稀土掺杂上转换发光纳米颗粒的合成及其在生物分析中的应用

附件2

论文中英文摘要

作者姓名：王猛

论文题目：稀土掺杂上转换发光纳米颗粒的合成及其在生物分析中的应用作者简介：王猛，男，1983年1月出生，2007年3月师从于东北大学徐淑坤教授，于2011年1月获博士学位。

中文摘要

稀土掺杂上转换发光纳米颗粒是一类重要的发光材料，它可以通过双光子或多光子机制将低频率的激发光转换成高频率的发射光。近年来，上转换纳米颗粒作为一种新型的生物标记物在生物方面的应用倍受人们关注。与传统的荧光标记物（如有机染料、量子点等）所不同，上转换纳米颗粒的激发光为红外光，可以有效避免生物体自体荧光的干扰，从而提高检测的灵敏度及信噪比。红外光对生物组织还有良好的穿透能力，对生物样品造成光损伤也较小。另外，上转换纳米颗粒还具有毒性低、稳定性好、发光强度高、Stokes位移大等优点，在生物标记和生物检测等领域有着非常好的应用潜力。迄今为止，Yb3+-Er3+、Yb3+-Tm3+离子掺杂的β-NaYF4上转换材料被公认为是所有上转换材料中发光效率最高的。因此，合成出高质量的稀土掺杂β-NaYF4上转换纳米颗粒是使其在生物等领域广泛应用的前提，具有十分重要的研究意义。

本项研究分别采用络合共沉淀法、热分解法以及溶剂热法合成了β-NaYF4:Yb,Er上转换纳米颗粒，并对反应机理进行了探讨。考察了反应条件对纳米颗粒的粒径、晶体类型以及发光强度等性能的影响。其中，采用溶剂热法合成的纳米颗粒具有粒径较小、晶型较纯、发光强度高等优点，在生物标记等应用中更具优势。又将NaYbF4作为发光基质材料，合成了Er3+、Tm3+、Ho3+离子单掺杂以及双掺杂的β-NaYbF4上转换纳米颗粒。这些纳米颗粒在980 nm红外光的激发下能够产生橙、黄、绿、青、蓝、紫六种颜色的发光，在多色标记和多元分析中有着广阔的应用前景。另外，将几种亲水性的聚合物作为配体，利用溶剂热法合成了表面聚合物包覆的亲水性β-NaYF4:Yb,Er上转换纳米颗粒。

采用经典的Stöber法将合成的上转换纳米颗粒表面包覆SiO2并氨基化修饰，使其具有良好的水溶性和生物相容性。将氨基修饰纳米颗粒与兔抗人CEA8抗体偶联，通过HeLa细胞表面的CEA抗原与兔抗人CEA8抗体之间的特异性结合，实现了上转换纳米颗粒对HeLa活细胞的免疫标记与成像。该免疫标记具有特异性良好、时效性高、无自体荧光干扰等优点。

将兔抗羊IgG偶联的NaYF4:Yb,Er纳米颗粒作为能量的供体、人IgG偶联的纳米金作为能

量的受体，构建了二者之间的发光共振能量转移体系，并探讨了该过程的机理。建立了在该

发光共振能量转移体系中利用“夹心法”检测羊抗人IgG抗体的模型，并用于羊抗人IgG抗

体的检测。当羊抗人IgG的浓度C在3~67 μg·mL-1范围内时，体系发光强度的淬灭∆I与C

之间呈良好的线性关系，其线性回归方程为∆I = 15.18+3.446C，线性相关系数R = 0.9994。该

方法的检出限（3σ/N）为0.88 μg·mL-1，相对标准偏差RSD为1.3%（C = 60 μg·mL-1，n = 11）。此外，将表面氨基修饰的NaYbF4:Tm纳米颗粒作为能量的供体、表面羧基修饰的CdTe量子

点作为能量的受体，构建了二者之间的发光共振能量转移体系，并探讨了该过程的机理。考

察了受体浓度的变化对体系中供体及受体发光性质的影响。以上建立的两种模型可以拓展到

其他具有特异性结合的体系（例如抗原-抗体体系、生物素-亲和素体系）中，进而用于相关

物质的定量检测。

关键词：上转换；稀土发光材料；纳米颗粒；生物探针；共沉淀；热分解；溶剂热；免疫标记；细胞成像；发光共振能量转移

Synthesis of Rare Earth Doped Upconversion Luminescent Nanoparticles and Their Applications in Biological Analysis

Wang Meng

ABSTRACT

Rare-earth (RE) doped upconversion (UC) luminescent nanoparticles (NPs), which can convert a longer wavelength radiation to a shorter wavelength luminescence via a two-photon or multi-photon mechanism, have emerged as an important class of luminescent materials. In recent years, UCNPs used as biolabels for biological detections have garnered a tremendous amount of attention due to their unique optical properties. Distinguished from the traditional fluorescent biolabels, such as organic dyes and quantum dots (QDs), UCNPs can be excited by infrared (IR) radiation, which results in an excellent signal-to-noise ratio and improves the detection sensitivity, owing to the absence of autofluorescence (background). Meanwhile, the IR excitation light can penetrate more deeply into biological tissues, with less photo damage to biological samples. In addition, UCNPs also have several advantages, such as low toxicity, good chemical and physical stability, high emission intensity, and large Stokes shifts. Consequently, UCNPs have great superiority as luminescent materials for biolabeling and biological detections. Up to now, the most efficient UC materials are based on hexagonal phased (β-phase) NaYF4, co-doped with Yb3+-Er3+ or Yb3+-Tm3+ion couples. Therefore, the synthesis of RE ion co-doped NaYF4UCNPs with high-quality is of importance, and the precondition for their biological applications.

In this study, β-NaYF4:Yb,Er UCNPs were synthesized by the coprecipitation, thermal decomposition, and solvothermal method, respectively, and the reaction mechanism of each method was discussed. The effects of reaction parameters on size, phase and luminescent intensity of the UCNPs were also investigated in detail. In particular, the UCNPs synthesized by solvothermal method have more prominent potentials in biological applications, due to their small size, pure phase, and high luminescent intensity. By co-doping or tri-doping with Er3+, Tm3+ and Ho3+ ions in a single NaYbF4 host, a series of UCNPs were also synthesized by the solvothermal method. These UCNPs could be excited by 980 nm IR radiation to give multicolor emissions, including orange, yellow, green, cyan, blue, and pink, which possesses prominent potentials in the multicolored biolabeling and multiplexed analysis. Furthermore, several kinds of polymer-coated hydrophilic