Leveraging bioconvergence to enhance organ-on-a-chip technology and revolutionize drug discovery and development

Background: Bioconvergence combines materials science, microelectronics with organoid biology to revolutionize organ-on-a-chip (OOC) technology, facilitating effective translational drug discovery. Our initiative aims to develop new generation of in vitro platforms by integrating human 3D cell cultures with a semiconductor-based, sensor-integrated microfluidic silicon chip, enabling the simulation of interconnected multi-organ physiology. Methods: We developed human gut and liver organoids from induced pluripotent stem cells (iPSCs) and patient-derived organoid (PDO). The organoids were validated for lineage identity and functionality through immunofluorescence for key markers, RT-qPCR for gene panels, and functional assays such as transepithelial electrical resistance (TEER) and enzyme activity. This validated biology was integrated by connecting it to fluidic and electrical interfaces in sterile conditions. Results: Duodenal PDO-derived gut organoids exhibited well-defined epithelial architecture and barrier integrity, along with the expression of essential transporters (BCRP) and metabolic enzymes (CYP3A4, UGT1A1). They also displayed lineage markers, including brush border (Villin), goblet (MUC2), Paneth (LYZ), and enteroendocrine (CHGA) cells. iPSC-derived mature liver organoids expressed markers for hepatocytes and cholangiocytes, including albumin, Sox9, CK7, and CK19, demonstrating Phase I/II metabolic competence and relevant drug transporters (CYP3A4, GST, MDR1/P-gp, MRP2). These organoid systems establish a solid foundation for exploring the viability and functionality of the platform. Conclusions: Integrating validated human organoid biology with scalable semiconductor microfluidics creates a microphysiological platform that significantly enhances translational relevance for toxicology, drug metabolism and pharmacokinetics (DMPK), and disease modeling. It supports the development of safer, more effective therapies while minimizing reliance on animal studies.