title: Enhancing the biocompatibility of microfluidics-assisted fabrication of cell-laden microgels with channel geometry.
abstract: Microfluidic flow-focusing devices (FFD) are widely used to generate monodisperse droplets and microgels with controllable size, shape and composition for various biomedical applications. However, highly inconsistent and often low viability of cells encapsulated within the microgels prepared via microfluidic FFD has been a major concern, and yet this aspect has not been systematically explored. In this study, we demonstrate that the biocompatibility of microfluidic FFD to fabricate cell-laden microgels can be significantly enhanced by controlling the channel geometry. When a single emulsion ("single") microfluidic FFD is used to fabricate cell-laden microgels, there is a significant decrease and batch-to-batch variability in the cell viability, regardless of their size and composition. It is determined that during droplet generation, some of the cells are exposed to the oil phase which is shown to have a cytotoxic effect. Therefore, a microfluidic device with a sequential ('double') flow-focusing channels is employed instead, in which a secondary aqueous phase containing cells enters the primary aqueous phase, so the cells' exposure to the oil phase is minimized by directing them to the center of droplets. This microfluidic channel geometry significantly enhances the biocompatibility of cell-laden microgels, while maintaining the benefits of a typical microfluidic process. This study therefore provides a simple and yet highly effective strategy to improve the biocompatibility of microfluidic fabrication of cell-laden microgels.
authors.affiliation: School of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, South Korea.
authors.forename: Suntae
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Mechanical Design Engineering, Chonbuk National University, Jeonju 561-756, South Korea.
authors.forename: Jonghyun
authors.initials: J
authors.lastname: Oh
authors.affiliation: School of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, South Korea. Electronic address: ccha@unist.ac.kr.
authors.forename: Chaenyung
authors.initials: C
authors.lastname: Cha
mesh_terms: D000818:Animals; D002470:Cell Survival; D005782:Gels / Q000737:chemistry*; D056656:Lab-On-A-Chip Devices; D008422:Materials Testing; D051379:Mice; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods*; D041681:NIH 3T3 Cells
chemical_list: D005782:Gels
keywords: Biocompatibility; Cell encapsulation; Flow-focusing geometry; Microfluidics; Microgel