Synthesis of a biocompatible fluorinated multiblock copolymer surfactant for water-in-fluorocarbon droplets and its application in droplet digital polymerase chain reaction

Droplet digital polymerase chain reaction (ddPCR) technology has attracted considerable attention in recent years. A multiblock surfactant based on perfluompolyethers (PFPE) has been widely used in droplet-based microfluidics and is known to provide high droplet stability and biocompatibility. We developed a multiblock copolymer surfactant synthesized by adjusting the proportions of the intermediates to enhance the stabilities of droplets at high temperatures. The surfactants were synthesized via amidation reactions that coupled the PFPE and diamine polyethylene glycol (PEG), and the introduction of triethylamine, as a catalyst, made the reaction more efficient. The as-synthesized surfactants were used to generate water-in- fluorocarbon (W/F) droplets with a microfluidic device and a ddPCR device was used to evaluate the performance of the droplets. When the molar ratio (PFPE-PEG:PFPE-PEG-PFPE) was 2:1 and the concentration reached 2 wt%, the droplets showed good thermal stability. Surfactant showed the best performance, lowering the interfacial tension to 2.5 mN/m, when it's critical micelle concentration (CMC) exceeded 50 mg/L. Furthermore, the use of an alkaline solution (pH = 9-10) as the washing buffer, improved the biocompatible of the surfactant. When applied to the detection of lambda DNA, the limit of detection was 0.52 copies/mu L. The as-synthesized surfactants showed promise in generating biocompatible and thermally stable droplets and providing a new surfactant option for future ddPCR technology.