CN107638176B

CN107638176B - Application of a hydrogel in the preparation of electrodes for detecting electrocortex

Info

Publication number: CN107638176B
Application number: CN201710806112.XA
Authority: CN
Inventors: 汪浩; 盛昊
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2017-09-08
Filing date: 2017-09-08
Publication date: 2020-05-08
Anticipated expiration: 2037-09-08
Also published as: WO2019047282A1; CN107638176A

Abstract

The invention discloses the application of a hydrogel in preparing an electrode for detecting electrocortex, and the invention initiates the electrocortex acquisition technology using a gel with low electrical conductivity as an electrode. In the liquid environment of the brain, the gel conducts electricity through its free ions, and the directional movement of the ions forms an electric current, achieving a detection effect comparable to that of highly conductive materials. At the same time, the gel can form an excellent mechanical property match with the brain tissue, and can closely fit the cerebral cortex. Its excellent biocompatibility can avoid biological rejection. This method not only greatly improves the physiology of traditional electrocorticography, but also promises to realize long-term electrocortical recording to achieve more functions.

Description

Application of hydrogel in preparation of electrode for detecting electroencephalogram of cerebral cortex

Technical Field

The invention relates to application of hydrogel with low electrical conductivity, in particular to application of hydrogel in preparing an electrode for detecting an electroencephalogram of a cerebral cortex.

Background

The electrocorticogram is an indispensable technical means in montreal therapy (for treating epilepsy in critically ill patients). The cortical potential is recorded by electroencephalography to determine the area of the cortical region that produces the seizure. This cortical region is then surgically removed to remove the source of the seizure. The signal emitted by brain cells is generally considered to be weak, and those skilled in the art generally adopt a metal material with high conductivity as a detection electrode of brain signals. But metal electrodes have very high hardness and poor biocompatibility, and have different conduction principles from the brain (the brain is ion-conductive and the metal is electron-conductive). During use, metal electrodes tend to damage brain tissue and fail to conform closely to the cerebral cortex. In addition, due to poor biocompatibility of the metal electrodes and the conduction principle different from that of the brain, long-term in-vivo recording cannot be realized.

Disclosure of Invention

In order to overcome the problems in the prior art, the invention overcomes the technical bias and provides the application of the hydrogel in preparing the electrode for detecting the electrocorticogram. The method is an original technique for collecting the electrocorticogram by using the gel as an electrode. Because the conductive principle of the gel and the brain tissue is ion conductive, even if the conductivity of the gel is low, the ion concentration difference of the brain can be conducted to the outside. The head of the gel electrode is directly contacted with the cerebral cortex, and the back part of the gel electrode is connected with an electrode wire which is externally connected and collected. The gel is wrapped in the flexible dielectric material to play a role in protection and insulation. With this method, the cerebral cortex is only connected to the gel and the dielectric material. The elastic modulus of the gel is low and adjustable, and can form excellent mechanical property matching with brain tissues. The soft gel can be tightly attached to the cerebral cortex. The gel has excellent biocompatibility as a conventional cell culture material. The method not only greatly improves the physiology of the traditional electrocorticogram, but also is expected to realize long-term electrocorticogram recording so as to realize more functions.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows: the application of hydrogel in preparing an electrode for detecting an electrocorticogram is disclosed, wherein the hydrogel is biocompatible and has an elastic modulus lower than 100 MPa.

Further, the hydrogel is formed by polymerizing a high molecular monomer dissolved in a biocompatible liquid.

Further, the biocompatible liquid is cerebrospinal fluid or physiological saline.

Further, the high molecular monomer is esters, alcohols, amides or organic salts.

Further, the high molecular monomer is polymerized by one or more of sodium acrylate, acrylic acid, hydroxyethyl methacrylate, sodium methallyl sulfonate, dimethylacrylamide, vinyl alcohol, ethylene glycol and sodium styrene sulfonate.

