Two-dimensional material modified neural electrode and preparation method thereof

Abstract

The invention discloses a two-dimensional material modified neural electrode and a preparation method thereof. The preparation method comprises the following steps: 1) preparing a neural electrode substrate; 2) immersing the neural electrode substrate in the insulating material solution, and taking out the neural electrode substrate; 3) cutting off at the near end of the neural electrode substrate to obtain a neural electrode with a cross section which is a recording site; and (4) connecting the neural electrode obtained in the step (3) as a working electrode, a platinum electrode and an Ag / AgCl electrode into an electrochemical workstation, and uniformly depositing a two-dimensional material on the surface of a recording site by using a two-dimensional material aqueous solution as a working solution. According to the neural electrode, the impedance of an electrode-tissue interface is reduced due to the high specific surface area of the modification layer; the sensitivity and the signal-to-noise ratio of the neural electrode are remarkably improved due to high conductivity, excellent charge transfer performance and excellent electro-catalytic performance, and the signal acquisition efficiency and precision are improved; the performance is stable as long as 30 days, and the composition is suitable for chronic stimulation and long-term recording.

Description

Technical Field

[0001] The invention belongs to the field of materials and relates to a neural electrode modified with two-dimensional materials and a preparation method thereof. Background Art

[0002] Neural electrodes are key tools for recording and activating neuronal activity, and play an important role in fields such as neuroscience, neuromodulation therapy, and brain-computer interfaces. These electrodes are implanted in neural tissue to record neural signals and explore the function of the nervous system. In scientific research, they help to understand the structure of neural networks, the mechanisms of neural diseases, and treatment methods; in clinical practice, they can treat neurological diseases such as Parkinson's disease and epilepsy; in the engineering field, they are used in technologies such as brain-computer interfaces and neural prostheses to help restore motor function and communication ability. Therefore, neural electrodes provide support for human health and technological development in many fields. In the past few decades, significant progress has been made in the design and manufacture of neural electrodes. Traditional neural electrodes are usually made of metal materials (such as platinum, tungsten, silver, etc.), but these materials have limitations such as poor compatibility between electrodes and tissues, high impedance, and poor long-term stability, making them difficult to use for chronic stimulation and long-term recording. Therefore, new materials and preparation technologies need to be explored to improve the performance and application of neural electrodes.

[0003] Two-dimensional materials have attracted extensive attention due to their excellent electrochemical properties, high surface area and good biocompatibility. However, there are currently no reports on the modification of neural electrodes with two-dimensional materials. Summary of the invention

[0004] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a neural electrode modified with two-dimensional materials that can be used for chronic stimulation and long-term recording.

[0005] The second object of the present invention is to provide a method for preparing a neural electrode modified with two-dimensional materials.

[0006] The technical solution of the present invention is summarized as follows:

[0007] A method for preparing a neural electrode modified with a two-dimensional material comprises the following steps:

[0008] 1) roughening the surface of a metal wire with a diameter of 10-200 microns with sandpaper, washing it with deionized water, ultrasonically cleaning it with acetone and anhydrous ethanol in sequence, and drying it to obtain a neural electrode substrate; preparing a polyimide solution as an insulating material solution;

[0009] 2) immersing the neural electrode substrate in the insulating material solution, taking it out, and drying it, or coating the surface of the neural electrode substrate with the insulating material solution, and drying it;

[0010] 3) at the proximal end of the neural electrode substrate with an insulating material on the outer surface obtained in step 2), cutting the neural electrode substrate perpendicular to the long axis of the neural electrode substrate with an insulating material on the outer surface to obtain a neural electrode with a cut surface, wherein the cut surface is a recording site;

[0011] 4) The neural electrode obtained in step (3) is used as a working electrode, a platinum electrode is used as a counter electrode, and Ag / AgCl is used as a reference electrode, and connected to an electrochemical workstation. An aqueous solution of the two-dimensional material with a concentration of 0.05-5 mg / mL is added to the electrolytic cell as an electro-deposition working solution to cover the recording site. The two-dimensional material is uniformly deposited on the surface of the recording site through electrochemical deposition, and the two-dimensional material is rinsed with deionized water and dried to obtain a neural electrode modified with a two-dimensional material.

