A low-injury implantable brain neurochemical electrode and a preparation method thereof
By employing a carbon fiber substrate and a conductive polymer modification layer in the design of the neurochemical electrode, the problem of tissue damage during microelectrode implantation is solved, enabling low-damage electrochemical detection that is suitable for in vivo neurochemical research.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- BEIJING NORMAL UNIVERSITY
- Filing Date
- 2023-02-15
- Publication Date
- 2026-07-14
AI Technical Summary
Existing microelectrodes implanted into brain tissue present both acute and long-term mechanical damage problems, especially tissue damage and inflammatory responses caused by excessively large rigid electrode sizes and modulus differences, which affect long-term neurochemical studies of the brain.
Using carbon fiber as a substrate, combined with an insulating layer and a conductive polymer modification layer, a low-damage implantable neurochemical electrode was prepared by vacuum evaporation and dip-coating. The electrode size was controlled within 10–50 μm, and a conductive polymer was used as a buffer layer to reduce implantation damage.
It significantly reduces damage to brain tissue caused by electrode implantation, improves the biocompatibility and mechanical buffering effect between the electrode and the tissue, is applicable to a variety of in vivo electrochemical analysis methods, and achieves highly sensitive detection of neurochemical substances.
Smart Images
Figure CN116327190B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a low-damage implantable neurochemical electrode for the brain and its preparation method, belonging to the field of electrochemical analysis technology. Background Technology
[0002] With the development of brain science and technology, in-situ real-time detection of neurochemical substances in the brain plays an increasingly important role in neurophysiological and pathological research. Electrochemical methods, due to their ability to achieve high spatiotemporal resolution, sensitivity, and selectivity, are gradually becoming an important tool in brain neurochemical research. Current electrochemical in-situ detection techniques rely on microelectrode technology, which involves implanting electrodes into target brain regions for analysis. However, electrode implantation can cause tissue damage and associated inflammatory reactions, significantly limiting its application in long-term brain neurochemical research. Therefore, minimizing implantation damage is a major challenge for the application of electrochemical analysis methods in in vivo in-situ analysis.
[0003] The main reasons for microelectrode damage to nerve tissue include: acute mechanical injury during implantation, mechanical injury caused by displacement of the electrode within the tissue during long-term implantation, and biotoxic damage caused by the chemical composition of the electrode surface. Current strategies for achieving low-damage long-term implantation primarily involve using small-sized (diameter no greater than 100 μm) rigid electrodes or low-modulus flexible electrodes. While these strategies alleviate the damage problem of implantable electrochemical electrodes to some extent, they still have some shortcomings: although rigid, small-sized electrodes can reduce acute injury during implantation, the difference in modulus between them and the tissue can still cause some tissue damage during long-term implantation. While flexible electrodes can conform well to the tissue and prevent slippage, rigid guides are usually required for implantation, which can lead to greater acute mechanical injury.
[0004] Carbon fiber is widely used in in-situ electrochemical analysis due to its excellent electrical conductivity, mechanical strength, chemical stability, and electrocatalytic properties. However, the inventors discovered that existing microelectrode fabrication methods typically use drawn glass tubes, and large-sized rigid electrodes can cause significant acute implantation damage during implantation and induce inflammatory responses during long-term implantation, affecting recording results. Through literature review, the inventors found that the main factors causing this problem are the excessively large size of the implanted electrode and the large difference between the material modulus and the tissue. Current solutions mainly involve fabricating thinner rigid electrodes or flexible electrodes. However, rigid electrodes still cannot solve the problem of modulus difference, and flexible electrodes usually require the use of rigid guides to assist implantation into the target brain region, meaning these methods may still cause additional tissue damage.
[0005] Therefore, it is very important to develop low-damage implantable microelectrodes that combine the advantages of rigid and flexible electrodes. Summary of the Invention
[0006] The purpose of this invention is to address the problem of significant brain tissue damage caused by traditional microelectrode implantation, and to provide a low-damage implantable neurochemical electrode and its preparation method. This invention uses carbon fiber as a framework, with an insulating layer and a biocompatible organic polymer modification layer directly modified onto the carbon fiber surface. This invention retains the excellent mechanical and electrochemical properties of carbon fiber while avoiding direct contact between rigid materials and tissue. Furthermore, when using a conductive polymer as a buffer layer, it can also be used as a counter electrode, further reducing the number of electrodes implanted during long-term recording. By adjusting the thickness of each modification layer during the counter electrode preparation process, the electrode size can be controlled within 10–50 μm while ensuring electrode performance, thereby significantly reducing implantation damage.
