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 e..., , , # An Omni-Mesoscope for multiscale high-throughput quantitative phase imaging of cellular dynamics and high-content molecular characterization [https://doi.org/10.5061/dryad.t76hdr88t](https://doi.org/10.5061/dryad.t76hdr88t) ## Description of the data and file structure #### File: Omni\_Mesoscope\_data.zip **Description:** Image data used in \"An Omni-Mesoscope for multiscale high-throughput quantitative phase imaging of cellular dynamics and high-content molecular characterization\" **Folder: \"Multiplex Fluorescent Images\"** This folder contains the stitched fluorescence images of multiple biomarkers, as used in Figure 6 of the main text. \"SW480_5Fu_3d_Cy1_H3K27me3_Ex650_Em676_Reg.tiff\": H3K27me3 channel of SW480 cells treated with 5-FU for 3 days. \"SW480_5Fu_3d_Cy1_LMNAC_Ex530_Em572_Reg.tiff\": LMNAC channel of SW480 cells treated with 5-FU for 3 days. \"SW480_5Fu_3d_Cy2_CENPA_Ex650_Em676_Reg.tiff\": CENPA channel of SW480 cells treated with 5-FU for 3 days. \"SW480_5Fu_3d_Cy2_H3_Ex4...