发光二极管激发的稀土上转换发光纳米材料的制备及生物成像应用

Rare-earth upconversion nanoprobes (UCNPs) have been widely investigated for bioimaging due to their unique Anti-Stokes shift properties that enable the conversion of low-energy photons into high-energy photons via multiphoton processes. To date, UCNPs are generally excited by laser devices for upconversion luminescence. However, the potential radiation risk, high price, limited life time and complex design of laser systems hinder the further application of the UCNPs. As an alternative, light-emitting diode (LED) holds great promise as an excitation source for bioimaging because of many inherent advantages. However, no photoluminescence upconversion has been reported upon LED excitation mainly due to the low upconversion efficiency of UCNPs and insufficient power density of LED. Base on the Nd-sensitized UCNPs (Nd-UCNPs), the energy transfer from Nd to Yb ions and excitation energy migration through Yb sublattice are optimized to largely enhance the upconversion luminescence of the Nd-UCNPs, and 740-nm LED lamp is adopted to excite these Nd-UCNPs. With the benefit of these novel LED-excited Nd-UCNPs, in-vivo and in-vitro bioimaging without high-costed laser or mercury vapour light sources are developed. Moreover, the using of LED as the excitation source enable the flexible LED array design towards novel strategies for the application and performance of the upconversion nanoprobes. Thus economic handheld LEDs devices are further developed for semi-quantitative visual measurement of UCNPs.

稀土上转换发光纳米材料作为一类新兴的生物荧光探针材料，由于其独特的反-斯托克斯位移发光特性，使其在应用至生物医学成像时具有诸多优势。然而其较低的上转换发光效率，使得具有足够强度的上转换发光以及基于此的各类生物医学应用，通常只能在激光光源的激发下完成。本项目采用发光二极管（LED）代替激光作为激发光源。为了实现LED激发下的明亮上转换发光，本项目选择新型的钕离子敏化的稀土上转换发光纳米颗粒为研究对象，通过解决钕离子到镱离子的能量转移最优化以及激发态能量在镱离子介质中的迁移效率最大化这两个关键问题，显著提高该上转换发光探针在低功率光源激发下的发光效率。该LED激发的上转换发光探针应用于体外细胞标记以及体内活体成像上，可以提高生物安全性，降低设备成本，提高使用寿命。本项目借助LED光源独有的封装与阵列技术，设计新颖的便携式检测设备，进一步拓展上转换发光材料在生物医学领域的应用。

稀土发光纳米颗粒由于镧系元素在可见光区及近红外光区优异丰富的发光性质，在生物光学成像技术上具有重要的应用价值。如何提高并优化这种新型发光探针材料的发光效率和生物兼容性，是其迈向临床生物学研究及应用道路上的关键问题。本项目通过对发光材料纳米尺度上的组分调控、异离子掺杂、晶相调控等手段，有效地提高了稀土发光纳米材料的上转换和下转换发光。采用高分子聚合物多种类、多层次地包覆手段，获得了具有优异生物兼容性的稀土纳米颗粒。在此基础上发展并实现了一系列先进的生物光学成像技术，有望进一步推动这种新型的发光探针材料在生物学研究以及临床上的应用。