Protocols for Reproducible, Increased-Scale Synthesis of Engineered Particles—Bridging the “Upscaling Gap”

Large-scale, reproducible synthesis of particles is key to achieving broader material accessibility and applicability. However, direct scaling of experimental parameters, such as reagent volume, does not always translate to the corresponding product yields and material property profiles. This is particularly relevant for particle systems, of which the properties and, subsequently, quality and application are determined from the synthesis methodology. Herein, large-scale synthesis protocols for the template-directed assembly of three particle systems used in our laboratory are detailed, and challenges and considerations with the assembly methods are discussed. These particle systems have potential in targeted drug delivery, imaging and catalysis, as functional coatings, and for heavy metal ion removal applications. The discrete assembly of metal–phenolic network (MPN) films on polystyrene (PS) templates is first detailed, followed by the self-assembly of MPN films onto oil/water emulsions, and finally the fabrication of silica supraparticles (Si-SPs) via gel-mediated electrospraying. For both MPN techniques, upscaling resulted in increases in yield (>450-fold for discrete assembly onto PS templates and 2-fold for self-assembly onto oil/water emulsions) without significant discrepancies in capsule properties. Similarly, up to a 4-fold increase in Si-SP yield (per hour) was achieved by upscaling the gel-mediated electrospraying without significant deviations in particle properties. A series of detailed, stepwise protocols are presented for each particle system with accompanying video footage. Challenges and considerations are discussed for each particle synthesis protocol, with strategies for mitigating issues and ensuring particle reproducibility and quality. These protocols are designed to be straightforward to implement by researchers with little-to-no prior experience in particle engineering, so as to facilitate the broad use and application of these particle systems.