A choline acrylate modified protein hydrogel brain-computer interface electrode and a preparation method and application thereof
Patent Information
- Application Number
- CN202610703420.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-21
- Publication Date
- 2026-08-21
AI Technical Summary
干电极常因为体位的移动而带来较大的电压偏移和佩戴舒适性差等问题，使其在脑电信号的采集过程中受到一定限制
[0040]本发明提供的一种基于胆碱丙烯酸酯修饰的蛋白水凝胶脑机接口电极及其制备方法和应用，使用高生物活性胆碱离子液体作为该水凝胶电极离子导电单元，具有稳定的离子导电传输通道；蛋白高分子材料为该水凝胶电极主体水凝胶网络，具备良好生物相容性和可调的机械稳定性；由胆碱丙烯酸酯修饰的蛋白水凝胶电极制备方法简单、材料易得、成本低廉、穿戴安全、佩戴舒适性好和易于规模化生产等特点，在脑机接口领域脑电信号采集方向亦有广阔应用前景。本发明的蛋白水凝胶电极具备导电活性高、生物活性高、长期佩戴舒适性好。基于胆碱丙烯酸酯修饰的蛋白水凝胶电极在制备过程中，成本低廉、材料来源广泛、且便于大规模生产。基于本发明的蛋白水凝胶电极，能够便携、长时效、安全地进行非植入式脑电信号的采集。使得本发明的蛋白水凝胶电极在工业安全生产、脑认知状态评估等脑机接口领域应用广泛。
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Figure CN122604385A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomaterials technology, and relates to a protein hydrogel brain-computer interface electrode based on choline acrylate modification, its preparation method and application. Background Technology
[0002] Brain-computer interface (BCI) electrodes can be classified into implantable and non-implantable types based on their acquisition location. Implantable BCI electrodes require insertion into the skull, directly or indirectly contacting brain tissue. This necessitates minimally invasive or invasive implantation surgery, which often poses potential biosafety risks to research subjects and animals. While implantable BCI electrodes hold significant scientific value in research on neurological diseases such as stroke, ALS, and Alzheimer's disease, they also face severe challenges in electrode material preparation, processing, and implantation. Furthermore, in other BCI application areas such as industrial safety production and cognitive status assessment, implantable BCI electrodes face challenges in large-scale production and application due to concerns about biosafety, low public acceptance, and ethical limitations.
[0003] To acquire EEG signals from research individuals more safely, effectively, and conveniently, the development of non-implantable brain-computer interface (BCI) electrode technology is urgently needed. Researchers, combining cutting-edge interdisciplinary fields such as materials science, micro / nano fabrication, and biomedical engineering, have developed various non-implantable BCI electrode technologies, such as carbon fiber electrodes based on inorganic materials and Ag / AgCl sintered electrodes based on metallic materials. Non-implantable BCI electrode technologies are mainly divided into three categories: dry electrodes, wet electrodes, and semi-dry electrodes. Dry electrodes often suffer from significant voltage shifts and poor wearing comfort due to body position changes, limiting their effectiveness in EEG signal acquisition. Wet electrodes also face a series of problems, including inconvenience during EEG signal acquisition and poor long-term stability. Semi-dry electrodes hold promise for simultaneously addressing the challenges of both dry and wet electrodes in EEG signal acquisition, including wearing comfort, biosafety, and long-term stability, and have attracted widespread interest from researchers, particularly the development of hydrogel semi-dry electrodes. Summary of the Invention
[0004] Objective: In view of at least one of the above technical problems, the present invention provides a protein hydrogel brain-computer interface electrode based on choline acrylate modification, its preparation method and application. The prepared protein hydrogel brain-computer interface electrode based on choline acrylate modification is an ion-conductive hydrogel semi-dry electrode, which can be used for the acquisition of EEG signals in non-implantable brain-computer interfaces.