[0012] Preferably, the metal is gold, silver, copper, platinum, tungsten, iridium, tantalum, nickel, palladium, chromium, niobium, indium, platinum-iridium alloy, nickel-titanium alloy, tungsten-platinum alloy, nickel-cobalt alloy, chromium-nickel alloy or stainless steel.

[0013] Preferably, the weight average molecular weight of the polyimide is 10,000-100,000; and the solvent of the polyimide solution is N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetrahydrofuran or acetone.

[0014] Preferably, the mass concentration of the polyimide solution is 30%-60%.

[0015] Preferably, the two-dimensional material is MXenes, WSe2, VSe 2、 WSe2P, Bi2O2Se, SeTe, TiO2, Si3N4, AlN, InSnN, CN, TiN, WS2 or h-BN.

[0016] Preferably, the electrochemical deposition is constant current deposition, constant voltage deposition or multi-potential step deposition.

[0017] Preferably, the deposition current of the constant current deposition is 0.005-0.5 mA, and the deposition time is 1-90 s.

[0018] Preferably, the deposition voltage of the constant voltage deposition is 0.05-3V, and the deposition time is 1-60s.

[0019] Preferably, the multi-potential step deposition has a step voltage of 0.05-3V and a deposition time of 1-35s.

[0020] A neural electrode modified with two-dimensional materials prepared by the above preparation method.

[0021] Advantages of the present invention:

[0022] A neural electrode modified with a two-dimensional material of the present invention, the high specific surface area of ​​the modified layer can increase the contact area between the electrode recording site and the surrounding nerve tissue, thereby reducing the impedance of the electrode-tissue interface; the high conductivity and excellent charge transfer performance and excellent electrocatalytic performance can significantly improve the sensitivity and signal-to-noise ratio of the neural electrode, and improve the signal acquisition efficiency and accuracy. The van der Waals heterojunction expected to be introduced during the modification process can maintain the stability of the structure during long-term use, and can be used for chronic stimulation and long-term recording; the polyimide insulating layer and the two-dimensional material modified layer both have low toxicity and excellent biocompatibility, can reduce tissue damage and inflammatory response after implantation, extend the service life of the neural electrode and improve stability, and meet clinical and scientific research needs. The polyimide insulating layer also has high mechanical strength and stability, reduces mechanical wear and fracture of the material, and improves the service life; chemical inertness and antioxidant properties can also effectively reduce the interaction between the neural electrode and the surrounding environment, resist the influence of the oxidative environment on it, and effectively improve the long-term stability of the neural electrode. In the preparation process, different types of two-dimensional materials can be flexibly selected according to needs, and the thickness, morphology and chemical properties of the modified layer can be adjusted to balance the contradiction between electrode size and impedance, and flexibly adapt to different application scenarios and needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Schematic diagram of a device for preparing a neural electrode modified with two-dimensional materials.

[0024] Figure 2 This is a structural characterization of a two-dimensional material modified neural electrode and a bare electrode, where: Figure 2 a and Figure 2 b is a neural electrode surface modified with a two-dimensional material prepared in Example 1 at different scales, Figure 2 c and Figure 2 d shows the surface of a neural electrode modified with a two-dimensional material at different scales.

[0025] Figure 3 Electrochemical impedance spectroscopy and 1kHz impedance of a neural electrode modified with a two-dimensional material.

[0026] Figure 4 Cyclic voltammetry curves and cathodic charge storage capacity of a neural electrode modified with a two-dimensional material.

[0027] Figure 5 Long-term stability of impedance of neural electrodes modified with a two-dimensional material.

[0028] Figure 6 Long-term stability of charge storage capacity of a neural electrode cathode modified with a two-dimensional material.

[0029] Figure 7Electrocatalytic activity of a neural electrode modified with a two-dimensional material.

[0030] Figure 8 Biocompatibility of neural electrodes modified with a two-dimensional material.

[0031] Fig. 9 Neural electrophysiological signals recorded by a neural electrode modified with a two-dimensional material.

[0032] The neural electrodes modified with two-dimensional materials are referred to as modified electrodes in the above figure. DETAILED DESCRIPTION

[0033] The present invention will be further described below by means of specific examples.

[0034] A device for preparing a neural electrode modified with two-dimensional materials by an electrochemical workstation, see Figure 1 The computer 5 is electrically connected to the electrochemical workstation 6, and the electrochemical workstation 6 is electrically connected to the working electrode 1, the platinum electrode 3 and the Ag / AgCl 2 electrode respectively. The electrolytic cell 7 is filled with a two-dimensional material aqueous solution 4.

