CN107638175B - A flexible electrode array-fiber composite nerve electrode and preparation method thereof - Google Patents

Abstract

The present invention provides a flexible electrode array-fiber composite nerve electrode, the nerve electrode includes a flexible electrode array, an optical fiber and a support structure, wherein a groove is provided on the surface of the support structure, and the optical fiber is fixed inside the groove, The flexible electrode array includes three regions of solder joints, interconnecting wires and recording sites that are connected in sequence, the solder joint regions are fixed on the surface of the support structure, and the interconnecting wires and the recording site regions are crimped and wrapped on the fiber surface. The composite neural electrode can be implanted into a specific brain region of the brain after being cured by polyethylene glycol (PEG), and can stimulate or inhibit the electrophysiological signal release of a specific type of neuron in a specific brain region by using an optical fiber. The electrode array detects the electrophysiological signal of the neuron, which can organically combine the electrophysiological signal detection and optogenetic technology, and has important application value for the research of neural circuits, neurological diseases and neural prostheses.

Description

A flexible electrode array-fiber composite nerve electrode and preparation method thereof

technical field

The invention relates to the technical fields of neuroscience and biological instrument engineering, in particular to a flexible electrode array/optical fiber composite nerve electrode and a preparation method thereof.

Background technique

Neural electrodes are a hot research topic in brain-computer interface technology, which can provide an information interaction interface between brain neurons and electronic systems, and have important application prospects in neurocognitive behavior and disease treatment. Existing neural electrodes include electroencephalography (EEG) electrodes, cerebral cortex (ECoG) electrodes and implantable electrodes, wherein implantable neural electrodes, especially implantable neural electrode arrays, can distinguish the electrical properties of individual nerve cells through action potentials. activity, achieving high spatiotemporal resolution and simultaneous detection of a wide range of neuronal electrical activity. Implantable neural electrode arrays usually take part of the channel electrical stimulation to induce the firing of nerve cells, and the remaining channels detect the electrical firing signals of the nerve cells. The main principle of stimulating electrodes is to directly apply electric field perturbation, and conduct the perturbation to a specific brain area of the brain through the electrode array, so that all nerve cells near the brain area are forced to fire. The advantage of electrical stimulation is that it can directly affect the electrical activity of nerves, and the platform construction is simple. However, because the electric field applied by electrical stimulation has a large range and no directionality, the normal electrical activity of the incoherent brain regions around the target brain region is often disturbed during the propagation process, and leads to the misactivation of the incoherent brain regions; in addition, , electrical stimulation often activates all types of neurons (even glial cells) in the target brain region, making it difficult to detect specific types of neuron activity in specific brain regions.

Optogenetics refers to a technology that combines optical and genetic means to precisely control neuronal activity in specific brain regions. The main principle is to use gene manipulation technology to transfer light-sensing genes into specific types of cells in the nervous system for the expression of special ion channels or G protein-coupled receptors (GPCRs). The photosensitive ion channel will be selective for the passage of cations or anions under the stimulation of different wavelengths of light, so that the membrane potential of the cell membrane changes, and the purpose of selectively exciting or inhibiting cells is achieved. This technology overcomes the shortcomings of traditional methods to control cell activity, and has the two characteristics of unique spatiotemporal resolution and cell type specificity, and can precisely position and stimulate neurons.

The photoelectric composite electrode adds a light transmission channel on the basis of the original recording electrode, and realizes electrophysiological recording at the same time of light stimulation of specific types of neurons in specific brain regions. The most commonly used optoelectronic composite electrode is realized by the integration of optical fiber and microwire electrode. This optoelectronic composite electrode is economical and practical, but has great limitations in spatial accuracy and mechanical properties. Therefore, it is necessary to study optoelectronic composite electrodes with new structures and applied new materials.

SUMMARY OF THE INVENTION

In view of the technical problems existing in the prior art, the present invention provides a flexible electrode array-optical fiber composite neural electrode and a preparation method thereof. Optical signals can stimulate or inhibit the electrophysiological signal emission of neurons in specific brain areas, and then the electrophysiological signals of the neurons are detected by flexible electrode arrays. , neurological diseases and neuroprosthesis research has important application value.

To achieve the above object, the present invention adopts the following technical solutions:

One of the objectives of the present invention is to provide a flexible electrode array-fiber composite neural electrode, the neural electrode includes a flexible electrode array, an optical fiber and a support structure, wherein the surface of the support structure is provided with grooves, and the optical fiber is fixed on the Inside the groove, the flexible electrode array includes three regions of solder joints, interconnecting wires and recording sites that are connected in sequence, the solder joint regions are fixed on the surface of the support structure, the interconnecting wires and recording sites are The dot area is crimped and coated on the surface of the fiber.

Among them, the flexible electrode array has good flexibility and hydrophilicity, and is coiled and wrapped on the surface of the optical fiber under the action of the surface tension of the liquid and the van der Waals force between the liquid and the electrode, and the optical fiber can guide the recording site.

As a preferred technical solution of the present invention, the flexible electrode array includes a flexible substrate layer, a conductive layer and a flexible insulating layer that are connected in sequence.

Preferably, the solder joint area of the flexible electrode array is combined with the base silicon wafer through a flexible substrate layer.

Preferably, the solder joint region is connected to the base silicon wafer and fixed to the surface of the support structure on the side where the groove is provided.

Preferably, the flexible electrode array is fixed to the surface of the support structure on the side where the groove is provided.

As a preferred technical solution of the present invention, the raw materials of the flexible substrate layer and the flexible insulating layer respectively independently include any one of SU8 photoresist, polyimide or parylene, or a combination of any at least two of them. Typical but non-limiting examples of such combinations are: a combination of SU8 photoresist and polyimide, a combination of polyimide and parylene, a combination of parylene and SU8 photoresist, or a SU8 photoresist , a combination of polyimide and parylene, etc.

Preferably, the thickness of the flexible substrate layer is 0.5-10 μm, such as 0.5 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm or 10 μm, etc., but not limited to the listed values, the The same applies to other non-recited numerical values within the numerical range, and it is preferably 1 to 8 μm, and more preferably 5 μm.

Preferably, the thickness of the flexible insulating layer is 0.5-10 μm, such as 0.5 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm or 10 μm, etc., but not limited to the listed values, the The same applies to other non-recited numerical values within the numerical range, preferably 0.5 to 5 μm, and more preferably 0.5 μm.

Preferably, the raw material of the conductive metal layer includes any one or a combination of at least two of gold, platinum or iridium. Typical but non-limiting examples of the combination include: a combination of gold and platinum, a combination of platinum and iridium, A combination of iridium and gold or a combination of gold, platinum and iridium, etc.

