CN112244848B - Preparation method of multichannel MEAs (membrane-associated systems) based on cortex electroencephalogram - Google Patents
Preparation method of multichannel MEAs (membrane-associated systems) based on cortex electroencephalogram Download PDFInfo
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2503/00—Evaluating a particular growth phase or type of persons or animals
- A61B2503/42—Evaluating a particular growth phase or type of persons or animals for laboratory research
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P70/00—Climate change mitigation technologies in the production process for final industrial or consumer products
- Y02P70/50—Manufacturing or production processes characterised by the final manufactured product
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Abstract
The invention discloses a preparation method of multichannel MEAs based on cortex electroencephalogram, belongs to the technical field of advanced micromachining, and aims to solve the problem that flexible MEAs are operated under high space-time resolution and low in production efficiency. The preparation method comprises the following steps: 1. plasma cleaning is carried out on the silicon substrate; 2. depositing an aluminum sacrificial layer on the surface of the silicon substrate; 3. spin-coating a non-photosensitive polyimide MEAs substrate on the aluminum sacrificial layer for a plurality of times; 4. patterning and shaping the photoetching polyimide layer, and performing inductively coupled plasma etching treatment; 5. forming a microelectrode network and an interconnection plate through a photoetching process; 6. spin coating a non-photosensitive polyimide MEAs substrate onto the underlying polyimide, masking the wafer with photoresist to define interconnect lines and pads; 7. and removing the aluminum sacrificial layer. In the invention, a 6-inch high-resistance silicon wafer is used as a substrate, and 25 MEAs can be produced on a single chip in large scale by combining flexible polyimide. The recording positions are compactly arranged with high space-time resolution.
Description
Technical Field
The invention belongs to the technical field of advanced micromachining, and particularly relates to a wafer-level manufacturing and assembling method of a multichannel microelectrode array (MEAs) based on cortical electroencephalogram (ECoG).
Background
The recording of electrical activity of a neural network can provide a large amount of information about physiology and physiological degradation that may lead to disease, such as parkinson's disease or alzheimer's disease. MEAs have been used to monitor nerve signals over time at regular intervals by cortical electroencephalography (ECoG). This approach helps to improve the researchers' insight into brain activity function. Flexibility and biocompatibility are the primary conditions for the use of MEAs for long-term recording of data in the body of a test sample. These properties allow the MEAs to be placed directly on the skull and connected to the nervous system. Typically, polyimide is selected as the substrate material to provide excellent biocompatibility and high flexibility for the manufacture of MEAs. Over the past few years, flexible MEAs have evolved to stimulate and register different neurons. Several highly sensitive MEAs have been developed by researchers that use microelectromechanical systems (MEMS), complementary metal-oxide-semiconductor (CMOS), and lab-on-a-chip micro-fabrication techniques to fabricate a large array of electrodes in a small area. Furthermore, in order to be able to record a large number of individual neurons simultaneously, the electrodes are preferably operated at a high spatial-temporal resolution. In addition, accurate wafer level processes can produce MEAs with superior uniformity, higher quality, and fault tolerance, thereby achieving high reliability. The current research focus is to prepare porous media by advanced micro-machining technology to reduce production cost and increase yield. Micromachining on a large wafer scale can greatly reduce manufacturing costs due to the possibility of mass production.
Disclosure of Invention
The invention aims to solve the problem that flexible MEAs are operated under high space-time resolution and have lower production efficiency, and provides a multichannel MEAs wafer-level manufacturing and assembling method based on cortex electroencephalogram.
