Preparation of conductive adhesion layer of polybenzazole derivatives for neural electrode modification

Abstract

The present invention belongs to the technical field of biomedical equipment, and discloses a preparation method of a polyindole derivative conductive adhesion layer for modifying a neural electrode, wherein the preparation method comprises preparing an electrochemical polymerization solution using an indole derivative monomer and a supporting electrolyte, and then subjecting the electrochemical polymerization solution to an electrochemical polymerization treatment, so that the indole derivative monomer is electrochemically polymerized and deposited on the surface of the neural electrode, thereby obtaining a polyindole derivative conductive adhesion layer located on the surface of the neural electrode. The present invention improves the composition of the adhesion layer and the corresponding preparation method, and for the first time uses a polyindole derivative to obtain a polyindole derivative conductive adhesion layer for modifying a neural electrode, thereby effectively solving the problem of reduced electrochemical performance of the electrode compared with the prior art while improving adhesion.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical equipment, and more specifically, relates to the preparation of a polybenzazole derivative conductive adhesion layer for modifying a neural electrode, which can be applied to an implantable neural electrode to perform surface modification on the neural electrode. Background Art

[0002] Neural interface technology has great application prospects in brain-computer interface, neural regulation and neural repair. In the past few years, neural interfaces for neural recording and stimulation have been mainly realized through device design and new electrode materials. The neural electrode interface refers to the contact surface between the neural electrode and the tissue (neural interface). The reliability and long-term stability of the neural interface mainly rely on the direct two-way communication between the electrode and the nerve. Therefore, the development of new electrode materials is the key to building a new generation of neural interfaces. Different types of materials are used to narrow the mismatch between neural tissue and neural interface, including capacitive materials (MXene, graphene, carbon nanotubes and other nanomaterials) and Faraday materials (conductive polymers). Taking the conductive polymer poly (3,4-ethylenedioxythiophene) (PEDOT) as an example, PEDOT has good electrical properties, excellent biocompatibility and tissue-like softness. Although PEDOT has been widely explored as an electroactive coating material for neural interfaces, the weak and unstable adhesion between PEDOT and the substrate can lead to interface failure, which in turn leads to the loss of PEDOT function, and ultimately affects the long-term operation reliability of neural interfaces in practical applications. In order to solve the adhesion problem of PEDOT, the method of modifying the EDOT monomer is generally adopted. Functional groups such as carboxyl, vinyl and aldehyde are introduced into the EDOT monomer. Since these functional groups have high reactivity during the electrodeposition process, they have excellent adhesion. However, the introduction of functional groups such as carboxyl, vinyl and aldehyde has a great influence on the charge transfer of PEDOT, greatly reducing the electrochemical performance of PEDOT. Another method is to add an adhesive layer between PEDOT and the substrate. By adding an adhesion-promoting layer between the conductive polymer and the electrode substrate, the interaction between PEDOT and the substrate is enhanced. However, the adhesion-promoting layers that have been reported are all insulators, which weaken the electrochemical performance of the electrode and substantially hinder the application of conductive polymers in high-performance neural interfaces.

[0003] Chinese patent CN107287631A discloses "Microelectrodes and their preparation methods and applications". Although it also discloses a method for preparing microelectrodes with certain mechanical properties and electrochemical performance stability, it still has problems such as poor stability under extreme conditions such as ultrasound and electrochemical performance that cannot meet long-term neural electrode requirements. Summary of the invention

[0004] In view of the above defects or improvement needs of the prior art, the purpose of the present invention is to provide a preparation of a polyindole derivative conductive adhesion layer for modifying neural electrodes, wherein the composition of the adhesion layer and the corresponding preparation method are improved, and the polyindole derivative conductive adhesion layer for modifying neural electrodes is obtained for the first time using polyindole derivatives, while improving the adhesion, and compared with the prior art, it can effectively solve the problem of reduced electrochemical performance of the electrode. The present invention forms a polyindole derivative conductive adhesion layer by introducing polyindole derivatives, which can be used to enhance the adhesion of conductive polymers on metal neural electrodes. Based on the present invention, a polyindole derivative polymer adhesion layer with good binding force and high conductivity can be achieved, especially it can be prepared by direct electrodeposition on the surface of the neural electrode.

