Cryo-electron microscopy (cryo-EM) has become a powerful tool for determining the structures of proteins, viruses and molecular complexes at near-atomic resolution. However, achievable resolution is fundamentally limited by the Nyquist sampling frequency, which is determined by detector pixel size and microscope magnification. Once this physical limit is reached, researchers typically must recollect data at higher magnification, requiring additional microscope time, increased storage capacity and often fewer particles per image.