The preparation method of the multichannel MEAs based on the cortex electroencephalogram is realized according to the following steps:
1. immersing a silicon substrate into an HF solution to remove an oxide layer, and cleaning the silicon substrate by utilizing plasma to obtain a cleaned silicon substrate;
2. depositing an aluminum sacrificial layer on the surface of the cleaned silicon substrate through an electron beam process;
3. spin-coating a non-photosensitive polyimide MEAs substrate on an aluminum sacrificial layer for multiple times, and sequentially carrying out soft baking and curing to obtain a substrate with a polyimide bottom layer with the thickness of 8-10 micrometers;
4. patterning and shaping the polyimide layer by adopting a photoetching process, wherein the cavity pressure is 440-460 mTorr, and the power is 620-680 and 680W, CF 4 The flow rate is 6-10 sccm, O 2 Performing inductively coupled plasma etching treatment on the polyimide layer under the condition of the flow rate of 70-80 sccm to obtain a patterned substrate;
5. forming a multichannel micro (recording) electrode network and an interconnection plate (Interconnection Pads) through a photoetching process, wherein the micro (recording) electrode is made of a chromium/platinum metal layer, and removing the redundant metal layer through a stripping process to obtain a wafer with the micro electrode network;
6. spin-coating a non-photosensitive polyimide MEAs substrate on a polyimide bottom layer, sequentially performing soft baking and curing to obtain a top layer of polyacetamide with the thickness of 8-10 micrometers, masking a wafer by using a photoresist to define interconnection lines and bonding pads, forming a chromium/platinum metal layer by using an electron beam evaporator, and stripping masks of the interconnection lines and the bonding pads;
7. and removing the aluminum sacrificial layer by adopting an aluminum etchant wet etching process to obtain the multi-channel MEAs based on the cortical electroencephalogram.
The invention relates to a multichannel MEAs based on cortex electroencephalogram, which is characterized in that a microelectrode array is arranged between two layers of flexible polyimide substrates, and the microelectrode array is arranged in the following way: the microelectrodes in each row are arranged at intervals in parallel, the microelectrode units in each row are arranged at intervals, the lead of each microelectrode unit is led out from the middle part of each row of microelectrodes, and the lead is connected with the interconnection plate.
In the invention, a 6-inch high-resistance silicon wafer is used as a substrate, and 25 MEAs can be produced on a single chip in large scale by combining flexible polyimide. The recording positions are compactly arranged with high space-time resolution. By optimizing the MEAs structure, interference between adjacent electrodes can be effectively reduced. In addition, interconnect pads are particularly added to the proposed work to connect the slot connector and the manufactured device. The maximum utilization that can be achieved in consideration of wafer edge defects and manufacturing tolerance factors is achieved. The surface mount device is fabricated with a slot connector without any additional bond wires. This configuration prevents electrical interconnection failure of the device, which may be caused by skull tissue during in vivo testing. Flexible printed circuit boards (FPCBs, polyimide based structures) are used to support MEAs and provide protection from physical damage. The top and bottom PCBs are fabricated with connector receptacles on the front side and interconnect pads on the back side. The FPCB is connected to the top and bottom PCBs by Vcut, which can be easily removed during in vivo testing. In general, the device can record the skull signal for a long period of time, from which several rounds of recording are preferred, to provide accurate and reliable measurements. Thus, the top, bottom PCB and the slot connector are designed to be detachable and can be detached during in vivo recording. This innovative circuit helps to alleviate pain for the patient due to the extra weight of the top and bottom PCBs. In addition, scalp surgery is not needed again in the next round of measurement, so that the cost is saved, the complexity is reduced, and the satisfaction degree of patients is improved.
10 samples of MEAs were evaluated by electrochemical impedance spectroscopy. The impedance spectrum proves that the assembled MEAs has good stability and can be used for simultaneously recording the neuron network with high selectivity and high sensitivity of a plurality of neurons. Finally, the skull of the adult male mouse was subjected to in vivo tests. High reliability and excellent yields can significantly reduce their price and provide opportunities for commercial success of MEAs in the future biomedical market.
