Small iron oxide nanoparticles (IONPs) were synthesised in water via co-precipitation by quenching particle growth after the desired magnetic iron oxide phase formed. This was achieved in a millifluidic multistage flow reactor by precisely timed addition of an acidic solution. IONPs (≤5 nm), a suitable size for positive T1 magnetic resonance imaging (MRI) contrast agents, were obtained and stabilised continuously. This novel flow chemistry approach facilitates a reproducible and scalable production, which is a crucial paradigm shift to utilise IONPs as contrast agents and replace currently used Gd complexes. Acid addition had to be timed carefully, as the inverse spinel structure formed within seconds after initiating the co-precipitation. Late quenching allowed IONPs to grow larger than 5 nm, whereas premature acid addition yielded undesired oxide phases. Use of a flow reactor was not only essential for scalability, but also to synthesise monodisperse and non-agglomerated small IONPs as (i) co-precipitation and acid addition occurred at homogenous environment due to accurate temperature control and rapid mixing and (ii) quenching of particle growth was possible at the optimum time, i.e., a few seconds after initiating co-precipitation. In addition to the timing of growth quenching, the effect of temperature and dextran present during co-precipitation on the final particle size was investigated. This approach differs from small IONP syntheses in batch utilising either growth inhibitors (which likely leads to impurities) or high temperature methods in organic solvents. Furthermore, this continuous synthesis enables the low-cost (<£10 per g) and large-scale production of highly stable small IONPs without the use of toxic reagents. The flow-synthesised small IONPs showed high T1 contrast enhancement, with transversal relaxivity (r2) reduced to 20.5 mM−1 s−1 and longitudinal relaxivity (r1) higher than 10 mM−1 s−1, which is among the highest values reported for water-based IONP synthesis.
Magneto-plasmonic nanocomposites can possess properties inherent to both individual components (iron oxide and gold nanoparticles) and are reported to demonstrate high potential in targeted drug delivery and therapy. Herein, we report on Fe3O4/Au magneto-plasmonic nanocomposites (MPNC) synthesized with the use of amino acid tryptophan via chemical and photochemical reduction of Au ions in the presence of nanosized magnetite. The magnetic field (MF) induced aggregation was accompanied by an increase in the absorption in the near-infrared (NIR) spectral region, which was demonstrated to provide an enhanced photothermal (PT) effect under NIR laser irradiation (at 808 nm). A possibility for therapeutic application of the MPNC was illustrated using cancer cells in vitro. Cultured HeLa cells were treated by MPNC in the presence of MF and without it, following laser irradiation and imaging using confocal laser scanning microscopy. After scanning laser irradiation of the MPNC/MF treated cells, a formation and rise of photothermally-induced microbubbles on the cell surfaces was observed, leading to a damage of the cell membrane and cell destruction. We conclude that the synthesized magneto-plasmonic Fe3O4/Au nanosystems exhibit magnetic field-induced reversible aggregation accompanied by an increase in NIR absorption, allowing for an opportunity to magnetophoretically control and locally enhance a NIR light-induced thermal effect, which holds high promise for the application in photothermal therapy.
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.
Thermochromic lateral flow assay is developed to detect recombinant dengue virus serotype 2 NS1 (DENV2-NS1) from solution. It shows significant improvement in limit of detection (1.56 ng mL−1) compared with a typical lateral flow assay (6.25 ng mL−1).