三维DNA纳米探针协同的肿瘤标志物联合检测SERS传感平台构建及性能研究

The project aims to design novel three-dimensional (3D) DNA nanoprobes for the construction of surface-enhanced Raman scattering (SERS) biosensing interfaces and to develop high sensitivity and specificity SERS sensing platform for combined detection of multiple low-abundance tumor biomarkers. The research focuses on the design, assembly of 3D DNA nanoprobes and the control strategy of their structures and functions. Then on the basis of systematically studying on the interaction between DNA nanoprobes and SERS substrate, and the sensing mechanism, several 3D DNA nanoprobe modified SERS sensing interfaces are constructed and further developed into "SERS substrate - 3D DNA nanoprobe - SERS tag" sensing systems. With the significant advantages of the special designed structure and function, the 3D DNA nanoprobes modified on the bio-sensing interface with high biological activity has good synergism with SERS hot spots enrichments and multiple detection capabilities for developing high-performance SERS sensing platform for detecting cancer-related biomarkers with high specificity and sensitivity. The research can provide new method and idea to achieve early detection of cancer via SERS, and is expected to be used for clinical cancer diagnosis.

本项目旨在设计新型的三维DNA纳米探针用于构建表面增强拉曼散射（SERS）传感界面，发展用于多种低丰度肿瘤核酸/蛋白标志物高灵敏、特异性联合检测的高性能SERS传感平台。重点研究三维DNA纳米探针的设计、组装与调控机理，并在系统研究DNA纳米探针与SERS基底相互作用及传感机制的基础上，构建三维DNA纳米探针修饰的SERS传感界面，发展“SERS基底--三维DNA纳米探针--SERS探针”构成的传感体系。利用三维DNA纳米探针独特的可精确编码、结构功能可调、易于实施界面修饰、生物活性高等特点，借助三维DNA纳米探针特殊设计的结构和功能，协同发挥传感体系生物识别效率高、SERS热点效应强和多元检测的优势，研发用于肿瘤多标志物联合检测的高性能SERS传感平台，为肿瘤早期检测提供特异性及敏感性俱佳的SERS传感新方法、新思路，为实现SERS技术在肿瘤早期临床诊断中的应用提供技术支持。

早期肿瘤检测是实施肿瘤早诊的有效的途径，早诊断早治疗可以大大降低癌症的致死率，如何准确检测极低丰度的肿瘤标志物是早期肿瘤筛查面临的关键科学问题。本项目针对肿瘤早期检测需要，设计新型的三维DNA纳米探针用于构建表面增强拉曼散射（SERS）传感界面，发展用于多种低丰度肿瘤核酸/蛋白标志物高灵敏、特异性联合检测的高性能SERS传感平台。重点研究了三维DNA纳米探针的设计、组装与调控机理，并在系统研究并阐明DNA纳米探针与SERS基底相互作用及传感机制的基础上，构建三维DNA纳米探针修饰的SERS传感界面，发展“SERS基底--三维DNA纳米探针--SERS探针”构成的传感体系，提出“靶标智能响应-物理/生物信号协同放大-SERS多元标志物高灵敏分析”传感技术。利用三维DNA纳米探针独特的可精确编码、结构功能可调、易于实施界面修饰、生物活性高等特点，借助三维DNA纳米探针特殊设计的结构和功能，协同发挥传感体系生物识别效率高、SERS热点效应强和多元检测的优势，研发用于肿瘤多标志物联合检测的高性能SERS传感平台，实现血清样本中核酸标志物~aM水平检测、核酸-蛋白标志物跨类别联合检测、循环肿瘤细胞单细胞水平检测，为肿瘤早期检测提供特异性及敏感性俱佳的SERS传感新方法、新思路，为实现SERS技术在肿瘤早期临床诊断中的应用提供技术支持。