Real-Space Quantitative Molecular Analysis at Single-Molecule Resolution

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.