CN110623655A - Implantable micro-nano electrode array chip for simulating weightless rat and preparation method thereof - Google Patents
Implantable micro-nano electrode array chip for simulating weightless rat and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
- A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
- A61B5/685—Microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2503/00—Evaluating a particular growth phase or type of persons or animals
- A61B2503/40—Animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/04—Arrangements of multiple sensors of the same type
- A61B2562/046—Arrangements of multiple sensors of the same type in a matrix array
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/16—Details of sensor housings or probes; Details of structural supports for sensors
- A61B2562/164—Details of sensor housings or probes; Details of structural supports for sensors the sensor is mounted in or on a conformable substrate or carrier
Abstract
An implanted micro-nano electrode array chip and a preparation method thereof, wherein the chip comprises a silicon needle substrate, a microelectrode array, a counter electrode, an electrochemical reference electrode and an electrophysiological reference electrode; the silicon needle substrate is distributed on an implantation part at the front end of the chip and an interface part at the rear end of the chip; a plurality of microelectrodes are distributed on the upper surface of the tip end of each silicon needle, and the microelectrodes form a microelectrode array; and a counter electrode, an electrochemical reference electrode and an electrophysiological reference electrode are arranged on the position, close to the microelectrode array, of the single silicon needle or the positions, close to the microelectrode array, of the different silicon needles. The length of the silicon needles of the micromotor array is gradually reduced, 4 groups of microelectrode arrays are distributed on 4 silicon needles, and the micromotor array is used for simultaneously detecting electrophysiological signals of cerebral cortex, hippocampus and thalamus, so that multiple implantation injuries are avoided, and long-time continuous detection can be realized.
Description
Technical Field
The invention relates to the technical field of micro-machining of a micro-electro-mechanical system (MEMS) of a biosensor, in particular to an implantable micro-nano electrode array chip for simulating a weightless rat and a preparation method thereof.
Background
In a long-term space flight task, astronauts can be in a continuous weightless environment, and the organism is in a stress state for a long time, so that the problems of a neuropsychiatric system, such as cognitive function reduction, can be induced. When Chinese astronauts work in a space capsule, the problem of serious insomnia occurs. Therefore, in order to ensure the on-orbit health and efficient work of astronauts, the mechanism of influence of aerospace special environmental factors on the nerve function, especially the sleep problem, needs to be further explained. A30-degree tail-suspended rat is adopted to simulate the effect of a weightlessness environment, the influence of the 21-28-day tail-suspended simulated weightlessness environment on the sleep of the rat is researched, so that the action mechanism of sleep disorder caused by microgravity is explained partially, and theoretical guidance is provided for aerospace medical protection.
The microelectrode array prepared based on the micro-electro-mechanical system (MEMS) technology provides an effective high-signal-to-noise-ratio and multichannel detection device for detecting and recording neural information, and is an important tool in the fields of research on mechanisms of neuroscience, neural network development, neural information coding, conduction, response and storage, treatment research on neurological diseases, high-throughput drug screening and safe pharmacology research. The electrode is implanted into a normal rat and a weightlessness model rat, and is matched with a special analysis and processing tool and software for living body minimally invasive electrophysiological detection and stimulation, so that the action mechanism of the weightlessness environment influencing sleep is explored. The invention provides a new detection tool for the study of insomnia problem of astronauts in on-orbit work, and has very important scientific significance and application value for the prevention, diagnosis and treatment of the insomnia problem.
In neuroscience research and clinical experiments, the record of the electrophysiological signals of the nerves of animals plays an indispensable role. Compared with the in vitro detection, the in vivo record can reflect the direct effect of the nervous system on the body.
David h.hubel started single neuron recording in the fifties of the twentieth century using insulated metal tungsten wire electrodes with an insulation layer with a tip diameter of only a few microns. The insulating tungsten wire is always an effective microwire electrode preparation material, metals with good biocompatibility such as gold, platinum and the like are also applied to the electrode recently, and the microwire electrode can be a single channel or a plurality of channels. With the development of MEMS technology, silicon material-based microelectrode probe arrays with two-dimensional and three-dimensional structures are developed. The electrode is mainly divided into two categories, one category is a needle-shaped microelectrode array developed by the university of Utah, the electrode takes monolithic monocrystalline silicon as a material to present a square electrode needle array, the tip is plated with a metal layer, the electrode is insulated by adopting a polyimide coating, the electrode is limited by the shape and the size, and the electrode is mainly used for detecting neuro-electrophysiological information of a cerebral cortical area or a shallower surface part and has limitation on deep measurement of the brain.
