基于eRAFT聚合的信号放大策略及蛋白酶活性高灵敏电化学生物传感研究

The highly sensitive and selective detection of protease activities is an important research focus in electrochemical biosensing. However, conventional signal amplification strategies are suffered from the drawbacks such as complex operation or high cost. On the basis of a detailed investigation of the electrochemically controlled reversible addition−fragmentation chain transfer (eRAFT) polymerization-based signal amplification strategy, in this project, we intends to develop a class of eRAFT polymerization-based electrochemical biosensors for the highly sensitive and selective detection of protease activities in a simple and convenient, fast, and low-cost manner. The main research contents of this project include 1) a detailed investigation of the eRAFT polymerization-based signal amplification strategy and of the interfacial charge-transfer kinetics, 2) investigations of the specific recognition of protease molecules and of the site-specific labeling of chain transfer agents (CTAs), and 3) the construction as well as the performance evaluation of the eRAFT polymerization-based electrochemical biosensors for the highly sensitive detection of protease activities. These studies are expected to provide a solid theoretical support and technical guarantee for the wide application of the eRAFT polymerization-based signal amplification strategy. By virtue of their merits such as high efficiency, easy operation, and low cost, the eRAFT polymerization-based electrochemical biosensors have broad application prospects in the highly sensitive detection of protease activities, as well as in the protease-related early diagnosis of cancers, drug screening, and molecular targeted therapy.

蛋白酶活性的高灵敏、高选择性检测，一直是电化学生物传感领域的一个重要的研究热点。然而，传统信号放大策略存在操作复杂或成本高昂等不足。鉴于此，本项目拟在对基于电化学调控可逆加成-断裂链转移（eRAFT）聚合的信号放大策略进行深入研究的基础上，探索构建一类基于eRAFT聚合的电化学生物传感器，实现对蛋白酶活性的简便、快速、低成本、高灵敏、高选择性检测。研究内容主要包括基于eRAFT聚合的信号放大策略及界面电荷转移动力学、蛋白酶分子的特异性识别与链转移剂的位点靶向性标记以及基于eRAFT聚合的蛋白酶活性高灵敏电化学生物传感器的构建及其性能评估。本项目研究可为基于eRAFT聚合的信号放大策略的广泛应用提供坚实的理论支撑与技术保障。基于eRAFT聚合的电化学生物传感器，具有高效、操作简便和成本低廉等优势，在蛋白酶活性的高灵敏检测以及相关癌症的早期诊断、药物筛选和分子靶向治疗等方面具有广阔的应用前景。

在项目21904026的资助下，我们对基于eRAFT聚合的信号放大策略进行了深入的研究，构建了几种基于eRAFT聚合信号放大的电化学生物传感器，实现了对蛋白酶等生物靶标的简便、快速、低成本、高灵敏、高选择性检测。主要研究了基于eRAFT聚合的信号放大策略及界面电荷转移动力学、蛋白酶分子的特异性识别及CTAs的位点靶向性标记、以及基于eRAFT聚合的蛋白酶活性高灵敏电化学生物传感这3个方面。本项目研究可为基于eRAFT聚合的信号放大策略的广泛应用提供坚实的理论支撑与技术保障，研究成果对于疾病诊断、药物筛选以及分子靶向治疗等方面具有十分重要的意义。项目实施期间，以第一作者/通讯作者身份在Analytical Chemistry（9篇）、Biosensors and Bioelectronics（2篇）、ACS Applied Materials & Interfaces（1篇）、Sensors and Actuators B: Chemical（1篇）、Journal of Materials Chemistry B（1篇）、《化工进展》（1篇）、《电化学》（1篇）、《材料研究与应用》（1篇）上发表学术论文17篇，以第二作者身份在The Innovation发表学术论文1篇；申请了3项发明专利；参加了4次国内学术会议，作邀请报告1次；指导培养硕士研究生3名。