High-spatiotemporal-resolution quantitative phase microscopy under unmatched illumination.

Abstract

Diffraction-based quantitative phase microscopy (QPM) conventionally requires stringent numerical aperture (NA) matching between illumination and objective lens (OL). We propose high-spatiotemporal-resolution QPM under unmatched illumination (HSR-QPM-UI) that fully eliminates this constraint. By introducing a 0.5π phase shift exclusively to the non-scattered components of object waves under symmetric unmatched illumination, we physically encode low-frequency phase information into intensity variations. A rigorous linear forward model and an explicit phase transfer function are derived, enabling non-iterative phase retrieval via frequency-adaptive deconvolution, achieving >700-fold reconstruction speedup over iterative methods. A shared phase modulation strategy permits acquisition speed limited only by the camera exposure time. The spatial light modulator (SLM)-based aberration compensation ensures robustness in real systems. Simulations and experiments collectively demonstrate the superior phase imaging performance of HSR-QPM-UI. This approach opens new avenues for high-throughput, real-time, label-free, and high-resolution quantitative phase imaging.