Drawings
FIG. 1 is a schematic illustration of a silicon wafer passing O in an embodiment 2 /H 2 A surface topography after plasma treatment;
FIG. 2 is a schematic diagram of a polyimide wafer through O in an embodiment 2 Surface topography after plasma treatment;
FIG. 3 is a schematic structural diagram of a cortical electroencephalogram-based multichannel MEAs, 1-microelectrodes, 2-interconnect plates, 3-interconnect wires;
FIG. 4 is a dimensional block diagram of a single cortical electroencephalogram-based multichannel MEAs;
FIG. 5 is a pictorial view of a single cortical electroencephalogram-based multichannel MEAs;
FIG. 6 is a pictorial representation of 25 MEAs on a fully fabricated 6 inch silicon wafer;
FIG. 7 is a block diagram of a connection of a cortical electroencephalogram based multichannel MEAs to a connector; wherein 4-FPCB, 5-top PCB, 6-bottom PCB, 7-V-cut, 8-connector;
FIG. 8 is a top view of a cortical electroencephalogram based multichannel MEAs mounted on a surface of a PCB;
FIG. 9 is a graph of measured impedance characteristics for 10 random channels in a cortical electroencephalogram based multi-channel MEAs;
FIG. 10 is a graph of ECoG channel measurements from 60 channels per MEAs in the example;
FIG. 11 is an image of flexible MEAs mounted on adult male mouse cranium in an embodiment;
FIG. 12 is a graph of an electroencephalogram sample measurement of the sudden seizures caused by intraperitoneal injection of GBL;
FIG. 13 is a microelectrode distribution map of multichannel MEAs based on cortical electroencephalogram in the examples.
Detailed Description
The first embodiment is as follows: the preparation method of the multichannel MEAs based on the cortex electroencephalogram in the embodiment is implemented according to the following steps:
1. immersing a silicon substrate into an HF solution to remove an oxide layer, and cleaning the silicon substrate by utilizing plasma to obtain a cleaned silicon substrate;
2. depositing an aluminum sacrificial layer on the surface of the cleaned silicon substrate through an electron beam process;
3. spin-coating a non-photosensitive polyimide MEAs substrate on an aluminum sacrificial layer for multiple times, and sequentially carrying out soft baking and curing to obtain a substrate with a polyimide bottom layer with the thickness of 8-10 micrometers;
4. patterning and shaping the polyimide layer by adopting a photoetching process, wherein the cavity pressure is 440-460 mTorr, and the power is 620-680 and 680W, CF 4 The flow rate is 6-10 sccm, O 2 Performing inductively coupled plasma etching treatment on the polyimide layer under the condition of the flow rate of 70-80 sccm to obtain a patterned substrate;
5. forming a multichannel micro (recording) electrode network and an interconnection plate (Interconnection Pads) through a photoetching process, wherein the micro (recording) electrode is made of a chromium/platinum metal layer, and removing the redundant metal layer through a stripping process to obtain a wafer with the micro electrode network;
6. spin-coating a non-photosensitive polyimide MEAs substrate on a polyimide bottom layer, sequentially performing soft baking and curing to obtain a top layer of polyacetamide with the thickness of 8-10 micrometers, masking a wafer by using a photoresist to define interconnection lines and bonding pads, forming a chromium/platinum metal layer by using an electron beam evaporator, and stripping masks of the interconnection lines and the bonding pads;
7. and removing the aluminum sacrificial layer by adopting an aluminum etchant wet etching process to obtain the multi-channel MEAs based on the cortical electroencephalogram.
In the fourth embodiment, the RMS of the polyimide wafer after the inductively coupled plasma etching treatment is 14-14.2 nm.
The second embodiment is as follows: the present embodiment differs from the specific embodiment in that the mass concentration of the HF solution in the step one is 10%.
And a third specific embodiment: the first difference between the present embodiment and the specific embodiment is that the plasma cleaning process in the first step is as follows:
in a plasma cleaning machine, control O 2 /H 2 The flow ratio of (2) is 9000:450sccm, substrate (chuck) temperature at 80 c, chamber pressure of 2Torr (Torr) at 650W rf power for 30 seconds.
The specific embodiment IV is as follows: this embodiment differs from the first or second embodiment in that the surface roughness of the silicon substrate in the first step has a Root Mean Square (RMS) value of 8.5 to 8.8nm.
The present embodiment controls the surface roughness of the silicon substrate to help enhance the adhesion between the silicon substrate and the aluminum sacrificial layer.
