Automation and High-Throughput Technologies
High-throughput screening with a genetically engineered 3D organoids system
Monday, February 5
10:30 AM - 11:00 AM
The development of organ-like 3D “organoids” with defined genomic background aims to recapitulate 3D architecture of tumors in an in vitro environment for cancer biology studies and therapeutic development. Here, we report the development of an organoid HTS culturing system for compound screening. We have adapted a single air-liquid interface Air (ALI) chamber system pioneered by the Kuo team for efficient culturing of organoids. The ALI system combines the accurate multilineage differentiation and physiology of in vivo system and allows vigorously expansion of primary organoids for in vitro manipulation and modeling. Using genetically engineered KRasG12D mouse pancreatic and colon organoids as a model system, we miniaturized the 3D culturing system for the growth of organoids from ALI to a 384-well format. The growth of organoids was monitored by automated imaging, which was implemented for the screening of anticancer agents. This study led to the discovery of compounds with genomic selectivity for therapeutic validation. Such a robust assay platform enables large-scale library screening to accelerate 3-D culture-based synthetic lethal screening and drug discovery.