SPIONs were coated with silica to form SPION@SiO 2 NPs, using a reverse microemulsion method, as described in the Experimental Section. The formation of a silica coating on NPs using reverse microemulsion is reliant on a number of factors, with the concentrations of the silica source and the basic catalyst being reported as the most important in controlling shell thickness, presence of undesirable (non-magnetic) by-products, and uniform populations. The SiO 2 shell thickness, for example, can be controlled by altering the number of moles of TEOS, with low concentrations resulting in ultra-thin 2 nm SiO 2 shell radii, due to the small amount of silica precursor available for coating. A similar effect can be achieved by changing the number of moles of NH 4 OH and/or the ratio of NH 4 OH-to-surfactant. In the former, adjusting the quantity of NH 4 OH affects the rate of silica hydrolysis and nucleation, where higher concentrations increase the rate of TEOS hydrolysis and increases the shell thickness; however this can also encourage the formation of non-magnetic silica by-product. The ratio of NH 4 OH-to-surfactant, on the other hand, determines the size and number of micelles formed, influencing the ultimate size of particles formed (since the coating step occurs within the micelle). It has also been found that the fractionated addition of TEOS can reduce particle polydispersity, simultaneously reducing the formation of by-product SiO 2 . Despite their identification as important experimental conditions in the formation of SPION@SiO 2 NPs, these parameters have not been investigated through a DoE approach, which allows for the simultaneous variation of experimental factors. This not only enables the evaluation of interactions between these factors, but also reduces the impact of random variation. Furthermore, by implementing 3 levels (low, centre, high), non-linear effects can also be measured. The resulting model can be manip- ulated to maximise a response, such as the size of core@shell NPs. Therefore, in the study herein, the numbers of moles of TEOS and NH 4 OH, and fractionated additions of TEOS were investigated as primary variables of importance in the production of core@shell particles. The responses of SiO 2 shell thickness, monodispersity, and population (where population is described as the percentage of single-core@shell particles with respect to the total number of particles) were analysed in order to optimise and control the properties of the NPs formed. A 3 3 full-factorial model was employed, and experimental conditions were generated according to Table1.