Microfluidic synthesis of superparamagnetic iron oxide nanocrystals for magnetic resonance imaging

Superparamagnetic iron oxide nanoparticles (SPIONs) are of significant interest in areas such as drug delivery, hyperthermic treatment, magnetic resonance imaging (MRI) and selective separation of biological fluids. For all these applications there is a recognised need for improved synthetic methods that are capable of yielding SPIONs of uniform size, geometry and stoichiometry. Microfluidic reactors offer an attractive route to nanoparticle synthesis due to the superior control they provide over reaction conditions and particle properties relative to traditional bulk methods. In 2002 Edel et al.1 proposed the use of microfluidic reactors for nanoparticle synthesis due to the high levels of control they provide over key reaction parameters such as temperature, reagent concentrations and reaction time. Since that report a diversity of metal, metal oxide, compound semiconductor and organic nanomaterials have been successfully synthesised in microfluidic systems. Most reports of nanoparticle synthesis in microreactors have involved single-phase mode of operation, in which continuous streams of miscible fluids are manoeuvred through microscale channels where nucleation and growth take place. Such reactors, however, are poorly suited to the synthesis of SPIONs due to their high susceptibility to fouling. An alternative approach is to use droplet-based reactors in which an immiscible liquid is injected alongside the reaction mixture, causing the latter to spontaneously divide into a series of near identical droplets. In this thesis microfluidic synthesis of SPIONs in a controlled and reproducible manner is described. This work is focussed on improving the microfluidic methods for controlled synthesis of SPIONs and utilise the produced nanoparticles directly as contrast enhancers in MR imaging. The droplet based reactions were initially performed on polydimethylsiloxane (PDMS) microfluidic devices, however on such devices, low throughput was obtained. To overcome fabrication difficulty and to increase throughput, droplet-based synthesis was performed on the capillary-based reactor.