[0005] To achieve the above-mentioned purpose, according to one aspect of the present invention, a method for preparing a polyindole derivative conductive adhesion layer for modifying a neural electrode is provided, characterized in that the method comprises preparing an electrochemical polymerization solution using an indole derivative monomer and a supporting electrolyte, and then subjecting the electrochemical polymerization solution to an electrochemical polymerization treatment using a cyclic voltammetry method, a constant potential method or a constant current method, so that the indole derivative monomer is electrochemically polymerized and deposited on the surface of the neural electrode, thereby obtaining a polyindole derivative conductive adhesion layer located on the surface of the neural electrode;

[0006] Furthermore, the temperature of the electrochemical polymerization treatment is 0-30°C; in addition,

[0007] When the electrochemical polymerization treatment is specifically performed by cyclic voltammetry, the potential window of the cyclic voltammetry is -0.1V to 1.8V, and the number of polymerization cycles is 5 to 200 cycles;

[0008] When the electrochemical polymerization process is performed by a constant current method, the current density of the constant current method is 0.001 mA cm -2 ~1mA cm -2 , polymerization time is 10~2000s;

[0009] When the electrochemical polymerization treatment is specifically carried out by a constant voltage method, the potential of the constant voltage method is 1.0V to 1.8V, and the polymerization time is 10 to 500s.

[0010] As a further preferred embodiment of the present invention, the solvent used in the electrochemical polymerization solution is selected from acetonitrile, water, dichloromethane, propylene carbonate, and benzonitrile.

[0011] As a further preferred embodiment of the present invention, the supporting electrolyte is selected from lithium perchlorate, H2SO4, tetrabutylammonium perchlorate, tetraethylammonium perchlorate, tetrabutylammonium boron tetrafluoride, and boron trifluoride etherate.

[0012] As a further preferred embodiment of the present invention, the ratio of the amount of the indole derivative monomer to the volume of the electrochemical polymerization solution satisfies (0.01-0.5) mol: (10-15) mL;

[0013] The ratio of the amount of the supporting electrolyte substance to the volume of the electrochemical polymerization solution satisfies (0.01-0.5) mol: (10-15) mL.

[0014] As a further preferred embodiment of the present invention, the indole derivative monomer is any one of 4-R indole, 5-R indole, 6-R indole and 7-R indole, wherein the R group is selected from nitro, amino, hydroxyl, carboxyl, aldehyde and cyano.

[0015] Through the above technical scheme conceived by the present invention, compared with the prior art, due to the introduction of polyindole derivatives, the obtained polyindole derivative conductive adhesion layer can be used to enhance the adhesion of conductive polymers at the neural electrode interface, and has good mechanical stability and electrical stability, and can be applied to the modification of 64-channel neural electrodes, etc. The polyindole derivative conductive adhesion layer obtained by the present invention uses indole derivatives instead of the commonly used polyethylene dioxythiophene derivatives (PEDOT), and while showing good adhesion performance, it also achieves the improvement of the electrochemical performance of the electrode.

[0016] The present invention utilizes electrochemical polymerization to deposit a conductive adhesion layer of polybenzazole derivatives on the surface of a neural electrode. The temperature of the electrochemical polymerization is controlled to be 0-30°C. If cyclic voltammetry is used, the potential window is controlled to be -0.1V to 1.8V. If constant current method is used, the current density is controlled to be 0.001mA cm -2 ~1mA cm -2 , the polymerization time is controlled to be 10 to 2000 s; if the constant voltage method is used, the potential is controlled to be 1.0 V to 1.8 V and the polymerization time is controlled to be 10 to 500 s, which can effectively ensure the adhesion of the obtained polybenzazole derivative layer.