Preferably, the thickness of the conductive metal layer is 20-500 nm, such as 20 nm, 30 nm, 40 nm, 50 nm, 80 nm, 100 nm, 150 nm, 200 nm, 250 nm, 300 nm, 400 nm or 500 nm, etc., but not limited to the listed values, The same applies to other non-recited numerical values within this numerical range, preferably 50 to 300 nm, and more preferably 200 nm.

Preferably, an adhesive layer is provided between the flexible insulating layer and the conductive metal layer.

Preferably, the raw material of the adhesion layer includes chromium or tantalum.

Preferably, the thickness of the adhesive layer is 1-50 nm, such as 1 nm, 2 nm, 5 nm, 8 nm, 10 nm, 15 nm, 20 nm, 25 nm, 30 nm, 35 nm, 40 nm, 45 nm or 50 nm, etc., but not limited to the listed ones. Numerical value, other non-recited numerical values within the numerical range are also applicable, preferably 3 to 15 nm, more preferably 5 nm.

As a preferred technical solution of the present invention, the flexible electrode array is provided with recording sites.

Preferably, the shape of the recording site is circular.

Preferably, the number of the recording sites is 1 to 800, such as 1, 10, 20, 50, 100, 200, 300, 400, 500, 600, 700 Or 800, etc., but not limited to the listed numerical values, other unlisted numerical values within the numerical range are also applicable, preferably 1 to 100, more preferably 10.

Preferably, the diameter of the recording site is 5 to 40 μm, such as 5 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm or 40 μm, etc., but not limited to the listed values, and other unlisted values within the numerical range Numerical values apply similarly, preferably 10 to 30 μm, more preferably 10 μm.

Preferably, when the number of the recording sites is greater than 1, the spacing of the recording sites is 50-500 μm, such as 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm or 500 μm, etc. Not limited to the numerical values listed, other numerical values not listed within the numerical range are also applicable, preferably 100 to 200 μm, and more preferably 150 μm.

As a preferred technical solution of the present invention, the nerve electrode is prepared by a micro-nano processing method.

Preferably, the micro-nano processing method includes sputtering a sacrificial layer, photolithography or etching to form a substrate layer, vapor deposition of a metal conductive layer, photolithography or etching to form an insulating layer and an etching sacrificial layer.

As a preferred technical solution of the present invention, the length of the optical fiber is 2 to 180 mm, such as 2 mm, 5 mm, 10 mm, 20 mm, 50 mm, 80 mm, 100 mm, 120 mm, 150 mm or 180 mm, etc., but is not limited to the listed values. The same applies to other non-recited numerical values within the numerical range, preferably 10 to 50 mm, and more preferably 25 mm.

Preferably, the diameter of the optical fiber is 100-400 μm, such as 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm or 400 μm, etc., but it is not limited to the listed values, and other unlisted values within this numerical range are also applicable. Preferably it is 100-300 micrometers, More preferably, it is 200 micrometers.

Preferably, the numerical aperture of the optical fiber is 0.22-0.48, such as 0.22, 0.25, 0.28, 0.30, 0.32, 0.35, 0.38, 0.40, 0.42, 0.45 or 0.48, etc., but not limited to the listed numerical values, the numerical range The same applies to other values not listed here.

Preferably, the diameter of the sleeve is 1.25-2.50mm, such as 1.25mm, 1.30mm, 1.40mm, 1.50mm, 1.80mm, 2.00mm, 2.20mm, 2.40mm or 2.50mm, etc., but not limited to those listed value, other non-recited values within this value range also apply.

As a preferred technical solution of the present invention, the raw material of the support structure is polylactic acid.

Preferably, the length of the support structure is 1-100mm, such as 1mm, 2mm, 5mm, 8mm, 10mm, 20mm, 50mm, 80mm or 100mm, etc., but is not limited to the listed values, and other values are not listed within this value range The same applies to the value of , preferably 10 to 30 mm, more preferably 18 mm.

Preferably, the width of the support structure is 5-100mm, such as 5mm, 8mm, 10mm, 15mm, 20mm, 25mm, 30mm, 50mm, 60mm, 70mm, 80mm, 90mm or 100mm, etc., but not limited to the listed values , and other non-recited numerical values within the numerical range are also applicable, preferably 10 to 20 mm, more preferably 15 mm.

Preferably, the thickness of the support structure is 0.5-5 mm, such as 0.5 mm, 1 mm, 1.5 mm, 2 mm, 3 mm, 4 mm or 5 mm, etc., but not limited to the listed values, and other unlisted values within the numerical range The same applies, preferably 0.8 to 2 mm, more preferably 1 mm.

Preferably, the diameter of the groove in the support structure is 1.15-2.40mm, such as 1.15mm, 1.20mm, 1.25mm, 1.30mm, 1.50mm, 1.80mm, 2.00mm, 2.20mm or 2.40mm, etc., but not only Limitation to the recited values applies equally to other non-recited values within the range of values.

Wherein, the support structure is prepared by a 3D printing method.

The second object of the present invention is to provide a method for preparing the above-mentioned nerve electrode, the method comprising the following steps:

(1) Assemble the sleeve at one end of the optical fiber in the groove of the support structure;

(2) fixing one side of the flexible electrode array base silicon wafer on the surface of the supporting structure on the side provided with the groove;

(3) placing the supporting structure equipped with the optical fiber and the flexible electrode array in water;

(4) aligning the flexible electrode array with the optical fiber, and pulling it out of the water, so that the flexible electrode array is crimped and wrapped on the surface of the optical fiber;

(5) Putting the flexible electrode array/fiber optic composite neural electrode into the curing material melted at high temperature for curing treatment to obtain the flexible electrode array array-fiber optic composite neural electrode.

As a preferred technical solution of the present invention, the curing material in step (5) is polyethylene glycol.

Preferably, the molecular weight of the polyethylene glycol is from 1000 to 8000, such as 1000, 2000, 3000, 4000, 5000, 6000, 7000 or 8000, etc., but is not limited to the listed values, and other values are not listed within this value range The same applies to the numerical value of , preferably 1000 to 4000, more preferably 2000.

As a preferred technical solution of the present invention, copper tape is used to fix the flexible electrode array and the supporting structure in the flexible electrode array-fiber composite nerve electrode obtained in step (5).

