"How low can dose go? Applications in ultra low dose electron diffraction of molecular crystals."

Abstract: Electron diffraction enables atomic structure determination from nano- or microcrystals, allowing for rapid structural analysis of crystalline powders or mixtures. However, electron dose is fundamentally limiting, especially for the determination of solvated molecular structures. Crystals of hydrated molecules often require lengthy optimization of vitrification conditions, an approach challenged by non-aqueous solvents. I will discuss my group's efforts to enable room-temperature electron diffraction of microcrystals suspended in solvent, using simple liquid cells composed of two TEM grids “sandwiched” together with a liquid layer in between. As room-temperature, hydrated microcrystals are particularly prone to electron beam radiation damage, we have also implemented new hardware and software measures to minimize the beam fluence delivered to each crystal. Those tactics enable study of molecular conformations only accessible in a room-temperature solvated state, which are otherwise inaccessible by MicroED, but can be of particular relevance for research and pharmaceuticals.