WO2021114119A1

WO2021114119A1 - Flexible recording electrode, and preparation method and implantation method therefor

Info

Publication number: WO2021114119A1
Application number: PCT/CN2019/124437
Authority: WO
Inventors: 王璐璐; 鲁艺; 钟成; 曹燚; 孙重阳; 王立平
Original assignee: 中国科学院深圳先进技术研究院
Priority date: 2019-12-11
Filing date: 2019-12-11
Publication date: 2021-06-17

Abstract

A flexible recording electrode, and a preparation method and an implantation method for a flexible recording electrode. The flexible recording electrode comprises an adapter (10), a plurality of pin headers (20), and a plurality of electrode wires (30); the plurality of pin headers (20) are arranged on the adapter (10) at intervals; one ends of the electrode wires (30) are connected to the pin headers (20) in a one-to-one correspondence manner; the ends of the plurality of electrode wires (30) away from the pin headers (20) are bonded by means of a tissue adhesive (40); the portions of the electrode wires (30) not covered with the tissue adhesive (40) are covered with a protective adhesive (50). The flexible recording electrode is featured by a small volume and good flexibility, so that the electrical activity of a target brain region having a small area can be recorded, and the load on the head of an animal can be reduced; the wound electrode wires (30) are fixed by means of the tissue adhesive (40), the tissue adhesive (40) can be degraded in brain tissue, and the electrode wires (30) recover flexibility and can move along with the movement of the brain tissue, so that the damage to the brain tissue is reduced.

Description

Flexible recording electrode, preparation method and implantation method thereof

Technical field

The invention belongs to the technical field of recording electrodes, and particularly relates to a flexible recording electrode, a preparation method and an implantation method thereof.

Background technique

In the nervous system, a large number of neurons continuously generate and transmit electrophysiological signals to realize the exchange of information between different brain regions and neurons. Electrophysiological technology has become a very important tool for us to study neuronal activity and then the function of neural circuits due to its high temporal and spatial resolution recording advantages. In the past few decades, a series of major breakthroughs have been made in the development of recording electrodes. These results have directly had a profound impact on neuroscience research, and have quickly led to four electrodes including the ability to better distinguish neuron types. , The development of various new electrode arrays such as Michigan microelectrodes distributed in recording sites of different depths and Utah microelectrode arrays in large-scale recording sites.

Using multi-channel electrodes to record neurons in the target brain area can analyze the loop functions related to specific behaviors. This is a relatively common method in the field of neuroscience. Cell action potentials are used to test the relevant behaviors of freely moving experimental animals, and the neural circuit functions related to the specific behavior can be analyzed by processing the obtained data signals. This is very helpful for the analysis of neural circuit functions.

However, most of the commonly used metal electrodes at present are relatively hard in texture, and their Young's modulus is very different from that of the brain tissue, and it is easy to cause mechanical damage to the brain tissue after implantation. And after implanting the animal's brain tissue, the electrode will repeatedly penetrate the nerve tissue during the animal's movement, causing continuous damage to it.

Summary of the invention

In view of this, it is necessary to provide a flexible recording electrode with less loss of brain tissue, and a preparation method and implantation method thereof.

The present invention provides a flexible recording electrode, which includes an adapter, a plurality of pin headers, and a plurality of electrode wires. The plurality of pin headers are arranged on the adapter at intervals, and one end of the electrode wire and the pin header are one In a corresponding connection, one end of the plurality of electrode wires away from the needle row is bonded by tissue glue, and the part of the electrode wires that is not covered with the tissue glue is covered with a protective glue.

In one embodiment, the protective glue is epoxy glue.

In one embodiment, the outer side of the tissue glue is also coated with polyethylene glycol.

In an embodiment, the diameter of the electrode wire is 12 μm, 17 μm or 25 μm.

