基于DNA三链SERS传感平台构建及生命分析应用

The development of high-effective and high-accurate techniques for the obtaining of bio-finformations is one of the key researches in analytical chemistry. In the present project, taking the research of sensing theory and new methods in bioinformation obtaining as the base, and aiming at the international frontier of chemo/biosensing such as important tumor markers(microRNA)sensing, the pioneer fundamental research will be carried out. This project focuses on the following several aspects: 1) Based on the obtained recognition elements of aptamer, and combining the molecular structure characteristic of the triplex DNA with the separation concept of probe recognizing-part and the signal reporting-part, new mechanism or new strategies about the signal response, transition and amplification will be explored by using surface-enhanced Raman scattering (SERS) spectrum. 2) Combining with nuclease and nanomaterials, highly sensitive detection of microRNA in cell lysate and even breast cancer tissues will be achieved by utilizing this constrcuted triplex-based SERS sensing platform. 3) Combing with special modified nucleotide analogues and nanomaterials, which exhibit faster cell penetration and uptake, the triplex-based SERS sensing platform thus affording great potential for microRNA real-time and in situ intracellular imaging. .From this project, some key techniques and fundamental research in biosensor and probe with the advantages of high specificity and high sensitivity will be developed, which will establish our own characteristic with the self-owned intellectual property right, and further to make some original progeny with the international influence.

发展准确高效的生物信息获取技术，是当前分析化学研究的核心内容之一。本项目以生物信息获取新原理与新方法为研究基点，瞄准化学生物传感国际前沿领域，开展原始创新的基础研究：针对重要的肿瘤标志物（如微小RNA），利用DNA三链结构的分子特性,从探针识别单元与信号报告单元分离中寻找新的突破点，结合核酸工具酶、纳米材料，以拉曼散射作为信号输出手段，系统开展信号转换新原理与方法研究，提出新的信号响应、转导和放大机制。在此基础上, 设计和发展多种功能化三链核酸探针传感平台并用于肿瘤标志物的放大检测。本项目的执行将进一步确立我国在具有自主知识产权的特异性、专一性、高灵敏传感与探针等关键技术及其基础研究方面的特色，取得具有国际影响的原创性成果。

本项目从发展分子探针技术及生物信息获取的需求出发，以分离探针识别单元与信号报告单元为突破点，设计基于三链DNA结构平台；同时，将相关功能化核酸工具酶及纳米材料等引入分子探针的信号识别转导过程，发展新的信号放大技术；在此基础上，研制出高选择性、高灵敏度的核酸生物传感器，以实现对重要生物信息的高灵敏、高选择性获取， 应用于乳腺癌等肿瘤的早期诊断及初步治疗，拓展分析化学的研究应用领域。