Microfluidic production of degradable thermoresponsive poly(N-isopropylacrylamide)-based microgels

Highly monodisperse and hydrolytically degradable thermoresponsive microgels on the tens-to-hundreds of micron size scale have been fabricated based on simultaneous on-chip mixing and emulsification of aldehyde and hydrazide-functionalized poly(N-isopropylacrylamide) precursor polymers. The microfluidic chip can run for extended periods without upstream gelation and can produce monodisperse (<10% particle size variability) microgels on the size range of ∼30-90 μm, with size tunable according to the flow rate of the oil continuous phase. Fluorescence analysis indicates a uniform distribution of each reactive pre-polymer inside the microgels while micromechanical testing suggests that smaller microfluidic-produced microgels exhibit significantly higher compressive moduli compared to bulk hydrogels of the same composition, an effect we attribute to improved mixing (and thus crosslinking) of the precursor polymer solutions within the microfluidic device. The microgels retain the reversible volume phase transition behavior of conventional microgels but can be hydrolytically degraded back into their oligomeric precursor polymer fragments, offering potential for microgel clearance following use in vivo.