Combinatorial drug screening on 3D Ewing sarcoma spheroids using droplet-based microfluidics
Romain Fevre,
Gaëtan Mary,
Nadia Vertti-Quintero,
Aude Durand,
Raphaël F.-X. Tomasi,
Elaine Del Nery,
Charles N. Baroud
Affiliations
Romain Fevre
Laboratoire d’ Hydrodynamique (LadHyX), CNRS, EcolePolytechnique, InstitutPolytechnique de Paris, 91128 Palaiseau, France; Institut Pasteur, Université Paris Cité, Physical microfluidics and Bioengineering, 25-28 Rue du Dr. Roux, 75015 Paris, France
Gaëtan Mary
Okomera, iPEPS, the HealthTech Hub, Paris Brain Institute, HôpitalPitiéSalpêtrière, 75013 Paris, France
Nadia Vertti-Quintero
Institut Pasteur, Université Paris Cité, Physical microfluidics and Bioengineering, 25-28 Rue du Dr. Roux, 75015 Paris, France
Aude Durand
Institut Pasteur, Université Paris Cité, Physical microfluidics and Bioengineering, 25-28 Rue du Dr. Roux, 75015 Paris, France
Raphaël F.-X. Tomasi
Laboratoire d’ Hydrodynamique (LadHyX), CNRS, EcolePolytechnique, InstitutPolytechnique de Paris, 91128 Palaiseau, France; Institut Pasteur, Université Paris Cité, Physical microfluidics and Bioengineering, 25-28 Rue du Dr. Roux, 75015 Paris, France; Okomera, iPEPS, the HealthTech Hub, Paris Brain Institute, HôpitalPitiéSalpêtrière, 75013 Paris, France
Elaine Del Nery
Biophenics High-Content Screening Laboratory, Translational Research Department, PICT-IBiSA, Institut Curie, PSL Research University, 75005 Paris, France; Corresponding author
Charles N. Baroud
Laboratoire d’ Hydrodynamique (LadHyX), CNRS, EcolePolytechnique, InstitutPolytechnique de Paris, 91128 Palaiseau, France; Institut Pasteur, Université Paris Cité, Physical microfluidics and Bioengineering, 25-28 Rue du Dr. Roux, 75015 Paris, France; Corresponding author
Summary: 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.