[0005] Based on choline acrylate and methacrylate-modified protein polymers, this application constructs a novel ion-conducting hydrogel brain-computer interface electrode suitable for non-implantable brain-computer interface applications. This ion-conducting hydrogel semi-dry electrode possesses inherent advantages such as long-term wearing comfort, ease of processing, high bioactivity, and high ion conductivity, and can play an important role in the field of non-implantable brain-computer interface electrodes. In the preparation process of this ion-conducting hydrogel semi-dry electrode, a large number of choline acrylate ionic liquids are covalently bonded to the hydrogel backbone network composed of protein polymer chains. The choline acrylate ionic liquids provide efficient ion conduction pathways within the hydrogel network, endowing the hydrogel semi-dry electrode with high ion conductivity, laying the foundation for the acquisition of EEG signals by this semi-dry hydrogel electrode. Therefore, this application develops a choline acrylate-modified protein hydrogel semi-dry electrode suitable for the acquisition of EEG signals in non-implantable brain-computer interfaces. Preliminary experimental results show that the semi-dry hydrogel electrode of this application has certain potential application value in EEG signal acquisition applications such as industrial safety production and brain cognitive state monitoring.
[0006] To achieve the above objectives, the present invention is implemented using the following technical solution:
[0007] In a first aspect, the present invention provides a method for preparing a protein hydrogel brain-computer interface electrode based on choline acrylate modification, comprising the following steps:
[0008] S1, choline acrylate was prepared by ion exchange method;
[0009] S2, based on the reaction of amino groups on the protein polymer chain with glycidyl methacrylate, a protein polymer modified with methacrylate is prepared;
[0010] S3, based on the free radical polymerization reaction between methacrylate-modified protein polymers and choline acrylate, and using a template replication method, a protein hydrogel brain-computer interface electrode was prepared.
[0011] In some embodiments, step S1 involves preparing choline acrylate using an ion exchange method, including:
[0012] Choline bicarbonate or choline hydroxide is reacted with acrylic acid via anion-cation exchange reaction to prepare choline acrylate.
[0013] Furthermore, in step S1, at least one of the following conditions must be met during the preparation of choline acrylate;
[0014] The molar ratio of added choline bicarbonate or choline hydroxide to acrylic acid is 0.01~2, preferably 1;
[0015] The reaction temperature is 20℃-100℃;
[0016] The reaction takes place under light-protected conditions.
[0017] In this application, biocompatible choline acrylate is prepared through step S1.
[0018] In some embodiments, in step S2, the preparation of a methacrylate-modified protein polymer based on the reaction of amino groups on the protein polymer chain with glycidyl methacrylate includes:
[0019] The protein polymer was dissolved in a solvent, and glycidyl methacrylate was added and mixed. The mixture was then reacted and purified to obtain a protein polymer modified with methacrylate.
[0020] Furthermore, in step S2, at least one of the following conditions must be met;
[0021] The protein polymer is selected from at least one of silk fibroin, gelatin, and collagen.
[0022] The solvent is selected from at least one of phosphate buffer, lithium bromide solution, sodium chloride solution, calcium chloride solution, and potassium chloride solution;
[0023] The mass concentration of protein polymers dissolved in solvents is 5-50 wt%.
[0024] The added glycidyl methacrylate accounts for 2-20 wt% of the mixed reaction solution;
[0025] The reaction temperature is 40-80℃.
[0026] In step S2 of this application, since the protein polymer chain contains a large number of amino functional groups, it can react with glycidyl methacrylate.
[0027] In some embodiments, in step S3, a protein hydrogel brain-computer interface electrode is prepared based on the free radical polymerization reaction between methacrylate-modified protein polymers and choline acrylates, using a template replication method, comprising:
[0028] A hydrogel precursor was obtained by mixing methacrylate-modified protein polymers, choline acrylates, and water.
[0029] The hydrogel precursor and photoinitiator or thermal initiator are mixed and poured into a template, and then subjected to ultraviolet light or thermal free radical polymerization to obtain a protein hydrogel brain-computer interface electrode.
