CN116616782A

CN116616782A - Multi-mode neural signal acquisition-oriented field effect transistor electrode structure and preparation method

Info

Publication number: CN116616782A
Application number: CN202310542636.8A
Authority: CN
Inventors: 刘景全; 肖俊羽; 王隆春; 曹佳炜
Original assignee: Shanghai Jiaotong University
Current assignee: Shanghai Jiaotong University
Priority date: 2023-05-15
Filing date: 2023-05-15
Publication date: 2023-08-22

Abstract

The invention provides a field effect tube electrode structure for multi-mode nerve signal acquisition and a preparation method thereof, wherein the electrode structure comprises a probe base and at least one probe, the probe base plays a role in fixation when an electrode is implanted, one end of the probe is fixed on the probe base, the probe comprises a substrate layer, a first insulating layer, a semiconductor film layer, a conducting layer and a second insulating layer which are sequentially laminated on the substrate layer, and the conducting layer comprises a field effect tube electrode, an acquisition electrode and a stimulation electrode which are sequentially arranged from the tip end position of the probe; the field effect tube electrode has an interdigital structure and is used for neurotransmitter monitoring; the acquisition electrode has a single-point structure and is used for receiving local field potential signals; the stimulating electrode is used for outputting an electric signal to a local part; the second insulating layer exposes the field effect transistor electrode, the acquisition electrode and the stimulation electrode. The invention can realize synchronous acquisition of the multi-mode nerve signals.

Description

Multi-mode neural signal acquisition-oriented field effect transistor electrode structure and preparation method

Technical Field

The invention relates to the technical field of brain-computer interface nerve microelectrode devices, in particular to a field effect tube electrode structure for multi-mode nerve signal acquisition and a preparation method thereof.

Background

Today's neuroscience is just like the chemistry before the appearance of the periodic table: elements and compounds are known, but there is a lack of a systematic theory to categorize their knowledge. The human brain is very large in size, with approximately 850 hundred million neurons, 100 trillion synapses, and 100 chemical neurotransmitters. The neuroscience field has been working on decoding information in the brain. The interpretation of brain information may help one understand the root cause of many neurological attacks.

The advanced platform is used as a medium for cracking brain information, and researchers develop implantable nerve probes as advanced tools for recording high-space-time resolution brain activities. Implantable nerve probes are mainly aimed at monitoring electrical signals in the brain, and classifying and analyzing the electrical signals. With the progress of micro-nano manufacturing technology, material science and biochemistry, the recording channel density of the implanted nerve probe is gradually increased. In 2019, neuropixels realized the integration of up to 5120 electrophysiology recording units on one implanted nerve probe, and although the electrophysiology recording density is greatly improved, the nerve recording type still has a large limitation. In addition to neuro-electrical signals, neurotransmitters in the brain play a central role in brain information processing. The article entitled "Implantable aptamer-field-effect transistor neuroprobes for in vivo neurotransmitter monitoring" was published by Zhao et al in journal Science Advances, 2021, and the first time that a FET biosensor was combined with a silicon-based implantable neural probe, enabled high spatial-temporal resolution recording of neurotransmitters such as serotonin, dopamine, glucose, the amino acid phenylalanine, and the like.

In summary, the current implantable nerve probe can independently realize the functions of electrophysiology recording, stimulation, monitoring of chemical neurotransmitters and the like, and in order to improve the working benefit of the implantable nerve probe, a new electrode structure is needed to get rid of the limitation of single function in the current nerve recording technology, and the dual-mode detection capability of synchronous electrophysiology and chemical transmitters is realized on the implantable nerve probe.

The Chinese patent application publication No. CN102390801A discloses an implantable dual-performance test microelectrode array which consists of at least one microelectrode and an external cable bundle, wherein each microelectrode comprises an electrophysiology microelectrode, an electrochemical microelectrode, an electrode substrate, an electrode inner lead, an electrophysiology lead interface, an electrochemical lead interface, a lead interface substrate, an electrophysiology electrode surface coating and an electrochemical surface electrode coating. The microelectrode with the coating is distributed on the surface of the electrode substrate, two microelectrodes which are relatively suitable in distance and correspond to each other are respectively used for electrophysiological and electrochemical measurement, a cable in an external cable bundle connects a lead interface with external equipment to output signals to the external equipment, the patent realizes the simultaneous detection of electrophysiological electrical signal recording and electrochemical transmitter of neurons, but the signal detection sensitivity realized by the nerve recording technology is lower, so that the application field of in-vivo experiments is very limited.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide a field effect transistor electrode structure oriented to multi-mode nerve signal acquisition and a preparation method thereof.

