CN113476050B - Nerve microprobe and preparation method thereof - Google Patents
Nerve microprobe and preparation method thereof Download PDFInfo
- Publication number
- CN113476050B CN113476050B CN202110746579.6A CN202110746579A CN113476050B CN 113476050 B CN113476050 B CN 113476050B CN 202110746579 A CN202110746579 A CN 202110746579A CN 113476050 B CN113476050 B CN 113476050B
- Authority
- CN
- China
- Prior art keywords
- electrode
- optical waveguide
- microprobe
- magneto
- electrochemical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 210000005036 nerve Anatomy 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 230000003287 optical effect Effects 0.000 claims abstract description 53
- 239000000758 substrate Substances 0.000 claims abstract description 47
- 230000001537 neural effect Effects 0.000 claims abstract description 43
- 230000005291 magnetic effect Effects 0.000 claims abstract description 38
- 230000005284 excitation Effects 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 21
- 230000000638 stimulation Effects 0.000 claims abstract description 19
- 210000004556 brain Anatomy 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 7
- 238000005530 etching Methods 0.000 claims description 20
- 238000001259 photo etching Methods 0.000 claims description 20
- 238000000151 deposition Methods 0.000 claims description 18
- 239000011248 coating agent Substances 0.000 claims description 11
- 238000000576 coating method Methods 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 11
- 238000000708 deep reactive-ion etching Methods 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 229910045601 alloy Inorganic materials 0.000 claims description 6
- 239000000956 alloy Substances 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 239000000523 sample Substances 0.000 claims description 6
- 239000002858 neurotransmitter agent Substances 0.000 claims description 5
- 229920000144 PEDOT:PSS Polymers 0.000 claims description 4
- 238000000137 annealing Methods 0.000 claims description 4
- 239000013307 optical fiber Substances 0.000 claims description 4
- 229910001020 Au alloy Inorganic materials 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910001260 Pt alloy Inorganic materials 0.000 claims description 3
- 229910021607 Silver chloride Inorganic materials 0.000 claims description 3
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 3
- 239000004020 conductor Substances 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 238000000835 electrochemical detection Methods 0.000 claims description 3
- 229910052737 gold Inorganic materials 0.000 claims description 3
- 239000010931 gold Substances 0.000 claims description 3
- 239000003353 gold alloy Substances 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- GQYHUHYESMUTHG-UHFFFAOYSA-N lithium niobate Chemical group [Li+].[O-][Nb](=O)=O GQYHUHYESMUTHG-UHFFFAOYSA-N 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 3
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 230000005641 tunneling Effects 0.000 claims description 2
- 238000004140 cleaning Methods 0.000 claims 1
- 238000001514 detection method Methods 0.000 abstract description 21
- 230000010354 integration Effects 0.000 abstract description 12
- 230000001360 synchronised effect Effects 0.000 abstract description 4
- 210000000653 nervous system Anatomy 0.000 abstract description 3
- 230000006870 function Effects 0.000 abstract description 2
- 238000005459 micromachining Methods 0.000 abstract description 2
- 239000010408 film Substances 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 7
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000013461 design Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 229910001297 Zn alloy Inorganic materials 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000007772 electrode material Substances 0.000 description 2
- 230000007831 electrophysiology Effects 0.000 description 2
- 238000002001 electrophysiology Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 229910044991 metal oxide Inorganic materials 0.000 description 2
- 150000004706 metal oxides Chemical class 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 238000004528 spin coating Methods 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910001030 Iron–nickel alloy Inorganic materials 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910000861 Mg alloy Inorganic materials 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 239000004642 Polyimide Substances 0.000 description 1
- 229920001486 SU-8 photoresist Polymers 0.000 description 1
- 229910052581 Si3N4 Inorganic materials 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- GSWGDDYIUCWADU-UHFFFAOYSA-N aluminum magnesium oxygen(2-) Chemical compound [O--].[Mg++].[Al+3] GSWGDDYIUCWADU-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- AJNVQOSZGJRYEI-UHFFFAOYSA-N digallium;oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Ga+3].[Ga+3] AJNVQOSZGJRYEI-UHFFFAOYSA-N 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 229910001195 gallium oxide Inorganic materials 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- SJCKRGFTWFGHGZ-UHFFFAOYSA-N magnesium silver Chemical compound [Mg].[Ag] SJCKRGFTWFGHGZ-UHFFFAOYSA-N 0.000 description 1
- PNHVEGMHOXTHMW-UHFFFAOYSA-N magnesium;zinc;oxygen(2-) Chemical compound [O-2].[O-2].[Mg+2].[Zn+2] PNHVEGMHOXTHMW-UHFFFAOYSA-N 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004377 microelectronic Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000008 neuroelectric effect Effects 0.000 description 1
- 229920000052 poly(p-xylylene) Polymers 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- HQVNEWCFYHHQES-UHFFFAOYSA-N silicon nitride Chemical compound N12[Si]34N5[Si]62N3[Si]51N64 HQVNEWCFYHHQES-UHFFFAOYSA-N 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- BSWGGJHLVUUXTL-UHFFFAOYSA-N silver zinc Chemical compound [Zn].[Ag] BSWGGJHLVUUXTL-UHFFFAOYSA-N 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
