Large FOV superresolution structured illumination microscopy using interferometric patterning and decoupled illumination and detection

Structured Illumination Microscopy (SIM) doubles the lateral resolution of conventional optical microscopy by projecting structured light patterns onto the sample and computationally extracting high-frequency information. Traditional SIM systems typically generate these patterns using mechanically moving gratings or spatial light modulators (SLMs), but gratings are susceptible to vibration-induced artifacts and slow imaging speeds, while SLMs can introduce pixelation and polarization-dependent limitations. To address these challenges, we introduce a novel SIM system that separates the illumination and detection pathways. Structured fringes are generated by a Michelson interferometer equipped with high-speed actuator-driven mirrors and a piezo-driven phase shifter, allowing rapid and precise control of pattern orientation and phase. This enables high-contrast fringe projection onto the sample, independent of the detection optics, significantly increasing imaging speed. We achieved 500 nm lateral resolution across a 10 mm × 8 mm field of view, enabling fast, high-resolution imaging for large-scale biological applications.