Compared with the prior art solutions, the present invention at least has the following beneficial effects:

(1) The flexible electrode array-optical fiber composite neural electrode of the present invention, the neural electrode is different from the conventional photoelectric composite neural electrode, and adopts a flexible electrode array, and the flexible electrode array has good flexibility, hydrophilicity It has high stability and biocompatibility, and can be attached to the surface of the optical fiber to reduce the damage of implantation;

(2) The flexible electrode array-fiber composite neural electrode of the present invention is prepared by micro-nano processing technology, which can accurately control the vertical distance and horizontal distribution of each recording site, and can perform three-dimensional signal detection on the brain.

Description of drawings

1a is a schematic structural diagram of a flexible electrode array-fiber composite nerve electrode provided by the present invention;

Figure 1b is an exploded view of the structure of the flexible electrode array-fiber composite nerve electrode provided by the present invention;

2a is a schematic structural diagram of a substrate layer of a flexible electrode array of a flexible electrode array-fiber composite neural electrode provided by the present invention;

2b is a schematic structural diagram of the conductive layer of the flexible electrode array of the flexible electrode array-fiber composite neural electrode provided by the present invention;

2c is a schematic structural diagram of the insulating layer of the flexible electrode array of the flexible electrode array-fiber composite neural electrode provided by the present invention;

2d is a schematic structural diagram of a flexible electrode array of a flexible electrode array-fiber composite neural electrode provided by the present invention;

3 is a micro-nano processing process diagram of the flexible electrode array of the flexible electrode array-fiber composite nerve electrode provided in Embodiment 1 of the present invention;

4a is a schematic diagram of the arrangement of recording sites of the flexible electrode array of the flexible electrode array-fiber composite neural electrode provided by the present invention;

4b is a schematic diagram of the arrangement of recording sites of the flexible electrode array of the flexible electrode array-fiber composite neural electrode provided by the present invention;

4c is a schematic diagram of the arrangement of recording sites of the flexible electrode array of the flexible electrode array-fiber composite neural electrode provided by the present invention;

FIG. 5 is a physical diagram of the flexible electrode array-fiber composite nerve electrode provided by the present invention;

Fig. 6 is a micrograph of the tip of the flexible electrode array-fiber composite neural electrode object shown in Fig. 5;

Fig. 7 is the animal experiment real picture of the flexible electrode array-fiber composite nerve electrode provided by the present invention;

Description of reference numbers:

1- Solder joint area; 2- Interconnect wire area; 3- Recording site area; 4- Optical fiber; 5- Support structure; 6- Base silicon wafer; 7- Flexible electrode array; 8- Substrate layer; 9- Conductive layer ; 10-insulation layer; 11-flexible electrode array; 12-silicon wafer; 13-spray; 14-S1813 photoresist; 15-exposure; 16-development; 17-magnetron sputtering; 18-Al layer; 19 - stripping; 20-spray; 21-SU82005 photoresist; 22-exposure; 23-development; 24-spray; 25-AZ4620 photoresist; 26-exposure; 27-development; 28-thermal evaporation; 29 - Au layer; 30 - stripping; 31 - sling; 32 - SU82000.5 photoresist; 33 - exposure; 34 - development.

Detailed ways

In order to better illustrate the present invention and facilitate the understanding of the technical solutions of the present invention, typical but non-limiting examples of the present invention are as follows:

Example 1

Fabrication of flexible electrode arrays

1. Electrode design;

(1) Grid electrode:

Solder joints: rectangular, 2mm long, 0.7mm wide, 1mm spacing, 10 channels evenly arranged.

Recording site: circular, 30 μm in diameter, the arrangement is shown in Figure 4.

Substrate layer SU8-1 layer: thickness of 5 μm, width of horizontal strips of 20 μm, length of 1.115 mm, spacing of 500 μm; width of vertical strips of 35 μm and length of 15 mm. The arc connection is added between the electrode longitudinal strip and the cable part to avoid stress concentration.

Conductive layer Au layer: the width of the conductive Au line is 15 μm, the thickness is 100 nm, and the thickness of the Cr layer of the adhesion layer is 5 nm.

Insulation layer SU8-2 layer: thickness 0.5μm, the difference from SU8-1 lies in the following points, the recording site diameter 30μm disk electrode is exposed, the first channel and the tenth channel are completely exposed as built-in grounding and reference, solder joints Begin to remove the back part so that the ACF glue will be stressed when pressing the flexible cable.

(2) Comb-shaped electrode:

Solder joint: rectangle, length 1mm, width 0.2mm, spacing 0.5mm, 18 channels evenly arranged.

Recording site: circular, 30 μm in diameter.

Substrate layer SU8-1 layer: thickness 5μm, horizontal strip width 50μm, length 3.44mm, spacing 150μm; vertical strip width 35μm, length 15mm, of which solid 3mm/grid 7mm/comb 5mm. The front end is made into a triangular pointed shape, which is convenient for electrode implantation. The arc connection is added between the electrode longitudinal strip and the cable part to avoid stress concentration.

Conductive layer Au layer: the width of the conductive Au line is 15 μm, the thickness is 100 nm, and the thickness of the Cr layer of the adhesion layer is 5 nm.

Insulation layer SU8-2 layer: thickness 0.5μm, the difference from SU8-1 lies in the following points, the recording site diameter 30μm disk electrode is exposed, the first channel and the eighteenth channel are completely exposed as built-in grounding and reference, solder Start to remove the back part of the point, so that the ACF glue will be stressed when the flexible cable is pressed.

2. Micro-nano processing technology:

(1) Al layer:

1) Washing: place a silicon wafer with a diameter of 4 inches in a petri dish, use acetone, isopropanol, and water with 60W power to ultrasonicate at room temperature for 10 minutes. After drying with nitrogen, place the silicon wafer on a 100°C hot plate and heat for 3 minutes to remove water vapor. , after the temperature dropped to room temperature, use oxygenplasma 100W power for 3min.

2) Glue: Place the cleaned silicon wafer in the center of the gluer to fix it, adjust the parameters of the gluer (500rpm10s & 2000rpm60s), use a dropper to drop an appropriate amount of S1813 glue to the center of the wafer, and cover the gluer with the protective cover , and start throwing glue.

3) Pre-baking: Place the silicon wafer with the glue on it on a hot plate at 115°C, and pre-bake for 3 minutes.

4) Exposure: Turn on the MA6 UV lithography machine, fix the Al layer mask, place the pre-baked silicon wafer, and expose for 65s.

5) Development: place the exposed silicon wafer in S1813 developer solution for 1min, then rinse with water and dry with high pressure nitrogen;

6) Residual glue removal: place the silicon wafer on a 100°C hot plate and bake for 30s, then use oxygen plasma 50W power to etch for 1min to remove the residual glue;

7) Deposition of Al: A 100 nm thick Al layer was deposited on the silicon wafer with a magnetron sputtering apparatus.

