Computational Microscopy beyond Perfect Lenses

Lens-based microscopy has played an important role in the evolution of modern science and technology. The development of coherent diffractive imaging (CDI) in 1999 that replaces the lens with coherent illumination and computational algorithms has transformed our conventional view of microscopy. Here we demonstrate through mathematical analysis and numerical experiments that in situ CDI, which harnesses the coherent interference between a strong beam illuminating a static structure and a weak beam illuminating a dynamic structure, could be the most dose-efficient imaging method. At low doses, in situ CDI can achieve higher resolution than perfect lenses with the point spread function as a delta function. We expect that computational microscopy based on in situ CDI can be implemented in different imaging modalities with photons and electrons for low-dose imaging of radiation-sensitive materials and biological samples.