DNA Base-Pairing Visualized by Liquid-Cell Transmission Electron Microscopy

We show that fragile biological samples including DNA can be imaged using in situ transmission electron microscopy (TEM) without metal staining. Reporting statistical analysis of large datasets concerning single-strand and double-stranded aqueous DNA trapped in creases between paired graphene sheets, we visualize individual molecules with ~1 nm spatial resolution and ~100 ms time resolution for up to ~3 min, apparently without significant perturbation from the electron beam. Inspecting the time-dependent base-pairing of single-stranded DNA base-pairing, some pathways are as anticipated while others are surprising.