title: Controlled production of sub-millimeter liquid core hydrogel capsules for parallelized 3D cell culture.
abstract: Liquid core capsules having a hydrogel membrane are becoming a versatile tool for three-dimensional culture of micro-organisms and mammalian cells. Making sub-millimeter capsules at a high rate, via the breakup of a compound jet in air, opens the way to high-throughput screening applications. However, control of the capsule size monodispersity, especially required for quantitative bioassays, was still lacking. Here, we report how the understanding of the underlying hydrodynamic instabilities that occur during the process can lead to calibrated core-shell bioreactors. The requirements are: i) damping the shear layer instability that develops inside the injector arising from the co-annular flow configuration of liquid phases having contrasting viscoelastic properties; ii) controlling the capillary instability of the compound jet by superposing a harmonic perturbation onto the shell flow; iii) avoiding coalescence of drops during jet fragmentation as well as during drop flight towards the gelling bath; iv) ensuring proper engulfment of the compound drops into the gelling bath for building a closed hydrogel shell. We end up with the creation of numerous identical compartments in which cells are able to form multicellular aggregates, namely spheroids. In addition, we implement an intermediate composite hydrogel layer, composed of alginate and collagen, allowing cell adhesion and thus the formation of epithelia or monolayers of cells.
authors.affiliation: Laboratoire Colloïdes et Matériaux Divisés, CNRS, Chemistry Biology & Innovation, ESPCI Paris, PSL Research University, 10 Rue Vauquelin, F-75005 Paris, France. nicolas.bremond@espci.fr.
authors.forename: Hugo
authors.initials: H
authors.lastname: Doméjean
authors.affiliation: Laboratoire Colloïdes et Matériaux Divisés, CNRS, Chemistry Biology & Innovation, ESPCI Paris, PSL Research University, 10 Rue Vauquelin, F-75005 Paris, France. nicolas.bremond@espci.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: de la Motte Saint Pierre
authors.affiliation: Laboratoire Colloïdes et Matériaux Divisés, CNRS, Chemistry Biology & Innovation, ESPCI Paris, PSL Research University, 10 Rue Vauquelin, F-75005 Paris, France. nicolas.bremond@espci.fr.
authors.forename: Anette
authors.initials: A
authors.lastname: Funfak
authors.affiliation: Laboratoire Colloïdes et Matériaux Divisés, CNRS, Chemistry Biology & Innovation, ESPCI Paris, PSL Research University, 10 Rue Vauquelin, F-75005 Paris, France. nicolas.bremond@espci.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Atrux-Tallau
authors.affiliation: LP2N, Université de Bordeaux, F-33400 Talence, France and LP2N, UMR 5298, Institut d'Optique & CNRS, F-33400 Talence, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Alessandri
authors.affiliation: LP2N, Université de Bordeaux, F-33400 Talence, France and LP2N, UMR 5298, Institut d'Optique & CNRS, F-33400 Talence, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Nassoy
authors.affiliation: Laboratoire Colloïdes et Matériaux Divisés, CNRS, Chemistry Biology & Innovation, ESPCI Paris, PSL Research University, 10 Rue Vauquelin, F-75005 Paris, France. nicolas.bremond@espci.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bibette
authors.affiliation: Laboratoire Colloïdes et Matériaux Divisés, CNRS, Chemistry Biology & Innovation, ESPCI Paris, PSL Research University, 10 Rue Vauquelin, F-75005 Paris, France. nicolas.bremond@espci.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bremond
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival; D057446:Hydrodynamics; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D011108:Polymers / Q000737:chemistry; D014783:Viscosity
chemical_list: D020100:Hydrogels; D011108:Polymers