Smart Fluorosurfactant-Assisted Microfluidics Powered On-Demand Generation and Retrieval of Cell-Laden Microgels

Abstract

Microfluidics have been widely employed as powerful tools to fabricate monodisperse, cell-laden hydrogel microdroplets with precise control for various biological applications, particularly in tissue engineering. While these systems enable high-throughput production of uniform microgel particles, the encapsulation and stabilization of water-in-oil hydrogel emulsions often require surfactants to reduce the surface tension of the microgel droplets. However, these surfactants must be removed with chemical demulsifiers to retrieve the cell-laden microgels for downstream applications, which often leads to toxic effects on the cells. Herein, a novel class of thermo-responsive “smart” surfactants is reported for on-demand demulsification of microfluidic droplets. These surfactants are synthesized by coupling perfluoropolyethers (PFPEs) with a thermo-responsive block of N-isopropylacrylamide (NIPAM) using reversible addition-fragmentation chain transfer (RAFT) polymerization. The resulting P(NIPAM)n-PFPE surfactants exhibited temperature-dependent amphiphilicity, enabling stabilization of water-in-oil droplets at low temperatures and destabilization at elevated temperatures. This approach offers a non-invasive and biocompatible method for microgel recovery without the need for harmful chemical demulsifiers or additional processing steps. The combination of precise control over surfactant properties and thermo-responsive behavior opens new avenues for developing smart, biocompatible emulsion systems for advanced droplet microfluidics applications in tissue engineering, drug delivery, and single-cell analysis.