The present invention also provides a method for preparing the above-mentioned flexible recording electrode, which includes the following steps:

S110. Provide a support, the support including a base, a first pillar, a second pillar, a third pillar, and a fourth pillar, the first pillar, the second pillar, the third pillar, and the fourth pillar One end of the first pillar, the second pillar, the third pillar, and the fourth pillar are all fixedly connected to the base, and the first pillar and the fourth pillar are distributed in a trapezoid shape on the base. Fourth pillars are respectively located at both ends of the bottom side of the trapezoid, and the second pillar and the third pillar are respectively located at both ends of the top side of the trapezoid;

S120. Fix the first end of the electrode wire on the first post;

S130. Then, the wire electrode goes around one side of the second pillar, the third pillar, and the fourth pillar in sequence, and after being bent around the fourth pillar, it goes around the third pillar in turn again . The second pillar and the first pillar, wherein the second pillar and the third pillar are located on the same side of the electrode wire;

S140. After the wire electrode is then bent around the first column, repeat S130 until the number of the wire electrode between the second column and the third column reaches a preset value, stop winding, and The second end of the electrode wire is fixed to the first post;

S150, bonding the electrode wire between the second pillar and the third pillar with tissue glue;

S160. Cut off the wire electrode on the first pillar and the fourth pillar, and cut off the wire electrode bonded with tissue glue between the second pillar and the third pillar to obtain an electrode Silk component

S170: Fix the wire electrode at the end of the wire electrode assembly without tissue glue to different pin headers in sequence;

S180: Cover the part of the electrode wire that is not covered with the tissue glue with a protective glue to obtain the flexible recording electrode.

In one embodiment, the bracket is printed by a 3D printer or welded by metal materials.

In one embodiment, polyethylene glycol is used to coat the outside of the tissue glue.

In one embodiment, after each winding of the wire electrode, the wire electrode is adjusted so that the wire electrode on the second pillar and the third pillar remain parallel and closely arranged.

The present invention also provides a method for implanting the above-mentioned flexible recording electrode, which includes the following steps:

S210: Calculate the depth of the target brain area;

S220. Perform brain region positioning surgery;

S230: According to the brain area that has been located, implant the flexible recording electrode into the target brain area;

S240: Fix the flexible electrode and encapsulate the flexible electrode to the skull to complete the implantation.

In one embodiment, in S240, dental cement is used to fix the flexible recording electrode.

The beneficial effects of the flexible recording electrode and its preparation method and implantation method of the present invention are:

The flexible recording electrode of the present invention has a small volume, and can not only record the electrical activity of a target brain area with a small area, but also can reduce the load of the animal's head. In addition, the above-mentioned flexible recording electrode has good flexibility. The wound electrode wire is fixed by tissue glue. The tissue glue is degradable in the brain tissue. The electrode wire restores its flexibility and can move with the movement of the brain tissue to reduce the damage to the brain tissue. . At the same time, the above-mentioned flexible recording electrode has a simple structure and low cost.

The preparation method of the flexible recording electrode of the present invention has simple operation, low cost, time-saving and high-efficiency, low technical requirements for experimenters, and can meet the daily use of the laboratory.

The implantation method of the flexible recording electrode of the present invention has simple operation, easy realization and good stability.

Description of the drawings

In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings that need to be used in the specific embodiments or the description of the prior art. Obviously, the appendix in the following description The drawings are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative work.

FIG. 1 is a schematic diagram of a flexible recording electrode according to an embodiment;

Figure 2 is a schematic diagram of the structure of the stent;

Figure 3 is a schematic diagram of the trapezoidal structure;

Figure 4 is a schematic diagram of the winding of the electrode wire;

FIG. 5 is a flow chart of a method for preparing a flexible recording electrode according to an embodiment;

FIG. 6 is a flow chart of a method for implanting a flexible recording electrode according to an embodiment.

Detailed ways

The technical solutions of the present invention will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.

In the description of the present invention, it should be noted that the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. indicate the orientation or The positional relationship is based on the position or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, and does not indicate or imply that the pointed device or element must have a specific orientation, be constructed and operated in a specific orientation, Therefore, it cannot be understood as a limitation to the present invention.

