稀土光功能晶态杂化材料及疾病诊断性能研究

The multi-species and accurate detection for disease markers is of clinical importance for diseases early diagnosis, prognosis and prediction of treatment efficacy and recurrence. However, the most developed probes for disease markers’ detection concentrate on detecting a single disease marker, which usually experiences with false positive or negative results and thus doesn’t satisfy the demand of clinical accurate detection. And it still suffers from limited specificity and quantitative accuracy issues for disease markers’ multi-species detection since the concentration of different biomarker in biofluids varies from a low to high concentration level. Therefore, it is urgent to develop a highly sensitive assay method to achieve the diseases markers’ precise and multi-species detection within a wide concentration range. Based on studying the disease markers’ structures/response performances, mechanism of luminescence enhancement and responses, and influences of probers’ structures on detection performances, this research will develop near-infrared/up-conversion and water-stable luminescent sensors based on rare earth-functionalized metal-organic frameworks to realize the multiplex detection of several diseases markers, respectively, offering a minimal/non--invasive path for diseases’ clinic diagnosis. Implementation of this project is excepted to help us develop a sensitive, effective and facile assay method for diseases markers’ multi-species detection, and lay solid theoretical and technical foundation for diseases early diagnosis and prognosis knowledge.

疾病标志物的多指标精准检测在重症疾病的早期预警、疗效评估及预后判断中具有重要的临床价值。目前报道的探针大多是对单个标志物的检测，而单个标志物易出现假阳/阴性结果，难以满足临床要求；同时由于疾病多元标志物中各标志物含量跨度大，使其同步检测仍面临定量精确性不佳的问题。因此，构建灵敏度高、线性范围宽的分析方法是实现多元标志物精准检测亟待解决的问题。本申请拟以多元标志物的结构和响应性能为导向，通过研究荧光增强与响应机制以及晶体结构与响应性能之间的关系，指导设计合成出具有近红外/上转换发光特性以及水稳定性好的稀土光功能金属-有机骨架微纳复合材料，实现对疾病标志物的多指标同步检测，以期为疾病诊断提供一个微创/无创平台。本项目的实施有望建立起灵敏高效、方便快捷的疾病标志物多重分析系统，为临床重症疾病的早期预警和预后奠定坚实的试验和理论研究基础。

精准检测疾病标志物对于疾病特别是癌症的早期诊断、提高患者存活率具有重要意义，但其面临着识别特异性和定量精确性不佳的问题，易出现假阳/阴性诊断结果。针对此，本项目以体液中疾病标志物的精准检测为导向，通过探索新颖荧光增强与响应机制以及晶体结构与响应性能之间的关系，构筑了系列稳定性高、荧光性能优异、识别能力强的稀土光功能金属-有机骨架（MOFs）杂化探针。重要的是，提出将两种竞争机制融合到单一传感界面的新思路，设计合成了一种“竞争机制驱动的稀土MOF荧光探针，实现了对DNA氧化损伤标志物8-羟基脱氧鸟苷的“光控双模式”响应，为检测结果提供了双重保障，提高了诊断的可靠性；发展了结构介导动态范围/灵敏度调控的新方法，成功构筑了“窄窗口响应倍增”型稀土MOFs荧光探针，实现了对嗜铬细胞瘤标志物（香草扁桃酸）的三重精准定量，提高了区分标志物阴阳性的精确性。此外，将荧光检测与逻辑运算有效结合，设计了具有多重刺激响应功能的稀土MOFs基荧光逻辑探针，实现了对两种生物信号分子“开-关-开”的同步逻辑分析，为疾病监测中的多重分析提供了思路。本项目的实施为精准识别功能导向组分/结构设计提供了新方法和新型材料体系，为重大疾病的早期精准诊断奠定理论研究基础，具有重要的临床应用前景。