Hybrid iterative ptychographic super-resolution microscopy

Abstract By utilizing an array detector to replace the single-element detector in confocal microscopy, Image Scanning Microscopy (ISM) overcomes the inherent trade-off between resolution and signal-to-noise ratio (SNR), thereby enhancing its ability to resolve sub-diffraction features. However, practical ISM performance often falls short of the theoretical ideal, leaving scope for further advancement. Here, we present hybrid iterative ptychographic super-resolution microscopy (HiM), which integrates a honeycomb array detection architecture with a hybrid high-frequency extension algorithm to achieve a 1.5-fold increase in detection efficiency and a spatial resolution of ~ 60 nm. Experiments demonstrate that HiM outperforms comparative algorithms, achieving a STED-like apparent resolution even in the absence of a depletion laser. The verified compatibility with modalities such as stimulated emission depletion microscopy (STED) and fluorescence lifetime imaging microscopy (FLIM) confirms the practical utility of HiM for various imaging requirements.