According to one aspect of the present invention, there is provided a field effect transistor electrode structure for multi-modal nerve signal collection, comprising a probe base and at least one probe, the probe base being fixed when an electrode is implanted, one end of the probe being fixed to the probe base, the probe comprising a substrate layer and a first insulating layer, a semiconductor thin film layer, a conductive layer and a second insulating layer laminated in this order on the substrate layer, wherein:

the first insulating layer;

the semiconductor thin film layer;

the conducting layer comprises a field effect tube electrode, a collecting electrode and a stimulating electrode which are sequentially arranged from the tip end position of the probe; the field effect tube electrode has an interdigital structure and is used for neurotransmitter monitoring; the acquisition electrode is provided with a single-point structure and is used for receiving local field potential signals; the stimulating electrode is used for outputting an electric signal to a local part;

the second insulating layer exposes the field effect transistor electrode, the acquisition electrode and the stimulation electrode.

Optionally, the field effect transistor electrode includes:

the first field effect tube and the second field effect tube are sequentially arranged along the longitudinal direction of the probe and from the tip of the probe, and the channel length of the first field effect tube is longer than that of the second field effect tube;

and leading out the first field effect tube and the second field effect tube by a non-crossing method through the electrode wires of the field effect tubes.

Optionally, the structure has one or more of the following options:

-the channel length of the first field effect transistor is 1-100 μm;

-the channel length of the second field effect transistor is 0.5-10 μm.

Optionally, the collection electrode includes collection electrode portion and collection electrode wire, collection electrode wire is used for drawing out collection electrode portion, through adjusting the diameter of collection electrode portion realizes the regulation and control to the impedance value.

Optionally, the diameter of the collecting electrode part is 5-30 μm.

Optionally, the stimulating electrode comprises a stimulating electrode part and a stimulating electrode lead, wherein the stimulating electrode lead is used for leading out the stimulating electrode part, and the diameter of the stimulating electrode part is adjusted to realize the regulation and control of the impedance value.

Optionally, the diameter of the stimulating electrode part is 30-60 μm.

Optionally, the semiconductor thin film layer adopts indium oxide as a channel material.

Optionally, the structure has one or more of the following options:

-the thickness of the substrate layer is 150-300 μm;

-the thickness of the first insulating layer is 100-1000nm;

-the thickness of the semiconductor thin film layer is 4-10nm;

-the thickness of the conductive layer is 40-200nm;

-the thickness of the second insulating layer is 100-1000nm.

According to another aspect of the present invention, there is provided a method for manufacturing the above-mentioned field effect transistor electrode structure for multi-modal neural signal acquisition, the method comprising:

providing a substrate, and forming a first insulating layer on the substrate;

forming a semiconductor thin film layer on the first insulating layer;

spin-coating photoresist on the semiconductor film layer, and sequentially performing pre-baking, exposure, development and post-baking to obtain a mask comprising a field effect transistor electrode pattern, a collecting electrode pattern and a stimulating electrode pattern;

after sputtering metal on the mask, stripping redundant photoresist to form a conductive layer;

forming a second insulating layer on the patterned conductive layer, wherein an opening is formed in the second insulating layer to expose the field effect transistor electrode, the acquisition electrode and the stimulation electrode;

and releasing the electrode array to obtain the field effect transistor electrode structure oriented to multi-mode nerve signal acquisition.

Compared with the prior art, the invention has at least one of the following beneficial effects:

1. the invention collects in-vivo neuron signals through the electrode array compounded by the field effect tube electrode, the collecting electrode and the stimulating electrode, can realize synchronous acquisition of multi-mode nerve signals, greatly promotes the progress of brain science and brain disease research, and has wide application value in the aspect of biological living body monitoring.

2. The invention adopts the field effect tube electrode with the interdigital structure, so that the monitoring sensitivity of the current field effect tube biosensor can be improved; the acquisition electrode with a single-point structure can be used for acquiring all neuron discharges in different distance ranges.

