面向复杂寡糖链检测分析的功能纳米通道器件

寡糖链广泛地分布在哺乳动物细胞和一些分泌蛋白质表面，参与了细胞识别、免疫响应、病毒感染、癌症发生发展等众多生命活动。寡糖链结构复杂、种类多样且丰度极低，其识别、鉴定及组成结构解析强烈地依赖生物质谱及其与核磁、色谱等技术的联用。然而，这些手段操作复杂，需要丰富的专业知识和经验积累，无法满足寡糖链的常规检测分析需求。针对这一问题，本项目拟采用功能纳米通道作为检测分析器件来提供一种解决方案。基于前期生物分子响应性聚合物研究基础，设计寡糖链特异性识别受体，与聚合物主体整合开发出功能聚合物，进一步修饰到纳米通道内部实现功能纳米通道器件的构筑。聚合物对寡糖链的多位点识别能够诱导聚合物链自身发生构象的转变，这使得对寡糖链的识别效应从单分子层面被放大到聚合物层面；进一步借助构象转变所造成的离子电流变化，则可实现对特征寡糖链的识别、检测、区分等，并探索形成一种简单、快速、低成本且高灵敏性的寡糖链分析方法。

Oligosaccharides are widely distributed on the surface of mammalian cells and most proteins, playing important roles in cell recognition, immune response, pathogen infection, the occurrence and progression of most cancers. Precisely recognizing oligosaccharides, discriminating different structure types, and decoding the composition and sequence can facilitate both the understanding of disease progression and the improvement of early diagnoses and targeted treatments. Due to the complicated composition, subtle structural differences, and ultralow abundance, the analysis approaches rely excessively on mass spectrography coupled with nuclear magnetic resonance spectroscopy or various chromatographic techniques. However, the requirements of complex operation processes, extensive expertise, complicated glycan derivatization, or high pure sample amounts have prevented these approaches becoming the routine methods. Concerning this issue, this project aims to develop functional polymer-modified nanochannel as a detection device of oligosaccharides to provide a solution. Based on the previous works of biomolecule-responsive polymers, we plan to design the specific receptor for oligosaccharides and develop receptor-bearing functional polymer, and further integrate the polymer with nanochannels substrate to achieve the construction of functional nanochannels device. The polymer can recognize and bind the characteristic oligosaccharide via a multivalent mode, which will trigger a conformational change of the polymer, remarkably amplifying the recognition effect from the small molecular level to the macromolecular level. By taking advantage of the sensitive ionic current changes resulting from the conformational change of the polymer modified on nanochannel inner surface, the functional nanochannel device enables the recognition, detection, and discrimination towards various characteristic oligosaccharides. Moreover, depending on the affinity of the polymer to the oligosaccharide, we plan to explore the feasibility of single-molecule detection and analysis for oligosaccharide based on the polymer-modified single nanochannel/nanopore. This project would contribute a simple, fast, low-cost, and highly sensitive detection analysis method for oligosaccharides.