Images
Classifications
-
- 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
- A61B5/25—Bioelectric electrodes therefor
- A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
- A61B5/294—Bioelectric electrodes therefor specially adapted for particular uses for nerve conduction study [NCS]
-
- 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
- A61B5/242—Detecting biomagnetic fields, e.g. magnetic fields produced by bioelectric currents
- A61B5/248—Detecting biomagnetic fields, e.g. magnetic fields produced by bioelectric currents specially adapted for magnetoneurographic [MNG] signals, e.g. magnetospinographic [MSG] signals
-
- 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
- A61B5/25—Bioelectric electrodes therefor
- A61B5/263—Bioelectric electrodes therefor characterised by the electrode materials
-
- 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
- A61B5/25—Bioelectric electrodes therefor
- A61B5/263—Bioelectric electrodes therefor characterised by the electrode materials
- A61B5/265—Bioelectric electrodes therefor characterised by the electrode materials containing silver or silver chloride
-
- 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
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/388—Nerve conduction study, e.g. detecting action potential of peripheral nerves
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Abstract
The invention provides a nerve microprobe and a preparation method thereof, wherein the nerve microprobe comprises the following components: the sensor comprises an optical waveguide, a magneto-resistance sensor, a planar coil and an excitation electrode; the optical waveguides are arranged on the first surface of the substrate, and the magnetoresistive sensors are arranged on the first surface of the substrate; the planar coil and the excitation electrode are both arranged on the second surface of the substrate, one end of the planar coil is connected with the excitation electrode, the excitation electrode applies direct current or alternating current to the planar coil, and the planar coil generates magnetic stimulation or provides a constant or alternating bias magnetic field for the magneto-resistance sensor, so that the magnetic control device is suitable for performing magnetic control on a designated brain area of a brain. The invention integrates the magneto-resistance sensor, the optical waveguide, the microelectrode and the micro-nano coil into a whole by the MEMS micromachining process, realizes the magneto-optical-electric regulation and multi-mode signal detection, can be used for carrying out invasive regulation and detection on the neural information of a nervous system, and has the advantages of miniaturization, integration, multiple functions and small damage to tissues while realizing synchronous regulation and detection.
Description
Technical Field
The invention relates to the field of microelectronics, in particular to a nerve microprobe and a preparation method thereof.
Background
The neural regulation refers to a biomedical engineering technology which utilizes invasive or non-invasive technologies, utilizes physical or chemical means such as magnetism, light, electricity and the like to change signal transmission of a nervous system, regulates the activity of neurons and a neural network where the neurons are located, and finally causes specific brain function change. The light stimulation can regulate and control neurons in a micro scale, the magnetic stimulation and the electric stimulation can regulate and control regional brain functional regions in a mesoscopic scale, and through nerve regulation and control of different means in the micro scale and the mesoscopic scale, neuroelectrophysiology, magnetophysiology and neurochemistry multimode signals are synchronously recorded, and combined analysis is performed, so that rich and comprehensive information can be obtained, and the method has important significance for researching neural circuits, analyzing brain functions, treating nervous system diseases and the like.
In the prior art, due to the lack of a tool integrating light stimulation, electric stimulation, magnetic stimulation and neuroelectric, magnetic and chemical multimode signal detection, light stimulation equipment, electric stimulation or magnetic stimulation and nerve signal recording equipment need to be operated simultaneously in actual use, so that high requirements are provided for experimenters, the experiment preparation time is long, the experiment operation is complicated, and the experiment efficiency is reduced. In addition, multiple devices are adopted to jointly carry out experiments, so that the synchronization of neural regulation and signal detection faces challenges, and information is easy to lose.
On the other hand, with the continuous development of MEMS technology, various types of nerve microprobes have been designed for stimulating and recording nerve signals. However, no relevant report exists at present on the design of realizing magnetic, optical and electrical stimulation on the same probe and synchronously recording electrical, magnetic and chemical neural multimode signals. Therefore, the integrated magnetic-optical-electric regulation and multimode signal detection neural microprobe has great scientific significance for enriching the neuroscience research means, improving the experimental efficiency and enhancing the synchronous performance of regulation and detection.
Disclosure of Invention
Technical problem to be solved
The invention provides a nerve microprobe and a preparation method thereof, which aim to solve the technical problems.
