单分子分辨率的实时空间定量分子分析
近日，苏州大学宋斌团队研究了单分子分辨率的实时空间定量分子分析。这一研究成果于2025年9月8日发表在《美国化学会志》上。
分子分析和表征技术的进步将彻底改变物理、化学和生物学的科学探索方法，从根本上颠覆他们对微观水平上控制分子行为的相互作用和过程的理解。目前，缺乏一种既能定量分子又能实现单分子空间分辨率的分子分析方法，阻碍了他们对复杂分子体系在吸附和催化中的研究。
研究组提出了一种基于低剂量透射电镜的小分子定量分析策略，该策略局限于ZSM-5（一种广泛用于催化和气体分离的沸石材料）中。这种方法使分子结构具有埃空间分辨率的可视化，并有助于通过详细的分子成像进行识别。通过将实验和模拟图像与吸附数据相结合，精确校准了每个沸石通道内小分子的数量，从而推进了ZSM-5通道内分子的吸附、运输和反应动力学的研究。
对这些过程的定量见解增强了他们对微观机制的理解，阐明了主客体相互作用、分子几何和外部刺激的作用。该工作扩展了低剂量电子显微镜在分子成像和分析中的应用，使其成为一种空间分辨和定量的工具，用于研究以前无法进入的真实空间中的分子行为。
附：英文原文
Title: Real-Space Quantitative Molecular Analysis at Single-Molecule Resolution
Author: Jiale Feng, Wenbo Li, Mengmeng Ma, Jiayi Zhang, Tongyu He, Tao Cheng, Sheng Dai, Bin Song, Boyuan Shen
Issue&Volume: September 8, 2025
Abstract: Advances in molecular analysis and characterization techniques should revolutionize the methods for scientific exploration across physics, chemistry, and biology, fundamentally overturning our understanding of interactions and processes that govern molecular behavior at the microscopic level. Currently, the absence of a molecular analysis method that can both quantify molecules and achieve single-molecule spatial resolution hinders our study of complex molecular systems in sorption and catalysis. Here, we propose a quantitative analysis strategy for small molecules confined in ZSM-5, a zeolite material extensively used in catalysis and gas separation, based on low-dose transmission electron microscopy. This approach enables the visualization of molecular structures with angstrom spatial resolution and facilitates their identification through detailed molecular imaging. By integrating experimental and simulated images with adsorption data, the quantity of small molecules within each zeolite channel is precisely calibrated, thereby advancing the study of the molecular sorption, transport, and reaction dynamics in ZSM-5 channels. The quantitative insights into these processes enhance our understanding of microscale mechanisms, elucidating the roles of host–guest interactions, molecular geometry, and external stimulus. This work expands the application of low-dose electron microscopy in molecular imaging and analysis, establishing it as a spatially resolved and quantitative tool for studying molecular behaviors in real space that is previously inaccessible.
DOI: 10.1021/jacs.5c08253