Fifth embodiment: the difference between the present embodiment and the first to fourth embodiments is that the thickness of the aluminum sacrificial layer in the second step is 3 μm.
Specific embodiment six: this embodiment differs from one to five of the embodiments in that the soft bake described in step three and step six is a bake at 100 ℃ for 3 minutes and the cure described in step three and step six is a cure at 300 ℃ for 3 minutes.
Seventh embodiment: the difference between the present embodiment and one of the first to sixth embodiments is that the thickness of the polyimide layer in both the third and sixth steps is 9 μm.
Eighth embodiment: the difference between the present embodiment and one of the first to seventh embodiments is that the arrangement manner of the microelectrode network in the fifth step is: the microelectrodes in each row are arranged at intervals in parallel, the microelectrode units in each row are arranged at intervals, and the lead of each microelectrode unit is led out from the middle part of each row of microelectrodes.
Detailed description nine: the eighth difference between the present embodiment and the specific embodiment is that the microelectrode network includes 50 to 70 microelectrode units, and 10 to 12 rows of microelectrodes are arranged in parallel and at intervals.
The microelectrode network of this embodiment has a "Christmas tree" structure, with the FPCB of the MEAs extending out of the mouse body through Vcut and connected to the top and bottom PCBs.
Detailed description ten: this embodiment differs from one of the first through ninth embodiments in that the deposition rates of chromium and platinum in the chromium/platinum metal layer in step five are each 3 angstrom/sec.
Examples: the preparation method of the multichannel MEAs based on the cortical electroencephalogram of the embodiment is implemented according to the following steps:
1. immersing the silicon substrate in a 10% HF solution to remove the oxide layer, and controlling O in a plasma cleaning machine (RF Plasma Cleaner) 2 /H 2 The flow ratio of (2) is 9000:450sccm, plasma cleaning with 650W radio frequency power, 80 ℃ chuck temperature and 2Torr chamber pressure for 30 seconds to obtain a cleaned silicon substrate, wherein the Root Mean Square (RMS) of the base roughness is 8.64nm, and the accurate surface roughness is favorable for enhancing the adhesive force between the silicon substrate and the aluminum sacrificial layer;
2. depositing an aluminum sacrificial layer with the thickness of 3 micrometers on the surface of the cleaned silicon substrate through an electron beam process;
3. a non-photosensitive polyimide MEAs substrate (HD Microsystems, PIX 1400) was spin coated onto the aluminum sacrificial layer three times, the polyimide substrate was deposited three times by a spin coater at 500/3000/500 rpm and corresponding times of 10/40/5s, each time 3 microns, soft baked at 100 ℃ for 3 minutes, and then cured in an oven at 300 ℃ for 3 minutes to give a substrate with a polyimide layer of 9 microns thickness that could alleviate the tensile stress created during the upcoming metallization process to overcome potential rolling problems and planarize the film, however, if the polyimide film thickness exceeded 9 microns, the consequent blocking problems would be incurred when attaching the film onto the mouse skull;
4. patterning and shaping polyimide layer by photolithography, treating at 90deg.C for 30min, and curing at 125deg.C for 60min to obtain stable height and shape with excellent aspect ratio, and processing at cavity pressure of 450mTorr and power of 650W, CF 4 The flow rate is 8sccm, O 2 Performing inductively coupled plasma etching treatment on the polyimide layer under the condition of the flow of 72sccm to promote adhesion between the first polyimide layer and the Cr/Pt metal layer and between the polyimide layer and the second polyimide layer, wherein the root mean square value is 14.01nm, so as to obtain a patterned substrate;
5. forming a 60 channel microelectrode network on the patterned substrate by photolithography, wherein a chromium/platinum (15/150 nm) metal layer is evaporated at a suitable deposition rate of 3 angstrom/sec and 3 angstrom/sec, then performing a lift-off process in which the device is cleaned using a pressure of 3 mpa, treated with acetone for 60 seconds, then with isopropanol for 30 seconds, and finally treated with deionized water for 60 seconds;
6. spin-coating a non-photosensitive polyimide MEAs substrate on a polyimide bottom layer, sequentially performing soft baking and curing to obtain a top layer of polyacetamide with the thickness of 9 micrometers, masking a wafer by using a photoresist to define interconnection lines and bonding pads, forming a chromium/platinum metal layer by using an electron beam evaporator, respectively depositing at the deposition rates of 3 angstroms/second and 3 angstroms/second, and stripping masks of the interconnection lines and the bonding pads;
7. and removing the aluminum sacrificial layer by adopting an aluminum etchant wet etching process to obtain the multi-channel flexible MEAs based on the cortical electroencephalogram.