[0035] The bare electrode without any modification is the metal wire of each embodiment, such as platinum-iridium alloy wire or gold wire.

[0036] Example 1

[0037] A method for preparing a neural electrode modified with a two-dimensional material comprises the following steps:

[0038] 1) The surface of a platinum-iridium alloy wire with a diameter of 100 microns was roughened by sandpaper, rinsed with deionized water, ultrasonically cleaned with acetone and anhydrous ethanol in sequence, and dried to obtain a neural electrode substrate; a polyimide N,N-dimethylformamide solution with a mass concentration of 50% was prepared as an insulating material solution (the weight average molecular weight of the polyimide was 10,000-50,000);

[0039] 2) immersing the neural electrode substrate in the insulating material solution, taking it out, and drying it;

[0040] 3) at the proximal end of the neural electrode substrate with an insulating material on the outer surface obtained in step 2), cutting the neural electrode substrate perpendicular to the long axis of the neural electrode substrate with an insulating material on the outer surface to obtain a neural electrode with a cut surface, wherein the cut surface is a recording site;

[0041] 4) The neural electrode obtained in step (3) was used as the working electrode, the platinum electrode as the counter electrode, and the Ag / AgCl as the reference electrode, and connected to the electrochemical workstation. Figure 1, add a 0.5 mg / mL aqueous solution of two-dimensional material (WSe2) into the electrolytic cell as the electrodeposition working solution, covering the recording site, and use electrochemical deposition (multi-potential step deposition, step voltage of 1 V, deposition time of 15 s) to make the two-dimensional material evenly deposited on the surface of the recording site. Rinse with deionized water and dry to obtain a neural electrode modified with a two-dimensional material.

[0042] Example 2

[0043] A method for preparing a neural electrode modified with a two-dimensional material comprises the following steps:

[0044] 1)-3) Same as Example 1)-3);

[0045] 4) The neural electrode obtained in step (3) was used as the working electrode, the platinum electrode as the counter electrode, and the Ag / AgCl as the reference electrode, and connected to the electrochemical workstation. Figure 1 , add a 0.5 mg / mL two-dimensional material (WS2) aqueous solution into the electrolytic cell as the electrodeposition working solution, covering the recording site, and deposit the two-dimensional material evenly on the surface of the recording site through electrochemical deposition (multi-potential step deposition, step voltage of 1 V, deposition time of 15 s). Rinse with deionized water and dry to obtain a two-dimensional material modified neural electrode.

[0046] Example 3

[0047] A method for preparing a neural electrode modified with a two-dimensional material comprises the following steps:

[0048] 1) The surface of a gold wire with a diameter of 50 microns was roughened by sandpaper, rinsed with deionized water, ultrasonically cleaned with acetone and anhydrous ethanol in sequence, and dried to obtain a neural electrode substrate; a polyimide N-methylpyrrolidone solution with a mass concentration of 30% was prepared as an insulating material solution; (the weight average molecular weight of the polyimide is 10,000-50,000);

[0049] 2) immersing the neural electrode substrate in the insulating material solution, taking it out, and drying it;

[0050] 3) at the proximal end of the neural electrode substrate with an insulating material on the outer surface obtained in step 2), cutting the neural electrode substrate perpendicular to the long axis of the neural electrode substrate with an insulating material on the outer surface to obtain a neural electrode with a cut surface, wherein the cut surface is a recording site;

[0051] 4) The neural electrode obtained in step (3) is used as a working electrode, a platinum electrode is used as a counter electrode, and Ag / AgCl is used as a reference electrode, and connected to an electrochemical workstation. A two-dimensional material (MXenes) aqueous solution with a concentration of 0.3 mg / mL is added to the electrolytic cell as an electro-deposition working solution, covering the recording site, and electrochemical deposition (multi-potential step deposition, using three samples, respectively: step voltage 0.05V, deposition time 35s, step voltage 0.5V deposition time 10s, step voltage 3V deposition time 1s) is performed to uniformly deposit the two-dimensional material on the surface of the recording site, rinse with deionized water, and dry to obtain a neural electrode modified with a two-dimensional material.

