Spatial biology provides unprecedented insights into cellular function within microenvironments, crucial for precision medicine. Yet, many commercial imaging systems, largely limited to fluorescence imaging of fixed samples, miss out on intrinsic cellular dynamics and are laborious with extended data acquisition, limiting their widespread use. We introduce a multiscale multimodal imaging platform that integrates quantitative phase, hyper-plex fluorescence imaging, and vast field of view at sub-micron precision. This platform also co-registers molecular-scale super-resolution images, linking molecular data with mesoscale cellular contexts. It can capture dynamic cell morphologies instantly, revealing cell states and molecular intricacies. With macro-scale optics and an astronomy camera, combined with an automated processing pipeline, our system delivers high-resolution imaging across mesoscale. We demonstrated its value in studying cancer cell resistance to chemotherapy, embracing a multi-scale, multimodal approach. Ultimately, this tool will enable profound insights into cell environment, heterogeneity, morphological changes, and molecular information across vast cell population.
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