基于磁性SERS编码水凝胶复合微球载体的多组分生物分子检测研究

Multiplex bioassay technology has important significance in the field of disease diagnosis and other fields. At present, biomolecular microspheres carriers with fluorescent dyes, quantum dots and structural colors as encoding elements have the disadvantages including instability or limited encoding. Based on surface enhanced Raman spectroscopy (SERS) with high sensitivity, narrow spectrum and light stability and other advantages, this project aims to build hydrogel composite microspheres by using monodisperse magnetic SERS-encoded particles as building block, and achieve efficient detection of multi-component tumor markers simultaneously. Magnetic SERS-encoded particles with the same surface and controllable interior structure are firstly constructed using monodisperse Fe3O4@SiO2 particles with yolk-shell structure as template, where the noble metal shell is generated in a controlled manner and different Raman reporters are encoded, and then the as-obtained SERS-encoded particles as building blocks are assembled uniformly and orderly, and solidified in the monodisperse hydrogel microspheres by using microfluidic, magnetic induction assembly and photopolymerization technologies, finally the magnetic separation and multiplex detection of tumor markers by monodisperse magnetic SERS encoding hydrogel composite microspheres will be realized. The ordered arrangement of the SERS-encoded particles and hierarchical structure of the microsphere carrier will enhance the stability and reproducibility of SERS-encoded signals. The implementation of this project has important theoretical and practical value for the simultaneous detection of multiplex bioassay.

多组分生物分析技术在疾病诊断等领域具有重要意义。目前以荧光染料、量子点、结构色等为编码元素的流动微球载体存在信号不稳定或编码有限等缺点。表面增强拉曼光谱（SERS）具有高灵敏度、窄谱峰和光稳定性等优势，本项目拟研发单分散磁性SERS编码探针，并以其为组装单元构筑水凝胶复合微球载体，实现对多组分肿瘤标志物的同时高效检测。以单分散Yolk-shell结构Fe3O4芯@SiO2壳颗粒为模板，利用其内部空间进行贵金属壳层可控生长和探针分子编码，制备出表面相同、结构可控的磁性SERS编码探针颗粒，通过微流控、磁诱导组装和光引发聚合将其均匀有序地组装并固化在单分散水凝胶微球内部，最终实现基于磁性SERS编码水凝胶复合微球对多组分肿瘤标志物的高效分离与拉曼检测。该微球载体的有序多级结构将极大提高SERS编码信号的重现性和稳定性。该项目的实施对多组分肿瘤标志物的同时检测具有重要的理论意义与实际应用价值。

多组分生物分析技术在疾病诊断等领域具有重要意义。本项目针对表面增强拉曼散射在多重免疫检测中存在的编码解码及可靠的信号获取等问题进行研究。基于表面增强拉曼光谱（SERS）具有高灵敏度、窄谱峰和光稳定性等优势，本项目提出开发一种SERS编码磁性光子晶体微珠。首先以单分散四氧化三铁微球为模板，设计合成高性能磁性SERS微球作为增强基底，并通过选取合适的拉曼分子开发出SERS编码颗粒作为组装单元；然后利用光微流控技术形成含有磁性编码SERS微球微乳液滴，通过磁性编码SERS微球在液滴表面的自组装和紫外辐照固化，实现具有光子晶体周期性结构的SERS编码磁性微珠；最后利用该微珠作为捕获基底与SERS探针结合，利用免疫结合对两种典型的肿瘤标志物进行检测。该项目设计的优势在于，联合运用了SERS编码的高容量和SERS检测的高灵敏度，且捕获基底的编码信号和探针信号可被同时收集。更重要的是，由于磁性编码SERS微球的周期性阵列分布，磁性SERS编码微珠的编码信号具有很好的重复性，作为信标可以在微珠载体上筛选出准确的探针拉曼信号，实现可靠的定量检测。该项目为SERS基多组分生物分子的可靠检测提供了一种优异的微珠载体和理论参考。