(II) technical scheme
According to an aspect of the present invention, there is provided a neural microprobe, including:
an optical waveguide disposed on the first face of the substrate; one end of the optical waveguide is arranged on the nerve microprobe, the optical waveguide extends along the nerve microprobe, and the other end of the optical waveguide is connected with an optical fiber;
the two magneto-resistance sensors are positioned on one side of the optical waveguide and arranged on the first surface of the substrate; the magneto-resistance sensor is suitable for detecting a neural magneto-physiological signal;
the planar coil and the excitation electrode are arranged on the second surface of the substrate, one end of the planar coil is connected with the excitation electrode, the excitation electrode applies direct current or alternating current to the planar coil, the planar coil generates magnetic stimulation or provides a constant or alternating bias magnetic field for the magneto-resistance sensor, and the planar coil is suitable for magnetically regulating and controlling a designated brain region of a brain;
the magneto-resistance sensor and the excitation electrode are connected with a contact through leads.
In some embodiments of the invention, further comprising:
the electrophysiological electrode group and the electrochemical electrode group are positioned on the other side of the optical waveguide and are arranged on the first surface of the substrate; the electrophysiological electrode group and the electrochemical electrode group are both connected with the contact through leads.
In some embodiments of the invention, the electrophysiology electrode set comprises:
the electrophysiological microelectrode and the electrophysiological reference electrode are positioned on one side of the optical waveguide and are arranged on the first surface of the substrate; the electrophysiological reference electrode is suitable for providing a reference potential in the process of detecting electrophysiological signals or applying electrical stimulation to the electrophysiological microelectrode;
the electrochemical electrode assembly includes:
the electrochemical microelectrode, the counter electrode and the electrochemical reference electrode are positioned on one side of the optical waveguide and arranged on the first surface of the substrate; the electrochemical microelectrode, the counter electrode and the electrochemical reference electrode form a current loop and are suitable for electrochemical detection of neurotransmitters.
In some embodiments of the invention, the electrochemical microelectrode is surface coated with an electrode coating; the electrode coating material is poly 3, 4-ethylenedioxythiophene-polystyrene sulfonate.
In some embodiments of the invention, the magnetoresistive sensor is one or more of an anisotropic magnetoresistive sensor, a giant magnetoresistive sensor, and a tunneling magnetoresistive sensor; the magnetic layer of the magnetoresistive sensor is generally formed of one or more alloys of Co, Fe, Ni, or a bilayer of two alloys.
In some embodiments of the present invention, the magnetoresistive sensor is in the shape of 5 segments of a fold with a length of 40-50 μm and a width of 3-6 μm, or a yoke with a width of 1-6 μm and a length of 40-120 μm.
In some embodiments of the invention, the material of the planar coil is a conductive material; the planar coil is in a spiral shape like a Chinese character 'hui', and the side length is 150-; the shape of the excitation electrode is a square with the side length of 20-50 mu m; the material of the optical waveguide is lithium niobate or lithium titanate; the thickness of the optical waveguide is 300-900nm, and the width of the optical waveguide is 1-2 μm.
In some embodiments of the invention, the shape of each of the electrophysiological microelectrodes is a square with a side length of 10-50 μm; the electrophysiological reference electrode is in the shape of a square with a side length of 20-100 μm.
In some embodiments of the present invention, the material of the counter electrode is any one or more of Pt and Au, or any one or more of a platinum alloy and a gold alloy, or a nanomaterial; the electrochemical reference electrode is made of Ag and AgCl; the counter electrode and the electrochemical reference electrode are both in a square shape with the side length of 20-100 mu m; the shape of the electrochemical microelectrode is a square with the side length of 10-50 mu m.
According to an aspect of the present invention, there is also provided a method of preparing a neural microprobe, including:
depositing an optical waveguide film layer on the first surface of the substrate layer, and photoetching and etching the optical waveguide shape;
depositing a magneto-resistance sensor film layer on the first surface of the substrate layer, and photoetching and etching to form a magneto-resistance sensor shape;
high-temperature magnetic field annealing defines the sensitive direction of the magneto-resistance sensor;
growing a conductive layer on the second surface of the substrate layer, and photoetching and etching the shapes of the planar coil and the excitation electrode;
the final probe shape was defined by Deep Reactive Ion Etching (DRIE).
(III) advantageous effects
According to the technical scheme, the nerve microprobe and the preparation method thereof have at least one or part of the following beneficial effects:
(1) the invention integrates the integration of magneto-optical regulation and multi-mode signal detection, realizes the miniaturization, integration and integration of the regulation and control and signal detection device on the basis of the MEMS processing technology, is convenient to use, and greatly improves the experimental efficiency.
(2) The invention integrates the integration of magnetic-optical-electric regulation and multi-mode signal detection, realizes the miniaturization, integration and integration of the regulation and control and signal detection device on the basis of the MEMS processing technology, is convenient to use, and greatly improves the experimental efficiency.
