Highly reproducible, high-yield flow synthesis of gold nanoparticles based on a rational reactor design exploiting the reduction of passivated Au(III)

Reproducibility in the synthesis of nanomaterials is a crucial aspect for their real-life applications. It is particularly pertinent in the context of gold nanoparticles, where a plethora of seeded-growth methods are being developed to control particle morphology and size. The translation of such methods to manufacturing can be hindered by poor reproducibility of the seed production step. This study focuses on the development of a highly reproducible platform for the synthesis of gold nanoparticles, as potential substrates for glucose sensing. A flow reactor was designed, starting from a detailed study of the synthesis in batch. The well-established Turkevich synthesis was investigated via in situ time-resolved UV-vis spectroscopy. In order to enhance the reproducibility of the synthesis the effect of passivating the gold precursor stock before its use in the synthesis was investigated. It is shown that starting from a pre-passivated precursor provided improved control over the initial reaction stage, at the expense of a small increase in the reaction time. At the optimal reaction conditions, the proposed modified Turkevich method allowed for the synthesis in batch of ∼12 nm monodisperse (RSD ∼10%) particles, with a variability from batch to batch of only ∼5%. The information gathered from the batch study, in particular the reaction time, was used to translate the synthesis from batch to flow. The system utilized for the flow synthesis consisted of a segmented flow reactor, where an organic stream was employed to segment the reactive aqueous stream to avoid reactor fouling and improve monodispersity. The use of segmented flow enables treating each droplet as a “travelling batch”, hence allowing the direct use of the kinetic data obtained in batch to design the flow reactor, leading to the rapid identification of the minimum residence time to allow for reaction completion. The flow reactor enabled the synthesis of ∼11 nm monodisperse (RSD ∼10%) particles, with full precursor conversion and reproducibility between reactor runs higher than that obtained in batch (variability of ∼2%). The flow-produced gold nanoparticles were tested for glucose sensing, exploiting their glucose oxidase-mimicking behaviour and demonstrated satisfactory glucose detection in the range of 1–10 mM

Kinetics-based design of a flow platform for highly reproducible on demand synthesis of gold nanoparticles with controlled size between 50 and 150 nm and their application in SERS and PIERS sensing

Seeded-growth synthetic protocols enable precise control of particle size and shape, crucial for many sensing applications. However, scaling-up these syntheses in a reproducible way is challenging, as minimal variation in process parameters such as seed size, concentration or reaction temperature can significantly alter the final product. Flow reactors enable tight control in the process parameters and high reproducibility of the synthesis, representing a potential technology to perform seeded-growth syntheses in large scale. This work reports the design of a flow platform for the controlled synthesis of spherical gold nanoparticles with size up to 150nm through a seeded-growth approach, and their use in Surface Enhanced Raman Scattering (SERS) and Photoinduced Enhanced Raman Spectroscopy (PIERS). The particle growth kinetics were studied via in situ time-resolved UV–Vis spectroscopy. The spectroscopic data were fitted with a kinetic model, which was subsequently used for the design of the reactor. The kinetics-based design approach enabled fast translation of the growth synthesis in flow, eventually allowing the on demand flow synthesis of particles with controllable size, ranging from 50 to 150nm, with high reproducibility and full precursor conversion. The particles were tested for SERS and PIERS for different substrates, including warfare agents and biomolecules, with enhancement factors between 103 and 108 depending on the analyte, demonstrating their potential for detection of various analytes

Microwave-assisted flow synthesis of multicore iron oxide nanoparticles

Coprecipitation is by far the most common synthesis method for iron oxide nanoparticles (IONPs). However, reproducibility and scalability represent a major challenge. Therefore, innovative processes for scalable production of IONPs are highly sought after. Here, we explored the combination of microwave heating with a flow reactor producing IONPs through coprecipitation. The synthesis was initially studied in a well-characterised microwave-heated flow system, enabling the synthesis of multicore IONPs, with control over both the single core size and the multicore hydrodynamic diameter. The effect of residence time and microwave power was investigated, enabling the synthesis of multicore nanostructures with hydrodynamic diameter between ∼35 and 70 nm, with single core size of 3–5 nm. Compared to particles produced under conventional heating, similar single core sizes were observed, though with smaller hydrodynamic diameters. The process comprised of the initial IONP coprecipitation followed by the addition of the stabiliser (citric acid and dextran). The ability of precisely controlling the stabiliser addition time (distinctive of flow reactors), contributed to the synthesis reproducibility. Finally, scale-up by increasing the reactor length and using a different microwave cavity was demonstrated, producing particles of similar structure as those from the small scale system, with a throughput of 3.3 g/h

Development of an in-line magnetometer for flow chemistry and its demonstration for magnetic nanoparticle synthesis

