Microfluidic generation of aqueous two-phase-system (ATPS) droplets by oil-droplet choppers

Abstract

Existing approaches for droplet generation with an ultra-low interfacial tension using aqueous two-phase systems, ATPS, are either constricted by a narrow range of flow conditions using passive methods or subjected to complex chip fabrication with the integration of external components using active actuation. To address these issues, we present a simple approach to produce uniform ATPS droplets facilitated by oil-droplet choppers in microfluidics. Our solution counts on the synchronized formation of high-interfacial-tension oil-in-water and low-interfacial-tension water-in-water droplets, where the ATPS interface is distorted by oil droplets and decays into water-in-water droplets. In the synchronization regime, the size and generation frequency of ATPS droplets can be controlled independently by tuning the flow rates of the dispersed aqueous and oil phases, respectively. Our method demonstrates high uniformity of droplets (coefficient of variation between 0.75% and 2.45%), a wide range of available droplet size (droplet radius from 5 μm to 180 μm), and a maximum generation frequency of about 2.1 kHz that is nearly two orders of magnitude faster than that in existing methods. We develop theoretical models to precisely predict the minimum and maximum frequencies of droplet generation and the droplet size. The produced ATPS droplets and oil choppers are separated in the channel using density difference. Our method would boost emulsion-based biological applications such as cell encapsulation, biomolecule delivery, bioreactors, and biomaterials synthesis with ATPS droplets.