[0052] Copper, platinum, iridium, tantalum, nickel, palladium, chromium, niobium, indium, nickel-titanium alloy, tungsten-platinum alloy, nickel-cobalt alloy, chromium-nickel alloy or stainless steel are used to replace the gold in this embodiment, and other aspects are the same as in this embodiment to prepare a two-dimensional material modified neural electrode.

[0053] Dimethyl sulfoxide and tetrahydrofuran were used to replace N-methylpyrrolidone in this embodiment, and other conditions were the same as in this embodiment to prepare a neural electrode modified with a two-dimensional material.

[0054] WSe2P, Bi2O2Se, SeTe, TiO2, Si3N4, AlN, InSnN, CN or TiN are used to replace the MXenes in this embodiment, and other parameters are the same as this embodiment to prepare a two-dimensional material modified neural electrode.

[0055] Example 4

[0056] A method for preparing a neural electrode modified with a two-dimensional material comprises the following steps:

[0057] 1) The surface of a tungsten wire with a diameter of 10 microns was roughened by sandpaper, rinsed with deionized water, ultrasonically cleaned with acetone and anhydrous ethanol in sequence, and dried to obtain a neural electrode substrate; a polyimide acetone solution with a mass concentration of 60% was prepared as an insulating material solution; (the weight average molecular weight of polyimide is 50,000-100,000)

[0058] 2) coating the surface of the neural electrode substrate with an insulating material solution and drying;

[0059] 3) at the proximal end of the neural electrode substrate with an insulating material on the outer surface obtained in step 2), cutting the neural electrode substrate perpendicular to the long axis of the neural electrode substrate with an insulating material on the outer surface to obtain a neural electrode with a cut surface, wherein the cut surface is a recording site;

[0060] 4) The neural electrode obtained in step (3) is used as a working electrode, a platinum electrode is used as a counter electrode, and Ag / AgCl is used as a reference electrode, and connected to an electrochemical workstation. An aqueous solution of the two-dimensional material (VSe2) with a concentration of 0.05 mg / mL is added to the electrolytic cell as an electro-deposition working solution, covering the recording site, and electrochemical deposition (constant current deposition, using three samples, respectively: deposition current 0.005 mA deposition 90 s, 0.05 mA deposition 60 s, 0.5 mA deposition 1 s); the two-dimensional material is uniformly deposited on the surface of the recording site, rinsed with deionized water, and dried to obtain a neural electrode modified with a two-dimensional material.

[0061] Example 5

[0062] A method for preparing a neural electrode modified with a two-dimensional material comprises the following steps:

[0063] 1) taking a silver wire with a diameter of 200 microns, grinding the surface with sandpaper for roughening treatment, rinsing with deionized water, ultrasonically cleaning with acetone and anhydrous ethanol in sequence, and drying to obtain a neural electrode substrate; preparing a polyimide N,N-dimethylacetamide solution with a mass concentration of 40% as an insulating material solution; (the weight average molecular weight of the polyimide is 10,000-40,000);

[0064] 2) coating the surface of the neural electrode substrate with an insulating material solution and drying;

[0065] 3) at the proximal end of the neural electrode substrate with an insulating material on the outer surface obtained in step 2), cutting the neural electrode substrate perpendicular to the long axis of the neural electrode substrate with an insulating material on the outer surface to obtain a neural electrode with a cut surface, wherein the cut surface is a recording site;

[0066] 4) The neural electrode obtained in step (3) was used as a working electrode, a platinum electrode was used as a counter electrode, and Ag / AgCl was used as a reference electrode, and connected to an electrochemical workstation. A 5 mg / mL aqueous solution of the two-dimensional material (h-BN) was added to the electrolytic cell as an electrodeposition working solution, covering the recording site, and electrochemical deposition (constant voltage deposition, using three samples, respectively:

[0067] The deposition voltage was 0.05 V for 60 s, 0.8 V for 30 s, and 3 V for 1 s) to make the two-dimensional material evenly deposited on the surface of the recording site, and then rinsed with deionized water and dried to obtain a neural electrode modified with a two-dimensional material.

[0068] Experimental Example 1

[0069] The two neural electrodes modified with two-dimensional materials obtained in Example 1 and Example 2 were scanned using a scanning electron microscope (SEM), and the obtained SEM images are shown in FIG. Figure 2 , the SEM image of Example 1 is Figure 2 a, b, SEM images of Example 2 Figure 2 c, d.