Despite the wide usage of magnetic nanoparticles, it remains challenging to synthesise particles with properties that exploit each application's full potential. Time consuming experimental procedures and particle analysis hinder process development, which is commonly constrained to a handful of experiments without considering particle formation kinetics, reproducibility and scalability. Flow reactors are known for their potential of large-scale production and high-throughput screening of process parameters. These advantages, however, have not been utilised for magnetic nanoparticle synthesis where particle characterisation is performed, with a few exceptions, post-synthesis. To overcome this bottleneck, we developed a highly sensitive magnetometer for flow reactors to characterise magnetic nanoparticles in solution in-line and in real-time using alternating current susceptometry. This flow magnetometer enriches the flow-chemistry toolbox by facilitating continuous quality control and high-throughput screening of magnetic nanoparticle syntheses. The sensitivity required to monitor magnetic nanoparticle syntheses at the typically low concentrations (<100 mM of Fe) was achieved by comparing the signals induced in the sample and reference cell, each of which contained near-identical pairs of induction and pick-up coils. The reference cell was filled only with air, whereas the sample cell was a flow cell allowing sample solution to pass through. Balancing the flow and reference cell impedance with a newly developed electronic circuit was pivotal for the magnetometer's sensitivity. To showcase its potential, the flow magnetometer was used to monitor two iron oxide nanoparticle syntheses with well-known particle formation kinetics, i.e., co-precipitation syntheses with sodium carbonate and sodium hydroxide as base, which have been previously studied via synchrotron X-ray diffraction. The flow magnetometer facilitated batch (on-line) and flow (in-line) synthesis monitoring, providing new insights into the particle formation kinetics as well as, effect of temperature and pH. The compact lab-scale flow device presented here, opens up new possibilities for magnetic nanoparticle synthesis and manufacturing, including 1) early stage reaction characterisation 2) process monitoring and control and 3) high-throughput screening in combination with flow reactors

Co-precipitation synthesis of stable iron oxide nanoparticles with NaOH: New insights and continuous production via flow chemistry

Co-precipitation is by far the most common synthesis for magnetic iron oxide nanoparticles (IONPs), as cheap and environmentally friendly precursors and simple experimental procedures facilitate IONP production in many labs. Optimising co-precipitation syntheses remains challenging however, as particle formation mechanisms are not well understood. This is partly due to the rapid particle formation (within seconds) providing insufficient time to characterise initial precipitates. To overcome this limitation, a flow chemistry approach has been developed using steady-state operation to “freeze” transient reaction states locally. This allowed for the first time a comprehensive analysis of the early stages of co-precipitation syntheses via in-situ Small Angle X-ray Scattering and in-situ synchrotron X-Ray Diffraction. These studies revealed that after mixing the ferrous/ferric chloride precursor with the NaOH base solution, the most magnetic iron oxide phase forms within 5 s, the particle size changes only marginally afterwards, and co-precipitation and agglomeration occur simultaneously. As these agglomerates were too large to achieve colloidal stability via subsequent stabiliser addition, co-precipitated IONPs had to be de-agglomerated. This was achieved by adding the appropriate quantity of a citric acid solution which yielded within minutes colloidally stable IONP solutions around a neutral pH value. The new insights into the particle formation and the novel stabilisation procedure (not requiring any ultra-sonication or washing step) allowed to design a multistage flow reactor to synthesise and stabilise IONPs continuously with a residence time of less than 5 min. This reactor was robust against fouling and produced stable IONP solutions (of ~1.5 mg particles per ml) reproducibly via fast mixing ( 500 ml/h) for low materials cost

Catalytic Teflon AF-2400 membrane reactor with adsorbed ex situ synthesized Pd-based nanoparticles for nitrobenzene hydrogenation

Among the unconventional approaches of supporting catalyst nanoparticles, the layer-by-layer assembly of polyelectrolyte multilayers for nanoparticle adsorption represents an easy and convenient method. It enables the deposition of singularly adsorbed nanoparticles and prevents them from aggregating. In this work, polydopamine was grafted on the internal surface of a Teflon AF-2400 tubular membrane, known for its excellent permeability to light gases and inertness to chemicals. Poly(acrylic acid) and poly(allylamine hydrochloride) were sequentially adsorbed on the modified surface of the membrane. Ex situ synthesised spherical, cubical, truncated octahedral palladium and dendritic platinum-palladium nanoparticles were then incorporated. The catalytic membranes were assembled in a tube-in-tube configuration and tested for 6 h of continuous nitrobenzene hydrogenation with molecular hydrogen. Stable conversion was observed for the truncated octahedral and dendritic nanoparticles, while a progressive deactivation was observed for the other nanoparticles. Due to their small size, the 3.7 nm spherical nanoparticles exhibited the highest reaction rate, 629 molreactant/(molcatalyst⋅h), while the cubical nanoparticles showed the highest turnover frequency, ∼3000 h−1. The reactor concept developed in this work demonstrates how such a tool can serve as platform for conducting continuous multiphase catalytic reactions in flow using singularly adsorbed and finely tuned nanoparticles. The small volume of pressurised gas present in the tube-in-tube reactor offers improved process safety compared to batch, while the Teflon AF-2400 membrane provides control over the gas permeation during reaction