[0030] Furthermore, in step S3, at least one of the following conditions must be met;
[0031] The mass ratio of methacrylate-modified protein polymers and choline acrylates is 1:1 to 5:1.
[0032] The solid content of the hydrogel precursor is 5-50 wt%.
[0033] The photoinitiator is selected from at least one of HMPP and photoinitiator 2959; the thermal initiator is selected from at least one of ammonium persulfate and potassium persulfate; the addition ratio of the photoinitiator or thermal initiator is 0.05-5 wt% of the hydrogel precursor.
[0034] The protein hydrogel brain-computer interface electrode is cylindrical, triangular pyramidal, or patch-type.
[0035] The above method described in this application can be used to prepare protein hydrogel brain-computer interface electrodes of various morphologies and to acquire and analyze EEG signals from non-implantable brain-computer interfaces.
[0036] Secondly, the present invention provides a protein hydrogel brain-computer interface electrode based on choline acrylate modification, which is prepared by the aforementioned preparation method.
[0037] Thirdly, the present invention provides the application of the protein hydrogel brain-computer interface electrode in non-implantable electroencephalogram (EEG) signal acquisition.
[0038] The aforementioned EEG signal acquisition involves EEG signal acquisition from different regions and with different numbers of channels. In some embodiments, the EEG signal acquisition is 16 channels, 32 channels, or 64 channels.
[0039] Compared with the prior art, the beneficial effects achieved by the present invention are as follows:
[0040] This invention provides a choline acrylate-modified protein hydrogel brain-computer interface electrode, its preparation method, and its applications. The electrode uses a highly bioactive choline ionic liquid as the ion-conducting unit, providing a stable ion-conducting transport channel. The main hydrogel network is composed of protein polymer materials, exhibiting good biocompatibility and adjustable mechanical stability. The choline acrylate-modified protein hydrogel electrode is simple to prepare, uses readily available materials, is low-cost, safe to wear, comfortable to wear, and easy to mass-produce, showing broad application prospects in the field of brain-computer interfaces for EEG signal acquisition. The protein hydrogel electrode of this invention possesses high conductivity, high bioactivity, and good long-term wearing comfort. The choline acrylate-modified protein hydrogel electrode is low-cost, uses widely available materials, and is easy to mass-produce. Based on this invention, the protein hydrogel electrode enables portable, long-term, and safe non-implantable EEG signal acquisition. This makes the protein hydrogel electrode of this invention widely applicable in brain-computer interface fields such as industrial safety production and brain cognitive state assessment. Attached Figure Description
[0041] Figure 1This is a schematic diagram illustrating the preparation of choline acrylate in an embodiment of the present invention;
[0042] Figure 2 This is a schematic diagram illustrating the preparation of methacrylate-modified protein polymers in an embodiment of the present invention;
[0043] Figure 3 This is a schematic diagram of the network structure of the protein hydrogel brain-computer interface electrode based on choline acrylate modification in an embodiment of the present invention;
[0044] Figure 4 This is a graph showing the electrochemical impedance spectroscopy results of gelatin protein hydrogel modified with choline acrylate in an embodiment of the present invention.
[0045] Figure 5 This is a graph showing the electrochemical impedance spectroscopy results of silk fibroin hydrogel modified with choline acrylate in an embodiment of the present invention.
[0046] Figure 6 This is a graph showing the electrochemical impedance spectroscopy results of bovine serum albumin hydrogel modified with choline acrylate in an embodiment of the present invention.
[0047] Figure 7 This invention provides an example of real-time contact impedance for silk fibroin hydrogel modified with choline acrylate during continuous electroencephalogram (EEG) acquisition.
[0048] Figure 8 The image shows the target position classification test results in the initial wearing state and after 6 hours of continuous wearing when the silk fibroin hydrogel based on choline acrylate is applied to the steady-state visual evoked potential paradigm in this embodiment of the invention. Detailed Implementation
[0049] The present invention will be further described below with reference to the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and should not be used to limit the scope of protection of the present invention.
