A Modular Millifluidic Platform for the Synthesis of Iron Oxide Nanoparticles with Control over Dissolved Gas and Flow Configuration

Gas–liquid reactions are poorly explored in the context of nanomaterials synthesis, despite evidence of significant effects of dissolved gas on nanoparticle properties. This applies to the aqueous synthesis of iron oxide nanoparticles, where gaseous reactants can influence reaction rate, particle size and crystal structure. Conventional batch reactors offer poor control of gas–liquid mass transfer due to lack of control on the gas–liquid interface and are often unsafe when used at high pressure. This work describes the design of a modular flow platform for the water-based synthesis of iron oxide nanoparticles through the oxidative hydrolysis of Fe2+ salts, targeting magnetic hyperthermia applications. Four different reactor systems were designed through the assembly of two modular units, allowing control over the type of gas dissolved in the solution, as well as the flow pattern within the reactor (single-phase and liquid–liquid two-phase flow). The two modular units consisted of a coiled millireactor and a tube-in-tube gas–liquid contactor. The straightforward pressurization of the system allows control over the concentration of gas dissolved in the reactive solution and the ability to operate the reactor at a temperature above the solvent boiling point. The variables controlled in the flow system (temperature, flow pattern and dissolved gaseous reactants) allowed full conversion of the iron precursor to magnetite/maghemite nanocrystals in just 3 min, as compared to several hours normally employed in batch. The single-phase configuration of the flow platform allowed the synthesis of particles with sizes between 26.5 nm (in the presence of carbon monoxide) and 34 nm. On the other hand, the liquid–liquid two-phase flow reactor showed possible evidence of interfacial absorption, leading to particles with different morphology compared to their batch counterpart. When exposed to an alternating magnetic field, the particles produced by the four flow systems showed ILP (intrinsic loss parameter) values between 1.2 and 2.7 nHm2/kg. Scale up by a factor of 5 of one of the configurations was also demonstrated. The scaled-up system led to the synthesis of nanoparticles of equivalent quality to those produced with the small-scale reactor system. The equivalence between the two systems is supported by a simple analysis of the transport phenomena in the small and large-scale setups.


SI 1 -XRD Spectra
XRD was used to determine the crystal structure of the particles produced with the various reactor systems described in the main text. All samples show a prevalence of magnetite/maghemite ( Figure S1a). The XRD pattern of the particles produced with Reactor System 1 also shows features of feroxyhyte ( Figure S1b,

SI 2 -Gas-liquid Tube-in-Tube Contactor Model
The model applied to design the tube-in-tube gas-liquid contactor was adapted from previous work [1,2], and the simulations were performed using COMSOL Multiphysics software (Version 5.2a). The following assumptions were made: • steady-state mass transfer in an axisymmetric geometry at isothermal conditions; • laminar flow (parabolic velocity profile with invariant axial position) in the inner tube; • Henry's law applied to the membrane-liquid interface; • ideal gas in gas phase; • negligible liquid pervaporation through the membrane to the gas phase. Table S1 summarizes the parameters used in the simulations. For Reactor System 2, the flow rate was set equal to 1 mL/min, while for Reactor System 4, the flow rate was set equal to 0.5 mL/min.. Henry constant of CO in water [6] 5.8 × 10 bar * As the membrane permeabilities for CO and H2 are not available, nitrogen permeability was used for the estimation [2]; ** value obtained by interpolating between the constants of H in n-hexane and n-octane. Figure S2 shows the concentration profile of the hydrogen in heptane and carbon monoxide in water inside the inner tube where the reaction mixture was flowing ( Figure S2a

SI 3 -Magnetic Properties of Fe3O4 Nanoparticles
Vibrating sample magnetometry (VSM) was employed to determine the magnetic properties of the particles produced from Reactor Systems 2, 3 and 4 at room temperature up to 2.5 T. All the samples exhibited a saturation magnetization of ~80 emu/g , close to that of bulk magnetite ( 92 emu/g ), supporting the phase purity of the particles produced. The particles exhibited a ferromagnetic behaviour, evidenced by a hysteresis loop (inset in Figure S3), with a coercivity increasing from ~2 mT (Reactor System 4, average particle size 26.5 nm) to ~4 mT (Reactor System 3, average particle size 34 nm) up to ~10 mT (Reactor System 2, average particle size 42 nm). These values are in line with those reported by Marciello et al. for similar particles [7].

SI 4 -Heating Curves upon Alternating Magnetic Field Exposure
Colloidal solutions of particles obtained from Reactor Systems 2, 3 and 4 were exposed to an alternate magnetic field in two different configurations (Frequency = 303 kHz, Field = 24.6 kA/m and Frequency = 759 kHz, Field = 19.9 kA/m) and the temperature of the colloidal solution was measured with the aid of a fibre optic placed inside the liquid sample. The results are reported in Figure S4.

SI 5 -Comparison of Products obtained from Different Scale Reactors
The particles produced with the scaled-up version of Reactor System 3 were analysed with XRD to determine the crystal structure of the product. No changes compared to the small-scale Reactor System were observed ( Figure S5a). The particles were tested in solution as potential heaters upon exposure to an alternating magnetic field ( Frequency = 759 kHz, Field = 19.9 kA/m ), leading to equivalent results as from those produced using the small-scale Reactor System ( Figure S5b).