(3) The invention integrates the regulation and control devices with the signal detection devices, is beneficial to the synchronism of the regulation and control and the detection, and reduces the loss of information.
(5) According to the invention, the electrode coating is coated on the surface of the electrochemical microelectrode, and the electrode coating, the counter electrode and the electrochemical reference electrode form a three-electrode system to form a current loop, so that the selectivity of detecting neurotransmitter dopamine is improved.
Drawings
Fig. 1 is a schematic structural view of a first side of a neural microprobe according to a first embodiment of the present invention.
FIG. 2 is a schematic structural view of a second side of the neural microprobe according to the first embodiment of the present invention.
FIG. 3 is a schematic view of a method for preparing a neural microprobe according to a first embodiment of the present invention.
FIG. 4 is a schematic view of a first side of a neural microprobe according to a second embodiment of the present invention.
FIG. 5 is a schematic view of a method for preparing a neural microprobe according to a second embodiment of the present invention.
[ description of main reference symbols of embodiments of the invention ] in the drawings
1-a substrate;
2-an optical waveguide;
3-an electrophysiological microelectrode;
4-an electrophysiological reference electrode;
5-an electrochemical microelectrode;
6-pair of electrodes;
7-an electrochemical reference electrode;
8-a magnetoresistive sensor;
9-a planar coil;
10-an excitation electrode;
11-lead wire.
Detailed Description
The invention provides a nerve microprobe and a preparation method thereof, wherein the nerve microprobe comprises the following components: the sensor comprises an optical waveguide, a magneto-resistance sensor, a planar coil and an excitation electrode; the optical waveguides are arranged on the magneto-resistance sensors and are arranged on the first surface of the substrate; the planar coil and the excitation electrode are both arranged on the second surface of the substrate, one end of the planar coil is connected with the excitation electrode, the excitation electrode applies direct current or alternating current to the planar coil, and the planar coil generates magnetic stimulation or provides a constant or alternating bias magnetic field for the magneto-resistance sensor, so that the magnetic control device is suitable for performing magnetic control on a designated brain area of a brain. The invention integrates the magneto-resistance sensor, the optical waveguide, the microelectrode and the micro-nano coil into a whole by the MEMS micromachining process, realizes the magneto-optical-electric regulation and multi-mode signal detection, can be used for carrying out invasive regulation and detection on the neural information of a nervous system, and has the advantages of miniaturization, integration, multiple functions and small damage to tissues while realizing synchronous regulation and detection.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to specific embodiments and the accompanying drawings.
Certain embodiments of the present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments of the invention are shown. Indeed, various embodiments of the invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements.
In a first exemplary embodiment of the present invention, a neural microprobe is provided. Fig. 1 is a schematic structural view of a first surface of a neural microprobe according to an embodiment of the present invention. FIG. 2 is a schematic structural view of a second side of the neural microprobe according to the embodiment of the present invention. As shown in fig. 1 and 2, the present invention provides a neural microprobe including: optical waveguide, magneto-resistive sensor, planar coil and excitation electrode. As shown in fig. 1, the optical waveguide is disposed on the first face of the substrate; one end of the optical waveguide is arranged on the nerve microprobe, the optical waveguide extends along the nerve microprobe, and the other end of the optical waveguide is connected with the optical fiber. The two magneto-resistance sensors are positioned on one side of the optical waveguide and arranged on the first surface of the substrate; the magneto-resistive sensor is suitable for detecting a neuro-magneto-physiological signal. As shown in fig. 2, the planar coil and the excitation electrode are both disposed on the second surface of the substrate, and one end of the planar coil is connected to the excitation electrode. Wherein, the second surface of the substrate is the surface opposite to the first surface of the substrate. The magneto-resistance sensor and the excitation electrode are connected with the PCB through leads. In the embodiment, the integration of magneto-optical regulation and multi-mode signal detection is realized, the miniaturization, integration and integration of the regulation and control and signal detection device are realized on the substrate through the MEMS processing technology, the use is convenient, and the experimental efficiency is greatly improved.
The following describes each component of the neural microprobe of this embodiment in detail.
The substrate is an SOI (silicon on insulator) sheet.
The optical waveguide is used for conducting light emitted by the light source and carrying out light regulation and control on a designated brain area of the brain. One end of the optical waveguide is arranged on the first surface of the substrate and extends along the longitudinal direction of the nerve microprobe, and the other end of the optical waveguide extends out of the nerve microprobe and is connected with the optical fiber. The material of the optical waveguide can be selected from thin film materials such as lithium niobate, lithium titanate and the like, the thickness is 900nm, the width is 1-2 mu m, and the optical waveguide has the advantages of small size, easy MEMS process integration and low transmission loss.
