A versatile non-fouling multi-step flow reactor platform: demonstration for partial oxidation synthesis of iron oxide nanoparticles.

In the last decade flow reactors for material synthesis were firmly established, demonstrating advantageous operating conditions, reproducible and scalable production via continuous operation, as well as high-throughput screening of synthetic conditions. Reactor fouling, however, often restricts flow chemistry and the common fouling prevention via segmented flow comes at the cost of inflexibility. Often, the difficulty of feeding reagents into liquid segments (droplets or slugs) constrains flow syntheses using segmented flow to simple synthetic protocols with a single reagent addition step prior or during segmentation. Hence, the translation of fouling prone syntheses requiring multiple reagent addition steps into flow remains challenging. This work presents a modular flow reactor platform overcoming this bottleneck by fully exploiting the potential of three-phase (gas-liquid-liquid) segmented flow to supply reagents after segmentation, hence facilitating fouling free multi-step flow syntheses. The reactor design and materials selection address the operation challenges inherent to gas-liquid-liquid flow and reagent addition into segments allowing for a wide range of flow rates, flow ratios, temperatures, and use of continuous phases (no perfluorinated solvents needed). This "Lego®-like" reactor platform comprises elements for three-phase segmentation and sequential reagent addition into fluid segments, as well as temperature-controlled residence time modules that offer the flexibility required to translate even complex nanomaterial synthesis protocols to flow. To demonstrate the platform's versatility, we chose a fouling prone multi-step synthesis, i.e., a water-based partial oxidation synthesis of iron oxide nanoparticles. This synthesis required I) the precipitation of ferrous hydroxides, II) the addition of an oxidation agent, III) a temperature treatment to initiate magnetite/maghemite formation, and IV) the addition of citric acid to increase the colloidal stability. The platform facilitated the synthesis of colloidally stable magnetic nanoparticles reproducibly at well-controlled synthetic conditions and prevented fouling using heptane as continuous phase. The biocompatible particles showed excellent heating abilities in alternating magnetic fields (ILP values >3 nH m2 kgFe-1), hence, their potential for magnetic hyperthermia cancer treatment. The platform allowed for long term operation, as well as screening of synthetic conditions to tune particle properties. This was demonstrated via the addition of tetraethylenepentamine, confirming its potential to control particle morphology. Such a versatile reactor platform makes it possible to translate even complex syntheses into flow, opening up new opportunities for material synthesis.

Gel-on-a-chip: continuous, velocity-dependent DNA separation using nanoscale lateral displacement.

We studied the trajectories of polymers being advected while diffusing in a pressure driven flow along a periodic pillar nanostructure known as nanoscale deterministic lateral displacement (nanoDLD) array. We found that polymers follow different trajectories depending on their length, flow velocity and pillar array geometry, demonstrating that nanoDLD devices can be used as a continuous polymer fractionation tool. As a model system, we used double-stranded DNA (dsDNA) with various contour lengths and demonstrated that dsDNA in the range of 100-10 000 base pairs (bp) can be separated with a size-selective resolution of 200 bp. In contrast to spherical colloids, a polymer elongates by shear flow and the angle of polymer trajectories with respect to the mean flow direction decreases as the mean flow velocity increases. We developed a phenomenological model that explains the qualitative dependence of the polymer trajectories on the gap size and on the flow velocity. Using this model, we found the optimal separation conditions for dsDNA of different sizes and demonstrated the separation and extraction of dsDNA fragments with over 75% recovery and 3-fold concentration. Importantly, this velocity dependence provides a means of fine-tuning the separation efficiency and resolution, independent of the nanoDLD pillar geometry.