Single particle imaging in cryoelectron microscopy (cryo-EM) is a challenging problem due low SNR micrograph data. The standard image processing chain requires extensive averaging of large number of “similar” particle images. A cryo-EM micrograph is an in-line hologram recorded with coherent electron beam where the typical macro-molecules behave as weak phase objects. We show that optical in-line holography methods for auto-focusing can be applied to cryo-EM data to get improved per-particle defocus estimates after including the effect of spherical aberration. Further a sparse iterative algorithm can provide quantitative phase information about single particles leading to a potentially new processing path.
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