CN110772251B - Soft double-sided nerve probe and preparation method thereof - Google Patents

Soft double-sided nerve probe and preparation method thereof Download PDF

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CN110772251B
CN110772251B CN201911032588.8A CN201911032588A CN110772251B CN 110772251 B CN110772251 B CN 110772251B CN 201911032588 A CN201911032588 A CN 201911032588A CN 110772251 B CN110772251 B CN 110772251B
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polymer film
substrate
metal layer
probe
layer
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CN110772251A (en
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赖欣怡
何婷婷
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Zhejiang University ZJU
Zhejiang Lab
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Zhejiang University ZJU
Zhejiang Lab
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
    • A61B5/4064—Evaluating the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
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Abstract

The invention discloses a soft double-sided nerve probe, which comprises a substrate and microelectrodes, wherein the microelectrodes are positioned on two sides of the substrate. The invention also discloses a preparation method of the soft double-sided nerve probe, which comprises the following steps: sticking any surface of the polymer film on the substrate; generating a first photoresist layer on the other surface; removing part of the first photoresist layer; plating a first metal layer; removing the rest part of the first photoresist layer, and removing the first metal layer on the surface of the rest part of the first photoresist layer; generating an insulating layer, wherein the thickness of the insulating layer is greater than that of the rest part of the first metal layer; removing the insulating layer on the surface of the rest part of the first metal layer, forming a first probe on the rest part of the first metal layer, and carrying out metal layer sputtering to form a microelectrode positioned on one side of the substrate; and adhering the other surface of the polymer film on the substrate to form a second probe and a microelectrode positioned on the other side of the substrate. The detection range and the detection accuracy of the nerve probe are improved, and the preparation method is simple and easy to implement.

