Organoids-based High Content Screening in Oncology

International audienceTo analyze the phenotypic consequences of genetic perturbation in mammalian cells with drugs, RNAi or expression vectors, there are increasing needs for systematic cell-based high content screening (HCS) approaches, particularly in oncology. Although several groups are performing HCS in human cell lines, the real challenge in translational research remains screening on a reduced number of primary cells directly obtained from patients in a microenvironment that would resemble the original tissues. While standard monolayer two-dimensional culture conditions or even spheroids resulting form the forced aggregation of cells are poor mimics of the tumour natural history, microfabricated systems enable three-dimensional clonal organoids cultures and have the potential to provide biological insight not achievable before. We use microfluidics and MEMS (MicroElectroMechanical Systems) to analyze the phenotypic consequences of genetic perturbations (RNAi-based HCS) in 3D organoids. Specifically, we present a novel approach based on a flowfocusing microfluidic system that encapsulates either single prostatic or mammary cell in Matrigel beads and assay for development of organoids. Furthermore, we developed new imaging technology to monitor live organoids self-assembly and inter organoids cell trafficking