Large field-of-view 3D computational phase imaging using differential structured illumination microscopy (dSIM)

We developed differential structured illumination microscopy (dSIM) for efficiently imaging and reconstructing 3D biological samples at high-resolution over a large field-of-view. Using plane wave and grating-based structured illumination pairs in a differential illumination scheme, dSIM encodes scattering information from high-angle, traditionally nonlinear "darkfield" illuminations into linear intensity measurements enabling efficient 3D object reconstruction with linear inverse scattering models. This illumination scheme exceeds the 2X resolution limit enhancement of traditional phase-based SIM techniques. We reconstruct 3D objects with 4.5X better resolution than the coherent imaging bandwidth while maintaining an almost 1mm2 field-of-view. We illustrate this technique in simulation and experimentally on cell cultures and other living biological specimens.