[0007] The objective of this invention is achieved through the following technical solutions.
[0008] A low-damage implantable neurochemical electrode for the brain comprises three parts: carbon fiber, an insulating layer, and a conductive polymer modification layer.
[0009] A method for preparing a low-damage implantable neurochemical electrode includes: (1) cutting carbon fiber and fixing one end of it to the end of a copper wire with conductive adhesive; (2) covering the surface of the copper wire with the fixed carbon fiber with an insulating layer; (3) covering the surface of the insulating layer with a conductive polymer modification layer; (4) leading out the conductive polymer layer with a copper wire through conductive adhesive, and reinforcing the connection with resin insulation; (5) cutting and polishing the end of the electrode fiber to expose the carbon fiber cross section, which can then be used as a low-damage implantable microelectrode; (6) the used electrode can be recut and polished to expose a fresh carbon fiber cross section for reuse.
[0010] The carbon fiber mentioned in step (1) is vapor-grown carbon fiber or polymer pyrolysis carbon fiber with a diameter of 5-10 μm. The cutting length is selected according to the depth of the target brain region to be implanted, and is usually 5-20 mm.
[0011] The insulating layer mentioned in step (2) is a 1-2 μm thick pyrene coating layer prepared by vacuum evaporation. The vacuum evaporation process can form an ultra-thin and dense insulating layer on the carbon fiber surface, preventing short circuits in the electrode implantation part. The inventors found through experiments that for the electrode design, an insulating layer with a thickness of 1-2 μm can provide good insulation. When the insulating layer is thinner (as described in Comparative Example 1, 500 nm), the insulating layer is prone to cracking and short circuits, leading to electrode failure.
[0012] Due to the small diameter of the electrode fibers and the strong hydrophobicity of the phenelzine coating, coating with conductive polymers presents challenges. Therefore, the inventors propose the following steps to modify the conductive polymer layer:
[0013] The conductive polymer modification step in step (3) includes: (1) mixing Nafion solution, EDOT, and FeCl3 in a molar ratio of 2:1:4 and stirring at room temperature for 24 hours. (2) dialyzing the reaction product using a 500 Da dialysis bag for purification. (3) centrifuging the product and dispersing it with ethanol to obtain a PEDOT:F dispersion. (4) coating the microelectrode surface with the PEDOT:F solution and drying it. (5) coating the microelectrode surface with a PEDOT:PSS modification layer using the dip-coating method. The thickness of this modification layer is 1–10 μm. It can be used as a mechanical buffer layer and has good biocompatibility. In addition, PEDOT:PSS also has good conductivity and can be further used as an electrode to realize in-situ detection of amperometric and voltammetric methods, reducing the need for additional electrode implantation.
[0014] According to embodiments of the present invention, during electrode implantation in deep brain regions, a polyethylene glycol coating with a thickness of 10–100 μm can be applied to the surface of the electrode fibers using an impregnation-lift method to support the unimplanted portion of the electrode. When the electrode is implanted, the polyethylene glycol used for support dissolves rapidly without causing additional tissue damage.
[0015] It supports two-electrode and three-electrode connection methods and is compatible with various in vivo electrochemical analysis methods; it can be used for the detection of electroactive neurochemical substances.
[0016] Beneficial effects
[0017] 1. The present invention uses carbon fiber as a substrate, which can provide good mechanical, electrical and electrochemical properties, which is conducive to electrode implantation and provides good electrochemical response.
[0018] 2. This invention uses organic polymers to insulate and functionalize carbon fibers. While significantly reducing the electrode diameter, it also effectively improves the biocompatibility of the electrode-tissue contact surface and reduces the modulus to provide mechanical cushioning, thereby effectively reducing damage caused by electrode implantation.
