All-Aqueous-Phase Microfluidics for Cell Encapsulation

Abstract

Cell-laden hydrogel microcarriers are widely used in diverse biomedical applications like three-dimensional (3D) cell culture, cellular therapy, and tissue engineering, where microcarriers were generally produced by oil, which is the common but not optimal choice, as oil may cause cytotoxicity or protein denaturation. Here, an all-aqueous-phase microfluidics is presented to achieve oil-free emulsification of cell-laden microcapsules and 3D cell culture. Aqueous solutions with different concentration gradients are used as an immiscible continuous phase and a dispersed phase, and oscillation from a solenoid valve facilitates the formation of microcapsules at the water–water interface. By adjusting aqueous-phase flow rates and oscillating frequencies, core–shell microcapsules with controllable structures can be stably and continuously generated. In further 3D cell culture, encapsulated cells maintained good viabilities and aggregated together. These features show that the oil-free microfluidic method may have broad prospects in many biomedical applications.

Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

“…The generated all‐aqueous droplets are collected in a CaCl 2 solution, where the middle aqueous phase is crosslinked into hollow shells of microcapsules, as shown in Figure 8d. Furthermore, the fabricated microcapsules can be used as promising vehicles for cell encapsulating and culturing, as demonstrated by the fluorescent images in Figure 8d . Moreover, gelation of phase‐separating droplets formed at the different time points of LLPS enables engineering the internal structures of the resultant capsules, as well as regulating the kinetics of the biochemical reactions in the droplet‐based bioreactors .…”

“…All‐aqueous emulsions, also called aqueous two‐phase system (ATPS), are immiscible aqueous phases generated by physical LLPS in aqueous polymer solutions . This emulsion system consists of droplets of one aqueous phase dispersed into the other aqueous phase.…”

“…Copyright 2010, Royal Society of Chemistry. d) Reproduced with permission . Copyright 2019, American Chemical Society.…”

“…d) Reproduced with permission. [92] Copyright 2019, American Chemical Society. e) Reproduced with permission.…”

“…All-aqueous emulsions, also called aqueous two-phase system (ATPS), are immiscible aqueous phases generated by physical LLPS in aqueous polymer solutions. [77,[91][92][93][94] This emulsion system consists of droplets of one aqueous phase dispersed into the other aqueous phase. To maintain the immiscibility, the aqueous mixtures are dissolved with at least two solute species, and each solute species are typically enriched in one aqueous phase.…”