With its ability to determine 3D protein structures, cryo-EM revolutionized drug discovery. But it is limited to imaging the body’s largest proteins. UC Berkeley and Biohub physicists have now added powerful lasers to the electron microscope to produce much higher contrast — like phase contrast in optical microscopes— and potentially allow cryo-EM to resolve proteins one-quarter today’s limit. The “laser phase plate” offers a new window into the molecular machinery of the cell.