[0019] 3. This invention uses carbon fiber as the working electrode and a conductive polymer coating as the counter electrode; additional reference electrodes and counter electrodes can also be used to form an in vivo in-situ electrochemical measurement system. Attached Figure Description
[0020] Figure 1 A is a schematic diagram of the low-damage implantable microelectrode described in this invention;
[0021] Figure 1B is a schematic cross-sectional view of the electrode fiber portion of the low-damage implantable microelectrode described in this invention;
[0022] Figure 1 C is a cross-sectional schematic diagram of the electrode connection portion of the low-damage implantable microelectrode described in this invention;
[0023] Figure 2 A is the cyclic voltammogram for the electrochemical characterization of the low-damage implantable microelectrode provided in Example 1;
[0024] Figure 2 B is the cyclic voltammogram for the electrochemical characterization of the conductive polymer-modified layer of the low-damage implantable microelectrode provided in Example 1;
[0025] Figure 3 A is a rapid scanning voltammetry diagram of the low-damage implantable microelectrode provided in Example 2 in dopamine solutions of different concentrations;
[0026] Figure 3 B is a rapid scanning voltammetric graph of the low-damage implantable microelectrode provided in Example 2 in ascorbic acid solutions of different concentrations.
[0027] Among them, 1—working electrode (carbon fiber) connecting wire, 2—counter electrode (polymer conductive layer) connecting wire, 3—insulating resin, 4—integrated electrode fiber, 5—carbon fiber, 6—insulating layer, 7—conductive polymer modification layer, and 8—conductive adhesive. Detailed Implementation
[0028] Embodiments of the present invention are described in detail below with reference to the accompanying drawings. However, the present invention is not limited to the following embodiments.
[0029] Example 1:
[0030] In this embodiment, a low-damage implantable electrochemical electrode was prepared according to the following method, and the schematic diagram of the electrode structure is shown below. Figure 1 As shown in A:
[0031] Step 1: Cut a 5mm long, 10μm diameter vapor-grown carbon fiber (5) and fix it to the end of a copper wire (1) using conductive silver paste (8).
[0032] Step 2: Use a vacuum evaporation apparatus to coat the surface of the copper wire with carbon fiber with a 2μm thick pyrrolidone modification layer (6).
[0033] Step 3: Apply a PEDOT:PSS modification layer of approximately 5 μm thickness to the surface of the Pyrene-insulated electrode fiber using the dip-coating method (7). A schematic diagram of the cross-section of the modified electrode fiber (4) is shown below. Figure 1 As shown in B.
[0034] Step 4: The conductive polymer modification layer is led out using copper wire (2) through conductive silver paste (8), and the electrode connection is reinforced with insulating resin (3). A cross-sectional view of the electrode connection is shown below. Figure 1 As shown in C.
[0035] Step 5: Use micro-scissors to trim the ends of the electrode fibers to expose the carbon fiber cross-section.
[0036] The low-damage implantable electrochemical electrode prepared according to the above method was immersed in a solution containing 1 mmol / L ferrocene methanol and 0.1 mol / L KCl. A three-electrode system was constructed using carbon fiber as the working electrode, an Ag / AgCl electrode as the reference electrode, and a platinum electrode as the counter electrode. Cyclic voltammetry was performed in the range of -0.05 to 0.45 V at a scan rate of 50 mV / s. The scan results are as follows: Figure 2 As shown in Figure A, the limiting diffusion current was 2.25 nA, which translates to an equivalent electrode diameter of 12.5 μm. This indicates that the prepared low-damage implantable microelectrode exhibits typical disk-shaped microelectrode volt-ampere characteristics and a good volt-ampere response, meeting the requirements for microelectrode electrochemical analysis and detection.
[0037] The low-damage implantable electrochemical electrode prepared by the above method was immersed in artificial cerebrospinal fluid. A three-electrode system was constructed, using a conductive polymer-modified layer as the working electrode, an Ag / AgCl electrode as the reference electrode, and a platinum electrode as the counter electrode. Cyclic voltammetry was performed at a scan rate of 50 mV / s within a potential range of -0.3 to 0.6 V. The scan results are as follows: Figure 2 As shown in Figure B, this indicates that the conductive polymer-modified layer has good conductivity and can be used as an electrode.
[0038] Example 2:
[0039] The low-damage implantable electrochemical electrode prepared according to the method described in Example 1 was immersed in artificial cerebrospinal fluid. A two-electrode system was constructed using carbon fiber as the working electrode and a conductive polymer-modified layer as the counter electrode. Rapid scan voltammetry analysis was performed at a scan rate of 400 V / s within a potential range of -0.4 to 1.1 V. When 500 nmol / L (a), 1 μmol / L (b), and 5 μmol / L dopamine were added, respectively, the background-subtracted voltammetric curves were obtained as shown below. Figure 3 As shown in Figure A. When 50 μmol / L (a), 100 μmol / L (b), and 200 μmol / L (c) of ascorbic acid were added respectively, the background-subtracted voltammetric curves were obtained as shown in Figure A. Figure 3 As shown in B, this demonstrates that the designed low-damage implantable electrochemical electrode possesses good selectivity and sensitivity, enabling the analysis and detection of neurochemicals such as dopamine and ascorbic acid.