Further, the electrode comprises a flexible substrate made of a dielectric material, a gel sheet made of hydrogel and an inert metal sheet embedded in the flexible substrate, wherein the gel sheet is arranged on the surface of the flexible substrate, and electric signals collected by the gel sheet are output through the inert metal sheet.

Further, the device also comprises an interface used for connecting an external instrument, and the interface is connected with the inert metal sheet.

Further, the flexible substrate is made of polydimethylsiloxane or platinum-gold silica gel.

Further, the inert metal sheet is platinum, gold or silver sheet or a metal sheet with platinum, gold or silver coating.

Further, the gel sheets are arranged in an array of m x n, where m, n are positive integers.

The working principle of the flexible electrode for the gel-based electroencephalogram is as follows:

the gel sheet is in direct contact with the cortex. The excitation of the cerebral cortex pumps positive ions outside the cerebral cells into the cells through ion channels on the cells, so that the concentration of the extracellular ions is reduced, and the positive ions in the gel sheet directionally move towards the direction of the cerebral cortex. The positive ions are reduced at the contact part of the gel sheet and the inert metal sheet, while the quantity of the negative ions is unchanged, and the induced potential is generated at the contact part of the inert metal sheet and the gel sheet and is conducted to an external instrument through an external instrument connector.

Compared with the prior art, the invention has the following advantages:

1. the gel electrode has an extremely low elastic modulus, and the elastic modulus can be adjusted to be the same as that of cerebral cortex tissue by changing the degree of crosslinking of the gel. Therefore, compared with the traditional hard metal electrode, the mechanical property of the gel electrode is matched with the brain tissue, and the damage to the cerebral cortex can be reduced in the process of recording signals by attaching the cerebral cortex.

2. The surface of the cerebral cortex is not flat and is covered with sulcus, and when the cortical field potential is measured, the electrode and the cerebral cortex are required to be well attached. Because the gel electrode has extremely low elastic modulus, compared with the traditional metal electrode, the gel can be better attached to the cerebral cortex, and the field potential recording is realized.

3. Gels are solid, polymeric networks filled with a liquid environment. This molecular organization is similar to biological tissue. As a traditional tissue culture material, the gel has good biocompatibility. By adopting the neutral gel polymer network and the cerebrospinal fluid, the gel electrode can provide a liquid environment close to the original state for the cells of the cerebral cortex when being attached to the cerebral cortex. Therefore, compared with the traditional metal electrode, the electrode has excellent biocompatibility and can reduce the generation of cerebral cortex glial cells.

4. Gels are solid, polymeric networks filled with a liquid environment. The gel conducts electricity through free ions in the liquid environment. Because the gel conducts the movement of ions in the process of conducting signals by contacting with the cerebral cortex and does not involve the conversion of electric signals from ions to electrons, the gel with weak conductivity has the detection effect which is comparable to that of a high-conductivity material.

Drawings

Fig. 1 and 2 are a schematic top view and a schematic front view of a structure of a gel electrode for an electro-corticogram according to the present invention.

FIG. 3 is a diagram showing the mouse cortical field potential recorded by the electrode two weeks after the implantation of the cerebral cortex electrogram gel electrode in the mouse cerebral cortex;

FIG. 4 is the immunohistochemical results after two weeks of gel and platinum implantation in, for example, mouse brain;

FIG. 5 is a stress-strain curve of a gel;

in the figure, a gel sheet 1, a flexible substrate 2, a metal sheet 3, and an external instrument connector 4.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.

Example 1

Dissolving polyethylene glycol diacrylate in cerebrospinal fluid, adding initiator to obtain gel sheet 1, embedding into flexible substrate 2 made of polydimethylsiloxane, closely attaching to embedded inert metal sheet 3 made of silver sheet, and connecting inert metal sheet 3 with external instrument connector 4. The flexible electrode is made as shown in fig. 1.

