Adaptive Optics-Assisted Large-Field Structured Illumination Microscopy via Coherent Aberration Sensing

Structured illumination microscopy (SIM) offers rapid, long-term super-resolution imaging, but its performance is fundamentally constrained by sample-induced aberrations that vary across large fields of view and imaging depths. Here, we present Fourier Ptychography-assisted SIM (FP-SIM), an adaptive optics-assisted, large-field SIM that enables in situ correction of spatially variant aberrations via Fourier ptychography (FP). By leveraging FP’s quantitative phase retrieval capability, FP-SIM reconstructs pupil phase maps directly from coherent, label-free measurements and applies them to fluorescence SIM reconstruction, enabling accurate aberration correction without relying on fluorescent guide signals. The approach performs guide-star-free, tile-by-tile wavefront sensing using coherent measurements, achieving high-resolution fluorescence imaging across extended fields of view. Experimental validation on various samples demonstrates significant improvements in resolution, contrast, and artifact suppression over state-of-the-art tiled and notch-filtered SIM methods. In addition to providing a complementary label-free imaging modality, FP-SIM offers a versatile and flexible solution for large-scale, depth-resolved, aberration-resilient fluorescence microscopy with high imaging fidelity.