8) Peeling: The silicon wafer after sputtering Al was placed in a petri dish containing an appropriate amount of acetone, and the desired pattern was peeled off. After cleaning and returning to Beijing, high-pressure nitrogen was used to dry it for use.

(2) Substrate layer SU8 layer/insulating layer SU8 layer:

1) Washing: Place the stripped silicon wafer on a hot plate at 100°C for 30s, dry it to room temperature, and clean it with oxygen plasma 100W for 3min.

2) Glue slinging: place the above silicon wafer in the center of the homogenizer sucker and fix it, adjust the homogenization parameters (500rpm10s&2000rpm60s), use a dropper to drop an appropriate amount of SU82005/SU82000.5 glue to the center of the silicon wafer, and cover the gluer to protect cover, and start the gluing.

3) Pre-baking: put the silicon wafers after the slinging on a hot plate at 95°C for 2 minutes.

4) Exposure: Turn on the MA6 UV lithography machine, fix the substrate SU8/insulation SU8 layer mask, place the pre-baked silicon wafer, and expose for 120s/150s.

5) Post-baking: place the exposed silicon wafer on a hot plate at 95°C and post-bake for 2 minutes;

6) Development: place the post-baked silicon wafer in a SU8 developer for 1 min, rinse with isopropyl alcohol after the development, and blow dry with high-pressure nitrogen.

7) Residual glue removal: heat the silicon wafer on a 100°C hot plate for 30s, thoroughly dry the silicon wafer, and then use oxygenplasma 50W power for 1 min to remove the residual glue after cooling to room temperature.

8) Hardening: After removing the adhesive residue, place the silicon wafer on a hot plate at 180°C for 30 minutes.

(3) Au layer:

1) Glue: After the SU8 layer of the substrate is finished, the silicon wafer is placed in the center of the gluer suction cup and fixed, and the parameters of the gluer are adjusted (1500rpm 5s & 4000rpm 60s), and an appropriate amount of AZ4620 glue is evenly dropped to the center of the wafer with a dropper. Cover the dispenser with the protective cover and start spinning.

3) Pre-baking: Put the silicon wafers after the slinging on the hot plate at 120℃, and pre-bake for 90s.

4) Exposure: Turn on the MA6 UV lithography machine, fix the Au layer mask, and expose in hard mode for 180s.

5) Development: Place the silicon wafer in AZ4620 developer solution for 1 min, then rinse with water and dry it with nitrogen for use.

6) Residual adhesive removal: place the silicon wafer on a 100°C hot plate and bake it for 30s, air it to room temperature, and clean it with oxygen plasma 50W for 1min.

7) Deposition of Au: A 5 nm Cr adhesion layer and a 100 nm Au conductive layer are sequentially deposited on the silicon wafer with an electron beam evaporation apparatus or a thermal evaporation apparatus.

8) Peeling: The silicon wafer on which the Au has been evaporated is placed in a petri dish containing an appropriate amount of acetone, the desired pattern is peeled off, and the high-pressure nitrogen is blown dry for use.

3. Electrode back end connection:

(1) Scribing: Use a silicon knife to scratch the electrode boundary lightly, and then lightly press both sides of the scratch to crack the silicon wafer. Repeat this step until all electrodes on the silicon wafer are scratched. The scratched electrode was then cleaned with high pressure nitrogen and placed in a clean disposable plastic petri dish.

(2) Press the flexible cable: mark the alignment mark of the ten-channel flexible cable, cut the appropriate length of ACF glue to cover the electrode solder joint, align the mark of the flexible cable with the electrode solder joint, and then heat the plate at 150 ℃ Heat press for 60s.

(3) Packaging: Take an appropriate amount of AB glue, evenly coat the interface between the flexible cable and the electrode, and place it in a 60°C oven for two hours before taking it out.

(4) Etching the sacrificial layer: the packaged electrodes are placed in a 0.5mol/L FeCl ₃ solution to remove the sacrificial layer aluminum. After etching, rinse with deionized water to remove excess silicon wafers, and finally place them in clean deionized water.

Example 2

3D printed support structure

Design the three-dimensional graphics of the support structure on the PROE three-dimensional graphics design software; the size parameters are as follows: the length of the support structure is 18mm; the width of the support structure is 15mm; the thickness of the support structure is 1mm; the aperture of the support structure is 2.40mm; save as . STL format.

On the CoLiDo 3D printer supporting software Print-Rite Repetier-Host, adjust the material parameters and the placement position and method of the printed object, click to automatically generate the Slic3r code, save it to the printer supporting memory card in .GCO format, and start printing.

Example 3

Flexible electrode array/fiber optic composite nerve electrode

光纤芯

The dimensions of the optical fibers used in the present invention are as follows:

fiber core

Assemble the fiber and the fiber support, and then place the electrode on the fiber support, pay attention to center the fiber and the electrode on the left and right, so that the electrode extends beyond the fiber by about 0.5mm; then put it in deionized water, remove it vertically, and make the electrode crimp. Cover the surface of the optical fiber, then put the flexible electrode array/fiber composite nerve electrode into the high-temperature melting curing material for curing, and finally fix the electrode and the supporting structure with copper tape.

Example 4

Fabrication of flexible electrode arrays

1. Electrode design:

(1) Grid electrode:

Solder joints: rectangular, 2mm long, 0.7mm wide, 1mm spacing, 10 channels evenly arranged.

Recording site: circular, 10 μm in diameter, the arrangement is shown in Figure 4.

Substrate layer polyimide layer: thickness of 2 μm, width of horizontal strips of 20 μm, length of 1.115 mm, spacing of 500 μm; width of vertical strips of 35 μm and length of 15 mm. The arc connection is added between the electrode longitudinal strip and the cable part to avoid stress concentration.

Conductive layer Pt layer: the conductive Pt line width is 15 μm, the thickness is 150 nm, and the thickness of the tantalum layer of the adhesion layer is 10 nm.

Insulation layer polyimide layer: thickness 2μm, the difference from the substrate layer polyimide layer is in the following points, the diameter of the recording site is 10μm, the disc electrode is exposed, the first channel and the tenth channel are completely exposed as built-in grounding and For reference, the solder joint begins to be partially removed so that the ACF glue will be stressed when the flexible cable is pressed.

(2) Comb-shaped electrode:

Solder joint: rectangle, length 1mm, width 0.2mm, spacing 0.5mm, 18 channels evenly arranged.

Recording site: circular, 10 μm in diameter.

