量子点微米马达生物传感器的设计、制备与传感性能

Micro/nanomotor-biosensors have a great potential in detecting of biomarkers due to its autonomous movement in aqueous solutions. Based on this property, micro/nanomotor-biosensors can realize integration of separation and detection. So far, the reported micro/nanomotor-biosensors were normally based on the speed of the micro/nanomotor as the signal readout. These biosensors are always unstable, because the movement of micro/nanomotors in aqueous solutions is easily affected by random Brownian motion or the local liquid disturbance. In addition, these biosensors could only detect one kind of target owning to its design. In this project, we will combine quantum dots and tubular micromotors to develop stable, effective and multifunctional quantum dots-based micromotor-biosensors. The fluorescence emission of quantum dots will be used as the signal readout, which will make the biosensors stable. The single-sequence DNA will be used as the recognition unit to recognize targets. The biosensors could detect various targets by changing the base sequence of the DNA. The hepatitis B virus (HBV) DNA and thrombin will be used as the targets. The design principles and fabrication methods of the quantum dots-based micromotor-biosensors will be studied. The effects of the experimental conditions on the performance of the biosensors will be investigated. Under the optimal conditions, the performance of the biosensors on multiplexed detection and in complex biological samples will be evaluated. This project will promote the development of micro/nanomotor-biosensors and provide a powerful tool for detecting biomarkers in the clinical application and relevant fundamental research.

微纳米马达生物传感器具有自主运动性能，可实现分离与检测一体化，因此在生物标志物分析中具有巨大潜力。但目前微纳米马达生物传感器的信号主要基于运动速率，存在稳定性差和检测功能单一的问题。本项目结合量子点与管状微米马达，以量子点的荧光发射作为输出信号、单链核酸作为目标物的识别单元，设计并制备稳定、高效、多功能的量子点微米马达生物传感器。以乙肝病毒DNA和凝血酶作为模型分子，深入研究量子点微米马达生物传感器的设计原理及制备方法；重点研究实验条件对量子点微米马达生物传感器分析性能的影响。在此基础上，考察该量子点微米马达传感器在多组分和复杂生物样品中的应用。通过本项目的实施，不仅丰富和发展微纳米马达生物传感器，而且能为临床及相关基础研究中生物标志物的检测提供一种有效的新方法。

微纳米马达由于具有自主运动性能，因此在生物传感、主动给药及微创手术等领域具有巨大的应用潜力。本项目旨在发展在复杂生物介质中能够保持自主运动的化学驱动微纳米马达，并应用于生物医学分析中。围绕这一目标，项目取得的主要研究成果如下：1. 采用电化学沉积法，制备了外表面含有羧基官能团、中间含有磁响应层、内表面含有驱动层的管状微米马达。2. 利用磁流体在外磁场作用下形成的动态拓扑轨道，实现了对管状微米马达运动轨迹实时、简单和多样化的控制。3. 通过在管状微米马达外表面修饰阳离子聚合物聚乙烯亚胺（PEI），在没有外界能量输入和机械泵协助的情况下实现了微体系中核酸的高效萃取。4. 利用蛋白质自组装技术在三维空间上增加催化位点，制备多层脲酶驱动双面神微米马达，显著提高了酶驱动微米马达的驱动力。5. 利用罐状结构的空间限制效应和脲酶与尿素之间的特异性催化反应，发展了一种能够感知燃料浓度变化而自主调节驱动机理和运动方向的酶驱动微米马达。研究成果可望促进化学驱动微纳米马达在生物医学领域的实际应用。在本项目基金的资助下，共发表论文11篇（其中SCI论文 10篇，IF > 10论文4篇），主要包括、ACS Nano（1篇）、Advanced Functional Materials（2篇）、Applied Materials Today（2篇）、Langmuir（1篇）、 Chemistry-An Asian Journal(1篇)和Micromachines（2篇），申请发明专利2项。另外，申请者受邀撰写管状微纳米马达的研究现状和微纳米马达在主动给药领域应用的综述。期间项目主持人晋升为副研究员，培养6名毕业生（3名硕士生和3名本科生）。