Combinatorial drug screening on 3D Ewing sarcoma spheroids using droplet-based microfluidics

• Published in: iScience Vol. 26; no. 5; p. 106651
• Main Authors: Fevre, Romain, Mary, Gaëtan, Vertti-Quintero, Nadia, Durand, Aude, Tomasi, Raphaël F.-X., Del Nery, Elaine, Baroud, Charles N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.05.2023; Elsevier
• Subjects: Biological science instrumentation; Cancer; Drug delivery system; Molecular biology experimental approach; Biological science instrumentation; Drug delivery system; Molecular biology experimental approach; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106651

Culturing and screening cells in microfluidics, particularly in three-dimensional formats, has the potential to impact diverse areas from fundamental biology to cancer precision medicine. Here, we use a platform based on anchored droplets for drug screening. The response of spheroids of Ewing sarcoma (EwS) A673 cells to simultaneous or sequential combinations of etoposide and cisplatin was evaluated. This was done by culturing spheroids of EwS cells inside 500 nL droplets then merging them with secondary droplets containing fluorescent-barcoded drugs at different concentrations. Differences in EwS spheroid growth and viability were measured by microscopy. After drug exposure such measurements enabled estimation of their IC50 values, which were in agreement with values obtained in standard multiwell plates. Then, synergistic drug combination was evaluated. Sequential combination treatment of EwS with etoposide applied 24 h before cisplatin resulted in amplified synergistic effect. As such, droplet-based microfluidics offers the modularity required for evaluation of drug combinations. [Display omitted] •A microfluidic protocol to subject cancer spheroids to drug combinations is developed•Image analysis yields data on hundreds of individual spheroids per experimental run•The device is benchmarked against standard plates and yields the same values of IC50•Drug synergy was quantified for simultaneous and sequential exposure protocols Drug delivery system; Molecular biology experimental approach; Cancer; Biological science instrumentation