活体微电极抗蛋白吸附的研究

In vivo monitoring the dynamics of neurochemicals becomes more and more important to unveil and understand brain activity and function. In vivo electrochemistry has been of great concern in both chemistry and neuroscience communities due to its capability to track the dynamics of neurochemicals with a high spatiotemporal resolution. However, the implanted electrode inevitably suffers from nonspecific adsorption of biomacromolecules (i.e., biofouling), proteins in particular, onto the surface, which hinders or completely prevents analyte from reaching the electrode and hence inactivates the implanted microsensor, leading to decreased sensitivity and prolonged response time, especially for long-time measurements. This project aims to resolve this key issue for in vivo monitoring of neurochemicals. To improve the anti-fouling property of the implanted microelectrodes, we will rationally design and modify anti-fouling materials onto the microelectrodes and systematically study the electrochemical performance of the electrodes toward electroactive neurochemicals. Based on this, we will be able to develop new electrochemical methods with improved anti-fouling performance of the electrodes to monitor physiologically important secies such as ascorbate and dopamine. We believe that this project will resolve the challenge of protein adsorption onto the tissue-implantable electrodes, which would form a straightforward basis to understand brain chemistry underlying various physiological and pathological processes.

脑内化学物质的动态分析对于从分子水平认识和理解大脑活动与功能具有重要的意义。活体原位电化学方法由于其较高的时空分辨率，在该领域受到广泛的应用。但是应用电化学方法进行活体检测过程中，植入微电极吸附蛋白质后会导致电极灵敏度和响应时间的下降，并且需要在活体实验后对电极进行校正方可实现化学信号的获取，进而影响活体电化学分析的准确性和可靠性。本项目针对活体电化学分析中蛋白质吸附的关键科学问题，系统研究抗蛋白吸附材料在微电极表面的可控修饰及其对脑内生理活性物质电化学行为的影响规律；针对特定化学物质，合理设计电极界面，建立不显著影响灵敏度的高抗蛋白质吸附的电化学分析新方法；利用所发展的抗污染电极，建立和发展新型活体电化学分析方法。本项目通过有效解决微电极在活体原位分析中蛋白质吸附的关键问题，为脑化学的研究提供重要基础。

基于植入微电极的活体原位电化学方法由于其高的时空分辨率在脑神经系统内化学物质的动态分析领域受到越来越广泛的关注和应用。但是微电极在植入脑组织进行活体检测过程时，脑内蛋白质等大分子物质在微电极上的吸附导致电极灵敏度下降，并且需要在活体实验后对电极进行校正才能分析在活体内获取的信号，进而影响活体电化学分析的准确性和脑组织的损伤。本项目针对活体电化学分析中蛋白质吸附的关键科学问题，取得了系列创新性研究成果：1）系统研究了蛋白吸附对生理活性物质电化学分析影响的规律，提出了在植入微电极表面通过聚多巴胺衍生可控修饰两性离子超薄膜，原位制备导电聚合物和水凝胶多孔结构等策略减小蛋白质吸附对电流响应的影响，提出了改变电化学信号为电位法的新策略克服蛋白质吸附对电化学信号的影响；2）建立了基于聚多巴胺构筑两性离子膜修饰电极，聚单宁酸掺杂的聚苯胺多孔膜和壳聚糖水凝胶修饰电极的抗蛋白质吸附的抗坏血酸、多巴胺、葡萄糖等物质的电化学原位分析新方法，建立了Ag2S/AgNP修饰碳纤维电极的脑内硫化氢的电位分析新方法，这些方法减小了活体植入电极的蛋白质吸附并减小了脑组织的炎症反应，实现了活体分析前校准，发现了维生素D的神经保护新功能；3）发展了无需基底的全聚合物柔性电极设计和制备方法，并通过掺杂和湿法纺丝实现了脑内生理活性物质的原位检测，减小了电极长时间植入的脑组织损伤。本项目有效的解决了微电极在活体原位分析中蛋白质吸附的关键问题，为更好的研究脑科学的分子机制奠定了重要基础。项目执行期间参加国内外会议7次，发表论文26篇，其中包括5篇Angew. Chem. Int. Ed，4篇Anal. Chem.和4篇Chem. Commun.。获中国分析测试协会科学技术一等奖(1/4)，培养博士6名，硕士5名，其中两名获得国家奖学金。目前在读博士6名，硕士5名。