High-speed live cell interferometry for screening bioprinted organoids

Abstract

AbstractThere is increasing interest in leveraging tumor organoids for high-throughput drug screenings to investigate tumor biology and identify therapeutic leads. However, functional precision medicine platforms are limited by the difficulties of creating, scaling, and analyzing physiological disease models. Most systems use manually seeded organoids and take advantage of destructive endpoint assays to rapidly characterize response to treatment. These approaches fail to capture transitory changes and intra-sample heterogeneity that underlies much of the clinically observed resistance to therapy. We therefore developed bioprinted tumor organoids linked to real-time growth pattern quantitation via high-speed live cell interferometry (HSLCI). We demonstrate that bioprinting gives rise to 3D organoid structures that preserve histology and gene expression. These are suitable for imaging with HSLCI, enabling accurate parallel mass measurements for thousands of bioprinted organoids. In drug screening experiments, HSLCI rapidly identifies organoids transiently or persistently sensitive or resistant to specific therapies. We show that our approach can provide detailed, actionable information to guide rapid therapy selection.