Advancing Intelligent Organ‐on‐a‐Chip Systems with Comprehensive In Situ Bioanalysis

Abstract In vitro models are essential to a broad range of biomedical research, such as pathological studies, drug development, and personalized medicine. As a potentially transformative paradigm for 3D in vitro models, organ‐on‐a‐chip (OOC) technology has been extensively developed to recapitulate sophisticated architectures and dynamic microenvironments of human organs by applying the principles of life sciences and leveraging micro‐ and nanoscale engineering capabilities. A pivotal function of OOC devices is to support multifaceted and timely characterization of cultured cells and their microenvironments. However, in‐depth analysis of OOC models typically requires biomedical assay procedures that are labor‐intensive and interruptive. Herein, the latest advances toward intelligent OOC (iOOC) systems, where sensors integrated with OOC devices continuously report cellular and microenvironmental information for comprehensive in situ bioanalysis, are examined. It is proposed that the multimodal data in iOOC systems can support closed‐loop control of the in vitro models and offer holistic biomedical insights for diverse applications. Essential techniques for establishing iOOC systems are surveyed, encompassing in situ sensing, data processing, and dynamic modulation. Eventually, the future development of iOOC systems featuring cross‐disciplinary strategies is discussed.