Liquid cell electron microscopy imaging is readily applied to study molecular self-assembly providing unprecedented nanomovies and unveiling those conventionally difficult-to-access dynamics. Problems include biomacromolecular interactions, polymer chemistry, and self-assembly.

    Our first demonstration was to image single-chain polymer dynamics and unravel the characteristic surface hopping and adsorption with whole backbone resolution. The second successful trial was the DNA hybridization process, the importance of which is self-evident yet has not been put into time-lapsed images. Beyond confirming simulation-predicted pathways, unpredicted ones were observed, with a clear elucidation of intermediate states and error production and correction mechanisms. Beyond immediate visual reading from structures and conformational adaptation, single-molecule analysis reveals the surprise in motion and relaxation from customized tracking and time-dependent analysis. These observations inspired us to think about how chemical energy is funneled from reaction to product in liquids at the nanoscale as well as transition pathways and dynamics. We further extended the imaging to chemically and biologically relevant systems including enzyme-catalyzed DNA growth, lipid assembly, new aggregation-induced polymerization mechanism, and protein dynamics.

    To gain chemical insights with superior spatial resolution, we are interested in developing correlative analytical methods with fluorescent-based imaging and electrochemical analysis including new liquid cell design, image analysis algorithm, and system automation. We envision this tool will continue to contribute to the understanding of the interplay of chemistry, biophysics, and assembly in liquid both at and out-of-equilibrium.