The electrodes were placed intracranial in a mouse (strain C57) and after 3 weeks, an external instrument was connected to detect the cortical field potential, and the field potential signals obtained are shown in fig. 3.

The field potential analysis can show that the field potential obviously shows different activity states of the mouse such as waking, sleeping and the like, and experiments prove that the electrode can still be used after 2 weeks in the mouse body and has good biocompatibility. The time for embedding the normal brain cortex electrograph electrode in a human body is 2 weeks, which explains the practicability of the electrode.

Example 2

Polyethylene glycol diacrylate was dissolved in cerebrospinal fluid, an initiator was added to make a gel, and the gel was injected into the brain of a mouse (strain C57). The filamentous material of platinum used by the traditional electrocorticogram electrode is inserted into the same rat brain. Immunohistochemical staining was performed after 2 weeks to observe gliocyte proliferation. As shown in FIG. 4, the left image is a gel and the right image is a wire. Glia cells are excited to fluoresce under a microscope by a laser. It was found that the gel had significantly fewer glial cells than the platinum wire. Indicating that the gel has good biocompatibility in the brain environment.

Example 3

Dissolving polyethylene glycol diacrylate in cerebrospinal fluid, adding initiator, and making into gel. The stress-strain curve of the gel measured by a stretcher is shown in fig. 5, and the elastic modulus of the gel is 200Kpa, while the elastic modulus of the conventional metal electrode is in the order of 100Gpa and the elastic modulus of brain tissue is 10 Kpa. The experiment proves that the elastic modulus of the gel is more matched with that of brain tissue, and the damage to the brain when the gel is contacted with the brain is smaller compared with that of a metal electrode.

The above description is only a specific embodiment of the invention, but the scope of the invention is not limited thereto, and the materials of hydrogel and the like are not limited to the exemplary types listed by the applicant, the number and position of the gel sheets of the electrode can be flexibly adjusted according to the actual detection requirement of the patient, the corresponding inert metal sheets can also be correspondingly arranged according to the arrangement of the electrode gel sheets, and any changes or substitutions without creative work can be covered within the scope of the invention.

Claims

1. the application of a hydrogel in the preparation of electrodes for detecting electrocortex, wherein the hydrogel is a biocompatible hydrogel with an elastic modulus lower than 100 MPa,

The hydrogel is a hydrogel formed by polymerizing polymer monomers dissolved in a biocompatible liquid,

The electrode comprises a flexible substrate (2) composed of a dielectric material, a gel sheet (1) made of hydrogel, and an inert metal sheet (3) embedded in the flexible substrate, the gel sheet ( 1) Set on the surface of the flexible substrate (2), the gel sheet (1) is in one-to-one correspondence with the inert metal sheet (3), and the electrical signals collected by the gel sheet (1) are output through the inert metal sheet (3).

2 . The application according to claim 1 , wherein the biocompatible fluid is cerebrospinal fluid or physiological saline. 3 .

3 . The application according to claim 1 , wherein the polymer monomers are esters, alcohols, amides or organic salts. 4 .

4. application according to claim 3 is characterized in that: described macromolecular monomer is composed of sodium acrylate, acrylic acid, hydroxyethyl methacrylate, sodium methacrylate sulfonate, dimethylacrylamide, vinyl alcohol, One or more of ethylene glycol and sodium styrene sulfonate are polymerized.

5. The application according to claim 1, characterized in that it further comprises an interface (4) for connecting an external instrument, the interface (4) being connected with the inert metal sheet (3).

6 . The application according to claim 1 , wherein the flexible substrate ( 2 ) is made of polydimethylsiloxane or platinum silica gel. 7 .

7 . The application according to claim 1 , wherein the inert metal sheet ( 3 ) is a platinum, gold, silver sheet, or a metal sheet with platinum, gold, and silver plating. 8 .

8 . The application according to claim 1 , wherein the gel sheets ( 1 ) are arranged in an m*n array, wherein m and n are positive integers. 9 .