[0050] The endpoints and any values of the ranges disclosed herein are not limited to the precise ranges or values, and should be understood to include values close to those ranges or values. For numerical ranges, the endpoint values of the various ranges, the endpoint values of the various ranges and individual point values, and individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.
[0051] For the purposes of this specification and the appended claims, unless otherwise stated, all expressions, percentages, or proportions, and other numerical values used in this specification and the appended claims, are to be understood to be modified by the term "about" in all cases. Furthermore, all scopes disclosed herein include their endpoints and can be combined independently.
[0052] This application provides a method for preparing a protein hydrogel brain-computer interface electrode based on choline acrylate modification, comprising the following steps:
[0053] S1, choline bicarbonate or choline hydroxide undergoes anion-cation exchange reaction with acrylic acid to prepare choline acrylate; the principle is as follows: Figure 1 As shown.
[0054] S2 involves dissolving the protein polymer in a solvent, adding a glycidyl methacrylate solution, reacting, and purifying to obtain a methacrylate-modified protein polymer. The principle is as follows... Figure 2 As shown.
[0055] S3 involves mixing methacrylate-modified protein polymers, choline acrylate, and water to obtain a hydrogel precursor; this precursor is then mixed with a photoinitiator or thermal initiator and poured into a template for UV- or thermal free radical polymerization to obtain a protein hydrogel brain-computer interface electrode. The principle is as follows... Figure 3 As shown.
[0056] Example 1: A method for preparing a protein hydrogel brain-computer interface electrode based on choline acrylate modification, comprising the following steps:
[0057] S1, using the ion exchange method, utilizes choline bicarbonate and acrylic acid to react in a molar ratio of 1:1 under light-protected conditions in a water bath at 60°C for 6 hours, followed by vacuum drying at 60°C to prepare choline acrylate.
[0058] S2, gelatin protein polymer was dissolved in phosphate buffer solution (solid content 20wt%), glycidyl methacrylate solution (solid content 5wt%) was slowly added dropwise, and the reaction was carried out at 60℃ for 10 hours. After purification processes such as dialysis and freeze drying, methacrylate-modified gelatin protein polymer was prepared.
[0059] S3, a hydrogel precursor was prepared by mixing choline acrylate- and methacrylate-modified gelatin protein polymers, choline acrylate, and water in a certain proportion (choline acrylate 0.05 g / ml; methacrylate-modified gelatin protein polymers 0.2 g / ml; the solid content of the hydrogel precursor was 13.5 wt%). 1 wt% of free radical thermal initiator ammonium persulfate was added to the hydrogel precursor, and the mixture was poured into a cylindrical template. After heat curing at 60℃ for 3 hours, a choline acrylate-modified gelatin protein hydrogel electrode was obtained.
[0060] Example 2: A method for preparing a protein hydrogel brain-computer interface electrode based on choline acrylate modification, comprising the following steps:
[0061] S1, using the ion exchange method, utilizes choline hydroxide and acrylic acid in a molar ratio of 1:1 under light-protected conditions, reacting in a water bath at 80°C for 5 hours, followed by vacuum drying at 60°C to prepare choline acrylate.
[0062] S2, silk fibroin polymer was dissolved in lithium bromide solution (solid content 30wt%), glycidyl methacrylate solution (solid content 3wt%) was slowly added dropwise, and the reaction was carried out at 60℃ for 6 hours. After purification processes such as dialysis and freeze drying, methacrylate-modified silk fibroin polymer was prepared.
[0063] S3, a hydrogel precursor was prepared by mixing choline acrylate- and methacrylate-modified silk fibroin polymer, choline acrylate, and water in a certain proportion (choline acrylate 0.05 g / ml; methacrylate-modified silk fibroin polymer 0.15 g / ml; and the solid content of the hydrogel precursor was 10.7 wt%). 2 wt% of potassium persulfate, a free radical thermal initiator, was added to the hydrogel precursor, mixed, and then poured into a triangular pyramidal template. After heat curing at 60°C for 5 hours, a choline acrylate-modified silk fibroin hydrogel electrode was obtained.