Description

Soft double-sided nerve probe and preparation method thereof
Technical Field
The invention belongs to the technical field of nerve probes, and particularly relates to a soft double-sided nerve probe and a preparation method thereof.
Background
The technique of nerve implantation began in the 1960 s. At that time, neurologists and neurosurgeons tried for the first time to electrically stimulate nerves using microelectrodes to locate specific sites in the brain, while using signal processors to analyze changes in neuronal activity. Meanwhile, they have studied the basic characteristics of the brain in controlling movement and the like, and have also found that electrically stimulating certain structures in the brain can produce the result of suppressing symptoms of neurological diseases (such as tremor and parkinson's disease). Since the brain is a large parallel processor. Researchers have therefore developed multi-channel neuro-implant devices to understand how brain neurons can neuroally code for specific behavioural movements, starting with simultaneous recording of neuron activity in different brain regions, in an attempt to understand the meaning of Neural languages. The technology simultaneously records the information of the neuron cell activities of a plurality of brain areas in the brain, so that researchers can obtain the knowledge of how neurons communicate and process information, the knowledge can be used for solving a plurality of important problems in neurobiology, ethology and cognitive science, and the technology is a breakthrough in the research of neuroscience methodology.
Conventional probes, which are part of silicon-based multi-channel microelectrode arrays, are known as Michigan Electrode arrays (Electrode array) or Michigan probes (Probe), in which a plurality of microelectrodes are disposed on a handle-like structure, and these microelectrode arrangements also provide high spatial resolution for more complete neural signal recording.
However, because the brain is complicated and is full of nerves, great care needs to be taken when performing relevant invasive tests, especially when a nerve probe is used to capture information about nerve activity in a specific brain region. In particular, the conventional microelectrode of the nerve probe can be disposed on only one side of the nerve probe, and the detection range is limited. If a wider range of brain region responses are to be detected, more nerve probes need to be implanted, increasing the probability of brain injury. Moreover, since the microelectrode is only disposed on one side of the nerve probe, if the position of the signal generated is deviated to the other side of the microelectrode (i.e. the position without electrode), there will be a difference in signal intensity, and for the high-precision brain structure, it will undoubtedly increase the chance of misjudgment, so how to increase the detection range of a single nerve probe and reduce the occurrence of misjudgment of signal intensity is a problem that needs to be overcome at present.
Furthermore, since the depth between the brain tissues is required to reduce the brain tissue damage caused during the implantation process, the size of the microelectrode needs to be smaller than that of a common test strip, the difference is more than thousand times, and the diameter of each microelectrode is about tens to hundreds of micrometers, so the microelectrode is more difficult to process. Therefore, how to provide a preparation method which is more convenient to process is also an urgent problem to be solved at present.
Disclosure of Invention
The invention aims to provide a soft double-sided nerve probe and a preparation method thereof, which can improve the detection range of the nerve probe and improve the detection accuracy, and the preparation method is simple and easy to implement.
The invention provides the following technical scheme:
a soft double-sided nerve probe comprises a substrate and microelectrodes, wherein the microelectrodes are positioned on two sides of the substrate.
The soft double-sided nerve probe provided by the invention can be used for detecting electrical or chemical signals of brain cells; the detection range can be enlarged by arranging the microelectrodes on the two sides, so that the limitation of the detection directivity on the existing nerve probe is improved, and the detection accuracy is improved.
The invention also provides a preparation method of the soft double-sided nerve probe, which comprises the following steps:
(a) sticking any surface of the polymer film as a matrix on the substrate through an adhesive;
(b) generating a first photoresist layer on the other surface of the polymer film;
(c) removing part of the first photoresist layer by using a photomask exposure technology;
(d) plating a first metal layer on the surface of the residual part of the first photoresist layer and the exposed polymer film after removing part of the first photoresist layer in the step (c);
(e) removing the rest of the first photoresist layer by using a yellow light exposure technology, and removing the first metal layer on the surface of the rest of the first photoresist layer;
(f) generating an insulating layer on the surfaces of the polymer film exposed after the residual part of the first photoresist layer is removed and the residual part of the first metal layer in the step (e), wherein the thickness of the insulating layer is greater than that of the residual part of the first metal layer;
(g) removing the insulating layer on the surface of the rest part of the first metal layer in the step (f) by using a photomask technology, forming a first probe on the rest part of the first metal layer, and sputtering a metal layer on the first probe to form a microelectrode positioned on one side of the substrate;
(h) and (e) sticking the other surface of the polymer film serving as the matrix on the substrate through an adhesive, and repeating the steps (b) to (g) to form a second probe and a microelectrode positioned on the other side of the matrix.
The substrate is an insulating substrate, and the material of the substrate is selected from glass, polyamide, polyester, polycarbonate, polyethylene terephthalate or polyvinyl chloride.
The material of the high molecular film is selected from a polyimide film aromatic ring polymer film, a heterocyclic polymer film, a trapezoidal polymer film, an organic polymer film or an inorganic polymer film.
The metal layer is made of palladium, gold, silver, platinum, copper, nickel, zinc, tin, chromium or an alloy of at least two of the palladium, the gold, the silver, the platinum, the copper, the nickel, the zinc, the tin and the chromium.
The heat-resistant temperature of the adhesive is more than 150 ℃, and the adhesive force between the adhesive and the substrate is more than that between the adhesive and the polymer film. The heat-resistant temperature is higher than 150 ℃, so that the defect that the adhesive is melted due to overhigh temperature in the manufacturing process can be avoided. When the polymer film is taken down from the substrate, because the adhesive force between the adhesive and the substrate is greater than that between the adhesive and the polymer film, the adhesive is left on the substrate and can not be left on the polymer film along with the tearing of the polymer film, thereby avoiding the error or other defects caused by adhesive residue when the probe test is carried out by using nerves subsequently.
In the preparation method provided by the invention, the steps of generating the first probe and the second probe are beneficial to the position accuracy of the small-sized nerve probe when the metal layer is sputtered. And by sputtering the metal layer, the metal thickness of the microelectrode can be increased to form a three-dimensional microelectrode structure, the robustness of the microelectrode can be enhanced, the impedance value of the microelectrode can be adjusted, and the signal recording quality can be improved.
Drawings
FIG. 1 is a flow chart of a method for preparing a soft double-sided nerve probe according to an embodiment of the present invention.
Fig. 2 is a schematic structural diagram of a nerve probe according to an embodiment of the present invention.
Detailed Description
The following embodiments are provided to illustrate the embodiments of the present invention, and those skilled in the art will appreciate further advantages and effects of the present invention. Moreover, the invention is capable of other and different embodiments and of being practiced or being carried out in various ways without departing from the spirit of the invention.
Example 1
As shown in FIG. 2, the flexible double-sided probe provided in this example includes a polymer film as a substrate and microelectrodes on both sides of the polymer film.
In this embodiment, the polymer film is a polyimide aromatic ring polymer film, and the micro-electrode is made of gold.
As shown in fig. 1, the method for preparing the flexible double-sided probe 10 provided in this embodiment includes the following steps:
(a) sticking any surface of the polymer film as a matrix on the substrate through an adhesive; wherein the heat-resistant temperature of the adhesive is more than 150 ℃, and the adhesive force between the adhesive and the substrate is more than that between the adhesive and the polymer film;
(b) generating a first photoresist layer on the other surface of the polymer film;
(c) removing part of the first photoresist layer by using a photomask exposure technology;
(d) plating a first metal layer on the surface of the residual part of the first photoresist layer and the exposed polymer film after removing part of the first photoresist layer in the step (c);
(e) removing the rest of the first photoresist layer by using a yellow light exposure technology, and removing the first metal layer on the surface of the rest of the first photoresist layer;
(f) generating an insulating layer on the surfaces of the polymer film exposed after the residual part of the first photoresist layer is removed and the residual part of the first metal layer in the step (e), wherein the thickness of the insulating layer is greater than that of the residual part of the first metal layer;
(g) removing the insulating layer on the surface of the rest part of the first metal layer in the step (f) by using a photomask technology, so that the rest part of the first metal layer forms a first probe 11, and sputtering the metal layer on the first probe to form a microelectrode 40 positioned on one side of the substrate;
(h) and (e) adhering the other surface of the polymer film serving as the matrix to the substrate through an adhesive, and repeating the steps (b) to (g) to form a second probe 12 and a microelectrode positioned on the other side of the matrix.
The soft double-sided probe provided by the embodiment can be used for capturing cranial nerve information, and the detection range and the detection accuracy are increased.
The above-mentioned embodiments are merely exemplary for convenience of description, and the claimed invention should not be limited to the above-mentioned embodiments, but should be limited only by the claims.

