单一粒子上转换发光可调的纳米探针及其生物标记方法

Dyes, quantum dots and upconversion luminescence nanoparticles have been widely used in biolabelling and imaging, one common feature is that they only produce a single wavelength emission under the fixed components and structures, which will affect the reliability of biolabelling and in vivo imaging, and then limit its scope of application, especially for the labelling and simultaneous imaging of multi-target. In this proposal, we will explore the way of multicolor luminescence on the individual upconversion nanoparticle and its mechanism of multicolor conversion, and develop individual upconversion nanoparticle-based multicolor labelling and imaging technique. (1) According to the principle of superposition tricolor, designing and synthesizing the individual upconversion nanoprobe containing with blue, green and red emitting units by doping rare earth ions Tm3+, Er3+ and Eu3+ in a core-shell nanostructure. (2) Constructing the upconversion nanoprobe with white color emission and exploring the way of multicolor conversion and explaining the basic rules of the energy transfer and its migration, achieving the light conversion of individual upconversion from white to others. (3) Further developing the principle and method of multicolor labelling and imaging by functional modification, achieving the multicolor labelling and simultaneous image analysis of targets by controlling the excited conditions. The obtained results in this proposal will provide a new means for the biolabelling and imaging.

染料、量子点和上转换稀土发光纳米粒子等已经被广泛应用于生物标记与成像，它们的一个共同特点是在成分和结构固定情况之下只能产生单一波长发射，将影响生物标记与活体成像的可靠性并限制其应用范围，尤其对多目标物的标记及其同步影像分析。本项目拟探索单个上转换纳米粒子实现多颜色发光的途径及其多色转换机制，发展基于单粒子上转换的多色标记及成像技术：（1）通过在核-壳结构中分别掺杂稀土离子Tm3+、Er3+和Eu3+等，根据三基色叠加原理，设计和合成具有蓝色、绿色和红色发射单元构成的单粒子上转换纳米探针；（2）构建发白光的上转换纳米探针，探索其多色转换的途径并阐明发光体系中能量传递及迁移的基本规律，实现单个上转换粒子从白光向其它各种颜色光的转变；（3）通过功能化修饰，发展基于单一粒子上转换的多色标记及成像的原理和方法，通过激发条件控制，实现对目标分析物的多色标记和影像分析。预期成果将为标记和成像提供新手段。

本项目针对目标物的多色标记及其同步影像分析，探索了在单一纳米粒子上实现多颜色发光的途径及其多色转换机制，构筑出具有白光发射的单个上转换纳米粒子，并通过改变激发光的功率密度，成功地实现了对其发光颜色的可控调制及目标物的多色标记。与此同时，在生物活性分子的原位检测与成像、肿瘤细胞的识别与鉴定、以及肿瘤的跨平台检测等方面也取得了多项具有创新性和系统性的研究成果。上述研究工作已经在Journal of the American Chemistry Society、Angewandte Chemie International Edition、ACS Nano、Analytical Chemistry等高影响力的国际期刊上发表SCI论文23篇。这些研究成果极大地扩展了纳米光学技术在生物研究和医学诊断中的应用，为生物标记及其活体检测与成像提供了一条有效的途径。