An integrated platform for mesoscale quantitative phase imaging and hyperplex fluorescence microscopy

Quantitative phase microscopy is a powerful labelfree imaging technique to assess morphology and architecture of biological cells and tissue. But its lack of molecular specificity often makes it difficult to assign specific subcellular structures and functional states. Here we combine quantitative phase imaging (QPI) with multiplex fluorescence microscopy at mesoscale that allow the simultaneous assessment of both morphological changes and their functional states over a field of view of a few millimeters at a sub-micron resolution. Further, quantitative phase images can also be used for automatic focusing and image registration, effectively overcoming the traditional hurdles posed by the markedly inconsistent fluorescence intensity encountered in various settings. This integrated system will serve as a vital instrument in understanding the molecular attributes and functional states underlying the morphological characteristics assessed quantitative phase imaging in spatial cell biology.