Substrate polyimide layer: thickness 2μm, width of horizontal strip 50μm, length 3.44mm, spacing 150μm; vertical strip width 35μm, length 15mm, of which solid 3mm/grid 7mm/comb 5mm. The front end is made into a triangular pointed shape, which is convenient for electrode implantation. The arc connection is added between the electrode longitudinal strip and the cable part to avoid stress concentration.

Conductive layer Pt layer: the conductive Pt line width is 15 μm, the thickness is 150 nm, and the thickness of the tantalum layer of the adhesion layer is 10 nm.

Insulation layer polyimide layer: thickness 2μm, the difference from the substrate layer polyimide layer is in the following points, the recording site diameter 10μm disc electrode is exposed, the first channel and the eighteenth channel are completely exposed as built-in grounding and For reference, the solder joint begins to be partially removed so that the ACF glue will be stressed when the flexible cable is pressed.

2. Micro-nano processing technology:

(1) Al layer:

1) Washing: place a silicon wafer with a diameter of 4 inches in a petri dish, use acetone, isopropanol, and water with 60W power to ultrasonicate at room temperature for 10 minutes. After drying with nitrogen, place the silicon wafer on a 100°C hot plate and heat for 3 minutes to remove water vapor. , after the temperature dropped to room temperature, use oxygenplasma 100W power for 3min.

2) Glue slinging: Place the cleaned silicon wafer in the center of the homogenizer sucker and fix it, adjust the parameters of the homogenizer (500rpm10s & 2000rpm60s), drop an appropriate amount of S1813 glue into the center of the silicon wafer with a dropper, and cover the homogenizer protective cover , and start throwing glue.

3) Pre-baking: Put the silicon wafer with the glue on it on a hot plate at 115°C, and pre-bake for 3 minutes.

4) Exposure: Turn on the MA6 UV lithography machine, fix the Al layer mask, place the pre-baked silicon wafer, and expose for 65s.

5) Development: place the exposed silicon wafer in S1813 developer solution for 1min, then rinse with water and dry with high pressure nitrogen;

6) Residual glue removal: place the silicon wafer on a 100°C hot plate and bake for 30s, then use oxygen plasma 50W power to etch for 1min to remove the residual glue;

7) Deposition of Al: A 100 nm thick Al layer was deposited on the silicon wafer with a magnetron sputtering apparatus.

8) Peeling: The silicon wafer after sputtering of Al is placed in a petri dish containing an appropriate amount of acetone, and the desired pattern is peeled off. After cleaning, dry it with high-pressure nitrogen for use.

(2) Polyimide layer of substrate layer/polyimide layer of insulating layer:

1) Washing: Place the silicon wafer with the Al or Pt layer peeled off on a hot plate at 100°C for 30s, and then properly clean it with oxygenplasma.

2) Glue slinging: place the above silicon wafer in the center of the homogenizer sucker and fix it, adjust the homogenization parameters (500rpm10s & 2000rpm60s), drop an appropriate amount of polyimide into the center of the silicon wafer with a dropper, and cover the homogenizer protective cover. Start throwing glue.

3) Pre-baking: Put the silicon wafers after the slinging on a hot plate at 120°C for 10 minutes.

4) Post-baking: put the pre-baking sheets into a 200 ℃ vacuum drying oven, vacuumize, keep for two hours, then turn off the heating, and cool down to room temperature with the oven;

(3) Pt layer:

1) Washing the film: soak the film after the polyimide layer of the substrate is completed with acetone for five minutes, stir the film properly with tweezers, then transition in isopropyl alcohol, and finally rinse the film with water, and dry the film with nitrogen ;

2) Glue slinging: place the cleaned wafer in the center of the gluer sucker and fix it, adjust the parameters of the gluer (500rpm10s & 2000rpm60s), drop an appropriate amount of S1813 glue into the center of the silicon wafer with a dropper, and cover the gluer with the protective cover. Start throwing glue.

3) Pre-baking: Put the silicon wafer with the glue on it on a hot plate at 115°C, and pre-bake for 3 minutes.

4) Exposure: Turn on the MA6 UV lithography machine, fix the Pt layer mask, place the pre-baked silicon wafer, and expose for 65s.

5) Development: place the exposed silicon wafer in S1813 developer solution for 1min, then rinse with water and dry with high pressure nitrogen;

6) Residual glue removal: place the silicon wafer on a 100°C hot plate and bake for 30s, then use oxygen plasma 50W power to etch for 1min to remove the residual glue;

7) Deposition of Pt: 10nm-thick tantalum and 150nm-thick Pt layers were sequentially deposited on the silicon wafer with a thermal evaporation apparatus.

8) Peeling: The silicon wafer after sputtering Pt is placed in a petri dish containing an appropriate amount of acetone, and the desired pattern is peeled off. After cleaning, dry it with high-pressure nitrogen for use.

(4) AZ4620 mask layer

1) Washing the film: soak the film after the insulating polyimide layer with acetone for five minutes, stir the film properly with tweezers, then transition in isopropyl alcohol, and finally rinse the film with water, and dry the film with nitrogen;

2) Glue slinging: place the cleaned wafer in the center of the suction cup of the homogenizer and fix it, adjust the parameters of the homogenizer (1500rpm10s&2000rpm60s), use a dropper to drop an appropriate amount of AZ4620 glue into the center of the silicon wafer, cover the protective cover of the homogenizer, start throwing glue;

3) Pre-baking: Put the silicon wafer with the glue on it on a hot plate at 120°C, and pre-bake for 3 minutes.

4) Exposure: Turn on the MA6 UV lithography machine, fix the mask, place the pre-baked film, and expose for 200s;

5) Development: place the exposed silicon wafer in AZ4620 developer solution for 3 minutes, then rinse with water and dry with high pressure nitrogen;

(5) Patterned polyimide

1) Put the finished AZ4620 mask layer in the reactive ion etching machine (RIE), adjust the RIE parameters (20pa, 200W, 20sccm O ₂ ), and etch for 7 minutes; then turn on the machine, depending on the etching conditions and the same conditions Then etch for 30-60s.

2) The etched sheet is cleaned with acetone, then transitioned in isopropanol, finally rinsed with clean water, and dried with nitrogen;

3. Electrode back end connection:

(1) Scribing: Use a silicon knife to scratch the electrode boundary lightly, and then lightly press both sides of the scratch to crack the silicon wafer. Repeat this step until all electrodes on the silicon wafer are scratched. The scratched electrode was then cleaned with high pressure nitrogen and placed in a clean disposable plastic petri dish.