The microelectrode network described in the fifth step of the embodiment is composed of 60-channel microelectrodes, the microelectrode array is in a Christmas tree shape (as shown in fig. 4), 12 rows of microelectrodes are arranged in parallel at intervals, microelectrode units in each row of microelectrodes are arranged at intervals, lead wires of each microelectrode unit are led out from the middle part of each row of microelectrodes, and the lead wires are connected with an interconnection plate. The FPCB of the "christmas tree" structure MEAs extends outside the mouse body through Vcut and is connected to the top and bottom PCBs (as shown in fig. 7 and 8).
This example produced flexible polyimide-based MEAs with 60 channels. The use of a flexible FPCB and a slot connector provides surface mount assembly without the need for additional wire bonding processes and provides an easier signal recording method for the manufactured MEAs. 10 samples of MEAs were evaluated by electrochemical impedance spectroscopy. The impedance demonstrates that the assembled MEAs have good robustness and can be used to record a highly selective and highly sensitive neuronal network of multiple neurons simultaneously. High reliability and excellent yields can significantly reduce prices and provide opportunities for commercial success of MEAs in the future biomedical market. Finally, the skull of the adult male mice was tested in vivo, and the skull construction proved to be very suitable for signal recording by this method.
Claims (7)
1. The preparation method of the multichannel MEAs based on the cortex electroencephalogram is characterized by comprising the following steps of:
1. immersing a silicon substrate into an HF solution to remove an oxide layer, and cleaning the silicon substrate by utilizing plasma to obtain a cleaned silicon substrate;
2. depositing an aluminum sacrificial layer on the surface of the cleaned silicon substrate through an electron beam process;
3. spin-coating a polyimide MEAs substrate on the aluminum sacrificial layer for multiple times, depositing the polyimide substrate three times by a spin coater at 500/3000/500 rpm and corresponding time of 10/40/5s, and sequentially carrying out soft baking and curing 3 micrometers each time to obtain a substrate with a polyimide bottom layer with the thickness of 9 micrometers;
4. patterning and shaping the polyimide layer by adopting a photoetching process, wherein the cavity pressure is 440-460 mTorr, and the power is 620-680 and 680W, CF 4 The flow rate is 6-10 sccm, O 2 Performing inductively coupled plasma etching treatment on the polyimide layer under the condition of the flow rate of 70-80 sccm to obtain a patterned substrate;
5. forming a multi-channel microelectrode network and an interconnection plate through a photoetching process, wherein microelectrode is made of a chromium/platinum metal layer, and removing the redundant metal layer through a stripping process to obtain a wafer with the microelectrode network;
6. spin-coating a non-photosensitive polyimide MEAs substrate on a polyimide bottom layer, sequentially performing soft baking and curing to obtain a top layer of polyacetamide with the thickness of 9 micrometers, masking a wafer by using a photoresist to define interconnection lines and bonding pads, forming a chromium/platinum metal layer by using an electron beam evaporator, and stripping masks of the interconnection lines and the bonding pads;
7. removing the aluminum sacrificial layer by adopting an aluminum etchant wet etching process to obtain multichannel MEAs based on cortex electroencephalogram;
the arrangement mode of the microelectrode network in the fifth step is as follows: the microelectrodes in each row are arranged at intervals in parallel, microelectrode units in each row are arranged at intervals, and leads of each microelectrode unit are led out from the middle part of each row of microelectrodes; the microelectrode network comprises 50-70 microelectrode units, and 10-12 rows of microelectrodes are arranged in parallel at intervals.