[0070] The two-dimensional material is uniformly deposited on the surface of the neural electrode recording site to form a loose and porous structure with a high specific surface area, which is conducive to charge transport and transfer. The neural electrodes modified with different types of two-dimensional materials of the present invention can all form a loose and porous structure.

[0071] Experimental Example 2

[0072] In order to verify the electrochemical performance of a neural electrode modified with a two-dimensional material described in Example 1, the specific steps of performing an electrochemical AC impedance test are as follows:

[0073] The experiments were performed in 1×PBS phosphate buffer (pH=7.4) at room temperature using a three-electrode system.

[0074] In the experiment, the platinum electrode was used as the counter electrode, the Ag / AgCl electrode was used as the reference electrode, and a neural electrode modified with a two-dimensional material was used as the working electrode. In the control group, a bare electrode without any modification was used as the working electrode.

[0075] When performing electrochemical impedance spectroscopy, set the test frequency range to 1 Hz to 10 5 Hz.

[0076] After the open circuit voltage stabilized, an AC signal with an amplitude of 10 mV was applied to the working electrode.

[0077] Electrochemical impedance spectroscopy was measured to evaluate the characteristics and response of the electrode interface.

[0078] Figure 3 , respectively, are the electrochemical AC impedance spectra and impedance at 1kHz of a neural electrode modified with a two-dimensional material (prepared in Example 1) and a bare electrode (platinum-iridium alloy wire). Among them, at a frequency of 1kHz, the impedance of the bare electrode is 3004.5Ohms, and the impedance of the neural electrode modified with a two-dimensional material is 1467.15Ohms. The modification of neural electrodes with two-dimensional materials can significantly reduce the impedance of neural electrodes, which is more conducive to the transmission of neural electrophysiological signals.

[0079] Experimental Example 3

[0080] In order to verify the electrochemical performance of a neural electrode modified with a two-dimensional material described in Example 1, an electrochemical cyclic voltammetry test experiment was performed, and the specific steps are as follows:

[0081] The experiments were performed in 1×PBS phosphate buffer (pH=7.4) at room temperature using a three-electrode system.

[0082] In the experiment, the platinum electrode was used as the counter electrode, the Ag / AgCl electrode was used as the reference electrode, and a neural electrode modified with a two-dimensional material was used as the working electrode. In the control group, a bare electrode without any modification was used as the working electrode.

[0083] When performing electrochemical cyclic voltammetry testing:

[0084] Set the scan rate to 50 mV s -1 .

[0085] Set the scanning potential range to 0.1V to -0.8V.

[0086] Set the number of loops to 2.

[0087] The cathode charge storage capacity was calculated by integrating the current in the second cycle of the cyclic voltammetry curve over the potential range of 0.1 V to -0.8 V and dividing it by the scan rate.

[0088] Figure 4 , respectively, are the cyclic voltammetry curves and cathode charge storage of a neural electrode modified with a two-dimensional material and a bare electrode. Among them, the cathode charge storage of a neural electrode modified with a two-dimensional material is 22.70mC / cm 2 , compared with 5.88mC / cm of bare electrode 2 It has been improved by nearly 4 times and is suitable for use as stimulation electrodes.

[0089] Experimental Example 4

[0090] In order to verify that the neural electrode modified with a two-dimensional material in Example 1 has long-term stability, electrochemical impedance spectroscopy and cyclic voltammetry tests were performed on it, and it was recorded as day 0. The neural electrode was placed for 1 day, 3 days, 7 days, 15 days, and 30 days, and electrochemical impedance spectroscopy and cyclic voltammetry tests were performed again. The specific implementation process of the test is as described in Experimental Examples 2 and 3.

[0091] Figure 5The electrochemical impedance spectra (upper and middle) and impedance at 1kHz (upper) of a two-dimensional material-modified neural electrode and a bare electrode at day 0, 1, 3, 7, 15, and 30. The impedance at 1kHz of the bare electrode is 3004.5Ohms, and the impedance at 1kHz of a two-dimensional material-modified neural electrode at day 0, 1, 3, 7, 15, and 30 are 1551Ohms, 1663.5Ohms, 1609.5Ohms, 1642.5Ohms, 1572Ohms, and 1581Ohms, respectively.

[0092] Figure 6 The cyclic voltammetry curves and cathode charge storage of a two-dimensional material modified neural electrode and a bare electrode at day 0, 1, 3, 7, 15, and 30. The cathode charge storage of the bare electrode is 5.88 mC / cm 2 The cathode charge storage capacity of the neural electrode modified with a two-dimensional material on day 0, day 1, day 3, day 7, day 15, and day 30 was 22.36 mC / cm 2 、20.58mC / cm 2 、17.35mC / cm 2 、13.37mC / cm 2 , 12.30mC / cm 2 and 12.56mC / cm 2 .

[0093] It can be seen that compared with the bare electrode, the 1kHz impedance of a neural electrode modified with a two-dimensional material did not change significantly after 30 days of placement, the cathode charge storage did not decrease significantly after 7 days of placement, and the cathode charge storage decreased slightly after 30 days of placement, but it was still much higher than the bare electrode. Therefore, a neural electrode modified with a two-dimensional material has long-term stability, can meet the needs of chronic implantation, and is suitable for chronic stimulation and long-term recording.

[0094] Experimental Example 5

[0095] In order to test the electrocatalytic activity of a two-dimensional material modified neural electrode described in Example 1, the electrocatalytic performance to H2O2 was evaluated in vitro by linear sweep voltammetry. The specific steps are as follows:

[0096] Sufficient N2 was introduced into 1×PBS phosphate buffer (pH=7.4) to remove dissolved oxygen in the solution.

[0097] The experiments were performed at room temperature using a three-electrode system.

[0098] The platinum electrode was used as the counter electrode, the Ag / AgCl electrode was used as the reference electrode, and a two-dimensional material-modified neural electrode was used as the working electrode. In the control group, a bare electrode without any modification was used as the working electrode.

[0099] The working solutions were 5 ml of 1×PBS solution with N2 flowing in it and 10 ml of 1×PBS solution containing H2O2, respectively. The test was carried out using linear voltammetry.

[0100] Set the potential range to -1.8V to -1.0V.

[0101] Set the scan rate to 50 mV s -1 .

[0102] The current density is the current density at an overpotential of -1.8V.

[0103] See Figure 7 Compared with the bare electrode in 1×PBS solution after passing a certain amount of N2, the introduction of H2O2 increased the negative current in the cyclic voltammetry curve, indicating that both the bare electrode and the neural electrode modified with a two-dimensional material have electrocatalytic activity in catalyzing the decomposition of H2O2. The neural electrode modified with a two-dimensional material can significantly increase the negative current density under overpotential, which is about twice that of the bare electrode, which fully demonstrates that the modified layer of the two-dimensional material has excellent electrocatalytic activity and can improve the signal transmission efficiency and sensitivity.

[0104] Experimental Example 6

[0105] In order to verify the biocompatibility of a neural electrode modified with a two-dimensional material described in Experimental Example 1, a cell activity test was performed on it. The specific steps are as follows:

[0106] 1. Direct contact experiment:

[0107] A 3cm neural electrode modified with a two-dimensional material was placed in a culture dish containing HT-22 neural cells, and the control group was a bare electrode.

[0108] Complete culture medium of HT-22 cell line was added, and the cells were incubated at 37° C. and 5% CO 2 for 24 hours and 48 hours respectively.

[0109] Fluorescence staining was performed using a cytotoxicity assay kit (Beyotime, C2015L) according to the instructions.

[0110] Observe and record the fluorescence staining results to evaluate cell viability and cell death.

[0111] 2. Indirect contact experiment:

[0112] A 3 cm neural electrode modified with a two-dimensional material was completely immersed in the complete culture medium of the HT-22 cell line and incubated for 24 hours to ensure that the electrode material in the culture medium was dissolved. The control group was a bare electrode.

[0113] The culture medium containing the electrode leachate was added to the culture dish containing HT-22 neural cells.

[0114] The cells were incubated at 37°C in a 5% CO2 environment for 12, 24, 36 and 48 hours, respectively.

[0115] Use CCK-8 kit to detect cell viability according to the instructions.

[0116] Measure and record the absorbance value to assess cell viability.

[0117] Figure 8 Compared with bare electrodes, a neural electrode modified with two-dimensional materials has no cytotoxicity. After 48 hours of direct contact with nerve cells, the cell activity is significantly higher, and there is no significant difference in indirect contact, indicating that it has good biocompatibility and safety, will not cause tissue damage and cell apoptosis, and can meet the needs of long-term implantation.

[0118] Experimental Example 7

[0119] In order to verify the recording ability of the neural electrophysiological signals of the two-dimensional material modified neural electrode prepared in Example 1, it was implanted into the hippocampus of Wistar rats, and the control group was implanted with a bare electrode on the contralateral side, and the neural electrophysiological signals were recorded using the Intan in vivo multi-channel recording system.

[0120] See Fig. 9 , respectively, the time domain diagram (left) and power spectrum density diagram (right) of the neural electrophysiological signals recorded by a neural electrode modified with a two-dimensional material and a bare electrode. Compared with the bare electrode, the signal amplitude and power spectrum density recorded by the neural electrode modified with a two-dimensional material have been significantly improved, indicating that it has higher sensitivity and stronger ability to record neural electrophysiological signals.

[0121] Experiments have shown that the electrochemical properties and long-term stability, electrocatalytic activity, biocompatibility, and neural electrophysiological signal recording capability of a two-dimensional material modified neural electrode prepared in Examples 3, 4, and 5 are similar to those of a two-dimensional material modified neural electrode prepared in Example 1.

Claims

1. A method for preparing a neural electrode modified with a two-dimensional material, characterized in that The steps include: 1) roughening the surface of a metal wire with a diameter of 10-200 μm by sandpaper, washing it with deionized water, ultrasonically cleaning it with acetone and anhydrous ethanol in sequence, and drying it to obtain a neural electrode substrate; preparing a polyimide solution as an insulating material solution; 2) immersing the neural electrode substrate in the insulating material solution, taking it out, and drying it, or coating the surface of the neural electrode substrate with the insulating material solution, and drying it; 3) at the proximal end of the neural electrode substrate with an insulating material on the outer surface obtained in step 2), cutting the neural electrode substrate perpendicular to the long axis of the neural electrode substrate with an insulating material on the outer surface to obtain a neural electrode with a cut surface, wherein the cut surface is a recording site; 4) The neural electrode obtained in step (3) is used as a working electrode, a platinum electrode is used as a counter electrode, and Ag / AgCl is used as a reference electrode, and connected to an electrochemical workstation. An aqueous solution of the two-dimensional material with a concentration of 0.05-5 mg / mL is added to the electrolytic cell as an electro-deposition working solution to cover the recording site. The two-dimensional material is uniformly deposited on the surface of the recording site through electrochemical deposition, and the two-dimensional material is rinsed with deionized water and dried to obtain a neural electrode modified with a two-dimensional material.

2. The preparation method according to claim 1, characterized in that The metal is gold, silver, copper, platinum, tungsten, iridium, tantalum, nickel, palladium, chromium, niobium, indium, platinum-iridium alloy, nickel-titanium alloy, tungsten-platinum alloy, nickel-cobalt alloy, chromium-nickel alloy or stainless steel.

3. The preparation method according to claim 1, characterized in that the weight average molecular weight of the polyimide is 10,000-100,000; and the solvent of the polyimide solution is N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetrahydrofuran or acetone.

4. The preparation method according to claim 1, characterized in that The mass concentration of the polyimide solution is 30%-60%.

5. The preparation method according to claim 1, characterized in that The two-dimensional material is MXenes, WSe2, VSe2, WSe2P, Bi2O2Se, SeTe, TiO2, Si3N4, AlN, InSnN, CN, TiN, WS2 or h-BN.

6. The preparation method according to claim 1, characterized in that The electrochemical deposition is constant current deposition, constant voltage deposition or multi-potential step deposition.

7. The preparation method according to claim 5, characterized in that The deposition current of the constant current deposition is 0.005-0.5 mA, and the deposition time is 1-90 s.

8. The preparation method according to claim 5, characterized in that The deposition voltage of the constant voltage deposition is 0.05-3V, and the deposition time is 1-60s.

9. The preparation method according to claim 5, characterized in that The multi-potential step deposition has a step voltage of 0.05-3V and a deposition time of 1-35s.

10. A neural electrode modified with a two-dimensional material prepared by the preparation method of any one of claims 1 to 9.

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