Innovative Metasurface Colorimetric Cell‐on‐a‐Chip Sensor for Continuous, Label‐Free, Non‐Destructive Assessment of Intestinal Barrier Dynamics

Assessing intestinal barrier function in organ- and cell-on-a-chip models is crucial for studying intestinal diseases and advancing drug development. However, current technologies lack methods for continuous, non-destructive monitoring of intestinal barrier dynamics. In this study, we developed a real-time, label-free, high-throughput cell-on-a-chip system based on a metasurface plasmon resonance colorimetric sensor (MetaSPRCS) to evaluate intestinal barrier function. Integrating MetaSPRCS with transmission microscopy enabled real-time visualization of cell adhesion, proliferation, and intestinal barrier layer formation, disruption, and repair. The MetaSPRCS platform non-destructively detects subtle epithelial cell damage caused by low ethanol concentrations, with a two-fold higher sensitivity than that of CCK-8 assays. In an alcohol-induced intestinal barrier injury model, MetaSPRCS validated a reliable evaluation of Dihydroquercetin (DHQ), consistent with endpoint methods. Animal experiments confirmed its ability to predict in vitro-to-in vivo dose conversion of DHQ, offering promising guidance for the administration of novel cell-repairing food ingredients. This study provides a high-throughput, visual, non-destructive tool for assessing intestinal homeostasis, establishing a preliminary dose conversion relationship between in vitro evaluation experiments and in vivo animal administration.