(2) Press the flexible cable: mark the alignment mark of the ten-channel flexible cable, cut the appropriate length of ACF glue to cover the electrode solder joint, align the mark of the flexible cable with the electrode solder joint, and then heat the plate at 150 ℃ Heat press for 90s.

(3) Packaging: Take an appropriate amount of AB glue, evenly coat the interface between the flexible cable and the electrode, and place it in a 60°C oven for two hours before taking it out.

(4) Etching the sacrificial layer: The packaged electrodes are placed in a 0.5mol/L FeCl3 solution to remove the sacrificial layer aluminum. After etching, rinse with deionized water to remove excess silicon wafers, and finally place them in clean deionized water.

Example 5

3D printed support structure

Design the three-dimensional graphics of the support structure on the PROE three-dimensional graphics design software; the size parameters are as follows: the length of the support structure is 20mm; the width of the support structure is 12mm; the thickness of the support structure is 0.5mm; the aperture of the support structure is 2.40mm; .STL format.

On the CoLiDo 3D printer supporting software Print-Rite Repetier-Host, adjust the material parameters and the placement position and method of the printed objects, click to automatically generate the Slic3r code, save it to the printer supporting memory card in .GCO format, and start printing.

Example 6

Flexible electrode array/fiber optic composite nerve electrode

The dimensions of the optical fibers used in the present invention are as follows: the sleeve is 10.5mm*φ2.5mm, and the fiber core is 25mm*φ100 microns.

Assemble the fiber and the fiber support, then place the electrode on the fiber support, pay attention to centering the fiber and the electrode on the left and right, so that the fiber extends beyond the electrode by about 0.1mm; then put it in deionized water, remove it vertically, and make the electrode crimp. Cover the surface of the optical fiber, then put the flexible electrode array/fiber composite nerve electrode into the high-temperature melting curing material for curing, and finally fix the electrode and the supporting structure with copper tape.

Example 7

Fabrication of flexible electrode arrays

1. Electrode design

Solder spot: rectangular, 1mm long, 1.5mm in length, 0.2mm in width, 0.5mm in width, 800 channels are arranged in a matrix of 10*80.

Recording site: circular, 40 μm in diameter.

Substrate layer parylene layer: thickness 10μm; horizontal strip width 50μm, length 79.960mm, spacing 150μm; vertical strip width 60μm, length 150mm, of which solid 40mm/grid 80mm/comb 30mm. The front end is made into a triangular pointed shape, which is convenient for electrode implantation. The arc connection is added between the electrode longitudinal strip and the cable part to avoid stress concentration.

Conductive layer Ir layer: the conductive Ir line width is 15 μm, the thickness is 500 nm, and the thickness of the adhesion layer Cr layer is 50 nm.

Insulating layer parylene layer: thickness 10μm, the difference from the substrate layer parylene layer lies in the following points, the recording site diameter 40μm disc electrode is exposed, the first channel and the eighth hundredth channel are completely exposed as built-in grounding and For reference, the solder joint begins to be partially removed so that the ACF glue will be stressed when the flexible cable is pressed.

2. Micro-nano processing technology:

(1) Al layer:

1) Washing: place the silicon wafer in a petri dish, use acetone, isopropanol, and water with 60W power to ultrasonicate at room temperature for 10 minutes. After drying with nitrogen, place the silicon wafer on a 100°C hot plate and heat for 3 minutes to remove water vapor and reduce the temperature. After reaching room temperature, use oxygen plasma100W power for 3min.

2) Glue slinging: Place the cleaned silicon wafer in the center of the homogenizer sucker and fix it, adjust the parameters of the homogenizer (500rpm10s & 2000rpm60s), drop an appropriate amount of S1813 glue into the center of the silicon wafer with a dropper, and cover the homogenizer protective cover , and start throwing glue.

3) Pre-baking: Put the silicon wafer with the glue on it on a hot plate at 115°C, and pre-bake for 3 minutes.

4) Exposure: Turn on the MA6 UV lithography machine, fix the Al layer mask, place the pre-baked silicon wafer, and expose for 65s.

5) Development: place the exposed silicon wafer in S1813 developer solution for 1min, then rinse with water and dry with high pressure nitrogen;

6) Residual glue removal: place the silicon wafer on a 100°C hot plate and bake for 30s, then use oxygen plasma 50W power to etch for 1min to remove the residual glue;

7) Deposition of Al: A 100 nm thick Al layer was deposited on the silicon wafer with a magnetron sputtering apparatus.

8) Peeling: The silicon wafer after sputtering of Al is placed in a petri dish containing an appropriate amount of acetone, and the desired pattern is peeled off. After cleaning, dry it with high-pressure nitrogen for use.

(2) Substrate layer parylene layer/insulating layer parylene layer:

The Parylene-C layer was prepared by chemical vapor deposition method. The method is accomplished in three steps:

1) The parylene dimer raw material is heated to gaseous state in the evaporation chamber;

2) Pass the raw material gas obtained by sublimation into the cracking chamber to obtain active parylene monomer;

3) The parylene monomer obtained in the second step is sent to a room temperature vacuum deposition chamber, and a parylene layer is deposited on the wafer. The deposition thickness is controlled by controlling the deposition time and the gas flow of the parylene monomer.

(3) Ir layer:

The parylene layer of the substrate was cleaned, and a layer of AZ4620 mask was prepared by plane lithography, and then a 50nm-thick adhesion layer metal Cr and 500nm thick conductive layer metal Ir, and finally peel off the pattern and clean it.

3. Electrode back end connection:

(1) Scribing: Use a silicon knife to scratch the electrode boundary lightly, and then lightly press both sides of the scratch to crack the silicon wafer. Repeat this step until all electrodes on the silicon wafer are scratched. The scratched electrode was then cleaned with high pressure nitrogen and placed in a clean disposable plastic petri dish.

(2) Press the flexible cable: mark the alignment mark of the ten-channel flexible cable, cut the appropriate ACF glue to cover the electrode solder joint, align the mark of the flexible cable with the electrode solder joint, and then heat it on a 150 ℃ hot plate Press for 90s.

(3) Packaging: Take an appropriate amount of AB glue, evenly coat the interface between the flexible cable and the electrode, and place it in a 60°C oven for two hours before taking it out.

(4) Etching the sacrificial layer: The packaged electrodes are placed in a 0.5mol/L FeCl3 solution to remove the sacrificial layer aluminum. After etching, rinse with deionized water to remove excess silicon wafers, and finally place them in clean deionized water.

Example 8

3D printed support structure

Design the three-dimensional graphics of the support structure on the PROE three-dimensional graphics design software; the size parameters are as follows: the length of the support structure is 100mm; the width of the support structure is 100mm; the thickness of the support structure is 0.5mm; the aperture of the support structure is 1.15mm; .STL format.