Claims (5)

1. The preparation method of the soft double-sided nerve probe is characterized in that the soft double-sided nerve probe comprises a substrate and microelectrodes, wherein the microelectrodes are positioned on two sides of the substrate, and the substrate is a polymer film;
the preparation method comprises the following steps:
(a) sticking any surface of the polymer film as a matrix on the substrate through an adhesive;
(b) generating a first photoresist layer on the other surface of the polymer film;
(c) removing part of the first photoresist layer by using a photomask exposure technology;
(d) plating a first metal layer on the surface of the residual part of the first photoresist layer and the exposed polymer film after removing part of the first photoresist layer in the step (c);
(e) removing the rest of the first photoresist layer by using a yellow light exposure technology, and removing the first metal layer on the surface of the rest of the first photoresist layer;
(f) generating an insulating layer on the surfaces of the polymer film exposed after the residual part of the first photoresist layer is removed and the residual part of the first metal layer in the step (e), wherein the thickness of the insulating layer is greater than that of the residual part of the first metal layer;
(g) removing the insulating layer on the surface of the rest part of the first metal layer in the step (f) by using a photomask technology, forming a first probe on the rest part of the first metal layer, and sputtering a metal layer on the first probe to form a microelectrode positioned on one side of the substrate;
(h) and (e) sticking the other surface of the polymer film serving as the matrix on the substrate through an adhesive, and repeating the steps (b) to (g) to form a second probe and a microelectrode positioned on the other side of the matrix.
2. The method for preparing a soft double-sided nerve probe as claimed in claim 1, wherein the substrate is an insulating substrate, and the material of the substrate is selected from glass, polyamide, polyester, polycarbonate, polyethylene terephthalate or polyvinyl chloride.
3. A method for preparing a soft double-sided nerve probe as claimed in claim 1, wherein the material of the polymer film is selected from a polyimide film, an aromatic ring polymer film, a heterocyclic polymer film, a ladder polymer film, an organic polymer film or an inorganic polymer film.
4. The method for preparing a soft double-sided nerve probe as claimed in claim 1, wherein the material of the metal layer is selected from palladium, gold, silver, platinum, copper, nickel, zinc, tin, chromium or an alloy of at least two thereof.
5. The method for preparing a soft double-sided nerve probe as claimed in claim 2, wherein the heat-resistant temperature of the adhesive is greater than 150 ℃, and the adhesion between the adhesive and the substrate is greater than the adhesion between the adhesive and the polymer film.
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CN113545790B (en) * 2020-07-21 2022-04-26 浙江大学 Preparation method of magnetic compatible nerve probe
CN116435457A (en) * 2023-03-23 2023-07-14 清华大学 Microelectrode and single particle electrode

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CN101172185B (en) * 2007-09-21 2011-06-01 中国科学院上海微系统与信息技术研究所 Process for producing implantation type two-sided flexible tiny array electrode
EP2087838A1 (en) * 2008-02-05 2009-08-12 Ikerlan, S. Coop. Metallization process to obtain a microelectrode on a photopatternable substrate and its biomedical application on an organ transplant monitoring device
CN102355854B (en) * 2009-01-21 2015-04-01 加州理工学院 Pocket-enabled chip assembly for implantable devices
TWI382007B (en) * 2009-11-09 2013-01-11 Nat Univ Tsing Hua A soft nerve probe structure for stimulating and measuring nerve cells and a method for manufacturing the same
WO2012100260A2 (en) * 2011-01-21 2012-07-26 California Institute Of Technology A parylene-based microelectrode array implant for spinal cord stimulation
CN105561469B (en) * 2015-12-12 2018-11-09 西安交通大学 A kind of miniature brain electrode array chip of implanted Multifunctional two-sided
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