Photonic-crystal hydraulic manometry quantifies epithelial basal compression for rapid, label-free functional screening.

Polarized epithelia integrate barrier sealing, vectorial ion-water transport, and cytoskeletal mechanics, yet scalable assays that report this coupled functional state in real time remain limited. Here, we introduce photonic-crystal hydraulic manometry (PCHM), which quantifies out-of-plane mechanical states from single-frame reflection images in standard culture formats. Using PCHM, we find that epithelial monolayers maintain a kilopascal-scale basal compression (∼3 kilopascals) at the cell-substrate interface. A systematic perturbation panel spanning ion transport and actomyosin contractility defines the sensitivity, dynamic range, and reversibility of the readout, establishing basal compression as an actionable state variable of epithelial physiology. Leveraging this physiology-anchored metric, we detect early infection with coxsackievirus as a collapse of basal compression within 2 hours, well before cytopathic effects become apparent (48 hours). In severe acute respiratory syndrome coronavirus 2 pseudovirus neutralization assays, PCHM provided a 2-hour readout that was consistent with matched 48-hour luciferase results. In viral titration assays, the same 2-hour PCHM readout extended the detectable low-input range by approximately one order of magnitude relative to the matched 48-hour luciferase end point. Together, PCHM links epithelial transport and mechanics to a scalable, stain-free assay framework for epithelial pathophysiology and therapeutic screening.