阅读说明：本技术 神经微探针及其制备方法 (Nerve microprobe and preparation method thereof ) 是由 陈嘉民 罗佳慧 于 2021-07-01 设计创作，主要内容包括：本发明提供了一种神经微探针及其制备方法,其神经微探针包括：光波导、磁电阻传感器、平面线圈和激励电极；光波导设置在磁电阻传感器均位于设置在基底第一面上；平面线圈和激励电极均设置在基底第二面上,平面线圈一端与激励电极连接,激励电极对平面线圈施加直流或交流,平面线圈产生磁刺激或者为磁电阻传感器提供恒定或交变的偏置磁场,适用于对大脑指定脑区进行磁调控。本发明通过MEMS微加工工艺集成磁电阻传感器、光波导、微电极和微纳线圈于一体,实现磁-光-电调控与多模信号检测,可用于对神经系统的神经信息进行侵入性的调控与检测,在实现同步调控与检测的同时具有微型化、集成化、多功能、对组织损伤小的优点。(The invention provides a nerve microprobe and a preparation method thereof, wherein the nerve microprobe comprises the following steps: 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.)

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 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 performing magnetic regulation and control on a designated brain area of a brain;

the magneto-resistance sensor and the excitation electrode are connected with a 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 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.

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) -poly (styrene 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 magnetoresistive sensor is generally formed of one or more alloys of Co, Fe, Ni, or a bilayer 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, 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 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.

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 nerve regulation and signal detection faces challenges, and information loss is easily caused.

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 performing magnetic regulation and control on a designated brain area 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) -poly (styrene 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 shapes of the electrochemical microelectrodes are all squares 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 is 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 together 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 steps: 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.

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 invention now will 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 neural microprobe of the present invention includes: 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 brain specified area. 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 a 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 yokes 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 region 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-resistance sensor film layer on the first surface of the substrate layer, and photoetching and etching to obtain the shape of the magneto-resistance 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 electrophysiology microelectrode and the electrochemical microelectrode is a square with the side length of 10-50 mu m, and the shape of the electrophysiology reference electrode and the counter electrode is a square with the side length of 20-100 mu m.

The electrochemical electrode group 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-poly (styrenesulfonate)). 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 that 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-resistance sensor film layer on the first surface of the substrate layer, and photoetching and etching to obtain the shape of the magneto-resistance 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.

From 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 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.