Development of a new generation of fluorescent labeling agents based on rare-earth doped phosphors

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Development of a new generation of fluorescent labeling agents based on rare-earth doped phosphors

 

Author: Tsang, Ming Kiu
Title: Development of a new generation of fluorescent labeling agents based on rare-earth doped phosphors
Degree: M.Phil.
Year: 2014
Subject: Nanoparticles.
Fluorescent probes.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Applied Physics
Pages: xvi, 96 leaves : ill. (some col.) ; 30 cm.
InnoPac Record: http://library.polyu.edu.hk/record=b2681827
URI: http://theses.lib.polyu.edu.hk/handle/200/7384
Abstract: Upconversion nanoparticles (UCNPs) have emerged as a new generation of fluorescent probes for bioimaging owing to their unique upconversion (UC) property. Traditional labeling agents, such as quantum dots (QDs), organic dyes and fluorescent proteins suffer from non-idealities such as autofluorescence and photobleaching. QDs have also inherent high toxicity which may pose potential health hazards. Therefore, these non-idealities limited their applications as labeling agents. In contrast, UCNPs are excited by near infrared (NIR) radiation and thus they offer reduced autofluorescence, photodamage and deep tissue penetration. Moreover, they have low toxicity and high resistance to photobleaching. This work aims to develop new types of UC materials for multi-modal bioimaging based on rare-earth doped UCNPs. The UCNPs are synthesized by one-step and facile hydrothermal synthesis and then characterized by transmission and scanning electron microscopy, Fourier transform infrared spectroscopy, photoluminescence, X-ray diffraction, vibrating sample magnetometer, confocal optical microscopy and cytotoxicity. Firstly, NaGdF4:Yb/Er phosphors are synthesized by various surface modifiers via hydrothermal synthesis. The red to green ratio of UC emission and crystal phase variations are observed. Therefore, rational choices of surface modifiers can tailor the UC and structural properties of UCNPs. Moreover, these phosphors demonstrate paramagnetic and cathodoluminescence properties, which are suitable for applications in magnetic resonance imaging (MRI) and bioseparation. Additionally, barium based UCNPs have pure simple cubic phase structure, eliminating the phase transition issue. Novel PEI-modified Ba2LaF7 UCNPs possess small average size suitable for bioimaging. The Ba2LaF7 UCNPs achieved in-vitro bio-imaging at low concentration and the corresponding images are clearly recorded in green and red channel. Besides, fluorescent imaging in HeLa cells and MRI with various concentrations are successfully demonstrated using multi-functional PEI-modified BaGdF5:Yb/Er UCNPs. The cytotoxicity assay confirms the low toxicity nature of BaGdF5:Yb/Er UCNPs. Moreover, PEG-modified BaGdF5:Yb/Er UCNPs consist of Ba and Gd elements which show strong X-ray k-edge absorption values. The BaGdF5:Yb/Er UCNPs are injected intravenously into a living mouse and the spleen is clearly imaged under irradiation of X-ray with a circulation time of 2 h. Importantly, a tri-modal UC/MRI/computed X-ray tomography bioprobe is developed in a single phased compound by one-step hydrothermal method. In conclusion, a facile technique for controlling UC and crystal phase provides a low cost and simple strategy for synthesizing tailor-made UC phosphors. Also, PEI-modified Ba2LaF7 UNCPs have no problem with phase transition and they are able to demonstrate clear fluorescent imaging. Moreover, multi-functional BaGdF5:Yb/Er UCNPs are very useful multi-modal bio-imaging agent because three imaging techniques are integrated in one simple system and the corresponding advantages of one imaging technique can compensate the weakness of the others. Owing to low inherent toxicity, it is expected that the barium based UC materials are useful multi-modal bio-imaging agent.

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