基于贵金属纳米粒子-咖啡环效应的生物传感机制研究及其在脑神经科学中的应用

The research on brain diseases is of great significance for social development. The project is proposed to combine coffee-ring effect, noble metal nanoparticles, specific molecular recognition and live on-line analysis techniques for studying biological sensing mechanism based on noble metal nanoparticles and coffee-ring effect. By integrated the surface/interface functionalized noble metal nanoparticles and specific molecular recognition process, the novel mechnisms and methods for effect biological sensing analysis will be established based on noble metal nanoparticles and coffee-ring effect. By choosing the forming and suppression of coffee-ring effect deposition as a signal output, the novel methods can realize the goal of high sensitive and specific detection of Aβ, γ-secretase, miRNA and other Alzheimer's disease (AD) associated markers in the relevant brain regions and cerebrospinal fluid in view of concentration distribution and changes over the course of development. The proposed novel biosening methods will be applied in the in vivo brain analysis system model of rats with AD pathology, and other related researches also will be conducted simultaneously on the complications of neurodegenerative diseases, e.g. acute and chronic cerebral ischemia, diabetes, etc. In the project, the research will start from the study of novel principles and novel methods, continue to detect single molecule involved in the nervous system diseases, investigate the direct interaction between related molecules, and then study the mechanism of diseases and explore the potential of early disease diagnosis by in vivo analysis, which can provide a scientific way to the research and treatment of nervous system diseases.

脑神经系统疾病研究是目前各相关领域的研究热点，对于社会发展也具有重要意义。本项目创新性地将咖啡环效应、贵金属纳米粒子、分子特异性识别和活体在线分析技术等相结合，拟开展基于贵金属纳米粒子-咖啡环效应的生物传感新机制研究；通过对贵金属纳米粒子表界面的功能化修饰和改性并整合特异性分子识别过程，构建基于贵金属纳米粒子-咖啡环效应的高效生物传感分析新机制、新方法，通过简便、快速的咖啡环效应沉积的形成和抑制作为信号输出，实现Aβ、γ-分泌酶、miRNA等阿尔兹海默症(AD)相关标志物的高灵敏、特异性检出；该方法拟用于大鼠AD病理模型的脑活体分析体系中，同时开展急慢性脑缺血等与神经退行性疾病相关并发症研究。项目将从新机制、新方法研究入手，从与神经系统疾病有关的单一分子检测，到相关分子间直接的交互作用研究，再到通过活体分析进行疾病机制及病理探讨和早期诊断的探索，因此具有重要的科学研究价值和广泛的应用前景。

近年来，各相关领域的科研工作者对咖啡环效应的理论和应用展开了多尺度的研究，但是在分析化学和生物传感领域还需要提高其灵敏度、选择性，并进一步扩大其应用范围。本项目中，我们针对纳米粒子-咖啡环效应的生物传感新机制这一方向开展研究工作。课题中，发展了基于Au@Ag@CD咖啡环效应与主-客体识别的邻苯二甲酸酯类的拉曼灵敏检测；构筑了中空磁性ZnO-ZnFe2O4@Ag纳米花球的咖啡斑拉曼基底并灵敏检测了炭疽杆菌标志物吡啶二羧酸；初步探究了基于DNA功能化FITC@SiO2材料的咖啡环效应并应用于检测microRNA-9；构筑了基于TPE-TS@Eu/GMP ICPs的炭疽生物标记物双比率型荧光传感并将其咖啡环试剂盒用于即时诊断；同时针对分子识别这一研究领域，发展了基于有机-无机杂化传感系统的模式识别分析以及基于刺激响应共聚物的电化学生物传感。至今，我们已完成了项目中的各项任务，在Anal. Chem., Chem. Commun., Biosens. Bioelectron.等国际知名期刊杂志上发表总计38篇SCI论文。