[0017] In the present invention, in particular, nitro, amino, hydroxyl, carboxyl, aldehyde or cyano groups can be used as substituent R groups, and 4-R-indole, 5-R-indole, 6-R-indole, and 7-R-indole can be used as indole derivative monomers to obtain conductive adhesion layers with different electrical properties, which can be used for subsequent functional modification.

[0018] Specifically, the present invention can achieve the following beneficial effects:

[0019] (1) The polyindole derivative conductive adhesive layer prepared by the present invention has good adhesiveness and electrical properties, and can be used for interface modification of neural electrodes. The preparation method is simple and the feasibility of large-scale preparation is high.

[0020] (2) The microelectrode array prepared by the present invention can be used as an adhesion-promoting layer of a conductive polymer neural electrode after being modified with a conductive adhesion layer of a polyindole derivative. The resulting conductive polymer coating has excellent electrochemical properties and high stability, and can be used for efficient recording of neural electrophysiological signals, and can be applied to neural engineering fields such as brain-computer interfaces.

[0021] The present invention uses polybenzazole derivatives as a conductive adhesion layer for the first time, replacing the commonly used polyethylene dioxythiophene derivatives, avoiding the direct introduction of functional groups such as carboxyl, vinyl, aldehyde and amino groups into PEDOT to hinder the electrochemical performance of PEDOT. The present invention preferably uses cyclic voltammetry, constant potential method or constant current method with fine control of potential window, polymerization potential or current density to optimize the electrochemical performance and adhesion of polybenzazole derivatives. The polybenzazole derivatives obtained by the present invention have significantly improved the impedance properties and charge storage capacity of the electrode, and show excellent ultrasonic mechanical stability.

[0022] In summary, the polyindole derivative conductive adhesion layer prepared by the present invention can be used for interface modification of neural electrodes; the obtained conductive adhesion layer has strong adhesion and good stability, and can be used to enhance the adhesion of conductive polymers. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 3 is a SEM image of the conductive adhesion layer of the polyindole derivative prepared in Example 1.

[0024] Figure 2 3 is an impedance curve of the conductive adhesion layer of the polyindole derivative prepared in Example 1.

[0025] Figure 3 3 is a charge storage capacity curve of the polybenzazole derivative conductive adhesion layer prepared in Example 1.

[0026] Figure 4 The ultrasonic before and after pictures of the conductive adhesive layer of polybenzazole derivative prepared in Example 1. Figure 4 (a) corresponds to before ultrasound. Figure 4 (b) corresponds to after ultrasound; the scale bars in the figure represent a length of 5 mm.

[0027] Figure 5: This is a graph of the impedance change before and after ultrasound of the polyindole derivative conductive adhesion layer prepared in Example 1. Among them, the legend "P-IN-5-NO2" corresponds to the poly-5-nitroindole conductive adhesion layer without ultrasound, and the legend "P-IN-5-NO2 30min" corresponds to the poly-5-nitroindole conductive adhesion layer after ultrasound for 30 minutes; the legend "PEDOT" corresponds to PEDOT without ultrasound, and the legend "PEDOT 5min" corresponds to PEDOT after ultrasound for 5 minutes; the legend "PEDOT on P-IN-5-NO2" corresponds to PEDOT on the poly-5-nitroindole conductive adhesion layer without ultrasound, and the legend "PEDOT on P-IN-5-NO230min" corresponds to PEDOT on the poly-5-nitroindole conductive adhesion layer after ultrasound for 30 minutes.

[0028] Figure 6 3 is a curve diagram of impedance change of the conductive adhesion layer of the polyindole derivative prepared in Example 2.

