Self-seeded coprecipitation flow synthesis of iron oxide nanoparticles via triphasic reactor platform: Optimising heating performance under alternating magnetic fields

Abstract

Liquid-liquid segmentation is a common method to prevent reactor fouling when synthesising nanoparticles in flow, despite limiting synthetic protocols to single reagent addition steps before segmentation. This work demonstrates how a modular triphasic (gas–liquid–liquid) flow reactor platform overcomes this limitation, facilitating a continuous and fouling-free four-step co-precipitation flow synthesis of iron oxide nanoparticles (IONPs) for magnetically induced hyperthermia cancer treatment (MHCT). For this and other biomedical applications water-based IONP syntheses such as co-precipitation are favoured, but producing IONPs > 10 nm as needed for MHCT remains challenging. To overcome this size barrier for co-precipitation syntheses, a seeded growth co-precipitation strategy was employed here for the first time. After demonstrating the synthesis in batch, a triphasic flow reactor was developed to translate the multistep batch protocol into flow. Nitrogen gas was used to space the liquid–liquid segmented slugs evenly, enabling self-synchronised solution addition into the aqueous slugs dispersed in heptane. Three additions of the iron precursor solution followed by citric acid solution addition formed the seeds, grew them to larger IONPs and stabilised them. The flow platform was used for screening of the synthetic parameters to optimise the IONP heating performance in an alternating magnetic field, hence investigating their potential as MHCT heating agents. The optimal reactor settings identified made it possible to continuously synthesise 0.46 gIONPs/h colloidally stable IONPs in the aqueous phase of size ∼15 nm. The fouling-free flow reactor operated at short overall residence times (<5 min) using just ferric and ferrous salts, sodium carbonate and citric acid. The IONPs exhibited high heating performance, with an intrinsic loss power up to 3.76 nH m2 kgFe-1.