In the description of the present invention, it should be noted that the terms "installed", "connected", and "connected" should be understood in a broad sense unless otherwise clearly specified and limited. For example, they can be fixed or detachable. Connected or integrally connected; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the internal communication between two components. For those of ordinary skill in the art, the specific meanings of the above-mentioned terms in the present invention can be understood in specific situations.

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

As shown in FIG. 1, the flexible recording electrode according to an embodiment includes an adaptor 10, a plurality of pin headers 20 and a plurality of electrode wires 30. Multiple pin headers 20 are arranged on the adapter 10 at intervals, one end of the wire electrode 30 and the pin header 20 are connected one-to-one, and the end of the multiple wire electrodes 30 away from the pin header 20 is bonded by tissue glue, and the wire electrode 30 is not covered The part of the tissue glue 40 is covered with a protective glue 50.

The above-mentioned flexible recording electrode has a small volume, and can not only record the electrical activity of a target brain area with a small area, but also reduce the load on the animal's head. In addition, the above-mentioned flexible recording electrode has good flexibility. The wound electrode wire 30 is fixed by the tissue glue 40. The tissue glue 40 is degradable in the brain tissue. The electrode wire 30 restores its flexibility and can move with the movement of the brain tissue to reduce the risk of damage. Damage to brain tissue. At the same time, the above-mentioned flexible recording electrode has a simple structure and low cost. Among them, the tissue glue 40 is not particularly limited, as long as it meets the requirements of being suitable for implantation and being degradable.

In one embodiment, the protective glue 50 is epoxy glue.

In one embodiment, the outer side of the tissue glue 40 is also coated with polyethylene glycol. Specifically, the polyethylene glycol may be polyethylene glycol with a molecular weight of 4000. When implanted into the brain of an experimental animal, if it is a superficial brain area, the hardness of the electrode wire 30 fixed with the tissue glue 40 is sufficient for implantation in the brain tissue. If it is a deep brain area, in order to improve the accuracy, a layer of polyethylene glycol can be coated on the outside of the tissue glue 40 to increase the hardness and then implanted. After reaching the target brain area, use saline to remove the polyethylene glycol on the outer layer of the electrode. Alcohol dissolves, and then uses dental cement to encapsulate and fix the entire flexible recording electrode and skull.

In an embodiment, the diameter of the electrode wire 30 may be 12 μm, 17 μm, or 25 μm. In order to be able to record signals of a small brain area, the size of the electrode wire 30 used should be as small as possible, and the damage to the brain tissue will be less. Further, the wire electrode 30 may be a metal wire electrode wire 30.

When the diameter of the electrode wire is 12 μm, the 8-channel flexible recording electrode has 8 electrode wires arranged closely next to each other, and the width is less than 100 μm. The volume is small, especially suitable for brain implants.

The above-mentioned flexible recording electrode can be prepared into 8 channels or 16 channels according to experimental requirements.

The above-mentioned flexible recording electrode is more suitable for shallow and small target brain areas.

In addition, referring to FIGS. 3 to 5, an embodiment of the above-mentioned preparation method of the flexible recording electrode is also provided, which includes the following steps:

S110. Provide support. The support includes a base 150, a first pillar 110, a second pillar 120, a third pillar 130, and a fourth pillar 140. One ends of the first pillar 110, the second pillar 120, the third pillar 130 and the fourth pillar 140 are all fixedly connected to the base 150. The first pillars 110, the second pillars 120, the third pillars 130, and the fourth pillars 140 are distributed in a trapezoid shape on the base 150. The first pillars 110 and the fourth pillars 140 are respectively located at both ends of the bottom side of the trapezoid, and the second pillars 120 The and third pillars 130 are respectively located at both ends of the top side of the trapezoid.

Specifically, please refer to Figure 3. The AD side of the trapezoid is the top side of the trapezoid, and the BC side is the bottom side of the trapezoid.

