We present IsoSense, a wavefront sensing method that mitigates sample dependency in image based sensorless adaptive optics applications in microscopy. Our method employs structured illumination to create additional, high spatial frequencies in the image through custom illumination patterns. This improves the reliability of image quality metric calculations and enables sensorless wavefront measurement even in samples with sparse spatial frequency content. We demonstrate the feasibility of IsoSense for aberration correction in a deformable mirror based structured illumination superresolution fluorescence microscope.
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