Drawings

Other features, objects and advantages of the present invention will become more apparent upon reading of the detailed description of non-limiting embodiments, given with reference to the accompanying drawings in which:

FIG. 1 is a schematic diagram of a structure of a FET electrode facing multi-modal neural signal acquisition in an embodiment of the present invention;

FIG. 2 is a schematic flow chart of a method for fabricating a field effect transistor electrode structure facing multi-modal neural signal acquisition in accordance with an embodiment of the present invention;

FIG. 3 is a schematic diagram illustrating the operation of the FET electrode for physiological pH monitoring according to an embodiment of the present invention;

FIG. 4 is a schematic diagram illustrating the operation of the FET electrode for monitoring the dopamine level in a physiological environment according to an embodiment of the present invention;

in the figure: 1 is a substrate layer, 2 is a first insulating layer, 3 is a semiconductor film layer, 4 is a field effect transistor electrode, 41 is a first field effect transistor, 42 is a second field effect transistor, 5 is a collecting electrode, 6 is a stimulating electrode, 7 is a second insulating layer, and 8 is a probe base.

Detailed Description

The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the present invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications could be made by those skilled in the art without departing from the inventive concept. These are all within the scope of the present invention.

Referring to fig. 1, the field effect transistor electrode structure for multi-mode nerve signal collection provided by an embodiment of the present invention includes a probe base 8 and at least one probe, wherein the probe base 8 is fixed when an electrode is implanted, one end of the probe is fixed on the probe base 8, the probe includes a substrate layer 1, and a first insulating layer 2, a semiconductor thin film layer 3, a conductive layer and a second insulating layer 7 sequentially laminated on the substrate layer 1, wherein: the first insulating layer 2 is used as a secondary bottom layer of the integral electrode structure, so that the conductive layer and the substrate layer 1 are not electrically interconnected; the second insulating layer 7 is used as the top layer of the integral electrode structure, and can protect most of metal wires of the conductive layer from being exposed to air and from oxidation and electrical interference; the semiconductor film layer 3 is used as a channel material of the field effect transistor electrode 4, and forms a typical field effect transistor structure together with the first insulating layer 2 and the field effect transistor electrode 4; the conducting layer comprises a field effect tube electrode 4, a collecting electrode 5 and a stimulating electrode 6 which are sequentially arranged from the position of the tip of the probe; the field effect tube electrode 4 is provided with an interdigital structure and is used for neurotransmitter monitoring, and the field effect tube electrode 4 adopting the interdigital structure is beneficial to improving the monitoring sensitivity of the current field effect tube biosensor; the acquisition electrode 5 has a single-point structure and is used for receiving local field potential signals, and the acquisition of all neuron discharges in different distance ranges can be realized by adopting the acquisition electrode 5 with the single-point structure; the stimulating electrode 6 is used for outputting an electric signal to a local part; the field effect tube electrode 4, the acquisition electrode 5 and the stimulation electrode 6 are sequentially arranged along the longitudinal direction of the probe from the position of the tip of the probe, and the specific arrangement positions of the three electrodes on the probe can be flexibly adjusted according to the requirements of in-vivo practical application on the premise; the field effect tube electrode 4, the acquisition electrode 5 and the stimulation electrode 6 are mutually independent in function, and the dual-mode detection function of synchronous electrophysiology and chemical transmitter can be realized by matching the two electrodes, so that the dilemma of single acquisition signal type of the current implanted nerve probe is eliminated. The second insulating layer 7 exposes the field effect transistor electrode 4, the collecting electrode 5 and the stimulating electrode 6.

The field effect tube electrode structure in the embodiment of the invention comprises a field effect tube electrode 4 for neurotransmitter monitoring, an acquisition electrode 5 for receiving local field potential signals and a stimulation electrode 6 for outputting local electric signals, and the acquisition of in-vivo neuron signals is carried out by utilizing an implanted brain-computer interface electrode array compounded by a plurality of acquisition electrode structures, so that the monitoring of in-vivo different types of signals and physiological environment indexes is realized, the synchronous acquisition of multi-modal neural signals is completed, the progress of brain science and brain disease research is greatly promoted, and the invention has wide application value in the aspect of biological living body monitoring.