And the magneto-resistance sensor is positioned on the other side of the optical waveguide and is used for detecting the neural magneto-physiological signal. The structure of the magneto-resistance sensor comprises a magnetic layer (anisotropic magneto-resistance sensor) or a sandwich structure of the magnetic layer, a middle layer and the magnetic layer (giant magneto-resistance sensor and tunnel magneto-resistance sensor), and has the advantages of high sensitivity and low power consumption at room temperature.
The magnetic layer of the magnetoresistive sensor is generally composed of one or more alloys of Co, Fe, Ni, or a bilayer of two alloys (e.g., a CoFe-NiFe bilayer); the intermediate layer of the magneto-resistance sensor is an insulating layer (when the magneto-resistance sensor is a tunnel magneto-resistance sensor), and generally comprises one of oxides such as aluminum oxide, magnesium aluminum oxide, magnesium gallium oxide, magnesium zinc oxide and the like, or a non-magnetic layer (giant magneto-resistance sensor), and generally comprises one of copper, silver, copper-zinc alloy, silver-zinc alloy and silver-magnesium alloy.
The sensor is in the shape of 5 segments of folds with the length of 40-50 mu m and the width of 3-6 mu m, or in the shape of a yoke with the width of 1-6 mu m and the length of 40-120 mu m.
The planar coil is positioned on the second surface of the substrate and is connected with the planar coil excitation electrode, and direct current or alternating current is applied to the planar coil through the excitation electrode, so that magnetic stimulation is generated or a constant or alternating bias magnetic field is provided for the magneto-resistance sensor, and the magnetic control is used for magnetic control of a designated brain area of a brain. The magnetic field intensity of the bias magnetic field is set in the linear working range of the magneto-resistance sensor, so that the magneto-resistance sensor obtains better linearity and sensitivity. The planar coil is made of conductive material, and the planar coil in this embodiment has a spiral shape with a side length of 150-. The electrode material of the exciting electrode can be selected from metal or metal oxide with good biocompatibility, and the shape of the electrode material is a square with the side length of 20-50 mu m.
The contact points are distributed at the tail parts of the probes on the two sides of the nerve microprobe, and the electrophysiological microelectrode, the electrophysiological reference electrode, the electrochemical microelectrode, the counter electrode, the electrochemical reference electrode, the magneto-resistance sensor and the planar coil excitation electrode are all connected to the contact points through lead wires. The lead and the contact can be selected from metal or metal oxide with good biocompatibility and the thickness is 150-400 nm.
The surface of the whole nerve microprobe is covered with an insulating layer except the electrode, so that the whole nerve microprobe is insulated, and the device is prevented from being corroded by a medium and losing efficacy when used in biological tissues. The material of the insulating layer can be selected from one or more of silicon dioxide, silicon nitride, silicon oxynitride, aluminum oxide, SU8, polyimide, or parylene.
In a first exemplary embodiment of the present invention, a method of preparing a neural microprobe is also provided. FIG. 3 is a schematic diagram of a method of preparing a neural microprobe according to an embodiment of the present invention. As shown in fig. 4, the method for preparing the neural microprobe of the present invention comprises:
step S11: the substrate was washed with acetone, absolute ethanol and deionized water in that order.
Step S12: and depositing an optical waveguide film layer on the first surface of the substrate layer, and photoetching and etching the optical waveguide shape.
Step S13: and depositing a magneto-resistor sensor film layer on the first surface of the substrate layer, and photoetching and etching to form the shape of the magneto-resistor sensor.
Step S14: high temperature magnetic field annealing defines the sensitive direction of the magnetoresistive sensor.
Step S15: and depositing an insulating layer, photoetching and etching a window.
Step S16: and depositing a metal film conductive layer on the second surface of the substrate layer, and photoetching and etching the shapes of the planar coil and the excitation electrode.
Step S17: and depositing an insulating layer, photoetching and etching a window.
Step S18: spin coating electrode coating, photoetching and etching to obtain electrochemical microelectrode shape.
Step S19: the final probe shape is defined by Deep Reactive Ion Etching (DRIE).
In a second exemplary embodiment of the present invention, a neural microprobe is provided. The difference from the first exemplary embodiment in providing a neural microprobe is that, in the second exemplary embodiment, as shown in fig. 4, there is provided a neural microprobe further comprising on a first side thereof: physiological electrode group, electrochemical electrode group. Preferably, the electrophysiological electrode set and the electrochemical electrode set are both located on the other side of the optical waveguide and are disposed on the first side of the substrate; the electrophysiological electrode group and the electrochemical electrode group are both connected with the PCB through leads.
The following describes each component of the neural microprobe of this embodiment in detail.