The other type of microelectrode array is widely applied, namely a Linear Silicon Electrode Array (LSEA), the developed microelectrode array is of a planar silicon needle structure, a required planar needle shape is formed on a silicon wafer by etching, the intensity is not as good as that of a Utah electrode, the damage to the brain is small, and the neural information of a deeper part can be analyzed.
Disclosure of Invention
In view of the above, the main objective of the present invention is to provide an implantable micro-nano electrode array chip for simulating a weightless rat and a preparation method thereof, so as to at least partially solve at least one of the above technical problems.
In order to achieve the above object, as an aspect of the present invention, an implantable micro-nano electrode array chip for simulating a weightless rat is provided, including: the probe comprises a silicon needle substrate, a microelectrode array, a counter electrode, an electrochemical reference electrode and an electrophysiological reference electrode;
the silicon needle substrate is distributed on an implantation part at the front end of the chip and an interface part at the rear end of the chip; a plurality of microelectrodes are distributed on the upper surface of the tip end of each silicon needle, and the microelectrodes form a microelectrode array; and a counter electrode, an electrochemical reference electrode and an electrophysiological reference electrode are arranged on the position, close to the microelectrode array, of the single silicon needle or the positions, close to the microelectrode array, of the different silicon needles.
The silicon needle substrate is a carrier of the whole micro-nano electrode array chip and is in a sheet shape.
The microelectrode in the microelectrode array is a circular microelectrode with the diameter of 20 +/-5 microns, and is used for bimodule detection of neuroelectrophysiological signals and neurotransmitter chemical signals.
The counter electrode, the electrochemical reference electrode and the electrophysiological reference electrode are less than or equal to 50 microns in size and are used for providing a reference point and keeping the potential stable.
The length of the implanted part is 4 silicon needles, 4 groups of microelectrode arrays are distributed on the 4 silicon needles, and the microelectrode arrays are used for simultaneously detecting electrophysiological signals of cerebral cortex, hippocampal region and thalamic region and electrochemical signals of dopamine and glutamate neurotransmitter or for detecting electrophysiological signals and electrochemical signals of paraventricular nuclei of thalamus.
Wherein, the material of the silicon needle substrate is selected from one of monocrystalline silicon, doped silicon, SOI insulated silicon or boron diffused silicon.
Wherein, the material of all electrodes is a metal or metal compound conductive film with good biocompatibility, and is preferably one of gold, platinum, titanium nitride or indium tin oxide.
The implanted micro-nano electrode array chip also comprises leads, pads and an insulating layer, wherein a plurality of pads are distributed on an interface at the rear end of the silicon needle substrate, a plurality of leads are arranged between the pads and the electrodes on the upper surface of the implanted part, and the pads and the electrodes are connected with tip electrode sites in a one-to-one correspondence manner through the leads; the upper surfaces of all the leads are covered with an insulating layer.
The material used for the insulating layer is an organic or inorganic insulating material with good biocompatibility, and is preferably one of silicon dioxide, silicon nitride, silicon oxynitride, SU8, polyimide or parylene.
As another aspect of the present invention, there is provided a method for preparing the micro-nano electrode array chip, including the following steps:
forming a conductive film layer of a microelectrode array, a counter electrode, an electrochemical reference electrode, an electrophysiological reference electrode, a lead and a bonding pad on a silicon wafer with an insulated surface by adopting methods of sputtering, evaporation and etching;
covering an insulating layer on the surface of the prepared conductive thin film layer by a deposition, sputtering or spin coating method, exposing the microelectrode array, the counter electrode, the electrochemical reference electrode, the electrophysiological reference electrode and the bonding pad by etching, and reserving the insulating layers on the surfaces of all leads;
forming the shapes of an interface part and an implanted part of the silicon needle substrate with required thickness by a deep etching or self-stopping wet etching method, and removing other redundant silicon layers to separate and release the whole microelectrode array chip from the silicon wafer;
setting round microelectrode surface modification nanometer materials or sensitive film materials with different functions in a microelectrode array according to requirements by electrochemical deposition or physical drop coating and adsorption methods, so as to form round microelectrodes with different functions.