The ability of a field effect tube biosensor to monitor chemical neurotransmitters is directly reflected by the output characteristic curve. Therefore, in order to design a biosensor having high sensitivity, it should be prioritized to design a field effect transistor having high transconductance. The field effect transistor transconductance formula is as follows:

increasing transconductance mainly takes into account three parameters: semiconductor mobility (μ), capacitance (C) and aspect ratio (W/L). First, indium oxide may be selected as a channel material because it has higher mobility than other materials such as an organic semiconductor, and the semiconductor thin film layer 3 is prepared by spin coating or atomic layer deposition, and is used as a channel material of a field effect transistor. The semiconductor thin film layer 3 employs indium oxide as a channel material. Then, the field effect transistor can maximize capacitance when it is operated in a physiological environment with a high dielectric constant (e.g., a phosphate buffer solution dielectric constant of 80), so that the field effect transistor in the electrolyte solution exhibits better electrical characteristics. Finally, the source and drain electrodes of the field effect transistor are designed into interdigital shapes, so that the channel width can be increased, and the width-to-length ratio is improved.

Therefore, the field effect tube with high transconductance is designed to remarkably improve the monitoring sensitivity of the implanted nerve probe to chemical neurotransmitters, and the acquisition electrode and the stimulation electrode are further designed, so that the dual-mode detection capability of the implanted nerve probe for synchronous electrophysiology and chemical transmitter is realized.

In some embodiments, the thickness of the substrate layer 1 is 150-300 μm, and the thickness is adjusted by selecting a silicon wafer with corresponding thickness specification; the thickness of the semiconductor thin film layer 3 is 4-10nm, and the thickness is controlled by spin-coating annealing at a rotation speed of 3000rmp by using an aqueous solution of indium nitrate with a concentration of 0.025-0.050M.

In some embodiments, the fet electrode 4 includes a first fet 41 and a second fet 42 that are sequentially disposed along the longitudinal direction of the probe and from the tip of the probe, where both are interdigital electrode structures with a line width of 5-10 μm, the channel length of the first fet 41 is longer than that of the second fet 42, the first fet 41 is closer to the tip of the probe than the second fet 42, and on the premise that the specific arrangement positions of the first fet 41 and the second fet 42 on the probe can be flexibly adjusted according to the implantation requirement, the size difference between the first fet 41 and the second fet 42 can help to realize synchronous monitoring of biological signals of different scales, and the difference in arrangement positions of the first fet 41 and the second fet 42 on the probe can help to realize synchronous monitoring of biological signals of different depths, preferably, the channel length of the first fet 41 is 1-100 μm; the channel length of the second field effect transistor 42 is 0.5-10 μm; the field effect tube electrodes 4 are distributed with two field effect tubes of different scales in the same longitudinal direction of the probe, the channel width of the larger first field effect tube 41 is regulated and controlled by the fork index number, and the channel width-to-length ratio can be flexibly adjusted according to the application scene requirement; the channel width of the smaller second field effect transistor 42 is regulated and controlled by the number of interdigital electrodes, and the channel width-to-length ratio can be flexibly adjusted according to the requirements of application scenes; the channel width-to-length ratio of the first field effect transistor 41 and the second field effect transistor 42 can be adjusted to obtain the sensitivity of the corresponding field effect transistor, and the channel width-to-length ratio and the sensitivity of the field effect transistor show positive correlation, so that high signal detection sensitivity and quick electrochemical response are realized, and compared with the existing nerve recording technology, the method can be suitable for more application scenes; the fet electrode 4 further includes a fet electrode wire, which leads out two different-scale first and second fets 41 and 42 by a non-intersecting method.

In the above embodiment, the field effect tube electrode 4 includes any one or several of three pairs, four pairs and five pairs of equal interdigital electrode structures, the more the interdigital index is, the higher the sensitivity is, the larger the occupied area is, and the chemical signal collection is performed by using the field effect tube electrode 4, so that the multi-modal neuron signal collection can be realized.

