A Scalable and Microfluidic Approach to Water-in-water Microdroplet Generation With a Passive, Membrane-based Cross-flow System

The generation of water-in-water droplets has recently received great attention for its applicability in biological applications over traditional oil-water droplet systems because of their high biocompatibility. An aqueous two-phase system (ATPS), aqueous mixture of polyethylene glycol (PEG) and dextran (DEX), has an ultra-low interfacial tension which makes monodispersed droplet formation challenging. Recent passive methods in microfluidics with flow-focusing configurations overcome this challenge, but they suffer either from polydispersity, narrow droplet size range, or low throughput. Successful droplet formation in such passive methods occurs in jetting flow regimes with low continuous phase flow rates, Qc<1ŒºLmin .Gravity-driven hydrostatic or highly precise pressure flow control has been used to apply constant, low flow rates that conventional syringe pumps struggle to emulate. Here, a new passive cross-flow configuration is introduced to generate monodispersed ATPS droplets. Our microfluidic device is membrane-integrated with constant flowrate syringe pumps. Additionally, the membrane with three uniform pores enables our device to operate as a parallel system capable of three controlled droplet formations simultaneously, with a wide range of monodispersed droplet diameters from ≈17 to 90 μm (coefficient of variation, CV ≤ 5%) and from ≈90 to 180 μm (CV ≤ 10%).