[0029] Figure 7 This is the cyclic voltammogram of the polyindole derivative conductive adhesion layer prepared in Example 1 after scanning 1000 cycles. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0031] In general, based on the present invention, any one of the nitro, amino, hydroxyl, carboxyl, aldehyde, and cyano indole substituted at positions 4, 5, 6, and 7 can be used as an indole derivative monomer to prepare an electropolymerization solution together with a supporting electrolyte (for example, 0.01-0.5 mol of an indole derivative can be added to 10-15 mL of a solvent, and 0.01-0.5 mol of a supporting electrolyte can be added and stirred to completely dissolve it, as an electropolymerization solution; some liquid supporting electrolytes, such as boron trifluoride etherate, can also be used as a solvent at the same time. In this case, they can be directly used as solvents without the need to add additional supporting electrolytes).

[0032] The following are specific embodiments (because gold electrodes and platinum electrodes are commonly used for neural electrodes, the following embodiments are all based on gold electrodes as neural electrodes; in addition, the indole derivative monomers used are all commercially available):

[0033] Example 1

[0034] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.5 mol of 5-nitroindole to 10 mL of acetonitrile, and adding 0.5 mol of lithium perchlorate, stirring to completely dissolve it, as an electropolymerization solution. The Au electrode is used as the electrode to be deposited, the electropolymerization method is cyclic voltammetry, and the electropolymerization temperature is 30°C. The potential window is -0.1V-1.4V, and the number of polymerization cycles is 20.

[0035] The performance of the polyindole derivative conductive adhesion layer obtained in Example 1 was tested, and the results were analyzed as follows:

[0036] like Figure 1 As shown, the obtained poly 5-nitroindole conductive adhesion layer is a uniform nano-island structure.

[0037] like Figure 2 As shown, when the number of polymerization turns of the obtained poly-5-nitroindole conductive adhesion layer is 20, the improvement of the 1 kHz impedance of the electrode is the largest, and the impedance can be reduced from 240Ω to 140Ω.

[0038] like Figure 3 As shown in the figure, the obtained poly-5-nitroindole conductive adhesion layer has the greatest improvement on the charge storage capacity of the electrode when the number of polymerization turns is 20, which can increase the charge storage capacity from ~0.2mC cm -2 Increased to ~0.9mC cm -2 .

[0039] like Figure 4 As shown, the mechanical stability of the poly 5-nitroindole conductive adhesive layer was characterized by ultrasound. It can be seen that there was no obvious shedding or delamination of the poly 5-nitroindole conductive adhesive layer before and after ultrasound.

[0040] like Figure 5 As shown (due to the physiological condition, the impedance is 1kHz, Figure 5 The impedance at 1000Hz is more valuable for analysis). The electrochemical stability of the poly 5-nitroindole conductive adhesion layer was characterized by ultrasound. It can be seen that there is no obvious change in the impedance of the poly 5-nitroindole conductive adhesion layer modified electrode before and after ultrasound, and when the electrode is used for subsequent electrodeposition of the conductive polymer PEDOT, it can significantly improve the stability of the electrochemical impedance of PEDOT.

[0041] like Figure 7 As shown, when the poly 5-nitroindole conductive adhesion layer modified electrode is used for subsequent electrodeposition of PEDOT, the electrochemical performance of the composite electrode material only slightly decays during long-term cyclic use (2000 cycles).

[0042] Example 2

[0043] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.01 mol of 5-aminoindole to 15 mL of 0.1 M dilute sulfuric acid (the solvent at this time is equivalent to water), stirring to completely dissolve it, and using the solution as an electropolymerization solution. The Au electrode is used as the electrode to be deposited, the electropolymerization method is a constant current method, and the electropolymerization temperature is 0°C. The current density is 0.001 mA cm -2 , the aggregation time is 2000s.

[0044] The polyindole derivative conductive adhesion layer obtained in Example 2 and the original Au electrode (i.e., the original neural electrode) were subjected to a performance comparison test, and the results were analyzed as follows:

[0045] like Figure 6 As shown in Figure 2, after modification with polypentaaminoindole, the impedance of the electrode at 1kHz dropped from 220Ω to 180Ω (due to the impedance of physiological conditions at 1kHz, Figure 6 The impedance at 1000Hz is more valuable for analysis).