In some embodiments, the collecting electrode 5 includes a collecting electrode part and a collecting electrode wire, the collecting electrode wire is used for leading out the collecting electrode part, and the diameter of the collecting electrode part is adjusted to realize the regulation and control of the impedance value, so as to realize the collection of all neuron discharges in different distance ranges. The larger the diameter of the collecting electrode part of the collecting electrode 5, the smaller the electrochemical impedance, so that local field potential signals in a larger range can be collected, preferably, the diameter of the collecting electrode part is 5-30 μm, the size is equivalent to the size of a single neuron, and the electrode point of the collecting electrode can be ensured to collect and send single neuron signals.

In some embodiments, the stimulating electrode 6 includes a stimulating electrode part and a stimulating electrode lead, where the stimulating electrode lead is used to lead out the stimulating electrode part, and the diameter of the stimulating electrode part is adjusted to realize the regulation and control of the impedance value, so as to realize the stimulation of all neurons in different distance ranges. The larger the diameter of the stimulating electrode part of the stimulating electrode 6, the smaller the electrochemical impedance, so that local field potential signals in a larger range can be stimulated, preferably, the larger the diameter of the stimulating electrode part is 30-60 mu m, the smaller the impedance is, the size of a stimulating area in a human body can be regulated through the regulation of the impedance, and the damage caused by the excessively high pressure drop of brain tissues is avoided.

In the above embodiment, the number of the field effect transistor electrodes 4, the collecting electrodes 5 and the stimulating electrodes 6 is set according to the requirement of acquiring signals, respectively. The arrangement density degree of the field effect tube electrode 4, the acquisition electrode 5 and the stimulation electrode 6 at different depths is set according to the characteristic that the number of neurons in different brain areas in the body is different. Specifically, the cerebral cortex can be divided into 6 layers according to functions and types of nerve cells, wherein the second layer (depth of about 500 μm) and the fourth layer (depth of about 1500 μm) have a relatively large number of nerve cells, and the third and fifth layers have the smallest number of the first and sixth layers. Therefore, in order to maximize the collection efficiency of the implantable neural electrode, the number of the second and fourth layers of depth field effect transistor electrodes 4, collection electrodes 5 and stimulation electrodes 6 is the largest, the third and fifth layers of depth field effect transistor electrodes 4, collection electrodes 5 and stimulation electrodes 6 are the largest, and the first and sixth layers of electrodes are the smallest. The multi-mode nerve signals can be synchronously acquired by utilizing the implanted brain-computer interface electrode array compounded by the plurality of acquisition electrode structures to acquire the in-vivo neuron signals, so that the needed nerve signals can be selected according to application requirements, and the progress of brain science and brain disease research is greatly promoted.

In the above embodiment, the forming manner of the conductive layer includes, but is not limited to, multi-target magnetron sputtering, electrochemical plating, electron beam evaporation, ion beam sputtering, and other metal film growth manners, and the material of the conductive layer includes, but is not limited to, gold, platinum, silver, and the like, and the thickness of the conductive layer is preferably 40-200nm in consideration of the overall thickness and the conductive effect of the implanted electrode.

The second insulating layer 7 is provided with an electrode point windowing exposed area for exposing an electrode point structure comprising the field effect transistor electrode 4, the collecting electrode 5 and the stimulating electrode 6, and the insulating layer is formed by a film growth process including but not limited to thermal oxidation growth, multi-target magnetron sputtering, plasma enhanced chemical vapor deposition, low-pressure chemical vapor deposition and the like. Insulating layer materials include, but are not limited to, polyimide, SU-8, parylene, polydimethylsiloxane, silicon oxide, silicon nitride, silicon oxynitride, silicon oxide/silicon nitride composite films, and the like. The thicker the insulating layer, the better the insulating effect and the insulating layer stability, but too thick an insulating layer increases the size of the implanted electrode, causing greater implant damage, preferably the thickness of the first insulating layer 2 is 100-1000nm and the thickness of the second insulating layer 7 is 100-1000nm.

The electrode array structure comprises a field effect tube electrode for collecting high-resolution single neuron chemical signals and a collecting electrode for collecting local field potential signals, and solves the problem of low sensitivity of current nerve signal collection by utilizing an interdigital electrode structure; collecting all neuron discharges in different distance ranges by utilizing the structure of the collecting electrode; the brain-computer interface electrode array compounded by the multiple acquisition electrode structures is used for acquiring in-vivo neuron signals, so that in-vivo different types of signals and physiological environment indexes are monitored, and the synchronous acquisition of multi-mode nerve signals is completed.