The electrophysiology electrode assembly comprises: an electrophysiological microelectrode and an electrophysiological reference electrode. And the electrophysiological microelectrode and the electrophysiological reference electrode are positioned on one side of the optical waveguide and are arranged on the first surface of the substrate. The electrophysiological microelectrode is used for detecting a neural electrophysiological signal or generating electrical stimulation; during electrophysiological signal detection or application of electrical stimulation, an electrophysiological reference electrode is used to provide a reference potential. The shape of the electrophysiological microelectrode and the electrochemical microelectrode is a square with the side length of 10-50 μm, and the shape of the electrophysiological reference electrode and the counter electrode is a square with the side length of 20-100 μm.
The electrochemical electrode assembly includes: an electrochemical microelectrode, a counter electrode and an electrochemical reference electrode. The electrochemical microelectrode, the counter electrode and the electrochemical reference electrode are all positioned on one side of the optical waveguide and are arranged on the first surface of the substrate. Specifically, the surface of the electrochemical microelectrode is coated with an electrode coating, and the electrode coating, a counter electrode and an electrochemical reference electrode form a three-electrode system together to form a current loop for the electrochemical detection of the neurotransmitter. To improve the selectivity of detecting the neurotransmitter dopamine, the electrode coating can be selected from PEDOT: PSS (poly 3, 4-ethylenedioxythiophene-polystyrene sulfonate). Specifically, the counter electrode is typically made of Pt, Au, platinum alloy, gold alloy, or nanomaterial, and the electrochemical reference electrode is made of Ag or AgCl. The shape of the electrochemical microelectrode is a square with the side length of 10-50 mu m, and the counter electrode and the electrochemical reference electrode are both squares with the side length of 20-100 mu m.
In a second exemplary embodiment of the present invention, a method of preparing a neural microprobe is also provided. FIG. 5 is a schematic diagram of a method of preparing a neural microprobe according to an embodiment of the present invention. As shown in fig. 5, the method for preparing the neural microprobe of the present invention comprises:
step S21: the substrate was washed with acetone, absolute ethanol and deionized water in this order.
Step S22: and depositing an optical waveguide film layer on the first surface of the substrate layer, and photoetching and etching the optical waveguide shape.
Step S23: and depositing a magneto-resistor sensor film layer on the first surface of the substrate layer, and photoetching and etching to form the shape of the magneto-resistor sensor.
Step S24: high temperature magnetic field annealing defines the sensitive direction of the magnetoresistive sensor.
Step S25: and depositing a metal thin film conductive layer on the first surface of the substrate layer, and defining an electrophysiological electrode group, an electrochemical electrode group, leads and contacts through a stripping process.
Step S26: and depositing an insulating layer, photoetching and etching a window.
Step S27: and depositing a metal film conductive layer on the second surface of the substrate layer, and photoetching and etching the shapes of the planar coil and the excitation electrode.
Step S28: and depositing an insulating layer, photoetching and etching a window.
Step S29: spin coating electrode coating, photoetching and etching to obtain electrochemical microelectrode shape.
Step S210: the final probe shape is defined by Deep Reactive Ion Etching (DRIE).
For the purpose of brief description, any technical features of the first embodiment that can be applied to the same are described herein, and the same description is not repeated.
So far, the embodiments of the present invention have been described in detail with reference to the accompanying drawings. It is to be noted that, in the attached drawings or in the description, the implementation modes not shown or described are all the modes known by the ordinary skilled person in the field of technology, and are not described in detail. Further, the above definitions of the various elements and methods are not limited to the various specific structures, shapes or arrangements of parts mentioned in the examples, which may be easily modified or substituted by those of ordinary skill in the art.
Based on the above description, those skilled in the art should clearly understand the present invention and the method for preparing the same.
In conclusion, the invention provides the integrated magnetic-optical-electric regulation and multimode signal detection integrated nerve microprobe and the preparation method thereof, and has great scientific significance for enriching the neuroscience research means, improving the experimental efficiency and enhancing the synchronous performance of regulation and detection.
It should also be noted that directional terms, such as "upper", "lower", "front", "rear", "left", "right", etc., used in the embodiments are only directions referring to the drawings, and are not intended to limit the scope of the present invention. Throughout the drawings, like elements are represented by like or similar reference numerals. Conventional structures or constructions will be omitted when they may obscure the understanding of the present invention.
And the shapes and sizes of the respective components in the drawings do not reflect actual sizes and proportions, but merely illustrate the contents of the embodiments of the present invention. Furthermore, in the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.
Unless otherwise indicated, the numerical parameters set forth in the specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the present invention. In particular, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about". Generally, the expression is meant to encompass variations of ± 10% in some embodiments, 5% in some embodiments, 1% in some embodiments, 0.5% in some embodiments by the specified amount.
Furthermore, the word "comprising" does not exclude the presence of elements or steps not listed in a claim. The word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements.
The use of ordinal numbers such as "first," "second," "third," etc., in the specification and claims to modify a corresponding element does not by itself connote any ordinal number of the element or any ordering of one element from another or the order of manufacture, and the use of the ordinal numbers is only used to distinguish one element having a certain name from another element having a same name.
