非酶基高分子凝胶的葡萄糖增强效应及传感响应性研究

Glucose sensing plays a key role in the molecular aspect study and the clinic diagnosis and treatment of diabetes mellitus. Polymer sciences should be put into the research in the field of glucose sensor, where the largest need at present is a suitable material and the working mechanism for true sensing. To this end, this project aims to synthesize a series of novel glucose-responsive polymer/inorganic hybrid nanogels of glucose-enhanced emission, by combinating the methodologies for the synthesis of phenylboronic acid-contained monomers of designed structures, free-redical precipition polymerization, and the controlled synthesis of inorganic particles, as well as the molecular imprinting technique for optimizing the network structure of the hybrid nanogels. The volume phase transition behaviors and the kinetics of the hybrid nanogels in very dilute aqueous solution will be studied in detail, so as to understand the interactional rules between the environmental glucose, the gel's volume phase transition, and the inorganic particles. On the basis of these studies, a new method should be builded up for the dynamic control of the fluorescence intensity of the hybrid nanogels.The model for the quantitative conversion of glucose concentration into fluorescent singnal will also be constructed, and thus these hybrid nanogels can serve as sensors for optically ratiometric readout of glucose concentrations. Therefore, this project should provide fundamental guidance for the construction of novel glucose sensor from the viewpoints of polymer chemistry and physics. As an outcome, a new class of glucose sensor of ultra-sensitive and high-selectivity will be developed in the form of a polymerized film of the hybrid nanogel sensors' array. At last but not the least, to evaluate the applicability of the developed hybrid nanogels and the polymerized films, they will be employed in the measurement of the fasting glucose (FG) levels in real blood serum samples, which should push the fundamental research on the non-enzymatic gels, a case of the complex soft maters, move towards our real world.

葡萄糖检测是糖尿病等疾病的分子机理研究和临床诊治的关键之一。解决当前葡萄糖传感器存在的主要挑战性问题（可持续检测葡萄糖的机制及其材料）有待高分子科学的投入，本项目拟通过苯硼酸基单体设计、自由基沉淀聚合、无机粒子可控合成相关方法以及凝胶网络的分子印迹技术优化来合成环境葡萄糖增强发光型的响应性高分子/无机杂化纳米凝胶，着重研究其在极稀溶液中的体积相转变行为和动力学，揭示环境葡萄糖、凝胶体积相转变和无机粒子之间的相互作用规律，建立杂化纳米凝胶荧光强度的动态调控新方法，并构建环境葡萄糖- - 荧光信号定量转换模型，为从高分子化学与物理的角度设计新型的葡萄糖传感器提供关键科学依据。在此基础上，提出提高对环境葡萄糖的传感响应性的有效策略，设计和研制具有超灵敏高选择性的聚合传感器阵列薄膜。项目还将精确评价所设计的葡萄糖传感器的性能，作为推动非酶基高分子凝胶这一复杂软物质体系的基础研究通往实际应用的一例尝试。

重点针对当前葡萄糖检测存在的挑战性科学问题（可持续检测葡萄糖的机制及其材料），本项目吸取前期探索及其他项目研究工作之精华，系统深入地研究了葡萄糖增强发光型葡萄糖响应微凝胶这一核心新体系。（1）相关合成方法探索：从设计不同的化学合成途径出发，我们发展了超小微凝胶、含染料/共轭高分子微凝胶、含天然生物高分子微凝胶、含金属离子/粒子微凝胶等的合成方法，以及以微凝胶等颗粒为组装基元的自组装体材料制备方法，并探讨形成机理，为探索可控合成葡萄糖响应微凝胶及其聚合传感器阵列薄膜提供合成技术储备。（2）葡萄糖增强发光型葡萄糖响应微凝胶的合成与性能研究：针对研究目标，我们着重提出两种实现葡萄糖增强发光的策略（微凝胶随葡萄糖浓度增大而溶胀，并通过体积相转变调节半导体和贵金属纳米粒子耦合，以实现葡萄糖增强发光；微凝胶随葡萄糖浓度增大而收缩，并通过体积相转变改变发色团微环境，以实现葡萄糖增强发光），分别设计合成出含氧化锌/金粒子微凝胶、含银粒子微凝胶、含石墨烯微凝胶这三类葡萄糖增强发光型聚苯硼酸微凝胶，阐明葡萄糖——荧光信号定量转换规律和动力学，进而将微凝胶用于定量检测人工泪液、血清等体系中葡萄糖浓度以评价其传感响应性能。（3）以微凝胶作为组装基元的聚合传感器阵列薄膜的制备与性能研究：针对研究目标，我们以优化合成的葡萄糖响应微凝胶作为阵列单元，制备了聚合传感器阵列薄膜，阐明葡萄糖——光学信号定量转换规律和动力学，并定量检测人工泪液、血清等体系中葡萄糖浓度以评价传感响应性能，进而将薄膜与隐形眼镜相结合，尝试发展快速、持续、定量检测葡萄糖的可穿戴式葡萄糖传感器。综上所述，本项目研究结果体现了非酶基高分子凝胶的合成、葡萄糖响应特性及其在生物医药等的应用，为从高分子科学角度来设计葡萄糖传感器提供了科学依据，也为理解普遍认为最关键的问题——材料结构与性能的关系——提供了有价值的视角。