Another embodiment of the present invention provides a method for preparing the above-mentioned field effect transistor electrode structure for multi-modal neural signal acquisition, where the method includes:

step one, providing a substrate, and forming a first insulating layer on the substrate, wherein silicon dioxide can be adopted as the first insulating layer;

step two, forming a semiconductor film layer on the first insulating layer; specifically, spin-coating a layer of semiconductor film layer hydrate solution on the first insulating layer, and annealing to obtain a semiconductor film layer;

spin-coating positive photoresist on the semiconductor film layer, and sequentially performing pre-baking, exposure, development and post-baking to obtain a mask comprising a field effect transistor electrode pattern, a collecting electrode pattern and a stimulating electrode pattern;

step four, after sputtering metal on the mask, stripping redundant photoresist to form a conductive layer;

step five, spin coating and patterning are carried out on the patterned conductive layer to form a second insulating layer, and the second insulating layer forms an opening to expose the field effect tube electrode, the acquisition electrode and the stimulation electrode;

and step six, after scribing the whole sample, releasing the electrode array to obtain the field effect transistor electrode structure oriented to multi-mode nerve signal acquisition.

The field effect transistor electrode structure oriented to multi-mode nerve signal acquisition and the preparation method thereof are further described in more detail.

The embodiment provides a field effect transistor electrode structure for multi-mode nerve signal acquisition, specifically a silicon-based field effect transistor electrode structure for multi-mode nerve signal acquisition, referring to fig. 2, the preparation method comprises:

s1, using a P-type heavily doped silicon wafer (resistivity is 0.005 omega/cm) as a substrate material of an electrode, respectively placing the silicon wafer into acetone, ethanol and deionized water for ultrasonic cleaning for 5 minutes, and then drying the silicon wafer by nitrogen, and placing the silicon wafer on a hot plate at 180 ℃ for more than 15 minutes, as shown in a figure 2 (1);

s2, depositing a layer of 100nm silicon dioxide, namely a first insulating layer, on the surface of the silicon wafer by LPCVD (low pressure chemical vapor deposition), as shown in FIG. 2 (2);

s3, spin-coating an aqueous solution of 0.025M indium nitrate on the first insulating layer at 3000rpm for 30S, and annealing the coated silicon wafer at 100 ℃ for 10 minutes and at 350 ℃ for 4 hours to form a continuous indium oxide film with the thickness of 4nm, namely an indium oxide layer or a semiconductor film layer, as shown in fig. 2 (3).

S4, spin-coating positive photoresist with the thickness of 100nm on the indium oxide layer, and performing pre-baking, photoetching, developing and post-baking to obtain a patterned photoresist mask which comprises an electrode and a lead-out wire pattern as shown in fig. 2 (4);

s5, sputtering 10nm titanium and 30nm gold on the surface of the indium oxide layer containing the photoresist mask, and removing positive photoresist by using acetone to obtain a conductive layer, wherein the conductive layer is shown in fig. 2 (5);

s6, spin coating photosensitive polyimide Durimide 7505 on the patterned conductive layer to obtain a second insulating layer with the thickness of 5 mu m, as shown in fig. 2 (6);

and S7, exposing, developing and curing the second insulating layer to form an open pore area exposing the electrode point, and scribing the substrate to finish the release of the electrode array, as shown in (7) of fig. 2.

In order to further improve the sensitivity of the electrode structure to the monitoring of the PH value of the physiological environment and effectively reduce the noise level, the process of silanization treatment is carried out on the indium oxide layer, and the silanization treatment comprises the following steps: flushing the released electrode array in ethanol for 5 minutes, and drying by using nitrogen; after cleaning, (3-aminopropyl) triethoxysilane and trimethoxy (propyl) silane (1:9, v/v) were thermally deposited on the exposed indium oxide layer at 40 ℃ for 1 hour and annealed at 60 ℃ for 10 minutes.