[0046] Example 3

[0047] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.5 mol of 6-hydroxyindole to 10 mL of boron trifluoride ether, stirring to completely dissolve it, as an electropolymerization solution. An Au electrode is used as the electrode to be deposited, the electropolymerization method is a constant voltage method, and the electropolymerization temperature is 25°C. The polymerization potential is 1.4V, and the polymerization time is 300s. The poly 6-hydroxyindole conductive adhesion layer obtained by this method has good adhesion, and the impedance of the electrode at 1kHz is reduced from 220Ω to 150Ω.

[0048] Example 4

[0049] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.5 mol of 7-formyl indole to 10 mL of propylene carbonate, stirring to completely dissolve it, and using 0.01 mol of tetrabutylammonium boron tetrafluoride as a supporting electrolyte to prepare an electropolymerization solution. The Au electrode is used as the electrode to be deposited, the electropolymerization method is a constant current method, and the electropolymerization temperature is 15°C. The current density is 1 mA cm -2 The polymerization time was 10 s. The poly-7-aldehyde indole conductive adhesive layer obtained by this method had good adhesion, and the impedance of the electrode at 1 kHz dropped from 220 Ω to 162 Ω.

[0050] Example 5

[0051] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.5 mol of 5-carboxyindole to 10 mL of benzonitrile, stirring to completely dissolve it, using tetrabutylammonium perchlorate as a supporting electrolyte, and preparing an electropolymerization solution. An Au electrode is used as the electrode to be deposited, the electropolymerization method is cyclic voltammetry, and the electropolymerization temperature is 25°C. The potential window is -0.1V-1.8V, and the number of polymerization cycles is 200. The poly 5-carboxyindole conductive adhesion layer obtained by this method has good adhesion, and the impedance of the electrode at 1kHz is reduced from 220Ω to 140Ω.

[0052] Example 6

[0053] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.1 mol of 5-cyanoindole to 10 mL of dichloromethane, stirring to completely dissolve it, using tetrabutylammonium perchlorate as a supporting electrolyte, and preparing an electropolymerization solution. An Au electrode is used as the electrode to be deposited, the electropolymerization method is cyclic voltammetry, and the electropolymerization temperature is 25°C. The potential window is -0.1V-1.6V, and the number of polymerization cycles is 100. The poly 5-cyanoindole conductive adhesion layer obtained by this method has good adhesion, and the impedance of the electrode at 1kHz is reduced from 220Ω to 162Ω.

[0054] Example 7

[0055] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.1 mol of 6-nitroindole to 10 mL of acetonitrile, stirring to completely dissolve it, using tetraethylammonium perchlorate as a supporting electrolyte, and preparing an electropolymerization solution. The Au electrode is used as the electrode to be deposited, the electropolymerization method is a constant current method, and the electropolymerization temperature is 25°C. The current density is 0.1 mA cm -2 The polymerization time was 500s. The poly-6-nitroindole conductive adhesion layer obtained by this method had good adhesion, and the impedance of the electrode at 1kHz dropped from 220Ω to 196Ω.

[0056] Example 8

[0057] A method for preparing a conductive adhesion layer of a polyindole derivative for modifying a neural electrode, specifically: adding 0.1 mol of 7-carboxyindole to 10 mL of 0.1 M dilute sulfuric acid, stirring to completely dissolve it, and preparing an electropolymerization solution. The Au electrode is used as the electrode to be deposited, the electropolymerization method is a constant voltage method, and the electropolymerization temperature is 25°C. The polymerization potential is 1.0 V, and the polymerization time is 500 s. The poly 7-carboxyindole conductive adhesion layer obtained by this method has good adhesion, and the impedance of the electrode at 1 kHz is reduced from 220Ω to 177Ω.

