液相电子显微镜解析高分子动态过程

Liquid-phase Electron Microscopy Imaging of Polymer Dynamics

电子显微镜被广泛用于表征高分子的形态、晶态结构、机械性质及组装行为,其在溶液态高分子的动态过程研究的应用中刚刚起步.近年来,由于在电镜真空腔中能稳定封存液体样品的纳米技术的发展以及对电子束与样品的作用机制的逐渐清晰,液相电镜实验实现了对溶液态高分子的高时空分辨、原位、实时、时空的“分子录影”.单分子原位成像实验提供了新的机遇去探索被传统系综测量掩盖的分子动力学行为.我们总结了液相电镜技术在高分子单链物理性质、单分子反应、组装体与组装行为、相分离等领域的研究进展,阐述了其中实验难点以及核心技术突破,详细讨论了电子束与样品相互作用和单分子成像实验揭示的关于高分子科学的新现象、新问题和新思考.最后,展望了突破目前纳米级空间分辨率和百毫秒时间分辨率可行的方案、面临的挑战和所需的技术支持,以及该目标实现后将给我们带来新的研究机遇.

The study of conformational changes in polymer chains,their assembly behavior,and the mechanisms behind these phenomena are fundamental problems in polymer science.These factors not only play a crucial role in determining the synthesis,properties and applications of polymer materials,but also have far-reaching implications for the study of biomolecular interactions and biochemical reaction systems.While substantial progress has been made in theoretical and computational methods,observing the dynamic behavior of single polymer chains and their assemblies in a solution state remains as a significant challenge.Liquid-phase transmission electron microscopy(LP-TEM)offers an unprecedented combination of atomic-level spatial resolution and millisecond temporal resolution.This innovative technique provides fresh opportunities to investigate the hidden dynamics of molecules that have traditionally been obscured by ensemble measurements.Electron microscopy has been widely used to analyze the morphology,crystalline structure,mechanical properties,and assembly structures of dry-state polymers.More recently,it has facilitated the study of the dynamic behavior of polymers in solution.The feasibility of LP-TEM experiments is largely owed to advancements in nanotechnologies,enabling the sealing of liquid samples within a chamber to prevent exposure to a vacuum environment.With a good understanding of electron beam-sample interactions and interface-sample interaction,real time imaging of individual macromolecules and their assembly pathways in solution have been successfully achieved despite their fragility.In this review,we first introduce the development of LP-TEM and its experimental setup,then summarize the progresses of LP-TEM experiments on the single chain dynamics of polymers,transient processes of macromolecular interactions,assembly pathways,and phase separations;with an emphasis on the experimental challenges and the corresponding methodological advancements that enabled these experiments.We also discuss the new questions triggered by observations from these experiments and the future directions including the challenges and possible technical assistance,as well as the new research opportunities that this goal will bring.