When the PH value in the physiological environment is changed, more and more groups are protonated/deprotonated on the surface of the indium oxide layer of the field effect transistor electrode structure, so that local charge change on the surface is generated, the effective gate voltage is changed, and the drain current is finally changed. Fig. 3 shows a schematic diagram of a measurement setup of a field effect transistor electrode when monitoring PH. Specifically, ag/AgCl is used as a liquid grid (such as Ag/AgCl liquid grid in fig. 3), a source electrode and a drain electrode are led out through metal wires, liquid test of the field effect tube is carried out, corresponding transfer and output characteristic curves of the field effect tube under different PH values are obtained, and real-time monitoring of the PH value of the physiological environment in the body is realized.

In order to realize the monitoring of electrode structures on neurotransmitters such as dopamine and the like in physiological environments, the indium oxide layer is subjected to functionalization treatment, and the process of the functionalization treatment comprises the following steps: immersing the interdigital electrode of the field effect tube electrode in a 1mM dodecyl ethanol solution for 1 hour, and insulating the interdigital electrode by using a self-assembled monolayer; 1mM of N-hydroxysuccinimide 3-maleimide benzoate was dissolved in a 1:9 (v/v) mixture of dimethyl sulfoxide and phosphate buffer salt solution, after which the electrode was immersed for 30 minutes; to immobilize the aptamer, the probe was immersed in 1uM of phosphorothioate solution overnight, and the electrode was rinsed with deionized water and dried with nitrogen before measurement.

The surface of the backbone of an aptamer, such as dodecyl mercaptan, PTMS, APTES, MBS, etc., is negatively charged and undergoes a conformational change when dopamine is captured in the physiological environment (electrolyte). When the dopamine level in the body fluctuates, the local charge on the surface of the indium oxide layer changes and causes a change in the effective gate voltage, resulting in a different drain current. Fig. 4 shows a schematic of a measurement setup of field effect tube electrodes to monitor dopamine levels in vivo. Specifically, ag/AgCl is used as a liquid grid (such as Ag/AgCl liquid grid in fig. 4), a source electrode and a drain electrode are led out through a metal wire, liquid test of the field effect tube is carried out, corresponding transfer and output characteristic curves of the field effect tube under different dopamine levels are obtained, and real-time monitoring of the dopamine levels in the physiological environment in vivo is realized.

The foregoing describes specific embodiments of the present invention. It is to be understood that the invention is not limited to the particular embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the claims without affecting the spirit of the invention. The above-described preferred features may be used in any combination without collision.

Claims

1. The utility model provides a field effect transistor electrode structure towards multimode nerve signal collection, its characterized in that includes probe base and at least probe, the probe base plays the fixed action when implanting the electrode, the one end of probe is fixed in the probe base, the probe includes the substrate layer and stacks gradually first insulating layer, semiconductor film layer, conducting layer and the second insulating layer on the substrate layer, wherein:

the first insulating layer;

the semiconductor thin film layer;

2. The multi-modal neural signal acquisition oriented field effect transistor electrode structure of claim 1, wherein the field effect transistor electrode comprises:

3. The multi-modal neural signal acquisition oriented field effect transistor electrode structure of claim 2, having one or more of the following options:

-the channel length of the first field effect transistor is 1-100 μm;

-the channel length of the second field effect transistor is 0.5-10 μm.

4. The field effect tube electrode structure for multi-mode nerve signal collection according to claim 1, wherein the collection electrode comprises a collection electrode part and a collection electrode lead, the collection electrode lead is used for leading out the collection electrode part, and the adjustment and control of the impedance value are realized by adjusting the diameter of the collection electrode part.

5. The multi-modal neural signal acquisition oriented field effect transistor electrode structure of claim 4, wherein the acquisition electrode portion has a diameter of 5-30 μm.

6. The field effect tube electrode structure for multi-modal nerve signal collection according to claim 1, wherein the stimulating electrode comprises a stimulating electrode part and a stimulating electrode lead, the stimulating electrode lead is used for leading out the stimulating electrode part, and the adjustment and control of the impedance value are realized by adjusting the diameter of the stimulating electrode part.

7. The multi-modal neural signal acquisition oriented field effect transistor electrode structure of claim 6, wherein the stimulating electrode portion has a diameter of 30-60 μm.

8. The multi-modal neural signal acquisition oriented field effect transistor electrode structure of claim 1, wherein the semiconductor thin film layer adopts indium oxide as a channel material.

9. The multi-modal neural signal acquisition oriented field effect transistor electrode structure of claim 1, having one or more of the following options: