基于荧光强度比的稀土上转换无机材料测温机理及其生物应用研究

For the non-contact temperature measurement based on the fluorescence intensity ratio, the rare earth doped upconversion nano-luminescent materials have important application prospects in biologic imaging and temperature detection without background fluorescence, because of their advantages of near infrared excitation, large Stokes shift and no influence on external excitation power et al.. However, due to the fact that the rare earth ions doped upconversion luminescent matrix materials for fluorescent temperature measurement are complex, and the lower luminescent efficiency of trivalent rare earth ions leads to the lower temperature sensitivity, it has become a bottleneck problem of restricting its application. This project will be devoted to the study of the temperature sensing mechanism and biological application of rare earth ions (Er3+/Tm3+/Ho3+/Yb3+) doped in upconversion inorganic luminescent materials. The relationship between the energy gap (∆E) and temperature sensitivity of rare earth ion thermal coupling level and non-thermal coupling will be studied by means of spectroscopy; combined with spectral data and the dielectric theory of chemical bond on complex crystals, the influence mechanism of crystal structure parameters on luminescent efficiency and temperature sensitivity will be investigated, the quantitative relationship between temperature sensitivity and matrix crystal chemical bond parameters can be found out finally. At the same time, the synthesis and surface modification methods of rare earth doped upconversion nanomaterials will be also researched and designed. The material properties will be optimized, a precise temperature measurement method based on fluorescence intensity ratio of rare earth doped upconversion luminescent nano-materials will be established.

基于荧光强度比的非接触测温用稀土上转换纳米发光材料因其近红外光激发、反Stokes位移大，不受外界激发功率影响等优点，在无背景荧光的生物成像及温度检测中具有重要应用前景。然而，由于目前用于荧光测温的稀土离子掺杂上转换发光基质材料繁杂，以及三价稀土离子发光效率低导致的测温灵敏度低等问题，成为制约其应用的瓶颈。本项目将致力于探索稀土离子（Er3+/Tm3+/Ho3+/Yb3+）在上转换无机发光材料中的测温机理及其生物应用研究。利用光谱学手段探究稀土离子热耦合能级以及非热耦合能级间的能级差与测温灵敏度之间的关系；结合光谱数据和复杂晶体化学键介电理论，探讨基质晶体结构参数对发光效率、测温灵敏度的影响机制，找出测温灵敏度与基质晶体化学键参数之间的定量关系。与此同时，研究设计纳米材料的合成及表面改性方法，优化材料性能，最终建立基于荧光强度比的稀土掺杂上转换纳米发光材料的生物体系精准测温方法。

随着现代生物医学技术的高速发展，对亚微米乃至纳米尺度的生物体内细胞的温度探测速度和精度也提出了更高要求。然而，对于生物体内只有10-100μm大小的细胞，传统接触式温度计由于测量尺度难以缩小导致在探测速度和精度上受到极大的限制。因此，发展具有较高的温度分辨率且能够实现快速响应的非接触式温度传感器对于现代生物医学研究具有非常重要的现实意义。本项目采用软化学合成方法设计合成了PEI包裹的CaF2：Yb3+/Er3+ 上转换纳米晶； YbF3:3%Er3+@SiO2@GQDs核壳结构；稀土掺杂哑铃型NaYF4@NaYF4@NaNdF4纳米晶以及CaF2: Nd3+, Nd3+/Yb3+@NaYF4纳米晶等。利用980nm可控温多模半导体光纤输出激光器作为激发光源激发样品，研究稀土离子在紫外-可见（200-900nm）光谱范围内的发射性质、发光机理及测温机理。利用复杂晶体化学键介电理论，拆分键子式，计算化学键参数，发现测温灵敏度与基质材料的共价性存在正相关；不仅如此，共价性与键体积极化率和离子极化率也存在相关性，实现了Er3+的热耦合测温性能的预测。应用Arrhenius方程分析了稀土离子基于非热耦合荧光强度比（NTCL-FIR）的温度传感特性，提出了NTCL-FIR测温模型。另外，选择具有高测温灵敏度的发光材料进行可控合成、表面改性、光谱微调、功能化修饰，初步获得模拟生物组织中基于荧光强度比的测温方法，同时，我们进一步探索了该测温计在模拟生物组织中进行测温时需要注意的问题，经过大量矫正后成功探测到生物组织的温度。项目执行期间共发表相关SCI论文24篇；应邀撰写《Phosphor Handbook》（CRC Press）中“Lanthanide-based Phosphors for Thermometry” 一章；2021年8月受邀担任全球发光学领域最高水平学术性会议—第19届国际发光会议（ICL’20）分会主席；培养博士生6人，硕士生14人。