Hydrodynamic Characterization of Phase Separation in Devices with Microfabricated Capillaries.

Capillary microseparators have been gaining interest in downstream unit operations, especially for pharmaceutical, space, and nuclear applications, offering efficient separation of two-phase flows. In this work, a detailed analysis of the dynamics of gas?liquid separation at the single meniscus level helped to formulate a model to map the operability region of microseparation devices. A water?nitrogen segmented flow was separated in a microfabricated silicon-glass device, with a main channel (width, W = 600 ?m; height, H = 120 ?m) leading into an array of 276 capillaries (100 ?m long; width = 5 ?m facing the main channel and 25 ?m facing the liquid outlet), on both sides of the channel. At optimal pressure differences, the wetting phase (water) flowed through the capillaries into the liquid outlet, whereas the nonwetting phase (nitrogen) flowed past the capillaries into the gas outlet. A high-speed imaging methodology aided by computational analysis was used to quantify the length of the liquid slugs and their positions in the separation zone. It was observed that during stable separation, the position of the leading edge of the liquid slugs (advancing meniscus), which became stationary in the separation zone, was dependent only on the outlet pressure difference. The trailing edge of the liquid slugs (receding meniscus) approached the advancing meniscus at a constant speed, thus leading to a linear decrease of the liquid slug length. Close to the liquid-to-gas breakthrough point, that is, when water exited through the gas outlet, the advancing meniscus was no longer stationary, and the slug lengths decreased exponentially. The rates of decrease of the liquid slug length during separation were accurately estimated by the model, and the calculated liquid-to-gas breakthrough pressures agreed with experimental measurements.

Stripping of acetone from water with microfabricated and membrane gas-liquid contactors.

Stripping of acetone from water utilizing nitrogen as a sweeping gas in co-current flow was conducted in a microfabricated glass/silicon gas-liquid contactor. The chip consisted of a microchannel divided into a gas and a liquid chamber by 10 µm diameter micropillars located next to one of the channel walls. The channel length was 35 mm, the channel width was 220 µm and the microchannel depth 100 µm. The micropillars were wetted by the water/acetone solution and formed a 15 µm liquid film between them and the nearest channel wall, leaving a 195 µm gap for gas flow. In addition, acetone stripping was performed in a microchannel membrane contactor, utilizing a hydrophobic PTFE membrane placed between two microstructured acrylic plates. Microchannels for gas and liquid flows were machined in the plates and had a depth of 850 µm and 200 µm respectively. In both contactors the gas/liquid interface was stabilized: in the glass/silicon contactor by the hydrophilic micropillars, while in the PTFE/acrylic one by the hydrophobic membrane. For both contactors separation efficiency was found to increase by increasing the gas/liquid flow rate ratio, but was not affected when increasing the inlet acetone concentration. Separation was more efficient in the microfabricated contactor due to the very thin liquid layer employed.

Microfluidic production of nanogels as alternative triple transfection reagents for the manufacture of adeno-associated virus vectors.

Adeno-associated viral vectors (AAVs) have proved a mainstay in gene therapy, owing to their remarkable transduction efficiency and safety profile. Their production, however, remains challenging in terms of yield, the cost-effectiveness of manufacturing procedures and large-scale production. In this work, we present nanogels produced by microfluidics as a novel alternative to standard transfection reagents such as polyethylenimine-MAX (PEI-MAX) for the production of AAV vectors with comparable yields. Nanogels were formed at pDNA weight ratios of 1 : 1 : 2 and 1 : 1 : 3, of pAAV cis-plasmid, pDG9 capsid trans-plasmid and pHGTI helper plasmid respectively, where vector yields at a small scale showed no significant difference to those of PEI-MAX. Weight ratios of 1 : 1 : 2 showed overall higher titers than 1 : 1 : 3, where nanogels with nitrogen/phosphate ratios of 5 and 10 produced yields of ≈8.8 × 108 vg mL-1 and ≈8.1 × 108 vg mL-1 respectively compared to ≈1.1 × 109 vg mL-1 for PEI-MAX. In larger scale production, optimised nanogels produced AAV at a titer of ≈7.4 × 1011 vg mL-1, showing no statistical difference from that of PEI-MAX at ≈1.2 × 1012 vg mL-1, indicating that equivalent titers can be achieved with easy-to-implement microfluidic technology at comparably lower costs than traditional reagents.

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.

In-Silico Conceptualisation of Continuous Millifluidic Separators for Magnetic Nanoparticles.

