基于系列性功能化离子液体的微渗析在体电化学分析方法的研究与应用

Our research mainly focuses on novel analytical methods and techniques design that is suitable for life science. Among various analytical methods to monitor neurotransmitters in the brain, microdialysis is the most frequently used in vivo by far. Due to its short analytical time, high sensitivity and specificity to provide near real-time measurements, microdialysis sampling can provide both the temporal and chemical information that we need to fully elucidate the biochemical processes. The on-line analytical system, consisting of microdialysis sampling and direct electrochemical detection, without any sample separation or pretreatment, are becoming increasingly advantageous for continuous measurement of glucose,lactic acid, dopamine and glutamate in biological samples. Meanwhile, for improving the sensitivity and selectivity of the analytical method, a series of promising nanomaterials based on metal nanoparticles or carbon materials (carbon nanotubes, graphene, etc) are employed in the construction of enzyme biosensors. Our previous work has proved that functionalized ionic liquids can be used as facile templates for the preparation of metal nanomaterials with controllable morphology and size. Based upon this, in this project, we put forward the design and screen of a series of functionalized ionic liquids, which will be acted as the template for the synthesis of metal nanomaterials and graphene. The systematic discussion for the relationship between the functional groups in the structure of the as-synthesized ionic liquids and the physical properties (morphology, size, stability, etc) as well as the electrocatalytic activity of the nanomaterials will be carried out. After that, those ionic liquids that possess higher electrocatalytic activity will be picked out and applied for the fabrication of enzyme biosensors. Combined with the microdialysis sampling technique, the effective on-line detection system for the real-time in vivo measurement of some important neurotransmitters (glutamate, dopamine, glucose and lactic acid)will be developed?in the field of life science.

本项目立足于适合生命科学领域的新型分析方法的新原理、新技术的研究，基于系列性功能化离子液体为平台，建立针对活体动物脑内多种生命活性物质如乳酸、葡萄糖、谷氨酸、多巴胺等神经递质的实时、在线分析的新方法。申请者在已有工作的基础上，拟通过系列性功能化离子液体的设计与合成，有目的的进行功能化离子液体结构的优化和筛选，并系统性地开展功能化离子液体对金属纳米材料和石墨烯结构以及电化学性质调控机制的研究，寻找能够满足活体在线分析高灵敏、高选择性的新型纳米材料；与微渗析活体取样技术联用，构建针对生命活性物质在线分析的微渗析活体取样-电化学生物传感系统，实现对大鼠脑区内乳酸、葡萄糖、谷氨酸、多巴胺等重要递质的实时、在线的精确定量，为从分子层面探讨关系人民身体健康的脑缺血及帕金森病的发病机制，以期实现疾病的诊断和治疗及相应药物的筛选与研制提供科学的理论和可靠的方法。

脑科学研究作为生命科学探索中的重要组成部分，一直是世界关注的热点。对大脑神经活动过程中多种重要生物标志物的高灵敏、高选择性测定，有助于全面、实时了解大脑的各种生理活动以及中枢神经系统疾病发生、发展过程中的神经递质水平及其相互关系，从而为中枢神经系统疾病的病理分子机制研究以及相关疾病的预防和治疗提供新的思路。本项目立足于适合生命科学领域的新型分析方法的新原理、新技术的研究，以功能化离子液体和微渗析活体取样技术为平台，建立了针对活体动物脑内多种生命活性物质如葡萄糖、乳酸等的一系列分析方法。通过将不同结构的咪唑环离子液体作为Pt纳米粒子沉积的载体，我们制备了四种Pt/离子液体/石墨烯复合材料，并考察了离子液体结构对所制得的纳米粒子的形貌、粒径及电催化性质的影响。此外，我们还尝试以功能化介孔碳（PDDA-CMM）为合成Pt纳米粒子的模板和稳定剂，实现了对金属纳米粒子的可控性合成。并以此为基础，研制了双通道微渗析-电化学在线分析系统，成功实现了对大鼠脑区内葡萄糖和乳酸的实时、在线、连续的精确定量和科学评价，为神经系统疾病机制的研究提供了一种科学有效的方法。. 在本课题的研究过程中，我们也尝试开展一些与阿尔兹海默症等重大脑疾病相关的重要标志物的分析与检测。我们首次利用gelsolin与Aβ之间类似抗体-抗原之间的特异性结合，构筑了两种能够用于对β-淀粉样蛋白单体的含量进行可靠评估的电化学免疫传感器，获得了较好的灵敏度和选择性，实现了对AD大鼠中脑部和血浆中Aβ单体的定量检测；此外，我们还利用比色分析技术，制备了一种性能良好的比色探针，实现了对AD大鼠脑中总Aβ单体的含量测定。上述几项工作的开展，为AD发病机制的探讨具有较强的指导意义，也为我们后续工作的顺利进行奠定了良好的基础。