Automation and High-Throughput Technologies
Screening & Profiling at higher throughput using physiologically relevant cell models
A novel multiplexed uHTS and uHCS (MuHTCS) platform in a 1536-well format for chemical biology screening using 3D patient-derived cancer organoids
Yuhong Du, Ph.D
Emory Chemical Biology Discovery center
Atlanta, GA USA
Xingnan Li, Mohammad Zaidi, Yuchen Zhang, Bassel Al-Rayes, Taofeek Owonikoko, Suresh Ramalingam, Gabe Sica, Greg Lesinski, Calvin Kuo, Haian Fu
The current effort to grow human tissues as 3D “organoids” for cancer research aims to recapitulate 3D architecture of tumors in an in vitro environment for cancer biology studies and therapeutic development. However, due to various technical challenges, primary 3D organoid culture has not been widely used in a high-throughput screening (HTS) format for chemical screening. Here, we report the miniaturization and development of a multiplexed uHTS and uHCS (MuHTCS) organoid culturing platform for effective compound screening in a 1536-well format. Using pancreatic patient tumor-derived organoids as a model system, we optimized the 3D organoid culturing conditions with extracellular matrix (ECM). The growth of organoids was monitored by automated imaging. We further developed a multiplexed screening platform to simultaneously monitor the effect of compounds on the growth of organoids for ultraHTS (uHTS) and on the morphological change of organoids for ultra-high-content screening (uHCS) in a 1536-well plate. The MuHTCS assay has achieved Z’ > 0.5 and signal-to-background (S/B) > 6. A pilot screening of ~2000 FDA approved and bioactive compound library has validated the assay for screening. Our data has demonstrated that it is feasible to utilize miniaturized 3D cancer organoids for large scale compound screening. The optimized MuHTC platform provides an efficient approach to accelerate 3-D organoids-enabled screening for drug discovery.