[0064] Example 3: A method for preparing a protein hydrogel brain-computer interface electrode based on choline acrylate modification, comprising the following steps:
[0065] S1, using the ion exchange method, utilizes choline hydroxide and acrylic acid in a molar ratio of 1:1 under light-protected conditions, reacting in a water bath at 100°C for 4 hours, followed by vacuum drying at 60°C to prepare choline acrylate.
[0066] S2, Bovine serum albumin polymer was dissolved in sodium chloride solution (solid content 30wt%), and glycidyl methacrylate solution (solid content 3wt%) was slowly added dropwise. The reaction was carried out at 80℃ for 5 hours. After purification processes such as dialysis and freeze drying, methacrylate-modified bovine serum albumin polymer was prepared.
[0067] S3, a hydrogel precursor was prepared by mixing bovine serum albumin polymer modified with choline acrylate and methacrylate, choline acrylate, and water in a certain proportion (choline acrylate 0.05 g / ml; bovine serum albumin polymer modified with methacrylate 0.25 g / ml; and the solid content of the hydrogel precursor was 16.4 wt%). 3 wt% of photoinitiator HMPP was added to the hydrogel precursor, mixed, and then poured into a patch template. After thermosetting at 60℃ for 5 hours, a bovine serum albumin hydrogel electrode modified with choline acrylate was obtained.
[0068] Based on the preparation methods described in Examples 1 to 3, this example provides a choline acrylate-modified protein hydrogel brain-computer interface electrode, prepared using the aforementioned method. The ion conductivity of the protein hydrogel brain-computer interface electrodes prepared in Examples 1 to 3 was analyzed to evaluate their EEG signal acquisition capability and long-term performance. Multichannel EEG signal acquisition and analysis were performed using the choline acrylate-modified silk fibroin hydrogel electrode.
[0069] The electrochemical performance testing method is as follows:
[0070] Electrochemical impedance spectroscopy (EIS) was performed using an electrochemical workstation. The open-circuit voltage was set to 0.1 V, and the scan frequency range was 0.1 Hz to 100,000 Hz. The hydrogel sample size was 10 × 10 × 1.1 mm. Figure 4 This is a graph showing the electrochemical impedance spectroscopy results of the gelatin protein hydrogel modified with choline acrylate in Example 1. Figure 5 This is a graph showing the electrochemical impedance spectroscopy results of the silk fibroin hydrogel modified with choline acrylate in Example 2. Figure 6 The image shows the electrochemical impedance spectroscopy results of the bovine serum albumin hydrogel modified with choline acrylate in Example 3.
[0071] Depend on Figures 4 to 6 It can be seen that the protein hydrogel brain-computer interface electrodes based on choline acrylate modified by Examples 1 to 3 of this application have high ion conductivity.
[0072] The physiological signal detection test method is as follows:
[0073] The prepared gel electrodes were implanted into the Linkme portable intelligent brain-computer interface device for EEG acquisition. The steady-state visual evoked potential paradigm (SSVEP) was used to evaluate the quality of the acquired EEG signals. During the test, the subjects were in a quiet environment and focused on the computer screen. Different locations on the screen presented visual stimuli with different flashing frequencies. In each trial, the subjects induced an SSVEP response by focusing on the target location according to an indicator prompt, for a total of 40 trials. The EEG signals were simultaneously recorded for subsequent classification and accuracy analysis.
[0074] Figure 7 This refers to the real-time contact impedance of the choline acrylate-modified silk fibroin hydrogel used in continuous electroencephalogram (EEG) acquisition in Example 2 of this invention. Figure 8 The image shows the target position classification test results in the initial wearing state and after 6 hours of continuous wearing when the silk fibroin hydrogel based on choline acrylate modified in Example 2 of the present invention is applied to the steady-state visual evoked potential paradigm.
