磷光金属配合物材料用于发光寿命生物成像与检测

With the fast development of microscopy and fluorescent probes, photoluminescence imaging has been widely employed in the research of life science owing to its specific, high contrast and real-time visualization of physiological and pathophysiological processes at cellular, subcellular, and molecular levels. Luminescence intensity is usually used to create images. However, when the probes are used in complicated biological environments, the accuracy and precision of the detection are reduced because the detected luminescence intensity is also affected by the uncertain intracellular or in vivo probe concentrations, fluctuated excitation laser power, and autofluorescence from endogenous fluorophores. Additionally, probes with similar excitation or emission wavelengths are difficult to be distinguished from each other. Luminescence lifetime is one of the most important parameter of a luminescence signal. It is neglectably affected by concentration variation of the intracellular luminophore or the excitation laser power. Even if probes display similar excitation or emission wavelengths, they can be distinguished based on their different decay rates. In this proposed project, we will design and synthesize long-lived transition-metal complexes, and demonstrate the utilization of these probes for accurate, sensitive, specific bioimaging and biosensing via photoluminescence lifetime imaging microscopy with high signal-to-noise ratio. We will realize bioimaging and detection of multiple analytes with multiple probes, and isolate and analyze different luminescence signal in the time domain. We anticipate the implementation of the proposed project will promote the development of the long-lived luminescent probes in photoluminescence lifetime imaging.

随着显微技术和荧光探针的高速发展，荧光成像以其可特异性标记、高对比度、动态示踪能力广泛应用于生命科学研究领域。然而，成像过程在一定程度上受制于生物样品背景荧光影响、多探针信号交叉干扰、探针浓度不确定、激发功率波动等因素，降低了生物显微成像检测的准确性、稳定性、灵敏度和信噪比。激发态寿命是发光信号的重要参数之一。其数值不受探针浓度或激发功率影响。同时，即使多个探针具有相同或相似的激发和发射波长，也可以通过它们不同的发射寿命进行区分。本项目拟设计、制备长发光寿命的磷光过渡金属配合物，利用发光寿命成像技术在时间尺度上分辨检测信号，实现准确、稳定、高灵敏度和高信噪比的生物成像与检测应用。在细胞和小动物层次实现利用多个磷光染料同时成像，多个磷光探针同时检测多种分析物。望通过本项目的实施，从结构设计、材料开发和成像应用等方面做出创新性的研究工作，推动长寿命磷光生物探针材料在寿命成像这一新兴领域的发展。

磷光过渡金属配合物因其优异的光物理与光化学性质，在电致发光器件、光伏电池、信息存储、生物传感等方面的应用成为国际研究的热点，吸引了国内外学者的广泛研究兴趣和科技产业界的广泛关注。其中，磷光铱配合物由于具有发光效率高、发射波长可调、Stokes 位移大、光稳定好等优点，作为一类性能优异的光电功能材料在有机光电子领域具有很好的应用前景，引起了广泛的研究兴趣。本项目围绕磷光铱配合物的激发态性质以及功能应用开展了系统研究并取得重要进展。主要研究内容包括（1）新型双磷光发射铱配合物在乏氧/富氧检测中的应用；（2）多吡啶铱配合物在区分活细胞中内/外源性分析物的应用。在本项目的支持下，项目负责人在Chemical Reviews、Journal of the American Chemical Society、Chemical Science等期刊发表SCI论文5篇，申请并公开中国发明专利2件。项目负责人的研究成果获得国内外同行的高度认可，1篇论文入选ESI高被引论文，1篇论文入选ESI热点论文。另外，在本项目的支持下，培养或协助培养了博士/硕士研究生和本科生十余名。