In one embodiment, the bracket is printed by a 3D printer or welded by metal materials. Preferably, the bracket adopts 3D printing, which is fast and low in cost.

In an embodiment, the material of the first pillar 110, the second pillar 120, the third pillar 130, and the fourth pillar 140 may be metal, wood or other hard materials.

S120: Fix the first end of the electrode wire 30 on the first pillar 110.

The diameter of the wire electrode 30 may be 12 μm, 17 μm, or 25 μm.

S130. Then the wire electrode 30 goes around one side of the second pillar 120, the third pillar 130 and the fourth pillar 140 in turn, and after being bent around the fourth pillar 140, it goes around the third pillar 130, the second pillar 120 and the third pillar in turn again. The first pillar 110, wherein the second pillar 120 and the third pillar 130 are located on the same side of the electrode wire 30.

S140. After the wire electrode 30 is then bent around the first pillar 110, repeat S130 until the number of the wire electrode 30 between the second pillar 120 and the third pillar 130 reaches the preset value, stop winding, and remove the first pillar of the electrode wire 30. The two ends are fixed to the first pillar 110.

It can be understood that when the 8-channel flexible recording electrode is prepared, when the number of electrode wires 30 between the second pillar 120 and the third pillar 130 reaches 8, that is, the number of electrode wires 30 of the 8-channel flexible recording electrode is reached. Quantity requirements. Afterwards, there is no need to wind the electrode wire 30 again. The preset value in S140 is set according to actual needs.

S150, bonding the electrode wire 30 between the second pillar 120 and the third pillar 130 with tissue glue. It can be understood that there are no special restrictions on the tissue glue, as long as it meets the requirements of being suitable for implantation and being degradable.

S160. Cut off the wire electrode 30 on the first pillar 110 and the fourth pillar 140, and cut off the wire electrode 30 between the second pillar 120 and the third pillar 130 that is bonded with tissue glue to obtain a wire electrode assembly.

It can be understood that when the electrode wire 30 bonded with the tissue glue between the second pillar 120 and the third pillar 130 is cut, the tissue glue has been sufficiently dried.

It can be understood that when the wire electrode 30 bonded with tissue glue between the second pillar 120 and the third pillar 130 is cut, the wire electrode 30 can be cut from the middle position of the second pillar 120 and the third pillar 130 .

S170: Fix the wire electrode 30 at the end of the wire electrode 30 assembly without tissue glue to different pin headers 20 in sequence.

S180: Cover the portion of the electrode wire 30 that is not covered with the tissue glue with a protective glue to obtain a flexible recording electrode.

The parts of the wire electrode 30 that are not covered with tissue glue are covered with protective glue to protect the wire electrode 30 from damage. One end of the electrode wire 30 bonded with tissue glue is used for implantation in the brain tissue.

The preparation method of the flexible recording electrode is simple in operation, low in cost, time-saving and high-efficiency, has low technical requirements for experimenters, and can meet the daily use of the laboratory.

In one embodiment, after each winding of the wire electrode 30, the wire electrode 30 is aligned so that the wire electrode 30 on the second pillar 120 and the third pillar 130 are kept parallel and tightly arranged.

Please refer to FIG. 6, the above-mentioned flexible recording electrode implantation method of an embodiment includes the following steps:

S210: Calculate the depth of the target brain area.

S220. Perform a brain region positioning operation.

S230: According to the already located brain area, implant the flexible recording electrode into the target brain area.

It can be understood that the flexible recording electrode may be a double electrode or a four electrode. And the wire electrode 30 of the flexible recording electrode may be a wire electrode of different sizes. After the flexible recording electrode is prepared, it needs to be modified and tested to ensure that the flexible recording electrode can record electrophysiological signals normally. Further, the flexible recording electrode needs to be able to record the spike of a single neuron after modification and inspection.

S240. Fix the flexible electrode and encapsulate the flexible electrode to the skull to complete the implantation.

In S240, dental cement or other methods are used to fix the flexible recording electrode to the skull.