[0058] Comparative Example 1

[0059] 0.01 mol of 5-nitroindole was added to 10 mL of 0.1 M dilute sulfuric acid, and 0.01 mol of lithium perchlorate was added, and stirred to completely dissolve, as an electropolymerization solution. The electropolymerization method was cyclic voltammetry, and the electropolymerization temperature was 25°C. The potential window was -0.1V-2.0V, and the number of polymerization cycles was 100.

[0060] Comparative Example 2

[0061] 0.8 mol of 6-aminoindole was added to 10 mL of 0.1 M dilute sulfuric acid, and 0.01 mol of tetrabutylammonium perchlorate was added and stirred to completely dissolve to prepare the electropolymerization solution. The electropolymerization method was constant current method, and the electropolymerization temperature was 50 °C. The current density was 2 mA cm -2 , the polymerization time is 60s.

[0062] Comparative Example 3

[0063] 1 mol of 7-formyl indole was added to 10 mL of boron trifluoride ether, and 0.01 mol of tetraethylammonium perchlorate was added, and stirred to completely dissolve, as an electropolymerization solution. The electropolymerization method was cyclic voltammetry, and the electropolymerization temperature was 60°C. The polymerization potential was 2 V, and the number of polymerization cycles was 400 s.

[0064] The above comparative examples 1-3 cannot meet the requirements of the present invention in terms of potential window, current density, potential value or electropolymerization temperature. The obtained polybenzazole derivative conductive adhesion layer cannot firmly adhere to the electrode surface and cannot enhance the adhesion of the conductive polymer.

[0065] It will be easily understood by those skilled in the art that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a conductive adhesion layer of a polybenzazole derivative for modifying a neural electrode and its application in improving the adhesion between a metal neural electrode and PEDOT, characterized in that: The method comprises preparing an electrochemical polymerization solution using an indole derivative monomer and a supporting electrolyte, and then subjecting the electrochemical polymerization solution to an electrochemical polymerization treatment using a cyclic voltammetry method, a constant potential method or a constant current method, so that the indole derivative monomer is electrochemically polymerized and deposited on the surface of a neural electrode, thereby obtaining a polyindole derivative conductive adhesion layer located on the surface of the neural electrode, thereby improving the adhesion between the metal neural electrode and PEDOT; wherein the indole derivative monomer is any one of 4-R-indole, 5-R-indole, 6-R-indole and 7-R-indole, and the R group is selected from a nitro group, an amino group, a hydroxyl group, a carboxyl group, an aldehyde group and a cyano group; Furthermore, the temperature of the electrochemical polymerization treatment is 0-30°C; in addition, When the electrochemical polymerization treatment is specifically performed by cyclic voltammetry, the potential window of the cyclic voltammetry is -0.1V to 1.8V, and the number of polymerization cycles is 5 to 200 cycles; When the electrochemical polymerization process is performed by a constant current method, the current density of the constant current method is 0.001 mA cm -2 ~1mA cm -2 , polymerization time is 10~2000s; When the electrochemical polymerization treatment is specifically carried out by a constant voltage method, the potential of the constant voltage method is 1.0V to 1.8V, and the polymerization time is 10 to 500s.

2. The use according to claim 1, characterized in that: The solvent used in the electrochemical polymerization solution is selected from acetonitrile, water, dichloromethane, propylene carbonate, and benzonitrile.

3. The use according to claim 1, characterized in that: The supporting electrolyte is selected from lithium perchlorate, H2SO4, tetrabutylammonium perchlorate, tetraethylammonium perchlorate, tetrabutylammonium boron tetrafluoride, and boron trifluoride etherate.

4. The use according to any one of claims 1 to 3, characterized in that: The ratio of the amount of the indole derivative monomer to the volume of the electrochemical polymerization solution satisfies (0.01-0.5) mol: (10-15) mL; The ratio of the amount of the supporting electrolyte substance to the volume of the electrochemical polymerization solution satisfies (0.01-0.5) mol: (10-15) mL.

Images