Robotic Generation and Kinetic Screening of Patient-Derived Glioblastoma Organoids Reveal Pharmaceutical Dynamics

Current preclinical models are highly variable, creating disparate patient-derived organoids. We developed a Robot-Directed Organoid Deposition (RODEO) system that reproducibly generates complex patient-derived GBM organoids for high-throughput screening.

RODEO-GBM organoids recapitulate the cellular heterogeneity, specific tumor niches, and complex vascularization of GBM. Integrating tissue-embedded microsensors in RODEO-GBM organoids allowed us to screen 126 FDA-approved oncology drugs, on 1,638 patient-derived organoids, generating 105 data points in 96 hrs. Our screen revealed distinct kinetic patterns of drug responses, identifying transient as well as slow-acting compounds often overlooked by conventional methods.