A universal microscope add-on for snapshot quantitative phase imaging by spectral encoding

Observing the dynamics of colorless or transparent samples quantitatively is vital in cellular-level biomedical research. Among existing techniques, fluorescent microscopy suffers from phototoxicity and photobleaching issues, while snapshot quantitative phase imaging (QPI) demands a complicated setup. Thus, an easily accessible tool allowing for long-period, high-contrast observation of transparent samples remains still lacking. To tackle this problem, we propose a one-shot QPI approach compatible with both off-the-shelf and customized microscopes, which encodes the phase informative cues into a snapshot using a thin, flat optical device and decodes the phase information through an advanced deep network algorithm. The encoding involves overlaying defocused images obtained through a wafer-thin highly-dispersive glass with dual-bandpass coating, acting as an ``add-on'' module located between the specimen and objective. The successive phase retrieval is conducted with a well-designed network structure and the high-quality training data supports the phase reconstruction at high axial resolution. By experimenting on T cell migration, T cell activation, and real-time live-cell drug screening on systems with various magnifications, we demonstrate high-precision phase retrieval of our method under different experimental settings and on various platforms, which is expected to obtain a wide range of potential applications in studies of clustered cell morphology, cell counting, and cell migration tracking.