Streamlined Liquid-Phase Electron Microscopy: Engineered Nanocontainers and Air-Free Loading for High-Resolution Imaging of Biospecimens

Abstract Liquid-phase electron microscopy has emerged as an advanced technique for observing dynamic phenomena in liquids at near-atomic spatial resolution. A newly developed technique offers an easier, faster, and more reproducible way to prepare liquid samples for transmission electron microscopy. Herein, we introduce proprietary nanocontainers and an air-free sample loading method that have significantly simplified the preparation of in-liquid specimens through straightforward drop-casting. By demonstrating this technique with ultrathin windows, we successfully imaged low-contrast vesicles and plasmid DNA. Our approach simplifies usage and enhances throughput and reproducibility, thereby lowering the entry barrier to this rapidly growing field.