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

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.

A sandwiched microarray platform for benchtop cell-based high throughput screening.

The emergence of combinatorial chemistries and the increased discovery of natural compounds have led to the production of expansive libraries of drug candidates and vast numbers of compounds with potentially interesting biological activities. Despite broad interest in high throughput screening (HTS) across varied fields of biological research, there has not been an increase in accessible HTS technologies. Here, we present a simple microarray sandwich system suitable for screening chemical libraries in cell-based assays at the benchtop. The microarray platform delivers chemical compounds to isolated cell cultures by 'sandwiching' chemical-laden arrayed posts with cell-seeded microwells. In this way, an array of sealed cell-based assays was generated without cross-contamination between neighbouring assays. After chemical exposure, cell viability was analyzed by fluorescence detection of cell viability assays on a per microwell basis using a standard microarray scanner. We demonstrate the efficacy of the system by generating four hits from toxicology screens towards MCF-7 human breast cancer cells. Three of the hits were identified in a combinatorial screen of a library of natural compounds in combination with verapamil, a P-glycoprotein inhibitor. A fourth hit, 9-methoxy-camptothecin, was identified by screening the natural compound library in the absence of verapamil. The method developed here miniaturizes existing HTS systems and enables the screening of a wide array of individual or combinatorial libraries in a reproducible and scalable manner. We anticipate broad application of such a system as it is amenable to combinatorial drug screening in a simple, robust and portable platform.