Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology 1 article published in JoVE Biochemistry Cryo-Electron Microscopy Screening Automation Across Multiple Grids Using Smart Leginon Anjelique Sawh-Gopal1,2, Aygul Ishemgulova*1, Eugene Y. D. Chua*1, Mahira F. Aragon*1, Joshua H. Mendez1, Edward T. Eng1, Alex J. Noble1 1Simons Electron Microscopy Center, New York Structural Biology Center, 2Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology Cryo-electron microscopy (cryoEM) multi-grid screening is often a tedious process that demands hours of attention. This protocol shows how to set up a standard Leginon collection and Smart Leginon Autoscreen to automate this process. This protocol can be applied to the majority of cryoEM holey foil grids.