The implantation method of the flexible recording electrode is simple to operate, easy to implement, and has good stability.

The flexible recording electrode of the present invention allows daily use in a wide range of laboratories, and solves the problem of stabilizing electrical activity recording of neurons in the target brain regions of freely moving animals, especially brain regions with small areas, under a specific behavioral paradigm, In order to analyze the related brain functions under this behavior. In actual use, the flexible recording electrode of the present invention is not limited to the recording of neuron signals. It can also be combined with optical fibers to form a photoelectrode and implant in a target brain area for optical stimulation.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: The technical solutions recorded in the foregoing embodiments are modified, or some or all of the technical features thereof are equivalently replaced; these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

A flexible recording electrode, characterized in that it comprises an adapter, a plurality of pin headers, and a plurality of electrode wires. The plurality of pin headers are arranged on the adapter at intervals, and one end of the electrode wire and the pin header One-to-one correspondence connection, one end of the plurality of electrode wires away from the needle row is bonded by tissue glue, and the part of the electrode wires that is not covered with the tissue glue is covered with a protective glue.
The embedding mold according to claim 1, wherein the protective glue is epoxy resin glue.
The embedding mold according to claim 1, wherein the outer side of the tissue glue is also covered with polyethylene glycol.
The embedding mold according to claim 3, wherein the diameter of the electrode wire is 12 μm, 17 μm or 25 μm.
A method for preparing a flexible recording electrode according to any one of claims 1 to 4, characterized in that it comprises the following steps:

S110. Provide a support, the support including a base, a first pillar, a second pillar, a third pillar, and a fourth pillar, the first pillar, the second pillar, the third pillar, and the fourth pillar One end of the first pillar, the second pillar, the third pillar, and the fourth pillar are all fixedly connected to the base, and the first pillar and the fourth pillar are distributed in a trapezoid shape on the base. Fourth pillars are respectively located at both ends of the bottom side of the trapezoid, and the second pillar and the third pillar are respectively located at both ends of the top side of the trapezoid;

S120. Fix the first end of the electrode wire on the first post;

S130. Then, the wire electrode goes around one side of the second pillar, the third pillar, and the fourth pillar in sequence, and after being bent around the fourth pillar, it goes around the third pillar in turn again . The second pillar and the first pillar, wherein the second pillar and the third pillar are located on the same side of the electrode wire;

S140. After the wire electrode is then bent around the first column, repeat S130 until the number of the wire electrode between the second column and the third column reaches a preset value, stop winding, and The second end of the electrode wire is fixed to the first post;

S150, bonding the electrode wire between the second pillar and the third pillar with tissue glue;

S160. Cut off the wire electrode on the first pillar and the fourth pillar, and cut off the wire electrode bonded with tissue glue between the second pillar and the third pillar to obtain an electrode Silk component

S170: Fix the wire electrode at the end of the wire electrode assembly without tissue glue to different pin headers in sequence;

S180: Cover the part of the electrode wire that is not covered with the tissue glue with a protective glue to obtain the flexible recording electrode.
7. The method for preparing a flexible recording electrode according to claim 5, wherein the bracket is printed by a 3D printer or welded by a metal material.
7. The method for preparing a flexible recording electrode according to claim 5, wherein the outer surface of the tissue glue is coated with polyethylene glycol.
7. The method for preparing a flexible recording electrode according to claim 5, wherein after each winding of the wire electrode, the wire electrode is adjusted so that the wires on the second column and the third column The electrode wires are kept parallel and closely arranged.
A method for implanting a flexible recording electrode according to any one of claims 1 to 4, characterized in that it comprises the following steps:

S210: Calculate the depth of the target brain area;

S220. Perform brain region positioning surgery;

S230: According to the brain area that has been located, implant the flexible recording electrode into the target brain area;

S240: Fix the flexible electrode and encapsulate the flexible electrode to the skull to complete the implantation.
9. The method for implanting a flexible recording electrode according to claim 9, wherein in S240, the flexible recording electrode is fixed by dental cement.