[0075] Depend on Figure 7 and Figure 8 As can be seen, the protein hydrogel brain-computer interface electrode prepared in this application embodiment is an ion-conductive hydrogel semi-dry electrode, which can be used for the acquisition and analysis of EEG signals in non-implantable brain-computer interfaces.
[0076] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method for preparing a protein hydrogel brain-computer interface electrode based on choline acrylate modification, characterized in that, Includes the following steps: S1, choline acrylate was prepared by ion exchange method; S2, based on the reaction of amino groups on the protein polymer chain with glycidyl methacrylate, a protein polymer modified with methacrylate is prepared; S3, based on the free radical polymerization reaction between methacrylate-modified protein polymers and choline acrylate, and using a template replication method, a protein hydrogel brain-computer interface electrode was prepared.
2. The preparation method according to claim 1, characterized in that, In step S1, choline acrylate is prepared using an ion exchange method, including: Choline bicarbonate or choline hydroxide is reacted with acrylic acid via anion-cation exchange reaction to prepare choline acrylate.
3. The preparation method according to claim 2, characterized in that, In step S1, at least one of the following conditions must be met during the preparation of choline acrylate; The molar ratio of added choline bicarbonate or choline hydroxide to acrylic acid is 0.01~2, preferably 1; The reaction temperature is 20℃-100℃; The reaction takes place under light-protected conditions.
4. The preparation method according to claim 1, characterized in that, In step S2, a methacrylate-modified protein polymer is prepared by reacting the amino groups on the protein polymer chain with glycidyl methacrylate, including: The protein polymer was dissolved in a solvent, and glycidyl methacrylate was added and mixed. The mixture was then reacted and purified to obtain a protein polymer modified with methacrylate.
5. The preparation method according to claim 4, characterized in that, In step S2, at least one of the following conditions must be met; The protein polymer is selected from at least one of silk fibroin, gelatin, and collagen. The solvent is selected from at least one of phosphate buffer, lithium bromide solution, sodium chloride solution, calcium chloride solution, and potassium chloride solution; The mass concentration of protein polymers dissolved in solvents is 5-50 wt%. The added glycidyl methacrylate accounts for 2-20 wt% of the mixed reaction solution; The reaction temperature is 40-80℃.
6. The preparation method according to claim 1, characterized in that, In step S3, a protein hydrogel brain-computer interface electrode is prepared based on the free radical polymerization reaction between methacrylate-modified protein polymers and choline acrylates, using a template replication method. The electrode includes: A hydrogel precursor was obtained by mixing methacrylate-modified protein polymers, choline acrylates, and water. The hydrogel precursor and photoinitiator or thermal initiator are mixed and poured into a template, and then subjected to ultraviolet light or thermal free radical polymerization to obtain a protein hydrogel brain-computer interface electrode.
7. The preparation method according to claim 6, characterized in that, In step S3, at least one of the following conditions must be met; The mass ratio of methacrylate-modified protein polymers and choline acrylates is 1:1 to 5:
1. The solid content of the hydrogel precursor is 5-50 wt%. The photoinitiator is selected from at least one of HMPP and photoinitiator 2959; the thermal initiator is selected from at least one of ammonium persulfate and potassium persulfate; the addition ratio of the photoinitiator or thermal initiator is 0.05-5 wt% of the hydrogel precursor. The protein hydrogel brain-computer interface electrode is cylindrical, triangular pyramidal, or patch-type.
8. A protein hydrogel brain-computer interface electrode based on choline acrylate modification, characterized in that, Prepared by the preparation method according to any one of claims 1 to 7.
9. The application of the protein hydrogel brain-computer interface electrode according to claim 8 in non-implantable electroencephalogram (EEG) signal acquisition.
10. The application according to claim 9, characterized in that, The EEG signal acquisition is performed in 16-channel, 32-channel, or 64-channel configurations.