Click chemistry approaches to expand the repertoire of PEG-based fluorinated surfactants for droplet microfluidics

We report the novel and simplified synthesis of fluorinated surfactants for droplet microfluidics. The range of applications of droplet microfluidics has greatly expanded during the last decade thanks to its ability to manipulate and process tiny amount of sample and reagents at high throughput in independent reactors. A critical component of the technology is the formulation of the immiscible oil phase that contains surfactants to stabilize droplets. The success of droplet microfluidics relies mostly on a single fluorinated formulation that uses a PFPE–PEG triblock surfactant. The synthesis of this surfactant is laborious and requires skills in synthetic chemistry preventing the wider community to explore the synthesis of surfactants with alternate structures. We sought to provide a simplified synthesis for novel PFPE–PEG surfactants based on click chemistry approaches such as copper-catalyzed azide-alkyne cycloaddition (CuAAC) and UV-activated thiol–yne reactions. Our strategy is based on converting a moisture sensitive intermediate typically used in the synthesis of the triblock PFPE–PEG surfactant into a stable and click ready molecule. We successfully combined that fluorinated tail with differently functionalized PEG and glycerol ethoxylate molecules to generate surfactants with diverse structures via CuACC and thiol–yne reactions. We report the characterization, biocompatibility and ability to stabilize emulsions of those surfactants, as well as the unique advantages and challenges of the strategy.