基于胶体晶体凝胶微载体的非标记多元生物分子检测

Genomics and proteomics reveal a growing number of important relationships between biological molecules and human health. By analyzing the information of the molecular biomarkers, we can detect some diseases of human body. Especially, with the information of multiplex biomarkers, many complex diseases could be diagnosed. In order to fast and accurately get the information of the biological markers in organisms, multiple analysis techniques have been widely used in the biological science. With the development of the multiplex and high-throughput assays, suspension arrays are attracting increasing attention because of their fast reaction speed, high sensitivity, and large encoding capacity for detection. In this project, we will develop a novel core-shell colloidal crystal hydrogel microcarrier that allows sensitive and selective detection of biomolecular in aqueous media. This novel microcarrier has close-packed opal colloidal crystal cores as their encoding units and responsive inverse-opal colloidal crystal hydrogel shells as their sensing units. In the case of label-free multiplex detection, the probes and their corresponding targets could be decoded by the diffraction peaks of the colloidal crystal cores. The specific recognition of the target and the cross-linked probes in the hydrogel shell of the microcarriers would cause the shell shrinking. This could be detected as a corresponding blue shift in the Bragg diffraction peak position of the colloidal crystal shell, which can be used to quantitatively estimate the amount of the target. This project will provide low cost, simple, real-time, label-free and multiplex monitoring of biomoecular.

基因组学和蛋白质组学研究揭示了越来越多的生物分子与人体健康状况的重要关系。为了快速准确地获取生物体内多种生物分子的信息，多元分析技术在生命科学领域得到了广泛的应用。流动载体编码技术由于其反应快速，灵敏度高，编码量大等特点受到广泛关注。本项目将从构建核壳结构的胶体晶体凝胶微载体入手，以密堆积的胶体晶体核为编码，同时结合胶体晶体凝胶壳层的环境响应特性和独特的光学特性，基于胶体粒子自组装的方法，设计和制备新型的适体功能化的多元生物分子检测胶体晶体凝胶微载体，并对该载体的功能和应用进行深入拓展研究，开发一种新的生物分子非标记多元分析技术。

随着生物科学、信息科学及材料科学的发展，生物传感技术得到空前发展。为了快速准确地获取多种目标物质的信息，多元分析技术在生命科学领域得到了广泛的应用。流动载体编码技术由于其反应快速，灵敏度高，编码量大等特点受到广泛关注。在本项目中，我们从构建胶体晶体入手，以核酸适体作为特异性识别单元，结合胶体晶体独特的光学性质，采用胶体粒子自组装的方法设计和制备了多种新型的多元检测胶体晶体凝胶传感器，并对该传感器的功能和应用进行深入研究，开发出了三种新型的实时快速的重金属离子生物检测方法。首先以适体修饰琼脂糖填充的二氧化硅光子晶体微球，利用光子晶体微球特有的反射峰作用编码，和琼脂糖表面修饰的适体与金属离子的特异性结合原理，使核算染料SYBR green I荧光发生改变，开发了可以用于应用于重金属多元检测的适体功能化光子晶体微球，实现了水体中的汞离子与银离子的同时检测。其次，基于刺激响应性的胶体晶体凝胶，以适体作为刺激响应单元，将适体链的两端通过化学修饰的方法连接在胶体晶体凝胶骨架上，利用适体结合目标分子前后构象的改变而导致的胶体晶体凝胶的颜色变化来构建可视化的重金属离子DNA逻辑门。最后我们以胶体晶体微球为模版，制备了核壳结构的胶体晶体凝胶微载体，该微载体以密堆积的二氧化硅胶体晶体为编码核，以具有反蛋白石结构的胶体晶体凝胶为响应壳，通过对胶体晶体微载体进行颜色观察或一次反射光谱检测就可以实现了重金属离子的非标记可视化检测，拓展了以适体为识别单元的胶体晶体非标记可视化检测技术的实际应用能力。