An Omni-Mesoscope for multiscale high-throughput quantitative phase imaging of cellular dynamics and high-content molecular characterization

The mesoscope has emerged as a powerful imaging tool in biomedical
research, yet its high cost and low resolution have limited its broader
application. Here, we introduce the Omni-Mesoscope, a
high-spatial-temporal and multimodal mesoscopic imaging platform built
from cost-efficient off-the-shelf components. This system uniquely merges
the capabilities of label-free quantitative phase microscopy to capture
live-cell morpho-dynamics across thousands of cells with highly
multiplexed fluorescence imaging for comprehensive molecular
characterization. This Omni-Mesoscope offers a mesoscale field of view of
approximately 5 mm² with a high spatial resolution down to 700 nm,
enabling the capture of detailed sub-cellular features. We demonstrate its
capability in delineating molecular characteristics underlying rare
morpho-dynamic cellular phenomena, including cancer cell responses to
chemotherapy and the emergence of polyploidy in drug-resistant cells. We
also integrate expansion technique to enhance 3D volumetric
super-resolution imaging of thicker tissues, opening new avenues for
biological exploration at unprecedented scales and resolutions.