On the CoLiDo 3D printer supporting software Print-Rite Repetier-Host, adjust the material parameters and the placement position and method of the printed objects, click to automatically generate the Slic3r code, save it to the printer supporting memory card in .GCO format, and start printing.

Example 9

Flexible electrode array/fiber optic composite nerve electrode

The size of the optical fiber used in the present invention is as follows: the sleeve is 10.5mm*φ1.25mm, and the fiber core is 180mm*φ100μm.

Assemble the fiber and the fiber support, then place the electrode on the fiber support, pay attention to centering the fiber and the electrode on the left and right, so that the electrode extends beyond the fiber by about 15mm; then put it in deionized water, remove it vertically, and make the electrode curl and coat Then, the flexible electrode array/fiber composite nerve electrode was put into the high-temperature melting curing material for curing treatment, and finally the electrode and the supporting structure were fixed with copper tape.

Example 10

Electrophysiological signal detection was performed on the nerve electrodes prepared in Examples 1-9, and the detection method was as follows:

1. Preoperative preparation:

Prepare gauze, electric blanket, operating table, lighting system, cranial drill, surgical instruments soaked in 75% C ₂ H ₅ OH, absorbent cotton balls, cotton swabs, saline, iodophor, anesthetic, and penicillin G sodium solution.

2, with the solution:

Anesthesia: weigh urethane according to the weight ratio of 2.6g/Kg, add normal saline to prepare a 2ml solution

3. Anesthesia:

Put the SD rat into a closed plastic box, add 0.2ml of isoflurane with a syringe, and close the box lid; while the rat is temporarily anesthetized, use a new syringe to absorb 1ml of the prepared anesthetic; after the rat faints, take out the rat, Lay the legs up, and inject anesthesia into the abdomen quickly; the needle should be inserted in parallel to avoid stabbing the internal organs.

4. Surgical process:

(1) Place the transgenic rat on an electric heating blanket padded with a clean cloth. The electric heating blanket is turned on to a medium temperature. Cover the body except the head of the rat with gauze. Insert the ear stick into the groove of the skull in front of the ear hole to limit the head of the rat. The degree of freedom of swinging left and right at the head was adjusted, and then the rat was allowed to open its mouth, bite the mouthguard, and tighten the knob of the mouthguard to limit the freedom of the rat's head to swing up and down.

(2) Use a cotton swab to absorb iodine to wet the rat hair on the head, so as to avoid flying dander when shearing, and use curved scissors to cut off the rat hair.

(3) Wipe iodophor for disinfection on the exposed scalp after cutting the hair, and cut the scalp with a straight scissor. Note that you should try to cut a large mouth at this time for subsequent operations. If bleeding occurs, a cotton swab can be used to absorb normal saline to stop the bleeding.

(4) Use a syringe to drop an appropriate amount of H ₂ O ₂ on the scalp, and use a cotton swab to wipe off the epithelium of the skull until the white skull is exposed.

(5) Positioning with bregama, mark the craniotomy site on the skull with a black thin-tip pen, turn on the power switch of the cranial drill, and drill a small rectangle of about 3 × 5mm under the microscope with the mark as the center, and grind the skull. Cerebrospinal fluid should be added from time to time and wiped off with a cotton swab to avoid filling with bone debris and blocking the field of view. When drilling quickly, the brain should be carefully damaged. At this time, the speed should be slowed down, and tweezers can be used to judge whether the drilling has been penetrated. Finally, lift the skull with a syringe needle and remove the skull with pointed forceps.

(6) Use a small syringe needle to puncture the dura mater at the avascular edge, and then gradually tear the dura mater with pointed forceps. Cover the brain tissue with the dura mater uncovered with a cotton ball moistened with normal saline to avoid contamination of the brain tissue.

(7) Connect 128 channels, connect the laser, and implant into the somatosensory cortex of the brain with the aid of a microscope and a stereotaxic instrument, and the implantation depth is 200-1500 μm, and the recording starts.

(8) During the recording process, 10 seconds of light stimulation was given every 10 seconds. The light stimulation was a 473nm laser with a power of 10mW, and the obtained data were band-pass filtered at 250-5000HZ to analyze the action potential of a single neuron.

5. Experimental conclusion

Light stimulation can significantly and rapidly increase the firing frequency of neuronal action potentials, but has little effect on the firing amplitude. After adding light stimulation, a response with a significant increase in the signal frequency of the single unit can be obtained in an instant. After turning off the laser, the signal frequency can instantly return to the firing level without light stimulation, which shows that light stimulation regulates the new number of neurons. The response of the release is very fast. In addition, since specific types of neurons can express light-sensitive proteins by viral transfection, the regulation of neuron signaling by light stimulation also has neuron-specific characteristics.

The applicant declares that the present invention illustrates the detailed structural features of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed structural features, that is, it does not mean that the present invention must rely on the above-mentioned detailed structural features to be implemented. Those skilled in the art should understand that any improvement to the present invention, the equivalent replacement of the selected components of the present invention, the addition of auxiliary components, the selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

The preferred embodiments of the present invention are described in detail above, but the present invention is not limited to the specific details of the above-mentioned embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention. These simple modifications All belong to the protection scope of the present invention.

In addition, it should be noted that the specific technical features described in the above-mentioned specific embodiments can be combined in any suitable manner unless they are inconsistent. In order to avoid unnecessary repetition, the present invention provides The combination method will not be specified otherwise.

In addition, the various embodiments of the present invention can also be combined arbitrarily, as long as they do not violate the spirit of the present invention, they should also be regarded as the contents disclosed in the present invention.

Claims (59)

1. The flexible electrode array-optical fiber composite nerve electrode is characterized by comprising a flexible electrode array, optical fibers and a supporting structure, wherein a groove is formed in the surface of the supporting structure, the optical fibers are fixed in the groove, the flexible electrode array comprises a welding spot, an interconnection lead and a recording site which are sequentially connected, the welding spot area is fixed on the surface of the supporting structure, and the interconnection lead and the recording site area are wrapped on the surface of the optical fibers in a curling mode;

the preparation method of the nerve electrode comprises the following steps:

(1) fitting a ferrule at one end of the optical fiber in a groove of the support structure;

(2) fixing one side of the flexible electrode array with the substrate silicon wafer on the surface of one side of the supporting structure provided with the groove;

(3) placing a support structure equipped with an optical fiber and a flexible electrode array in water;

(4) aligning the flexible electrode array with the optical fiber, and fishing out from water to enable the flexible electrode array to be wrapped on the surface of the optical fiber in a curling manner;

(5) and putting the flexible electrode array/optical fiber composite nerve electrode into a high-temperature molten curing material for curing treatment to obtain the flexible electrode array-optical fiber composite nerve electrode.