2. The method for producing a cortical electroencephalogram based multi-channel MEAs according to claim 1, wherein the mass concentration of the HF solution in step one is 10%.
3. The method for preparing the cortical electroencephalogram-based multichannel MEAs according to claim 1, wherein the plasma cleaning process in the step one is as follows:
in a plasma cleaning machine, control O 2 /H 2 The flow ratio of (2) is 9000:450sccm, and cleaning at a radio frequency power of 650W, a substrate temperature of 80℃, and a chamber pressure of 2Torr for 30 seconds.
4. The method for producing a cortical electroencephalogram based multi-channel MEAs according to claim 1, wherein the root mean square value of the surface roughness of the silicon substrate in the step one is 8.5 to 8.8nm.
5. The method for producing cortical electroencephalogram based multichannel MEAs according to claim 1, wherein the thickness of the aluminum sacrificial layer in step two is 3 μm.
6. The method for producing a multi-channel MEAs based on cortical electroencephalogram according to claim 1, wherein the soft baking in step three and step six is baking at 100 ℃ for 3 minutes, and the curing in step three and step six is processing at 300 ℃ for 3 minutes.
7. The method for preparing the cortical electroencephalogram-based multichannel MEAs according to claim 1, wherein the deposition rates of chromium and platinum in the chromium/platinum metal layer in the fifth step are 3 angstrom/second.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1852634A (en) * | 2006-04-29 | 2006-10-25 | 中国科学院上海微系统与信息技术研究所 | Projected electrode based on polymer substrate, its making method and use |
| CN101138663A (en) * | 2007-10-25 | 2008-03-12 | 上海交通大学 | Preparation method of biological microelectrode array based on flexible substrate |
| CN102544052A (en) * | 2012-03-08 | 2012-07-04 | 中国科学院深圳先进技术研究院 | Flexible intracranial cortex microelectrode chip, and preparation method and packaging method and packaging structure thereof |
| CN108751116A (en) * | 2018-05-08 | 2018-11-06 | 上海交通大学 | Warpage type flexible electrode and preparation method thereof for biological electrographic recording or electro photoluminescence |
| CN109350846A (en) * | 2018-11-29 | 2019-02-19 | 深圳先进技术研究院 | A kind of functionalization wide cut implantation micro-electrode array and the preparation method and application thereof |
| CN110327544A (en) * | 2019-06-20 | 2019-10-15 | 上海交通大学 | A kind of implanted high-density electrode point flexible stylet electrode and preparation method |
| CN110367978A (en) * | 2019-06-26 | 2019-10-25 | 上海交通大学 | A kind of three-dimensional buckling structure flexibility nerve electrode and its preparation process |
-
2020
- 2020-09-29 CN CN202011051491.4A patent/CN112244848B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1852634A (en) * | 2006-04-29 | 2006-10-25 | 中国科学院上海微系统与信息技术研究所 | Projected electrode based on polymer substrate, its making method and use |
| CN101138663A (en) * | 2007-10-25 | 2008-03-12 | 上海交通大学 | Preparation method of biological microelectrode array based on flexible substrate |
| CN102544052A (en) * | 2012-03-08 | 2012-07-04 | 中国科学院深圳先进技术研究院 | Flexible intracranial cortex microelectrode chip, and preparation method and packaging method and packaging structure thereof |
| CN108751116A (en) * | 2018-05-08 | 2018-11-06 | 上海交通大学 | Warpage type flexible electrode and preparation method thereof for biological electrographic recording or electro photoluminescence |
| CN109350846A (en) * | 2018-11-29 | 2019-02-19 | 深圳先进技术研究院 | A kind of functionalization wide cut implantation micro-electrode array and the preparation method and application thereof |
| CN110327544A (en) * | 2019-06-20 | 2019-10-15 | 上海交通大学 | A kind of implanted high-density electrode point flexible stylet electrode and preparation method |
| CN110367978A (en) * | 2019-06-26 | 2019-10-25 | 上海交通大学 | A kind of three-dimensional buckling structure flexibility nerve electrode and its preparation process |
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