Based on the technical scheme, compared with the prior art, the implantable micro-nano electrode array chip for simulating the weightless rat and the preparation method thereof have at least one of the following beneficial effects:
(1) the implantable nerve information dual-mode detection micro-nano electrode array integrates the functions of in-vivo multichannel neuroelectrophysiology detection and electrochemical detection of neurotransmitters such as dopamine and glutamic acid, and has the advantages of small chip volume and small damage to tissues.
(2) The length of the silicon needles of the micromotor array is gradually reduced, 4 groups of microelectrode arrays are distributed on 4 silicon needles, and the micromotor array is used for simultaneously detecting electrophysiological signals of cerebral cortex, hippocampus and thalamus, so that multiple implantation injuries are avoided, and long-time continuous detection can be realized.
(3) The implanted nerve information dual-mode detection micro-nano electrode array provided by the invention can realize high-flux, in-situ, synchronous and dual-mode detection of nerve information in vivo, breaks through the limitation that the prior art can only separately detect two nerve information modes and has poor real-time performance, provides a more convenient and effective tool for researching the relationship between the two nerve information modes, provides a new detection means and a new tool for deeply researching the insomnia problem of astronauts in on-orbit work, and has very important scientific significance and application value for prevention, diagnosis and treatment of the insomnia problem.
Drawings
FIG. 1 is a schematic structural diagram of an implantable neural information dual-mode detection micro-nano electrode array chip;
FIG. 2 is a schematic diagram showing a partial enlargement of a tip site of a microelectrode array;
FIG. 3 is a flow chart of a method for preparing an implantable neural information dual-mode detection micro-nano electrode array chip according to the invention;
FIG. 4 is a process flow chart of the method for preparing the implantable neural information dual-mode detection micro-nano electrode array chip;
FIG. 5 is a schematic diagram of an experiment of inserting a microelectrode array into a rat brain;
fig. 6 is a schematic diagram of simulated weightlessness rat multichannel neuroelectrophysiological signals recorded by adopting the implantable neural information dual-mode detection micro-nano electrode array chip.
In the above drawings, the reference numerals have the following meanings:
1. a microelectrode array; 2. A counter electrode; 3. An electrochemical reference electrode;
4. an electrophysiological reference electrode; 5. A silicon needle substrate; 6. A lead wire;
7. an insulating layer; 8. A pad;
9. a microelectrode for electrophysiological or neurotransmitter detection.
Detailed Description
In order that the objects, technical solutions and advantages of the present invention will become more apparent, the present invention will be further described in detail with reference to the accompanying drawings in conjunction with the following specific embodiments.
The invention discloses a design and a preparation method of an implanted micro-nano electrode array special for simulating the detection of chemical transmitter signals of deep nerve signals of a heavy rat brain. The micro-nano electrode array comprises: the probe comprises a silicon needle substrate, 4 groups of microelectrodes arranged as required, a counter electrode, an electrochemical reference electrode, an electrophysiological reference electrode, a plurality of leads, a plurality of bonding pads and a silicon nitride insulating layer. The chip is processed and prepared by adopting a Micro Electro Mechanical System (MEMS) technology. The tip part of the silicon needle is implanted into the brain of a simulated heavy rat and can be used for carrying out in-situ and synchronous detection on intracerebral nerve electrical signals and neurotransmitter chemical signals such as dopamine and glutamic acid of the rat brain nervous system. By comparing the difference of the key nucleus signals of the brain of the weightlessness mouse and the normal mouse, the method for influencing the brain function of the rat and further influencing the sleep of the rat by simulating the weightlessness environment can be searched.
The technical solution of the present invention will be further explained by the following examples and drawings. Fig. 1 shows a 4 silicon needle type implanted nerve information dual-mode detection micro-nano electrode array chip provided by the invention. The method comprises the following steps: a silicon needle substrate 5, a microelectrode array 1, a counter electrode 2, an electrochemical reference electrode 3 and an electrophysiological reference electrode 4;
wherein, the silicon needle substrate 5 is distributed on the implantation part at the front end of the chip and the interface part at the rear end; a plurality of microelectrodes are distributed on the upper surface of the tip end of each silicon needle, and the microelectrodes form a microelectrode array 1; a counter electrode 2, an electrochemical reference electrode 3 and an electrophysiological reference electrode 4 are arranged on a single silicon needle or a plurality of different silicon needles at positions close to the microelectrode array 1.
Further, the silicon needle substrate 5 is a carrier of the whole micro-sodium electrode array chip, is in a sheet shape, and has a thickness of about 30 μm. The front ends are arranged in parallel, the tips of the needle-shaped branches are at an angle of 30 degrees and widen backwards, the widest part is 100 mu m, and the branch spacing is 200 mu m.
4 circular microelectrodes are arranged in a trapezoidal distribution on each of the branched surfaces, and all of these patterns constitute a 4X 4 microelectrode array 1. FIG. 2 is a partially enlarged schematic view of the micro-electrode array 1 on a single branch. Wherein the diameter of the microelectrode 9 is 20 μm, and can be used for bimodully detecting neuroelectrophysiological signals and neurotransmitter chemical signals.
In this embodiment, a pair of electrodes 2, an electrochemical reference electrode 3, an electrophysiological reference electrode 4, each having a size of 50 μm, are provided on each branch at a distance of 0.5mm from the microelectrode array. In the process of detecting the electrophysiological signals, the electrophysiological reference electrode 4 is used for providing a reference point; in the process of detecting the electrochemical signal of the neurotransmitter, the counter electrode 2 is used for providing a current loop and forms a three-electrode system for electrochemical detection together with the electrochemical reference electrode 3.
Furthermore, the implanted part is 4 silicon needles, the lengths of the silicon needles are respectively 6mm, 5mm, 4mm and 3mm, 4 groups of microelectrode arrays are distributed on the 4 silicon needles, and the microelectrode arrays are used for simultaneously detecting electrophysiological signals of cerebral cortex, hippocampus and thalamus and electrochemical signals of dopamine and glutamate neurotransmitters or for detecting electrophysiological signals and electrochemical signals of paraventricular nuclei.
In this embodiment, the material of the silicon needle substrate is selected from one of single crystal silicon, doped silicon, SOI silicon-on-insulator, or boron-diffused silicon.
In this embodiment, the implanted micro-nano electrode array chip further comprises leads, pads and an insulating layer, wherein a plurality of pads are distributed on an interface at the rear end of the silicon needle substrate, a plurality of leads are arranged between the pads and the electrodes on the upper surface of the implanted part, and are connected with the tip electrode sites in a one-to-one correspondence manner through the leads; the upper surfaces of all the leads are covered with an insulating layer.
The material used by the insulating layer is an organic or inorganic insulating material with good biocompatibility, and is one of silicon dioxide, silicon nitride, silicon oxynitride, SU8, polyimide or parylene.
In this embodiment, the materials of the microelectrode array 1, the counter electrode 2, the electrochemical reference electrode 3, the electrophysiological reference electrode 4, and the lead 6 are platinum metal films, and nano platinum black particles can be modified on the surface of the microelectrode 9 to improve the signal-to-noise ratio. In order to improve the selectivity of detecting neurotransmitter dopamine, an ion-selective Nafion membrane can be modified on the surface of the microelectrode 9. The surface of the lead 6 is covered with a silicon nitride film insulating layer.
All the electrodes extend to the tail end of the silicon needle substrate 1 through the lead 6 and are connected with the square bonding pad 8. The pad size is 200 μm for connecting the electrode to an external circuit by means of pressure welding.
Implanting a branch part at the tip of the silicon needle substrate 5 into a simulated weightlessness rat and a nerve tissue in the brain of a normal rat, enabling the microelectrode array 2 to be in close contact with the nerve tissue, and combining a matched detection system to carry out dual-mode detection and related experiments of the in-vivo nerve information of the rat, wherein the specific operation of the experiment is as follows:
dividing rats into two groups, wherein one group of rats is placed in a tail suspension molding device, taking out after 28 days of molding, and identifying the learning and memory function damage condition of the rat of the simulated weightlessness model by using a water maze behavioural experiment; another group of rats was housed separately. All rats in both groups were kept in the same environment during the rearing process.
After the model building is finished, the invention is implanted into two groups of rat brains, the implantation position is shown as figure 5, and the rat brains are implanted into brain areas: cortex, hippocampus and thalamus; the implantation coordinates are AP: 3.6mm, ML: 1.8m, DV: 1.8mm, 2.8mm, 3.8mm and 4.8mm (the depth of cortex is 0-2 mm, the depth of hippocampus is 2-4 mm, and the depth of thalamus is 4-6 mm); and thalamotocyclic Paraventricular (PVT) brain region, implanted with the coordinates AP: -2.52mm, mL: 0mm, DV: 4.75 mm.