2. The neural electrode of claim 1, wherein the flexible electrode array comprises a flexible substrate layer, a conductive layer, and a flexible insulating layer connected in series.

3. The neural electrode of claim 2, wherein the pad areas of the flexible electrode array are bonded to a base silicon wafer through a flexible backing layer.

4. The neural electrode of claim 1, wherein the pad region is attached to a silicon substrate and fixed to the surface of the support structure on the side where the recess is formed.

5. The neural electrode of claim 1, wherein the flexible electrode array is secured to a surface of the support structure on a side where the recess is provided.

6. The neural electrode of claim 2, wherein the materials of the flexible substrate layer and the flexible insulating layer each independently comprise any one of SU8 photoresist, polyimide, or parylene, or a combination of at least two thereof.

7. The neural electrode of claim 2, wherein the flexible substrate layer has a thickness of 0.5-10 μm.

8. The neural electrode of claim 7, wherein the flexible substrate layer has a thickness of 1-8 μm.

9. The neural electrode of claim 8, wherein the flexible substrate layer is 5 μm thick.

10. The neural electrode according to claim 2, wherein the thickness of the flexible insulating layer is 0.5 to 10 μm.

11. The neural electrode according to claim 10, wherein the thickness of the flexible insulating layer is 0.5 to 5 μm.

12. The neural electrode of claim 11, wherein the flexible insulating layer has a thickness of 0.5 μ ι η.

13. The neural electrode of claim 2, wherein the material of the conductive layer comprises any one of gold, platinum or iridium or a combination of at least two thereof.

14. The neural electrode according to claim 2, wherein the conductive layer has a thickness of 20 to 500 nm.

15. The neural electrode of claim 13, wherein the conductive layer has a thickness of 50 to 300 nm.

16. The neural electrode of claim 15, wherein the conductive layer has a thickness of 200 nm.

17. The neural electrode of claim 2, wherein an adhesion layer is disposed between the flexible insulating layer and the conductive layer.

18. The neural electrode of claim 17, wherein the material of the adhesion layer comprises chromium or tantalum.

19. The neural electrode of claim 17, wherein the adhesive layer has a thickness of 1 to 50 nm.

20. The neural electrode of claim 19, wherein the adhesive layer has a thickness of 3 to 15 nm.

21. The neural electrode of claim 20, wherein the adhesive layer has a thickness of 5 nm.

22. The neural electrode of claim 1, wherein the array of flexible electrodes has recording sites disposed thereon.

23. The neural electrode of claim 22, wherein the recording sites are circular in shape.

24. The neural electrode according to claim 22, wherein the number of recording sites is 1 to 800.

25. The neural electrode according to claim 24, wherein the number of recording sites is 1 to 100.

26. The neural electrode of claim 25, wherein the number of recording sites is 10.

27. The neural electrode of claim 22, wherein the recording sites have a diameter of 5-40 μm.

28. The neural electrode of claim 27, wherein the recording sites have a diameter of 10-30 μm.

29. The neural electrode of claim 28, wherein the recording sites are 10 μm in diameter.

30. The neural electrode according to claim 22, wherein when the number of recording sites is greater than 1, the pitch of the recording sites is 50 to 500 μm.

31. The neural electrode according to claim 30, wherein when the number of recording sites is greater than 1, the pitch of the recording sites is 100 to 200 μm.

32. The neural electrode of claim 31, wherein when the number of recording sites is greater than 1, the pitch of the recording sites is 150 μm.

33. The nerve electrode of claim 1, wherein the nerve electrode is prepared by a micro-nano machining method.

34. The neural electrode of claim 33, wherein the micro-nano machining method comprises sputtering a sacrificial layer, forming a substrate layer by lithography or etching, evaporating a metal conductive layer, forming an insulating layer by lithography or etching, and corroding the sacrificial layer.

35. The neural electrode according to claim 1, wherein the optical fiber has a length of 2 to 180 mm.

36. The neural electrode of claim 35, wherein the optical fiber has a length of 10-50 mm.

37. The neural electrode of claim 36, wherein the length of the optical fiber is 25 mm.

38. The neural electrode according to claim 1, wherein the optical fiber has a diameter of 100 to 400 μm.

39. The neural electrode of claim 38, wherein the optical fiber has a diameter of 100-300 μm.

40. The neural electrode of claim 39, wherein the optical fiber has a diameter of 200 μm.

41. The neural electrode according to claim 1, wherein the optical fiber has a numerical aperture of 0.22 to 0.48.

42. The neural electrode of claim 1, wherein a side of the optical fiber not covered by the flexible electrode array is provided with a sleeve.

43. The neural electrode of claim 42, wherein the cannula has a diameter of 1.25-2.50 mm.

44. The neural electrode of claim 1, wherein the support structure is formed from polylactic acid.

45. The neural electrode of claim 1, wherein the support structure has a length of 1-100 mm.

46. The neural electrode of claim 45, wherein the support structure has a length of 10-30 mm.

47. The neural electrode of claim 46, wherein the support structure is 18mm in length.

48. The neural electrode of claim 1, wherein the support structure has a width of 5-100 mm.

49. The neural electrode of claim 48, wherein the support structure has a width of 10-20 mm.

50. The neural electrode of claim 49, wherein the support structure has a width of 15 mm.

51. The neural electrode of claim 1, wherein the support structure has a thickness of 0.5mm to 5 mm.

52. The neural electrode of claim 51, wherein the support structure has a thickness of 0.8-2 mm.

53. The nerve electrode of claim 52, wherein the support structure is 1mm thick.

54. The neural electrode of claim 1, wherein the grooves in the support structure have a diameter of 1.15-2.40 mm.

55. The neural electrode of claim 1, wherein the solidifying material of step (5) is polyethylene glycol.

56. The neural electrode of claim 55, wherein said polyethylene glycol has an average molecular weight of 1000 to 8000.

57. The neural electrode of claim 56, wherein said polyethylene glycol has an average molecular weight of 1000 to 4000.

58. The neural electrode of claim 57, wherein the polyethylene glycol has an average molecular weight of 2000.

59. The nerve electrode of claim 1, wherein the flexible electrode array and the supporting structure in the flexible electrode array-optical fiber composite nerve electrode obtained in the step (5) are fixed by using a copper adhesive tape.

Images