In addition, unless steps are specifically described or must occur in sequence, the order of the steps is not limited to that listed above and may be changed or rearranged as desired by the desired design. The embodiments described above may be mixed and matched with each other or with other embodiments based on design and reliability considerations, i.e., technical features in different embodiments may be freely combined to form further embodiments.
Similarly, it should be appreciated that in the foregoing description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the invention and aiding in the understanding of one or more of the various disclosed aspects. However, the disclosed method should not be interpreted as reflecting an intention that: that the invention as claimed requires more features than are expressly recited in each claim. Rather, as the following claims reflect, disclosed aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.
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. A neural microprobe, comprising:
an optical waveguide disposed on the first face of the substrate; one end of the optical waveguide is arranged on the nerve microprobe, the optical waveguide extends along the nerve microprobe, and the other end of the optical waveguide is connected with an optical fiber;
the two magneto-resistance sensors are positioned on one side of the optical waveguide and arranged on the first surface of the substrate; the magneto-resistance sensor is suitable for detecting a neural magnetic physiological signal;
the planar coil and the excitation electrode are arranged on the second surface of the substrate, one end of the planar coil is connected with the excitation electrode, the excitation electrode applies direct current or alternating current to the planar coil, the planar coil generates magnetic stimulation or provides a constant or alternating bias magnetic field for the magneto-resistance sensor, and the planar coil is suitable for performing magnetic regulation and control on a designated brain area of a brain;
the magnetic resistance sensor and the excitation electrode are connected with the contact through leads.
2. The neural microprojection of claim 1, further comprising:
the electrophysiological electrode group and the electrochemical electrode group are positioned on the other side of the optical waveguide and are arranged on the first surface of the substrate; the electrophysiological electrode group and the electrochemical electrode group are both connected with the contact through leads.
3. The neural microprobe of claim 2, wherein the set of electrophysiological electrodes comprises:
the electrophysiological microelectrode and the electrophysiological reference electrode are positioned on one side of the optical waveguide and are arranged on the first surface of the substrate; the electrophysiological reference electrode is suitable for providing a reference potential during the process of detecting electrophysiological signals or applying electrical stimulation by the electrophysiological microelectrode;
the electrochemical electrode assembly includes:
the electrochemical microelectrode, the counter electrode and the electrochemical reference electrode are positioned on one side of the optical waveguide and arranged on the first surface of the substrate; the electrochemical microelectrode, the counter electrode and the electrochemical reference electrode form a current loop and are suitable for electrochemical detection of neurotransmitters.
4. The neural microprobe according to claim 3, wherein the electrochemical microelectrodes are surface-coated with an electrode coating; the electrode coating material is poly 3, 4-ethylenedioxythiophene-polystyrene sulfonate.
5. The neural microprobe according to claim 1 or 2, wherein the magnetoresistive sensor is one or more of an anisotropic magnetoresistive sensor, a giant magnetoresistive sensor and a tunneling magnetoresistive sensor; the magnetic layer of the magneto-resistance sensor is formed by one or more alloys of Co, Fe and Ni, or formed by double layers of two alloys.
6. The neural microprobe according to claim 1 or 2, wherein the magnetoresistive sensor is shaped as a 5-segment accordion having a length of 40 to 50 μm and a width of 3 to 6 μm, or a yoke having a width of 1 to 6 μm and a length of 40 to 120 μm.
7. The neural microprobe according to claim 1 or 2, wherein a material of the planar coil is a conductive material; the planar coil is in a spiral shape like a Chinese character 'hui', and the side length is 150-; the shape of the excitation electrode is a square with the side length of 20-50 mu m; the material of the optical waveguide is lithium niobate or lithium titanate; the thickness of the optical waveguide is 300-900nm, and the width of the optical waveguide is 1-2 μm.
8. The neural microprobe according to claim 3, wherein the electrophysiological microelectrodes are each in the shape of a square having a side of 10 to 50 μm; the electrophysiological reference electrode is in the shape of a square with a side length of 20-100 μm.
9. The neural microprobe according to claim 3, wherein a material of the counter electrode is any one or more of Pt and Au, or any one or more of a platinum alloy and a gold alloy; the electrochemical reference electrode is made of Ag and AgCl; the counter electrode and the electrochemical reference electrode are both in a square shape with the side length of 20-100 mu m; the shapes of the electrochemical microelectrodes are all squares with the side length of 10-50 mu m.
