级联信号放大疾病标志物高灵敏、多组分同时电化学生物传感研究

Under the support of the National Natural Science Foundation of China (NSFC) for young investigators, we have achieved highly sensitive detection of uropathogens based on enzyme and quantum dot labels. We also developed label-free, sensitive strategies for electrochemical detection of uropathogens. At the same time, by using labels with distinct electrochemical signatures, we have developed methods for one-spot, simultaneous detection of different biomolecular targets and proposed several dual signal amplification approaches for highly sensitive electrochemical detections via enzyme-assisted redox-recycling. These research results were published in some of the high impact peer-reviewed journals, including 2 in Anal. Chem., 5 in Chem. Commun., 1 in Chem. Eur. J. and 5 in Biosens. Bioelectron. Based on the excellent progress on the NSFC funded project, here we apply for continuous support from the NSFC to develop new cascade signal amplification strategies for ultrasensitive and simultaneous detection of protein biomarkers for various cancers and DNA biomarkers for different virus. The cascade signal amplification will be achieved through the integration of the biobarcode signal enhancement with enzyme-assisted redox-recycling, target DNA recycling as well as quantum dot-labeled amplification. The proposed study is expected to provide new opportunities for early diagnosis of various diseases. This future project is a further continuation and expansion of the previously NSFC funded project.

围绕青年基金项目研究主题，我们根据鸟嘌呤的电化学响应以及酶、量子点为标记，实现了尿路感染病原体免标记、高灵敏电化学检测。通过研究我们还建立了同一电极界面多组分生物分子的同时电化学传感及基于双重分析信号放大的高灵敏生物分子电化学检测技术。研究成果已发表SCI 论文17 篇，其中IF>5.0的论文13篇(Anal. Chem. 2篇，Chem. Commun. 5篇，Chem. Eur. J. 1篇， Biosens. Bioelectron. 5篇)。基于青年基金研究的良好进展及基础，在此我们申请青年-面上连续资助。申请项目拟以前列腺癌标志物，肝癌三种联合检测标志物及三种病毒的DNA标志物为研究对象，结合生物条形码信号放大技术与酶辅助氧化还原循环、目标DNA循环及量子点信号增强功能，建立级联分析信号放大策略，实现标志物超灵敏、多组分同时电化学检测。该项目是青年基金研究工作的进一步深化与拓展。

高灵敏度一直是生物传感设计的关键因素之一。在许多疾病的早期阶段，与疾病相关的标志物通常以非常低的含量存在。这些低含量疾病标志物的超灵敏检测，对相关疾病的早期诊断与治疗具有十分重要的意义。我们以癌症及核酸等疾病标志物为研究对象，利用电化学检测技术的优势，结合生物条形码信号放大技术与酶、量子点辅助的信号增强功能，构建新型级联分析信号放大策略，发展多种标志物的高灵敏、多组分同时电化学传感新方法，解决疾病标志物高灵敏、多组分同时电化学检测机制的构建及电化学检测背景信号降低机制两个关键问题。通过研究，我们成功构建酶辅助目标物循环高灵敏电化学DNA检测及microRNA多组分同时电化学检测；目标物诱导组装/拆卸DNA纳米结构的高灵敏生物分子检测；新型纳米复合材料和双酶催化循环氧化信号放大高灵敏生物传感；链置换无酶驱动分子机器分析信号放大高灵敏检测癌细胞中microRNA等方法。该项目研究将为高灵敏疾病标志物实际临床检测方法的建立提供有价值的借鉴和参考。