Hybrid-illumination multiplexed Fourier ptychographic microscopy with robust aberration correction

Abstract Fourier ptychographic microscopy (FPM) is a powerful computational imaging modality that achieves high space–bandwidth product imaging for biomedical samples. However, its adoption is limited by slow data acquisition due to the need for sequential measurements. Multiplexed FPM strategies have been proposed to accelerate imaging by activating multiple light-emitting diodes simultaneously, but they typically require careful parameter tuning, and their lack of effective aberration correction makes them prone to image degradation. To address these limitations, we introduce hybrid-illumination multiplexed Fourier ptychographic microscopy (HMFPM), which integrates analytic aberration retrieval capability with the efficiency of multiplexed illumination. Specifically, HMFPM employs a hybrid illumination strategy and a customized reconstruction algorithm with analytic and optimization methods. This hybrid strategy substantially reduces the number of required measurements while ensuring robust aberration correction and stable convergence. We demonstrate that HMFPM achieves 1.08 µ m resolution, representing a four-fold enhancement over the system’s coherent diffraction limit, across a 1.77 × 1.77 mm 2 field of view using 20–28 measurements. HMFPM remains robust under diverse aberrations, providing up to 78 µ m digital refocusing capability, and effectively corrects both field-dependent and scanning-induced aberrations in whole-slide pathology imaging. These results establish HMFPM as a practical, high-throughput, and aberration-free solution for biological and biomedical imaging.