10. A method of preparing a neural microprobe of any one of claims 1 to 9, comprising:
cleaning the substrate by using acetone, absolute ethyl alcohol and deionized water in sequence;
depositing an optical waveguide film layer on the first surface of the substrate layer, and photoetching and etching the optical waveguide shape;
depositing a magneto-resistance sensor film layer on the first surface of the substrate layer, and photoetching and etching to form a magneto-resistance sensor shape;
high-temperature magnetic field annealing defines the sensitive direction of the magneto-resistance sensor;
depositing a metal film conductive layer on the first surface of the substrate layer, and defining a lead and a contact through a stripping process;
depositing an insulating layer, and photoetching and etching a window;
growing a conductive layer on the second surface of the substrate layer, and photoetching and etching the shapes of the planar coil and the excitation electrode;
depositing an insulating layer, and photoetching and etching a window;
the final probe shape is defined by deep reactive ion etching.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110746579.6A CN113476050B (en) | 2021-07-01 | 2021-07-01 | Nerve microprobe and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110746579.6A CN113476050B (en) | 2021-07-01 | 2021-07-01 | Nerve microprobe and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113476050A CN113476050A (en) | 2021-10-08 |
| CN113476050B true CN113476050B (en) | 2022-09-27 |
Family
ID=77939243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110746579.6A Active CN113476050B (en) | 2021-07-01 | 2021-07-01 | Nerve microprobe and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113476050B (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008268154B2 (en) * | 2007-06-27 | 2013-06-20 | Second Sight Medical Products, Inc. | Flexible circuit electrode array |
| JP2013176406A (en) * | 2010-05-27 | 2013-09-09 | Hitachi Ltd | Brain function measuring device |
| WO2014204429A1 (en) * | 2013-06-17 | 2014-12-24 | The Massachusetts Institute Of Technology | Methods and apparatus for stimulating and recording neural activity |
| CN106108858A (en) * | 2016-09-21 | 2016-11-16 | 中国科学院电子学研究所 | A kind of light regulation and control nerve information detecting system |
| CN111134654B (en) * | 2019-12-25 | 2021-06-29 | 上海交通大学 | Photoelectric nerve probe integrated with internal metal shielding layer and preparation method thereof |
| CN111613964B (en) * | 2020-05-27 | 2021-07-27 | 杭州电子科技大学温州研究院有限公司 | Flexible nerve photoelectric electrode for nerve recording and stimulation and preparation method thereof |
| CN112842366B (en) * | 2020-12-30 | 2024-02-06 | 中国科学院空天信息创新研究院 | Multimode nerve stimulation regulation and control and synchronous detection system |
-
2021
- 2021-07-01 CN CN202110746579.6A patent/CN113476050B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN113476050A (en) | 2021-10-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102783942B (en) | Implantable neural information dual-mode detection microelectrode array chip and manufacturing method thereof | |
| CN102445477B (en) | Ex-vivo nerve information dual-mode detection microelectrode array chip and preparation method thereof | |
| KR101310767B1 (en) | Tetrode for measuring bio-signal and method of manufacturing the same | |
| EP3515303B1 (en) | Drift correction method for dual-reporter electrochemical sensors | |
| US20070088208A1 (en) | Linear device | |
| US10768139B2 (en) | Electrochemical probe | |
| JP4878633B2 (en) | Flexible nerve probe | |
| WO2007116978A1 (en) | Planar substrate type patch-clamp device for measuring ion channel activity, substrate for fabricating patch-clamp device and method of producing the same | |
| CN101543406B (en) | Method for assembling microwire electrode array by using silicon array hole | |
| CN110623655A (en) | Implantable micro-nano electrode array chip for simulating weightless rat and preparation method thereof | |
| CN103199020A (en) | Preparing method and detecting method of liquid grid type grapheme field-effect tube based on polyimide (PI) | |
| US20190380635A1 (en) | Dual-Sided Biomorphic Polymer-based Microelectrode Array and Fabrication Thereof | |
| CN113476050B (en) | Nerve microprobe and preparation method thereof | |
| CN114715840B (en) | Differential suspension single-layer graphene nanopore sensor and preparation method and application thereof | |
| US20210038883A1 (en) | Auditory implant | |
| JP3979574B2 (en) | Array electrode for biological sample and production method thereof | |
| EP3539614B1 (en) | Micro coils suitable for magnetic neural stimulation | |
| CN113456089B (en) | Miniature fluorescence imaging system capable of recording electrophysiological signals | |
| US20130190586A1 (en) | Multi-Terminal Nanoelectrode Array | |
| Chu et al. | Design and fabrication of novel three-dimensional multi-electrode array using SOI wafer | |
| CN115054261A (en) | Flexible electrode and manufacturing method thereof | |
| CN108368537A (en) | improved device for analyzing nucleic acid molecules | |
| CN113466754B (en) | Neural pole and preparation method thereof | |
| Liu et al. | Flexible Dual-Sided Polymer Microelectrode Array for Neurophysiological Recordings from an Insect Brain | |
| CN103663342B (en) | Connect up microelectrode array chip and preparation method thereof altogether |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |