Silk fibroin-based multi-channel flexible nerve interface material for electroencephalogram monitoring and regulation and preparation method of silk fibroin-based multi-channel flexible nerve interface material

Abstract

The invention belongs to the technical field of high polymer material processing and forming, and relates to a silk fibroin-based multi-channel flexible nerve interface material for electroencephalogram monitoring and regulation and a preparation method thereof.The preparation method comprises the steps that firstly, patterned laser scanning is conducted on the surface of a poly (3, 4-ethylenedioxythiophene): polystyrolsulfon acid (PEDOT: PSS) membrane, and PEDOT and PSS on a pattern scanned through laser are separated; then developing the PEDOT: PSS film subjected to laser scanning by adopting water as a developing solution to obtain a patterned PEDOT film; finally, a silk fibroin solution is poured on the surface of the patterned PEDOT film, and after the silk fibroin solution is dried and formed, the silk fibroin-based multi-channel flexible nerve interface material is obtained. The silk fibroin-based multi-channel flexible nerve interface material comprises a silk fibroin film substrate and a patterned PEDOT film deposited on the surface of the silk fibroin film substrate. The preparation process is simple and convenient, the consumed time is short, and the patterning precision is high; the prepared silk fibroin-based multi-channel flexible nerve interface material has good conductivity and flexibility, and has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer material processing and forming, and relates to a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation and a preparation method thereof. Background Art

[0002] Electroencephalogram (EEG) monitoring and regulation are of great significance for the diagnosis, treatment, and pathological research of neurological diseases (such as Parkinson's disease, epilepsy, etc.). Integrating multi-channel conductive patterns on the surface of a silk fibroin substrate using micro-nano processing technology has become an effective strategy for preparing silk fibroin-based flexible neural interface devices for EEG monitoring and regulation. Such neural interface devices are highly favored due to their excellent biocompatibility. At the same time, their good flexibility also helps to reduce the damage to surrounding tissues during implantation and can significantly improve the efficiency of neural signal acquisition. Among many conductor materials, poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is regarded as a highly potential conductive polymer material for manufacturing implantable electronic devices due to its good electrochemical stability and mechanical flexibility. However, due to the precision limitations of existing processing technologies and the inherent water-soluble characteristics of PEDOT:PSS, there are still technical challenges in firmly integrating high-resolution PEDOT:PSS patterns on a silk fibroin substrate, which is directly related to the in-vivo stability of neural interface devices and the accuracy of signal acquisition.

[0003] Traditionally, metal vapor deposition has been widely used to integrate conductive patterns on a silk fibroin substrate, and commonly used metals include gold, silver, and platinum nanoparticles. However, considering that neural interface devices are long-term in a highly humid environment in the living body, these metal electrodes are prone to breakage or corrosion, which will lead to the degradation of device performance. In contrast, due to its polymer long-chain structure, PEDOT:PSS exhibits more excellent electrochemical stability and flexibility than metal nanoparticles. So far, the reported methods for integrating PEDOT:PSS patterns on a silk fibroin substrate include photolithography modification technology, electrochemical deposition, and inkjet printing technology. The development of these methods is of great significance for improving the performance and reliability of neural interface devices. However, they still have some deficiencies.

[0004] For example, patent CN202011512381.3 discloses a method for reducing the resistance of conductive polymer PEDOT:PSS based on femtosecond laser modification. The method uses a femtosecond laser to focus on the surface of the PEDOT:PSS film, adjusts the matching relationship between the laser processing parameters and the laser scanning processing path, and uses the characteristic that the stability of PSS molecules is not as good as that of PEDOT molecules. The relative content of insulating PSS is reduced without causing significant damage to the conductive PEDOT, thereby thinning the PSS shell in PEDOT:PSS and enhancing the conductivity of the PEDOT:PSS film material. However, the patent only explains that the use of laser treatment can reduce the relative content of PSS in PEDOT:PSS, thereby improving its conductivity, but does not perform subsequent development and patterning of the treated PEDOT:PSS.

[0005] Patent CN202310512558.7 discloses a silk fibroin conductive film material and its heat-assisted stripping process. By inducing the mutual entanglement between silk fibroin molecules and PEDOT molecules through heat-temperature, the PEDOT:PSS conductive layer prepared by inkjet printing is transferred to the surface of the silk fibroin substrate to prepare a silk fibroin conductive film material with excellent electrical properties. However, the inkjet printing method described in the patent has the defects of being time-consuming and having a low PSS material removal rate. In addition, the inkjet process is greatly affected by environmental, voltage and other conditions, which can easily lead to the problem of low resolution of the PEDOT:PSS pattern. It is observed that the width of the PEDOT:PSS pattern in the patent is 350μm, which needs to be further refined.

[0006] Reference 1 (ACS Appl. Mater. Interfaces 2017, 9, 19231-19237) reports an innovative photopolymerization supramolecular method for modifying PEDOT:PSS. This method enhances the sensitivity of PEDOT:PSS to ultraviolet light by introducing the photopolymerizable diacetylene monomer 2-pentacyl-10,12-diacetylene amide ethyl sulfate. Under ultraviolet light irradiation, the water stability of specific regions of PEDOT:PSS increases, while the unirradiated parts retain their original water solubility, thereby achieving precise ultraviolet lithography of PEDOT:PSS materials. This technological advancement provides an effective way to pattern PEDOT:PSS. However, in actual operation, the diacetylene monomer PCDSA itself has the function of cross-linking PEDOT:PSS materials. After the introduction of the photopolymerizable diacetylene monomer PCDSA, PEDOT:PSS becomes water-insoluble even without ultraviolet light in a short period of time, making subsequent patterning difficult. In addition, the biocompatibility of the diacetylene monomer PCDSA in vivo remains to be verified.

[0007] Reference 2 (Adv. Mater. 2019, 31, 1902869) proposed an electrochemical gelation method for rapidly patterning conductive PEDOT:PSS hydrogels on a sacrificial metal layer conductive template. In the experiment, copper was selected as the sacrificial metal, and by adjusting the concentration and volume of the PEDOT:PSS electrolyte, the thickness and mechanical properties of the hydrogel could be precisely controlled, providing a new approach for manufacturing high-performance conductive hydrogels. However, due to the need for a conductive template and the intrinsically non-conductive property of silk fibroin, this method is difficult to be used for constructing silk fibroin-based flexible neural interfaces. In addition, the precision of the PEDOT:PSS hydrogel also needs to be improved.

[0008] Although the above PEDOT:PSS patterning technology has made certain progress in terms of process and improving the conductivity of PEDOT, the precision of its PEDOT:PSS pattern is still insufficient, and whether it can construct neural interface devices for electroencephalogram monitoring and regulation has not been demonstrated yet.

[0009] Therefore, it is of great significance to study a preparation method of silk fibroin-based multi-channel flexible neural interface materials for electroencephalogram monitoring and regulation to solve the problems existing in the prior art. Summary of the Invention

[0010] The object of the present invention is to solve the problems existing in the prior art and provide a preparation method of silk fibroin-based multi-channel flexible neural interface materials for electroencephalogram monitoring and regulation.

[0011] To achieve the above object, the technical scheme adopted by the present invention is as follows:

[0012] A preparation method of silk fibroin-based multi-channel flexible neural interface materials for electroencephalogram monitoring and regulation. First, pattern laser scanning is performed on the surface of the PEDOT:PSS film, and phase separation occurs between PEDOT and PSS on the pattern scanned by the laser; then water is used as the developer to develop the PEDOT:PSS film after laser scanning to obtain a patterned PEDOT thin film; finally, a silk fibroin solution is poured on the surface of the patterned PEDOT thin film, and after the silk fibroin solution dries and forms, silk fibroin-based multi-channel flexible neural interface materials for electroencephalogram monitoring and regulation are obtained.

[0013] The femtosecond laser method disclosed in the prior art (the femtosecond laser has short pulses and high energy) induces an increase in the oxidation level of PEDOT through an annealing effect, promotes the benzene-quinone structure transformation of PEDOT molecules, and thus improves the conductivity of PEDOT:PSS. Although the femtosecond laser can make the PSS shell in PEDOT:PSS thinner (the reason for thinning is that part of the PSS is carbonized), there is still PSS wrapping PEDOT, and the PEDOT:PSS after femtosecond laser treatment is still water-soluble, unable to be developed subsequently, and a patterned PEDOT thin film cannot be obtained; therefore, the femtosecond laser method of the prior art cannot be used to integrate PEDOT patterns on a silk fibroin substrate.

[0014] In the present invention, PEDOT:PSS is scanned by laser scanning (long pulses, low energy) to weaken the Coulomb force between PEDOT and PSS, thereby realizing the phase separation of PEDOT and PSS (that is, completely removing the PSS shell, and only a little PSS exists inside PEDOT). After laser scanning, most of the PSS in PEDOT:PSS is separated. The PEDOT film after separating PSS is a water-insoluble material. After developing and dissolving PEDOT:PSS and the separated PSS, patterning can be achieved (that is, obtaining a patterned PEDOT thin film). After preparing a patterned PEDOT thin film on a polymer substrate in the present invention, the patterned PEDOT thin film is then transferred to a silk fibroin substrate to prepare a silk fibroin-based multi-channel flexible neural interface material.

[0015] As a preferred technical solution:

[0016] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is as described above, and the specific steps are as follows:

[0017] (1) Preparation of PEDOT:PSS film;

[0018] The PEDOT:PSS dispersion with a concentration of 4 - 12 mg / mL is uniformly cast on a polymer substrate by a casting method, and then dried into a film by heating in an oven until the PEDOT:PSS dispersion is dried to obtain a PEDOT:PSS film;

[0019] (2) Preparation of silk fibroin solution;

[0020] The degummed silk is obtained by boiling the silk fiber in a sodium bicarbonate solution for degumming, and then the degummed silk is dissolved in a 9.3 M lithium bromide solution, dialyzed with deionized water, and finally the concentration of the silk fibroin solution is adjusted (the solvent during adjustment is deionized water) to obtain a silk fibroin solution with a concentration of 1 - 15 wt.%. If the concentration of the silk fibroin solution exceeds this range, it will become flocculent (non-solution state);

[0021] (3) Laser-scan the PEDOT:PSS film;

[0022] Use a Venus LaserPro C180II instrument to perform a patterned laser scan on the surface of the PEDOT:PSS film. The laser power is 20 - 50 W. After one scan, a scanned pattern appears on the PEDOT:PSS film.

[0023] (4) Develop the PEDOT:PSS film with water to obtain a patterned PEDOT thin film.

[0024] (5) Pour a silk fibroin solution with a concentration of 1 - 15 wt.% on the surface of the patterned PEDOT thin film. After the silk fibroin solution dries and forms, remove the polymer substrate to obtain a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation.

[0025] Since the silk fibroin molecules and PEDOT molecules are combined through intermolecular forces and intermolecular entanglement forces, and this binding force is much greater than the binding force between PEDOT and the polymer substrate, the patterned PEDOT thin film can be transferred from the polymer substrate to the silk fibroin-based substrate layer, and then a silk fibroin-based multi-channel flexible neural interface material with silk fibroin as the substrate and PEDOT as the electrode can be prepared.

[0026] For the preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation as described above, in step (1), the material of the polymer substrate is polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), or polyimide (PI).

[0027] For the preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation as described above, in step (1), the temperature of oven heating is 20 - 120 °C, and the time is 30 min.

[0028] For the preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation as described above, in step (1), the PEDOT:PSS dispersion is a pure PEDOT:PSS dispersion or a PEDOT:PSS derivative dispersion; the PEDOT:PSS derivative is one or more of poly(3,4-ethylenedioxythiophene) grafted phosphocholine: polystyrene sulfonic acid (PEDOT-PC:PSS), poly(3,4-ethylenedioxythiophene) grafted amino: polystyrene sulfonic acid (PEDOT-NH 2 :PSS), and poly(3,4-ethylenedioxythiophene) grafted hydroxyl: polystyrene sulfonic acid (PEDOT-OH:PSS).

[0029] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation as described above, in step (2), the dosage ratio of the lithium bromide solution to the degummed silk is 5-10 mL: 1 g.

[0030] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation as described above, in step (4), water is used to develop the PEDOT:PSS film. After obtaining the patterned PEDOT film, the developed PEDOT film is soaked in ethylene glycol for 5-30 min, and then washed with water to remove PSS and ethylene glycol and air-dried.

[0031] Principle of developing the PEDOT:PSS film: The PEDOT:PSS film is a water-soluble material. Laser can induce phase separation of PEDOT and PSS molecules. The PEDOT film after separating PSS is a water-insoluble material. The un-scanned PEDOT:PSS dissolves in water, while the PEDOT:PSS pattern scanned by laser still remains on the polymer substrate. However, in the present invention, the surface of the PEDOT:PSS film is scanned by laser, and there is still un-separated PEDOT:PSS inside the obtained patterned PEDOT film. Since water has low polarity and cannot enter the inside of the patterned PEDOT film to dissolve the un-separated PEDOT:PSS, ethylene glycol has high polarity and can enter the inside of the patterned PEDOT film to weaken the Coulomb force between PEDOT and PSS in PEDOT:PSS and dissolve PSS. After that, PSS and ethylene glycol are removed by washing with water, and a patterned PEDOT film with higher purity can be obtained.

[0032] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation as described above, in step (5), the drying and forming temperature is 20-80 °C, and the time is 20-60 min.

[0033] The present invention also provides a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation prepared by the method as described in any one of the above, including a silk fibroin film substrate and a patterned PEDOT film deposited on its surface;

[0034] The thickness of the silk fibroin substrate is 20-100 μm, the thickness of the patterned PEDOT film is 1-10 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 120-300 μm, with high precision;

[0035] The sheet resistance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 1×10 1 ~2×10 2 Ω, and the Young's modulus under 100% relative humidity is 20-100 MPa.

[0036] Beneficial effects:

[0037] (1) The preparation method of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation of the present invention can be used for quickly and precisely patterning PEDOT:PSS and its derivative materials, and preparing the silk fibroin-based multi-channel flexible neural interface; the preparation process is simple, time-consuming is short, and the patterning accuracy is high;

[0038] (2) The silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation of the present invention has good electrical conductivity and good flexibility, and has good application prospects. Description of the drawings

[0039] Figure 1 It is a schematic structural diagram of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation;

[0040] Figure 2 It is a schematic diagram of the surface of the patterned PEDOT film after being washed with water and air-dried;

[0041] Figure 3 It is a schematic diagram of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation;

[0042] Figure 4 It is an XPS diagram of the patterned PEDOT film of Comparative Example 1;

[0043] Figure 5 It is an XPS diagram of the patterned PEDOT film of Example 1 (not soaked in ethylene glycol for 30 min);

[0044] Among them, 1 is a silk fibroin film substrate, and 2 is a patterned PEDOT film. Specific embodiments

[0045] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0046] The test methods for the performance indicators in the embodiments and comparative examples of the present invention are as follows:

[0047] Sheet resistance: The sheet resistance Rs (Ω) of the sample surface was measured using a Keithley 236 precision digital multimeter and the four-probe method. The sample was cut into a size of 2 cm × 0.5 cm and placed on a four-probe stage. The four probes were made to contact the sample surface and were arranged in a straight line. The distance between adjacent probes was 0.5 cm. The measurement was carried out by the Keithley 236 precision digital multimeter, and the sheet resistance value Rs of the sample could be directly read on the digital display screen.

[0048] Young's modulus: Tensile tests of the samples were performed in a wet environment using a universal tensile tester (Instron 5969, USA). All samples were pre-soaked in deionized water for 5 min to ensure sufficient wetting. The sensor used for the test was 10 N, and the tensile rate was 2 mm / min. Young's modulus was calculated based on the slope of the straight line within the strain range of 0 - 0.5%.

[0049] Ratio of PEDOT:PSS: Although both PEDOT and PSS contain S elements, the S in PEDOT exists in the form of a thiophene ring, while the S in PSS exists in the form of a sulfonic acid group. Therefore, the relative ratio of PEDOT and PSS can be indirectly reflected by XPS analysis. Among them, the larger the ratio of PEDOT:PSS, the greater the degree of phase separation of PEDOT and PSS molecules.

[0050] The sources of some substances in the present invention are as follows:

[0051] PC: Phosphorylcholine, CAS: 107 - 73 - 3, Guide Chemical Industry.

[0052] Polyethylene terephthalate: T60 from Toray Industries, Inc., Japan.

[0053] Polydimethylsiloxane: Sylgard 184 from Dow Corning Corporation.

[0054] Polyimide: Kapton 100HN from DuPont Company.

[0055] Example 1

[0056] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation, the specific steps are as follows:

[0057] (1) Preparation of PEDOT:PSS film;

[0058] A pure PEDOT:PSS dispersion with a concentration of 12 mg / mL was evenly cast on a polymer substrate made of polyethylene terephthalate by the casting method, and then dried into a film in an oven at 60 °C for 30 min to obtain a PEDOT:PSS film.

[0059] (2) Preparation of silk fibroin solution;

[0060] The degummed silk was obtained by boiling the silk fiber in a 0.5% sodium bicarbonate solution for degumming, and then the degummed silk was dissolved in 9.3M lithium bromide solution. After dialysis with deionized water, the silk fibroin solution was prepared. Finally, the concentration of the silk fibroin solution was adjusted to obtain a silk fibroin solution with a concentration of 5 wt.%;

[0061] Among them, the dosage ratio of lithium bromide solution to degummed silk is 10 mL:1 g;

[0062] (3) Laser scanning of PEDOT:PSS film;

[0063] The surface of the PEDOT:PSS film was subjected to one-time patterned laser scanning with a laser power of 50 W;

[0064] (4) After developing the PEDOT:PSS film with water to obtain a patterned PEDOT film, the developed PEDOT film was soaked in ethylene glycol for 30 min, and then washed with water and air-dried; The patterned PEDOT film after washing with water and air-drying is as Figure 2 shown. The PEDOT:PSS that has not been laser-scanned is dissolved in water, while the laser-scanned PEDOT:PSS pattern remains on the polymer substrate;

[0065] As Figure 5 shown, when laser-scanned at 50 W without ethylene glycol soaking treatment, in the XPS spectrum, the slanted area represents the PEDOT content, and the square grid area represents the PSS content. The areas of each region were integrated separately, and the ratio of PEDOT to PSS obtained by dividing the former by the latter is 0.95;

[0066] After XPS analysis and fitting, the ratio of PEDOT to PSS in the patterned PEDOT film after soaking in ethylene glycol for 30 min is 1.52;

[0067] (5) Pour the silk fibroin solution in step (2) onto the surface of the patterned PEDOT film. After the silk fibroin solution is dried and formed at 60 °C for 30 min, a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is obtained.

[0068] As Figure 1 、 Figure 3As shown in the figure, the finally prepared silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate 1 and a patterned PEDOT film 2 deposited on its surface; the thickness of the silk fibroin substrate is 25 μm, the thickness of the patterned PEDOT film 2 is 2 μm, and the width of the widest part of the pattern in the patterned PEDOT film 2 is 120 μm; the sheet resistance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 10 Ω, and the Young's modulus at 100% relative humidity is 25 MPa.

[0069] Comparative Example 1

[0070] A preparation method of a silk fibroin-based multi-channel flexible neural interface material is basically the same as that of Example 1, except that: step (3) laser scanning and step (4) operation are omitted.

[0071] The sheet resistance of the silk fibroin-based multi-channel flexible neural interface material is 200 Ω, and the Young's modulus at 100% relative humidity is 25 MPa.

[0072] As Figure 4 shown, when not undergoing laser scanning and not undergoing ethylene glycol immersion treatment, in the XPS diagram, the slanted area represents the PEDOT content, and the square grid area represents the PSS content. Integrating the areas of each region respectively, and dividing the former by the latter can obtain the ratio of PEDOT to PSS as 0.48.

[0073] Comparing Comparative Example 1 with Example 1, it can be found that the ratio of PEDOT to PSS in the patterned PEDOT film of Comparative Example 1 significantly decreases, while the sheet resistance of the silk fibroin-based multi-channel flexible neural interface material increases. This is because there is a strong Coulomb force between PEDOT and PSS. Without laser scanning and ethylene glycol immersion, PEDOT and PSS will not phase separate. Therefore, the ratio of PEDOT to PSS decreases. In addition, PSS is intrinsically non-conductive, and the PSS content in Comparative Example 1 is higher than that in Example 1, resulting in an increase in the sheet resistance of the silk fibroin-based multi-channel flexible neural interface material. The Young's modulus at 100% relative humidity does not change because the Young's modulus of the silk fibroin-based multi-channel flexible neural interface mainly comes from silk fibroin and has little correlation with PEDOT and PSS.

[0074] Comparative Example 2

[0075] A preparation method of a silk fibroin-based multi-channel flexible neural interface material is basically the same as that of Example 1, except that: step (3) laser scanning operation is omitted, that is, patterning cannot be achieved.

[0076] After XPS analysis and fitting, the ratio of PEDOT to PSS in the PEDOT film is 1.04.

[0077] Comparing Comparative Example 2 with Example 1, it can be found that in Comparative Example 2, the ratio of PEDOT to PSS in the PEDOT film becomes smaller. This is because both laser scanning and ethylene glycol immersion can promote the phase separation between PEDOT and PSS, thereby increasing the ratio of PEDOT to PSS. Compared with Example 1, Comparative Example 2 omits the laser scanning operation in step (3), so the ratio of PEDOT to PSS in the PEDOT film becomes smaller.

[0078] Example 2

[0079] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is basically the same as that of Example 1, except that: in step (3), the laser power is 20 W, and in step (4), the ethylene glycol immersion time is 5 min; after XPS analysis and fitting, the ratio of PEDOT:PSS in the patterned PEDOT film is 0.51.

[0080] The finally prepared silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 25 μm, the thickness of the patterned PEDOT film is 2 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 300 μm; the sheet resistance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 180 Ω, and the Young's modulus at 100% relative humidity is 25 MPa.

[0081] Example 3

[0082] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is basically the same as that of Example 1, except that: in step (3), the laser power is 30 W, and in step (4), the ethylene glycol immersion time is 10 min; after XPS analysis and fitting, the ratio of PEDOT:PSS in the patterned PEDOT film is 0.88.

[0083] The finally prepared silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 25 μm, the thickness of the patterned PEDOT film is 2 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 210 μm; the sheet resistance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 100 Ω, and the Young's modulus at 100% relative humidity is 25 MPa.

[0084] Example 4

[0085] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is basically the same as that of Example 1, except that: in step (3), the laser power is 40 W, and in step (4), the soaking time in ethylene glycol is 20 min; after XPS analysis and fitting, the ratio of PEDOT:PSS in the patterned PEDOT film is 1.3.

[0086] The finally prepared silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 25 μm, the thickness of the patterned PEDOT film is 2 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 180 μm; the square impedance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 50 Ω, and the Young's modulus under 100% relative humidity is 25 MPa.

[0087] Example 5

[0088] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is as follows:

[0089] (1) Preparation of PEDOT:PSS film;

[0090] The PEDOT-PC:PSS dispersion (the molar ratio of PEDOT to PC is 1:2) with a concentration of 4 mg / mL is uniformly cast on a polymer substrate made of polydimethylsiloxane by the casting method, and then dried into a film by heating in an oven at 40 °C for 30 min, so as to obtain the PEDOT:PSS film;

[0091] (2) Preparation of silk fibroin solution;

[0092] The degummed silk is obtained by boiling and degumming silk fibers with a 0.5% sodium bicarbonate solution by mass fraction, and then the degummed silk is dissolved with a 9.3 M lithium bromide solution, dialyzed with deionized water, and finally the concentration of the silk fibroin solution is adjusted to obtain a silk fibroin solution with a concentration of 1 wt.%;

[0093] Among them, the dosage ratio of the lithium bromide solution to the degummed silk is 10 mL:1 g;

[0094] (3) Laser scanning of the PEDOT:PSS film;

[0095] The surface of the PEDOT:PSS film is subjected to a single patterning laser scan with a laser power of 30 W;

[0096] (4) After developing the PEDOT:PSS film with water to obtain a patterned PEDOT film, soak the developed PEDOT film in ethylene glycol for 10 min, then wash with water and air dry;

[0097] After XPS analysis and fitting, the ratio of PEDOT to PSS in the patterned PEDOT film without ethylene glycol soaking is 0.51, and the ratio of PEDOT to PSS in the patterned PEDOT film is 0.87;

[0098] (5) Pour the silk fibroin solution in step (2) onto the surface of the patterned PEDOT film. After the silk fibroin solution dries and forms for 55 min at a temperature of 30 °C, a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is obtained.

[0099] The finally prepared silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 20 μm, the thickness of the patterned PEDOT film is 1 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 210 μm; the square impedance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 100 Ω, and the Young's modulus at 100% relative humidity is 20 MPa.

[0100] Example 6

[0101] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation, the specific steps are as follows:

[0102] (1) Preparation of PEDOT:PSS film;

[0103] The PEDOT-NH 2 :PSS dispersion (the molar ratio of PEDOT to -NH 2 is 1:2) is uniformly poured onto a polymer substrate made of polyimide, and then heated in an oven at 60 °C for 30 min until the PEDOT-NH 2 :PSS dispersion dries into a film, thereby obtaining a PEDOT:PSS film;

[0104] (2) Preparation of silk fibroin solution;

[0105] The silk fiber is degummed by boiling in a sodium bicarbonate solution with a mass fraction of 0.5% to obtain degummed silk, and then the degummed silk is dissolved with a 9.3 M lithium bromide solution. After dialysis with deionized water, a silk fibroin solution is obtained. Finally, the concentration of the silk fibroin solution is adjusted to obtain a silk fibroin solution with a concentration of 5 wt.%;

[0106] Among them, the dosage ratio of the lithium bromide solution to the degummed silk is 5 mL:1 g;

[0107] (3) Laser scanning of the PEDOT:PSS film;

[0108] Perform one-time patterned laser scanning on the surface of the PEDOT:PSS film, with a laser power of 40 W;

[0109] (4) Develop the PEDOT:PSS film with water. After obtaining the patterned PEDOT film, soak the developed PEDOT film in ethylene glycol for 20 min, then wash it with water and air-dry it;

[0110] After XPS analysis and fitting, the ratio of PEDOT to PSS in the patterned PEDOT film without ethylene glycol soaking is 0.84, and the ratio of PEDOT to PSS in the patterned PEDOT film is 1.31;

[0111] (5) Pour the silk fibroin solution in step (2) on the surface of the patterned PEDOT film. After the silk fibroin solution dries and forms at 40 °C for 50 min, a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is obtained.

[0112] The finally prepared silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 25 μm, the thickness of the patterned PEDOT film is 1.2 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 180 μm; the square impedance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 45 Ω, and the Young's modulus under 100% relative humidity is 30 MPa.

[0113] Example 7

[0114] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation, the specific steps are as follows:

[0115] (1) Preparation of the PEDOT:PSS film;

[0116] Adopt the casting method to uniformly pour a PEDOT-OH:PSS dispersion solution with a concentration of 8 mg / mL (the molar ratio of PEDOT to -OH is 1:2) on a polymer substrate made of polyimide, and then use an oven at 80 °C to heat for 30 min until the PEDOT-OH:PSS dispersion solution dries into a film, thereby obtaining the PEDOT:PSS film;

[0117] (2) Preparation of the silk fibroin solution;

[0118] The degummed silk is prepared by boiling degumming the silk fiber with a sodium bicarbonate solution with a mass fraction of 0.5%. Then, the degummed silk is dissolved with a 9.3 M lithium bromide solution, and after dialysis with deionized water, a silk fibroin solution is obtained. Finally, the concentration of the silk fibroin solution is adjusted to obtain a silk fibroin solution with a concentration of 15 wt.%.

[0119] Among them, the dosage ratio of the lithium bromide solution to the degummed silk is 5 mL:1 g.

[0120] (3) Laser scanning the PEDOT:PSS film;

[0121] Perform one - time patterned laser scanning on the surface of the PEDOT:PSS film, and the laser power is 50 W.

[0122] (4) Use water to develop the PEDOT:PSS film. After obtaining the patterned PEDOT film, soak the developed PEDOT film in ethylene glycol for 30 min, and then wash it with water and air - dry it.

[0123] After XPS analysis and fitting, the ratio of PEDOT to PSS in the patterned PEDOT film without ethylene glycol soaking is 0.90, and the ratio of PEDOT to PSS in the patterned PEDOT film is 1.5.

[0124] (5) Pour the silk fibroin solution in step (2) onto the surface of the patterned PEDOT film. After the silk fibroin solution is dried and formed at 50 °C for 45 min, a silk fibroin - based multi - channel flexible neural interface material for electroencephalogram monitoring and regulation is obtained.

[0125] The finally prepared silk fibroin - based multi - channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 100 μm, the thickness of the patterned PEDOT film is 1.6 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 120 μm; the sheet resistance of the silk fibroin - based multi - channel flexible neural interface material for electroencephalogram monitoring and regulation is 20 Ω, and the Young's modulus at 100% relative humidity is 100 MPa.

[0126] Example 8

[0127] A preparation method of a silk fibroin - based multi - channel flexible neural interface material for electroencephalogram monitoring and regulation, the specific steps are as follows:

[0128] (1) Preparation of the PEDOT:PSS film;

[0129] The pure PEDOT:PSS dispersion with a concentration of 10 mg / mL was evenly cast on a polymer substrate made of polydimethylsiloxane by the casting method, and then dried into a film in an oven at 100 °C for 30 min until the pure PEDOT:PSS dispersion was dried, thereby obtaining the PEDOT:PSS film;

[0130] (2) Preparation of the silk fibroin solution;

[0131] The degummed silk was obtained by boiling the silk fiber in a 0.5% sodium bicarbonate solution to remove the gum, and then the degummed silk was dissolved in a 9.3 M lithium bromide solution. After dialysis with deionized water, the silk fibroin solution was obtained. Finally, the concentration of the silk fibroin solution was adjusted to obtain a silk fibroin solution with a concentration of 5 wt.%;

[0132] Among them, the dosage ratio of the lithium bromide solution to the degummed silk is 8 mL:1 g;

[0133] (3) Laser scanning of the PEDOT:PSS film;

[0134] The surface of the PEDOT:PSS film was subjected to a single patterning laser scan with a laser power of 20 W;

[0135] (4) The PEDOT:PSS film was developed with water. After obtaining the patterned PEDOT film, the developed PEDOT film was soaked in ethylene glycol for 5 min, and then washed with water and air-dried;

[0136] After XPS analysis and fitting, the ratio of PEDOT to PSS in the patterned PEDOT film without ethylene glycol soaking was 0.57, and the ratio of PEDOT to PSS in the patterned PEDOT film was 0.58;

[0137] (5) The silk fibroin solution in step (2) was cast on the surface of the patterned PEDOT film. After the silk fibroin solution was dried and formed at 60 °C for 40 min, a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation was obtained.

[0138] The finally obtained silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 25 μm, the thickness of the patterned PEDOT film is 1.8 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 300 μm; the square impedance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 150 Ω, and the Young's modulus at 100% relative humidity is 28 MPa.

[0139] Example 9

[0140] A preparation method of a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation, the specific steps are as follows:

[0141] (1) Preparation of PEDOT:PSS film;

[0142] The pure PEDOT:PSS dispersion with a concentration of 12 mg / mL is uniformly cast on a polymer substrate made of polyethylene terephthalate by the casting method, and then dried into a film in an oven at 120 °C for 30 min until the pure PEDOT:PSS dispersion is dried into a film, thereby obtaining the PEDOT:PSS film;

[0143] (2) Preparation of silk fibroin solution;

[0144] The degummed silk is obtained by boiling the silk fiber in a 0.5% sodium bicarbonate solution for degumming, and then the degummed silk is dissolved in a 9.3 M lithium bromide solution, dialyzed with deionized water, and finally the concentration of the silk fibroin solution is adjusted to obtain a silk fibroin solution with a concentration of 10 wt.%;

[0145] Among them, the dosage ratio of the lithium bromide solution to the degummed silk is 8 mL:1 g;

[0146] (3) Laser scanning of the PEDOT:PSS film

[0147] The surface of the PEDOT:PSS film is subjected to one-time patterned laser scanning with a laser power of 50 W;

[0148] (4) The PEDOT:PSS film is developed with water, and after obtaining the patterned PEDOT film, the developed PEDOT film is soaked in ethylene glycol for 30 min, and then washed with water and air-dried;

[0149] After XPS analysis and fitting, the ratio of PEDOT to PSS in the patterned PEDOT film without ethylene glycol soaking is 0.90, and the ratio of PEDOT to PSS in the patterned PEDOT film is 1.52;

[0150] (5) The silk fibroin solution in step (2) is cast on the surface of the patterned PEDOT film. After the silk fibroin solution is dried and formed at 80 °C for 20 min, a silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is obtained.

[0151] The finally obtained silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on its surface; the thickness of the silk fibroin substrate is 50 μm, the thickness of the patterned PEDOT film is 2 μm, and the width of the widest part of the pattern in the patterned PEDOT film is 120 μm; the square impedance of the silk fibroin-based multi-channel flexible neural interface material for electroencephalogram monitoring and regulation is 15 Ω, and the Young's modulus under 100% relative humidity is 60 MPa.

Claims

1. A method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation, characterized in that: First, the surface of the PEDOT:PSS film is patterned by laser scanning, and PEDOT and PSS are phase separated on the laser scanned pattern; then, water is used as a developer to develop the laser-scanned PEDOT:PSS film to obtain a patterned PEDOT film; finally, a silk fibroin solution is poured on the surface of the patterned PEDOT film, and after the silk fibroin solution is dried and formed, a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation is obtained.

2. The method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation according to claim 1, characterized in that: The specific steps are as follows: (1) Preparation of PEDOT:PSS membrane; A PEDOT:PSS dispersion having a concentration of 4 to 12 mg / mL is uniformly cast on a polymer substrate by a casting method, and then heated in an oven until the PEDOT:PSS dispersion is dried to form a film, thereby preparing a PEDOT:PSS film; (2) Preparation of silk fibroin solution; The silk fibers are degummed by boiling with a sodium bicarbonate solution to obtain degummed silk, and then the degummed silk is dissolved with a 9.3M lithium bromide solution, and a silk fibroin solution is obtained after dialyzing with deionized water, and finally the concentration of the silk fibroin solution is adjusted to obtain a silk fibroin solution with a concentration of 1 to 15 wt.%; (3) Laser scanning of PEDOT:PSS film; The surface of the PEDOT:PSS film was subjected to a patterned laser scan with a laser power of 20 to 50 W; (4) developing the PEDOT:PSS film using water to obtain a patterned PEDOT film; (5) A silk fibroin solution with a concentration of 1 to 15 wt.% is poured on the surface of the patterned PEDOT film, and after the silk fibroin solution is dried and formed, a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation is obtained.

3. The method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation according to claim 2, characterized in that: In step (1), the material of the polymer substrate is polyethylene terephthalate, polydimethylsiloxane or polyimide.

4. The method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation according to claim 2, characterized in that: In step (1), the oven is heated at a temperature of 20 to 120° C. for 30 minutes.

5. The method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation according to claim 2, characterized in that: In step (1), the PEDOT:PSS dispersion is a pure PEDOT:PSS dispersion or a PEDOT:PSS derivative dispersion; the PEDOT:PSS derivative is one or more of PEDOT-PC:PSS, PEDOT-NH2:PSS and PEDOT-OH:PSS.

6. The method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation according to claim 2, characterized in that: In step (2), the ratio of lithium bromide solution to degummed silk is 5-10 mL: 1 g.

7. The method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation according to claim 2, characterized in that: In step (4), the PEDOT:PSS film is developed with water to obtain a patterned PEDOT film, and then the developed PEDOT film is soaked in ethylene glycol for 5 to 30 minutes, and then washed with water and air-dried.

8. The method for preparing a silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation according to claim 2, characterized in that: The drying temperature in step (5) is 20 to 80° C. and the drying time is 20 to 60 minutes.

9. A silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation, prepared by the method according to any one of claims 1 to 8, characterized in that: A silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation includes a silk fibroin film substrate and a patterned PEDOT film deposited on the surface thereof; The thickness of the silk fibroin substrate is 20 to 100 μm, the thickness of the patterned PEDOT film is 1 to 10 μm, and the widest width of the pattern in the patterned PEDOT film is 120 to 300 μm; The square impedance of the silk fibroin-based multi-channel flexible neural interface material for EEG monitoring and regulation is 1×10 1 ~2×10 2 Ω, and the Young's modulus at 100% relative humidity is 20 to 100 MPa.

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