[0040] Comparative Example 1:
[0041] Ten low-damage implantable electrochemical electrodes were prepared according to the method described in Example 1, but with an insulating layer thickness of 500 nm. Testing revealed that only 40% of the electrodes were usable, while the remaining electrodes exhibited short-circuit failure.
[0042] Ten low-damage implantable electrochemical electrodes were prepared according to the method described in Example 1, wherein the insulating layer thickness was 2 μm. All electrodes were tested and found to be functional.
[0043] The above detailed description further illustrates the purpose, technical solution, and beneficial effects of the invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. A low-damage implantable neurochemical electrode, characterized in that: The chemical electrode uses carbon fiber as a skeleton and directly modifies the surface of the carbon fiber with an insulating layer and a biocompatible conductive polymer modification layer; the overall thickness of the chemical electrode does not exceed 50 μm. The method for preparing the low-damage implantable neurochemical electrode includes the following steps: (1) Cut carbon fiber and fix one end of it to the end of copper wire with conductive glue; (2) Cover the surface of the copper wire with carbon fiber fixed with an insulating layer; (3) A conductive polymer modification layer is coated on the surface of the insulating layer; (4) The conductive polymer modification layer is led out with copper wire through conductive adhesive, and the connection is reinforced with resin insulation; (5) The ends of the electrode fibers are cut and polished to expose the cross section of the carbon fiber for use as a low-damage implantable microelectrode. (6) The used electrodes can be recut and polished to expose fresh carbon fiber cross sections for reuse.
2. The low-damage implantable neurochemical electrode as described in claim 1, characterized in that: The carbon fiber mentioned in step (1) is a vapor-grown carbon fiber or a polymer pyrolysis carbon fiber with a diameter of 5 to 10 μm; the cut length is 5 to 20 mm. The insulating layer mentioned in step (2) is a pyrene coating layer with a thickness of 1 to 2 μm prepared by vacuum evaporation.
3. The low-damage implantable neurochemical electrode as described in claim 1, characterized in that: The specific wrapping method for step (3) is as follows: (1) Mix Nafion solution, EDOT and FeCl3 in a molar ratio of 2:1:4 and stir evenly at room temperature; after dialysis purification, centrifuge and disperse with ethanol to obtain PEDOT:F dispersion; (2) Coat the microelectrode surface with PEDOT:F solution and dry; (3) A PEDOT:PSS modified layer was coated on the surface of the microelectrode using the dip-coating method; the thickness of the modified layer was 1 to 10 μm; it could be used as a mechanical buffer layer and had good biocompatibility; In addition, PEDOT:PSS has good conductivity and can be used as a counter electrode to realize in-situ detection of amperometric and voltammetric methods, reducing the need for additional electrode implantation; According to an embodiment of the present invention, during electrode implantation in deep brain regions, a polyethylene glycol coating with a thickness of 10 to 100 μm can be applied to the surface of the electrode fibers using an impregnation and lifting method to support the unimplanted portion of the electrode. When the electrode is implanted, the polyethylene glycol used as support will dissolve rapidly without causing additional tissue damage.
4. The low-damage implantable neurochemical electrode as described in claim 1, characterized in that: It is used for in-situ detection of neurochemicals in the brain; carbon fiber is used as the working electrode and a conductive polymer coating is used as the counter electrode; additional reference electrodes and counter electrodes can also be used to form an in-situ electrochemical measurement system.
5. The low-damage implantable neurochemical electrode as described in claim 4, characterized in that: It supports two-electrode and three-electrode connection methods and is compatible with various in vivo electrochemical analysis methods; it can be used for the detection of electroactive neurochemical substances.
6. The low-damage implantable neurochemical electrode as described in claim 4, characterized in that: Before electrode implantation, a 10–100 μm polyethylene glycol coating is applied to the surface of the electrode fibers using an impregnation and lifting method for support, enabling implantation in deep brain regions.