基于核酸适体的纳米管/孔分子开关生物分析体系研究

The high specific recognition reaction between aptamer and its target molecules are promising to be used in the development of novel methods and molecular devices for bioanalysis. Combination of aptamer and nanotube/pore for the construction of molecular valve system will provide theoretical guidance and experimental evidence for the understanding of mass transfer in confined nanospace. The central scientific question in the study of nanotube/pore-molecular valve system is to uncover and understanding the interaction mechanism of aptamer-target recognition to the mass transfer in nanotube/pore. In the present project, porous anodic alumina (PAA) membrane and mesoporous silica nanospheres (MSN) will be adopted as the substrate material and aptamer will be chemically attached in the the nanotube/pore. Electrochemical measurement, fluorescence, UV-Vis spectroscopy will be selected for understanding of the steric hindrance and electrostatic repulsion effects caused by the aptamer-target recognition. Then, these analytical methods will be applied for measuring the dynamics of drug release through nanotube/pore. Morpholino, an neutral analog of DNA which bears strong anti-enzymolysis ability, is designed to be applied in the nanotube/pre-molecular valve system in order to develop a series of novel bioanalytical methods for practical application. Successful functioning of this project will yield valuable knowledge for solving problems in the field of separation and detection of analytes in complicated system and targeted drug deliver.

适体与靶分子间的高特异性识别作用为发展生物分析新方法以及新型分子器件提供了潜在手段。将适体与纳米管/孔结合构建分子开关体系将为理解纳米空间中外场对物质传输的影响提供理论依据和实验指导。纳米管/孔分子开关生物分析体系研究的核心科学问题是认识和理解适体-靶分子识别反应影响物质传输的作用机制。本项目将以氧化铝阵列纳米通道膜和介孔纳米二氧化硅为基质材料，将适体分子键合在纳米管/孔口形成纳米分子开关体系,利用电化学、荧光及光度法研究空间位阻、电荷效应等对物质传输性质的影响规律，考察识别反应发生前后模型药物分子的释放动力学。同时，结合DNA中性类似物吗啉核酸的抗酶解特性设计和测试具有抗酶解能力的新型适体分子开关生物分析体系，发展一系列新型靶分子检测方法。成果将为解决复杂样品的选择性分离检测与药物靶向输运技术中的核心问题提供必要的基础研究信息。

适体与靶分子间的高特异性识别作用为发展生物分析新方法以及新型分子器件提供了潜在手段。将适体与纳米管/孔结合构建分子开关体系将为理解纳米空间中外场对物质传输的影响提供理论依据和实验指导。纳米管/孔分子开关生物分析体系研究的核心科学问题是认识和理解适体-靶分子识别反应影响物质传输的作用机制。经过4年研究，本项目在适体-纳米管/孔模型体系的建立、物质传输过程的测量与调节、以及胞内检测等方面都取得了较大进展。基于适体与其他生物分子修饰，已经发展出胞内ATP传感器件，发表了相关论文并申请了专利。