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

ABSTRACT 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.