纳米四面体的拉曼增强效应及生物标志物的高灵敏多重检测

Noble nanoparticles assemblies showed structure dependent strong optical properties, in which Plasma interaction exhibited collective amplification effect. Nanoparticle pyramids possess unique structures, good biological reactivity and biocompatibility that have a great advantage in the sensor detection of biomarkers. This project will perform nanoparticle controllable synthesis, aptamer DNA skeleton design, nanoparticle interface modification to achieve functional nano-probes fabrication. Through the molecular recognition based nanoparticle self-assembly technology, this project will construct silver nanoparticle pyramids and the pyramids with proteins co-assembly structures, and investigate the dynamic assembly process. This project will also carry out the relationship and mechanism study between optical properties and different configuration structures of nanoparticle pyramids and its proteins co-assembly structures. The optical models will be established and Raman enhancement effect of nanoparticle pyramids will be demonstrated. The nanoparticle pyramids will be modified to improve stability against physiological solution, then the surface enhanced Raman scattering spectra based high sensitive and multiple cancer markers detection method will be constructed. This project provide new ideas to build medical sensor devices for simultaneous determination of multiple cancer markers.

贵金属纳米粒子自组装表现出结构相关联的强光学特性，等离子相互作用呈现整体放大效应。纳米四面体拥有独特结构及良好的生物反应活性和生物相容性使其在生物标志物传感分析方面具有极大的优势。本项目拟进行纳米粒子可控合成、适配体核酸骨架设计及纳米粒子界面修饰，实现功能性纳米探针制备。基于分子识别纳米材料自组装技术，构筑银纳米粒子四面体及其与蛋白共组装结构，进行动态组装过程研究。开展纳米粒子四面体及其与蛋白共组装体的不同结构构型和光谱学关联及机制研究；建立光学模型，阐释纳米四面体拉曼增强效应。进行纳米粒子四面体对生理溶液稳定性修饰，构建基于表面增强拉曼散射光谱的癌症标志物高灵敏、多重检测方法，为多种癌症标志物同时测定的医学检测器件构筑提供新的思路。

多重生物靶标的高灵敏、选择性检测会大大的降低分析时间和样品体积，在临床诊断上是必要的特别是对于疾病例如癌症的检测。本项目通过多种纳米粒子可控制备，核酸适配体嵌入的四面体骨架设计，纳米粒子功能化修饰，成功构筑了银纳米粒子四面体和银纳米粒子四面体与蛋白共组装结构，进行动态组装研究。我们基于核酸框架构筑的银纳米粒子四面体的产率高达80%，具有以下优越的性能：1）由于纳米四面体具有核酸构成的六条边，因此具有多重目标检测的能力；2）由于多间隙的存在，靶标可以实现驱动产生强表面增强拉曼信号；3）基于强拉曼信号的多重靶标检测具有抗基质干扰的性能。基于银纳米粒子四面体自组装，实现了前列腺特异性抗原、凝血酶及粘蛋白的多重靶标同时、高灵敏检测，检测限分别达到1.2 aM，158 aM 和 26 aM，并对检测方法进行了特异性和实际样品检测评价。基于三维四面体结构解析，通过电磁场理论计算阐释了拉曼信号增强机制，最终构建了高灵敏纳米粒子与蛋白共组装体系。