Triple Emulsion-Based Rapid Microfluidic Production of Core-Shell Hydrogel Microspheres for Programmable Biomolecular Conjugation.

Abstract

We report a simple and rapid microfluidic approach to produce core-shell hydrogel microspheres in a single step. We exploit triple emulsion drops with sacrificial oil layers that separate two prepolymer phases, forming poly(ethylene glycol)-based core-shell microspheres via photopolymerization followed by spontaneous removal of the oil layer. Our technique enables the production of monodisperse core-shell microspheres with varying dimensions of each compartment by independently and precisely controlled flow rates. This leads to stable and uniform incorporation of functional moieties in the core compartment with negligible cross-contamination into the shell layer. Selective conjugation of biomolecules is enabled through a rapid bioorthogonal reaction with functional groups in the core compartment with minimal non-specific adsorption. Finally, in-depth protein conjugation kinetics studies using microspheres with varying shell porosities highlight the capability to provide tunable size-selective diffusion barriers by simple tuning of prepolymer compositions for the shell layer. Combined, these results illustrate a significant step forward for programmable high-throughput fabrication of multifunctional hydrogel microspheres, which possess substantial potential in a large array of biomedical and biochemical applications.