DNA-金属荧光纳米材料的制备及其无标记放大检测转录因子的应用研究

Owing to the pivotal role of TFs in gene expression as well as its close relationship with human diseases, the accurate measurement of transcription factors is of great importance in early diagnosis and high-throughput drug screening for specific inhibitors to treat or prevent diseases. Inspired by the requirement of label-free and sensitivity in the fluorescent analysis of TFs, this program plans to design, prepare and assemble the novel DNA-metal fluorescent nanomaterials with distinguished fluorescence and recognition function as the fluorescent probe, combining with the DNA based signal amplification, to construct the label-free and sensitive TFs fluorescent biosensor and develop the novel mechanism and method. Based on the structural, assembly and recognition features, DNA sequences will be designed systematically; With the template of DNA, DNA-metal nanomaterials are prepared and the luminescent mechanism will be studied. The relationship and rules between the fluorescent features of different sequences based DNA-metal nanomaterials and the bases, structure will be investigated for the extension of novel fluorescent character of the DNA-metal nanomaterials; the recognition and amplification mechanism will be discussed for the provide the theoretical direction of the biosensor fabrication. The sensing device unit for label-free and sensitive detection of TFs will be constructed and the mechanism of recognition, detection and sensing will be studied, which provide the technical support and theoretical base. It also provides novel idea for the recognition of TFs and synchronous exploration of the TFs process monitoring in biological system.

转录因子的快速、灵敏检测对于临床诊断、高通量药物筛选以及疾病的预防和治疗起着重要的作用。本项目针对目前荧光检测转录因子的无标记、高灵敏的需求，设计、制备和组装具有高荧光亮度、分子识别性能的新型DNA-金属荧光纳米材料作为信号分子，结合简便有效的DNA基信号放大模式，发展基于DNA-金属纳米荧光探针的无标记、灵敏检测转录因子的新原理和新方法；研究不同序列DNA-金属纳米材料的荧光性质与碱基和结构之间的联系和规律，揭示DNA-金属纳米材料的发光机制，为拓展DNA-金属纳米材料的荧光性质提供理论基础；考察信号放大的影响及机理，并探讨传感器响应规律，为转录因子在线探测提供理论指导方向。本项目的成功实施，将会为新型DNA-金属纳米荧光材料的设计、制备以及转录因子的高效检测提供理论依据与技术支撑，在技术与应用层面上为生物体内转录因子的识别和转录过程的探究提供新的途径。

本项目针对目前生命标志物荧光分析探针无标记、灵敏度的需求，拟设计、制备和组装具有高荧光亮度、分子识别性能的新型DNA-金属荧光纳米材料作为信号分子，结合简便有效的DNA基信号放大模式，发展基于DNA-金属纳米荧光探针的无标记、灵敏检测的新原理和新方法。项目执行期间申请人开发了系列DNA为模板的金属纳米材料，发展和证明其DNA空间构象依赖的光、电、催化性质，创建时空可控的有序探针界面并构建系列信号放大、多模式协同光电传感平台，实现DNA相关的生命及环境健康分析物(包括目标基因序列、莱克多巴胺、转录因子、microRNA、黄曲霉毒素等)的高灵敏、高选择分析，同时通过研究碱基数目类型与发光性质的关系，揭示DNA-金属纳米材料的发光机制，为该类分析物的实际分析提供依据和基础，也为类似材料的生物分析应用提供途径。本项目的成功实施，将会为新型DNA-金属纳米荧光材料的设计、制备以及一些重要生命标志物的高效检测提供理论依据与技术支撑，在技术与应用层面上为生物体内转录因子的识别和转录过程的探究提供新的途径。