马达式微/纳米生物探针的构建与动态传感新方法研究

Micro intelligent sensing probe shows important application value in realization of the direct, rapid and real-time detection of biological molecules. This project aims to design and synthesize asymmetric micro/nano-materials at various shapes by template assisted electrochemical growth and nano-spray technologies, and further develop motor-based micro/nano-bioprobes with good motion performance by constructing molecular drive layer on specific surface part of the asymmetric micro/nano-materials through chemical modification and in situ assembly, in which nucleic acid strands and different enzymes (or nanoparticles) are employed as frame and drive elements, respectively. According to the motion conditions and patterns, the project will further study the movement mechanism and explore the new propel principle of the micro/nano-bioprobes. The control of the motion pattern and performance of micro/nano-bioprobes is realized based on the target-triggered regulation of drive elements in the molecular drive layer through the bio recognition between target (such as DNA、protein biomarkers) and the frame nucleic acid strands. By introducing nano assembly, proximity hybridization and enzymatic cycling amplification into the target recognition process, new sensitive dynamic sensing methods are established for real-time, label-free and rapid detection of target biomolecules. The outcomes provide new idea for the design of micro/nanomotors and their biosensing applications, show new ways for the development of intelligent micro-biosensors, and promote the development of analytical chemistry and interdisciplinary.

微型智能检测探针在生物分子的免处理、快速、实时监测中具有重要的应用价值。本项目拟利用电化学模板生长与纳米喷射技术，合成不同形状的不对称微/纳米材料，以核酸链为框架基元，通过化学修饰和在位组装，在微/纳米材料的部分特定表面构建含动力元素(如生物酶、纳米粒子)的分子驱动层，制备具有良好运动性能的马达式微/纳米生物探针；根据微/纳米生物探针的运动条件和模式，探讨运动机制，提出新的驱动原理；通过生物靶标分子(如DNA、蛋白质标志物)与分子驱动层中核酸链的特异性识别，调控微/纳米生物探针上的动力元素，实现其运动模式与性能的控制，进一步设计纳米组装、邻位诱导效应和核酸酶循环等放大策略，建立生物靶标分子的实时、无标记、高灵敏动态检测方法。本项目工作将为新型微/纳米马达的设计及其生物传感应用提供新思路，为智能微型生物传感器的发展提供新途径，并对生命分析化学的发展与学科交叉具有促进作用。

微纳米马达由于其自驱动特性，对制备微型智能传感探针及发展快速均相生物分析方法具有重要意义。针对现今微纳米马达生物传感方法的检测灵敏度低、需额外信标探针等缺点，本项目提出了传感-驱动一体化策略，利用DNA组装技术，分别制备了微管马达传感探针和仿水母微马达传感探针，通过直接观察微马达探针的运动速度，实现了DNA的动态灵敏检测；另外，通过纳米溅射和不对称化学修饰，制备了酶反应驱动的微金碗马达，研究了其运动方式、驱动机理和尺寸效应，探讨了其储能式运动性能和储能机制；进一步结合邻位诱导效应和核酸放大策略，发展了简单、快速、高灵敏的蛋白质分析方法。本项目所发展的微马达传感探针及马达式传感方法，对于多功能化微纳米马达的制备、高灵敏动态传感方法的发展具有重要意义。另外，本项目所提出的多种蛋白质分析方法为高灵敏、一步式、通用化生物检测方法的发展提供了新途径。