the conductive layer, developing after exposure, post-baking, and then forming a wire layer by using wet etching;

forming a second insulating layer on the wire layer;

forming a top electrode point on the second insulating layer by using a micro-processing technology;

throwing positive photoresist on the second insulating layer, developing and baking after photoetching to form a groove around the top layer electrode point and an electrode overall contour line; etching the whole outlines of the tail end connecting port and the electrode which are not covered by the positive glue;

and finally tearing off the formed electrode from the substrate to obtain the flexible double-sided nerve probe.

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