After extracting signals, carrying out comparative analysis on data of the simulated weightlessness rat and the normal rat, wherein the analysis method comprises the following steps: contrast the firing rate (number of discharges of nerve cells per second), the time delay rate of spike peak-to-peak, the firing power over a period of time, etc.
The invention also provides a preparation method of the implanted micro-nano electrode array chip, which comprises the following steps:
forming a conductive film layer of a microelectrode array, a counter electrode, an electrochemical reference electrode, an electrophysiological reference electrode, a lead and a bonding pad on a silicon wafer with an insulated surface by adopting methods of sputtering, evaporation and etching;
covering an insulating layer on the surface of the prepared conductive thin film layer by a deposition, sputtering or spin coating method, exposing the microelectrode array, the counter electrode, the electrochemical reference electrode, the electrophysiological reference electrode and the bonding pad by etching, and reserving the insulating layers on the surfaces of all leads;
forming the shapes of an interface part and an implanted part of the silicon needle substrate with required thickness by a deep etching or self-stopping wet etching method, and removing other redundant silicon layers to separate and release the whole microelectrode array chip from the silicon wafer;
setting round microelectrode surface modification nanometer materials or sensitive film materials with different functions in a microelectrode array according to requirements by electrochemical deposition or physical drop coating and adsorption methods, so as to form round microelectrodes with different functions.
The specific preparation process of the invention refers to fig. 3 and fig. 4, wherein fig. 4 is described in detail as follows:
1. spin-coating a layer of positive photoresist AZ1500 on the SO1 silicon wafer with insulated surface, the thickness is 1 μm, and forming patterns of all microelectrode arrays 1, counter electrodes 2, electrochemical reference electrodes 3, leads 6 of electrophysiological reference electrodes 4 and bonding pads 8 on a mask plate after photoetching and development (FIG. 4 a).
2. And sputtering a Ti metal seed layer with the thickness of 30nm on the surface of the photoresist pattern to increase the adhesion of the Pt conductive thin film layer and the silicon wafer substrate, and then sputtering a Pt thin film layer with the thickness of 250nm (figure 4 b).
3. A lift-off process is used to remove the excess Ti/Pt thin film layer, leaving the desired electrodes, leads 6 and pads 8 (fig. 4 c).
4. And electrochemically depositing a silicon nitride insulating layer on the surface of the substrate with the prepared Pt thin film layer, wherein the thickness of the silicon nitride insulating layer is 800 nm. By photolithography and SF6And (3) exposing the microelectrode array 1, the counter electrode 2, the electrochemical reference electrode 3, the electrophysiological reference electrode 4 and the bonding pad 8 by using a plasma etching method, and reserving the silicon nitride insulating layers on the surfaces of all the leads 6. (FIG. 4 d).
5. Spin-coating a layer of thick photoresist, forming a mask pattern required by etching the silicon needle substrate after photoetching and developing, and etching the front surface of the SOI silicon wafer into a needle-shaped shape of the silicon needle substrate with required thickness by an inductive ion coupling deep etching method (figure 4 e).
6. And etching off the silicon layer on the back of the SOI silicon wafer by a wet etching method, and breaking the silicon dioxide film carried by the SOI silicon wafer by an ultrasonic oscillation method to separate and release the whole microelectrode array chip taking the silicon needle substrate as a carrier from the silicon wafer (fig. 4 f).
FIG. 6 shows two spike signals of rat hippocampal region measured by the electrode designed by the present invention. The waveform and amplitude of the two signals are different, and the single cell level signal can be detected by the method.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention and are not intended to limit the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An implanted micro-nano electrode array chip is characterized by comprising: the probe comprises a silicon needle substrate, a microelectrode array, a counter electrode, an electrochemical reference electrode and an electrophysiological reference electrode;
the silicon needle substrate is distributed on an implantation part at the front end of the chip and an interface part at the rear end of the chip; a plurality of microelectrodes are distributed on the upper surface of the tip end of each silicon needle, and the microelectrodes form a microelectrode array; and a counter electrode, an electrochemical reference electrode and an electrophysiological reference electrode are arranged on the position, close to the microelectrode array, of the single silicon needle or the positions, close to the microelectrode array, of the different silicon needles.
2. The implantable micro-nano electrode array chip according to claim 1, wherein the silicon needle substrate is a carrier of the whole micro-nano electrode array chip and is in a sheet shape.
