Controlled Formation of All-Aqueous Janus Droplets by Liquid-Liquid Phase Separation of an Aqueous Three-Phase System

Janus droplets have been demonstrated in a wide range of applications, ranging from drug delivery, to biomedical imaging, to bacterial detection. However, existing fabrication strategies often involve nonaqueous solvents, such as organic solvent or oil, which largely limits their use in fields that require a high degree of biocompatibility. Here, we present a method to achieve all-aqueous Janus droplets by liquid-liquid phase separation of an aqueous three-phase system (A3PS). An aqueous droplet containing two initially miscible polymers is first injected into an aqueous solution of another concentrated polymer, and then it spontaneously phase-separates into a Janus droplet due to the diffusive mass exchange between the drop and bulk phases during equilibration. To achieve continuous generation of the Janus droplets, the A3PS is further integrated with microfluidics and electrospray. The size and shape of the phase-separated Janus droplets can be easily controlled by tuning the operation parameters, such as the flow rate and/or the initial composition of the drop phases. Dumbbell-shaped and snowman-shaped Janus droplets with average sizes between 100 and 400 μm can be generated by both coflow microfluidics and electrospray. In particular, the phase-separated Janus droplets can simultaneously load two different liposomes into each compartment, which are promising carriers for combination drugs. The obtained Janus droplets are superior templates for biocompatible materials, which can serve as building blocks such as high-order droplet patterns for constructing advanced biomaterials.