Mixing and Flow-Induced Silk Fibroin Self-Assembly in Microfluidic and Semi-Batch Nanoprecipitation

Here, we report the modulation of silk fibroin self-assembly by varying factors which control shear and mixing during nanoprecipitation in semi-batch and micro-mixers. For feeds processed at low shear in a semi-batch format, the properties of secondary assemblies (nanoparticles) were scalable by reducing the mixing time by stirring (0 < 400 rpm). For low mixing times, moving from low to high shear processing increased the extent of self-assembly (0.017 < 16.96 mL min-1) for 0.5, 2 and 3% w/v silk. In high shear regimes, the size and polydispersity index of assemblies decreased with mixing time, as stirring rate (800, 400 < 0 rpm) and feed addition height (3.5 < 0 cm) increased. Finally, in conditions of high shear and low mixing time, the feed concentration controlled the assembly shape, size, and polydispersity index in microfluidic (0.5, 3.0 < 2% w/v) and semi-batch format (3.0 < 0.5% w/v). This work provides new insight into the manufacture of low polydispersity, spherical and worm-like silk nanoparticles.