3. The implantable micro-nano electrode array chip according to claim 1, wherein the micro-electrodes in the micro-electrode array are circular micro-electrodes with a diameter of 20 ± 5 μm, and are used for dual-mode detection of neuroelectrophysiological signals and neurotransmitter chemical signals.
4. The implantable micro-nano electrode array chip according to claim 1, wherein the counter electrode, the electrochemical reference electrode and the electrophysiological reference electrode have a size of less than or equal to 50 μm and are used for providing a reference point and keeping a potential stable.
5. The implantable micro-nano electrode array chip according to claim 1, wherein the implanted part is 4 silicon needles, the lengths of the silicon needles are sequentially decreased, and 4 groups of microelectrode arrays are distributed on the 4 silicon needles and are used for simultaneously detecting electrophysiological signals of cerebral cortex, hippocampus and thalamus regions and electrochemical signals of dopamine and glutamate neurotransmitters or for detecting electrophysiological signals and electrochemical signals of parathalamic nuclei.
6. The implantable micro-nano electrode array chip according to claim 1, wherein the silicon needle substrate is made of one material selected from monocrystalline silicon, doped silicon, SOI silicon-on-insulator (SOI) or boron-diffused silicon.
7. The implantable micro-nano electrode array chip according to claim 1, wherein the material of all electrodes is a metal or metal compound conductive film with good biocompatibility, preferably one of gold, platinum, titanium nitride or indium tin oxide.
8. The implantable micro-nano electrode array chip according to claim 1, further comprising leads, pads and an insulating layer, wherein a plurality of pads are distributed on an interface at the rear end of the silicon needle substrate, a plurality of leads are arranged between the pads and the electrodes on the upper surface of the implanted part, and are connected with the tip electrode sites in a one-to-one correspondence manner through the leads; the upper surfaces of all the leads are covered with an insulating layer.
9. The implantable micro-nano electrode array chip according to claim 8, wherein the insulating layer is made of an organic or inorganic insulating material with good biocompatibility, preferably one of silicon dioxide, silicon nitride, silicon oxynitride, SU8, polyimide or parylene.
10. A method for preparing an implantable micro-nano electrode array chip according to any one of claims 1 to 9, comprising the following steps:
forming a conductive film layer of a microelectrode array, a counter electrode, an electrochemical reference electrode, an electrophysiological reference electrode, a lead and a bonding pad on a silicon wafer with an insulated surface by adopting methods of sputtering, evaporation and etching;
covering an insulating layer on the surface of the prepared conductive thin film layer by a deposition, sputtering or spin coating method, exposing the microelectrode array, the counter electrode, the electrochemical reference electrode, the electrophysiological reference electrode and the bonding pad by etching, and reserving the insulating layers on the surfaces of all leads;
forming the shapes of an interface part and an implanted part of the silicon needle substrate with required thickness by a deep etching or self-stopping wet etching method, and removing other redundant silicon layers to separate and release the whole microelectrode array chip from the silicon wafer;
setting round microelectrode surface modification nanometer materials or sensitive film materials with different functions in a microelectrode array according to requirements by electrochemical deposition or physical drop coating and adsorption methods, so as to form round microelectrodes with different functions.
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| CN111956218A (en) * | 2020-08-10 | 2020-11-20 | 中国科学院上海微系统与信息技术研究所 | Flexible brain electrode with electrochemical and electrophysiological detection functions and preparation method thereof |
| CN112006685A (en) * | 2020-09-07 | 2020-12-01 | 中国科学院空天信息创新研究院 | Cortical epilepsy brain function positioning flexible micro-nano electrode array and preparation method thereof |
| CN113181549A (en) * | 2021-04-28 | 2021-07-30 | 中国科学院空天信息创新研究院 | Flexible micro-nano electrode array for positioning deep brain of epileptogenic focus and preparation method thereof |
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| CN115128140A (en) * | 2022-06-15 | 2022-09-30 | 南京师范大学 | Needle-shaped coaxial multi-electrode device and construction method thereof |
| KR102630332B1 (en) * | 2022-11-09 | 2024-01-30 | 한국과학기술원 | Bio-probe module, bio-signal detector having the same and method of manufacturing the bio-probe module |
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| CN115128140A (en) * | 2022-06-15 | 2022-09-30 | 南京师范大学 | Needle-shaped coaxial multi-electrode device and construction method thereof |
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