Brust-Schiffrin synthesis of thiol-stabilised gold nanoparticles using a three-phase continuous flow reactor

Abstract Thiol-capped ultra-small gold nanoparticles are a highly versatile material with key applications in biomedicine, sensing and catalysis. However, translation of the widely used Brust–Schiffrin batch synthesis to continuous flow remains a significant challenge due to multiphase mass transfer limitations, hydrogen gas evolution and reactor fouling. In this work, we report the development of a continuous three-phase (gas–liquid–liquid) millifluidic reactor for the Brust–Schiffrin synthesis of dodecanethiol-stabilised gold nanoparticles. Nitrogen was introduced as a third phase to capture evolving hydrogen gas, enabling stable flow patterns and controlled interfacial contact between aqueous and organic phases. Systematic optimisation of reactor geometry, tubing diameter, reagent concentrations, and precursor delivery strategy was performed to improve particle size control and reproducibility. A separated-feed configuration, in which Au(III) and thiol precursors were mixed in flow immediately prior to reduction, minimised uncontrolled Au(I)-thiolate formation and significantly narrowed the particle size distribution. Using the optimised reactor design, gold nanoparticles with a mean diameter of 3.1 ± 0.45 nm were continuously produced in toluene without fouling over extended operation, achieving a production rate of 3.5 mg Au(0)/h. This work demonstrates a robust and scalable continuous-flow platform for producing high-quality thiol-capped gold nanoparticles and provides key design principles for gas-evolving multiphase nanoparticle syntheses in flow.