Spontaneous Formation of Core–Shell Microdroplets during Conventional Coacervate Phase Separation

We report the single-step formation and stability of protocell-like, core-shell coacervate droplets comprising a polyelectrolyte-rich shell and a solvent-rich vacuole core from the poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) system. These double emulsion (DE) coacervate droplets coexist with single emulsion (SE) droplets, suggesting a kinetic mechanism of formation. We use high-throughput microscopy and machine learning to classify droplet morphologies across various final compositions (polyelectrolyte ratios and salt concentrations) and processing routes (mixing rate and thermodynamic path). We find that DE droplets form preferentially over SE droplets at a wide range of compositions using a slow injection mixing rate. DE droplet formation is enhanced at lower salt (NaCl) levels and near 1:1 charge stoichiometry, showing a preference for polycation excess. DE droplets are stable to the micron scale and retain their core-shell structure even after coalescence. Nevertheless, they are metastable; direct observations of various coarsening phenomena suggest that they are primarily stabilized by the viscoelasticity and high viscosity of the polymer-rich shell. Overall, the scalable, simple mixing process used herein offers a novel mechanism to produce multiphase coacervate droplets that is orthogonal to existing routes, which require either dropwise synthesis or thermodynamic tuning.