Modulation of Oil/Polymer Nanocapsule Size via Phase Diagram-Guided Microfluidic Coprecipitation

Flow-based nanoprecipitation of different solutes via rapid mixing of two miscible liquids is a scalable strategy for manufacturing nanoparticles with various shapes and morphologies. Controlling the size of nanoparticles in flow-based nanoprecipitation, however, is often left to empirical variations in the flow rate ratios or the total flow rate of the two streams. In this work, we investigate the coprecipitations of oil and polymer to form nanocapsules via the Ouzo effect using glass capillary microfluidics across a range of mixing conditions. In the range of flow rates studied, the two streams mix convectively in micro-vortices formed at the junction of the two stream inlets. Using computational fluid dynamics simulations and glass capillary microfluidic nanoprecipitation, we establish a relationship between the precipitation conditions occurring experimentally in situ and the location on the ternary Ouzo phase diagram where precipitation is taking place. We find that a key variable in the resulting average diameter of the fabricated capsules is the degree of supersaturation experienced by both the oil and the polymer in the vortex zone of the device, showing a strong correlation between the two values. The control over the nanocapsule size by varying the extent of supersaturation of both precipitants is demonstrated by using two oils having distinct phase diagrams. This work provides a systematic approach to controlling the size of nanoparticles fabricated via continuous nanoprecipitation by linking the in situ flow conditions to ternary phase diagram behavior, enabling accurate control over nanocapsule size.