Magnetic nanoparticles are researched intensively not only for biomedical applications, but also for industrial applications including wastewater treatment and catalytic processes. Although these particles have been shown to have interesting surface properties in their bare form, their magnetisation remains a key feature, as it allows for magnetic separation. This makes them a promising carrier for precious materials and enables recovery via magnetic fields that can be turned on and off on demand, rather than using complex (nano)filtration strategies. However, designing a magnetic separator is by no means trivial, as the magnetic field and its gradient, the separator dimensions, the particle properties (such as size and susceptibility), and the throughput must be coordinated. This is showcased here for a simple continuous electromagnetic separator design requiring no expensive materials or equipment and facilitating continuous operation. The continuous electromagnetic separator chosen was based on a current-carrying wire in the centre of a capillary, which generated a radially symmetric magnetic field that could be described using cylindrical coordinates. The electromagnetic separator design was tested in-silico using a Lagrangian particle-tracking model accounting for hydrodynamics, magnetophoresis, as well as particle diffusion. This computational approach enabled the determination of separation efficiencies for varying particle sizes, magnetic field strengths, separator geometries, and flow rates, which provided insights into the complex interplay between these design parameters. In addition, the model identified the separator design allowing for the highest separation efficiency and determined the retention potential in both single and multiple separators in series. The work demonstrated that throughputs of ~1/4 L/h could be achieved for 250-500 nm iron oxide nanoparticle solutions, using less than 10 separator units in series.

Study of Liquid-Solid Mass Transfer and Hydrodynamics in Micropacked Bed with Gas-Liquid Flow.

The volumetric liquid-solid (L-S) mass transfer coefficient under gas-liquid (G-L) two-phase flow in a silicon-chip-based micropacked bed reactor (MPBR) was studied using the copper dissolution method and was related to the reactor hydrodynamic behavior. Using a high-speed camera and a robust computational image analysis method that selectively analyzed the bed voidage around the copper particles, the observed hydrodynamics were directly related to the L-S mass transfer rates in the MPBR. This hydrodynamic study revealed different pulsing structures inside the packed copper bed depending on the flow patterns established preceding the packed bed upon increasing gas velocity. A "liquid-dominated slug" flow regime was associated with an upstream slug flow feed. A "sparse slug" flow regime developed with an upstream slug-annular flow feed. At higher gas velocity, a "gas continuous with pulsing" regime developed with an annular flow feed, which had similar features to the pulsing flow in macroscale packed beds, but it was sensitive and easily destabilized by disturbances from upstream or downstream pressure fluctuations. The volumetric L-S mass transfer coefficient decreased with increasing gas velocity under the liquid-dominated slug flow regime and became rather less affected under the sparse slug flow regime. By resolving the transition from the liquid-dominated slug flow to the sparse slug flow and capturing the onset of the gas-continuous with pulsing regime, we gained new insights into the hydrodynamic effects of G-L flows on the L-S mass transfer rates in a MPBR.

A study of the interaction of cationic dyes with gold nanostructures.

The interaction of methylene blue and crystal violet dyes with a range of gold nanoparticles (AuNPs), gold nanoclusters and gold/silver nanoclusters is reported. It is found that 20 nm citrate-capped AuNPs have strong interactions with these two dyes that result in red-shifted absorption peaks in their electronic absorption spectra. Transmission electron microscopy and dynamic light scattering measurements show that this can be attributed to these AuNPs combining into large agglomerates. Eventually, precipitation is observed. The agglomeration process is triggered when the dye reaches or exceeds a threshold concentration and then does not stop until all the AuNPs have agglomerated into large particles and precipitated. Calculations suggest that the threshold concentration corresponds to having sufficient dye molecules to form a monolayer on the surface of AuNPs. We also observe similar red-shifting in the absorption peaks of the electronic absorption spectra of 11-50 nm citrate-capped AuNPs formed by both single step and seeded growth methods. No such interactions were observed in the UV-vis spectra of the dyes with Tris-capped AuNPs, gold nanoclusters or gold/silver nanoclusters.

Microfluidic synthesis of protein-loaded nanogels in a coaxial flow reactor using a design of experiments approach.

Ionic gelation is commonly used to generate nanogels but often results in poor control over size and polydispersity. In this work we present a novel approach to the continuous manufacture of protein-loaded chitosan nanogels using microfluidics whereby we demonstrate high control and uniformity of the product characteristics. Specifically, a coaxial flow reactor (CFR) was employed to control the synthesis of the nanogels, comprising an inner microcapillary of internal diameter (ID) 0.595 mm and a larger outer glass tube of ID 1.6 mm. The CFR successfully facilitated the ionic gelation process via chitosan and lysozyme flowing through the inner microcapillary, while cross-linkers sodium tripolyphosphate (TPP) and 1-ethyl-2-(3-dimethylaminopropyl)-carbodiimide (EDC) flowed through the larger outer tube. In conjunction with the CFR, a four-factor three-level face-centered central composite design (CCD) was used to ascertain the relationship between various factors involved in nanogel production and their responses. Specifically, four factors including chitosan concentration, TPP concentration, flow ratio and lysozyme concentration were investigated for their effects on three responses (size, polydispersity index (PDI) and encapsulation efficiency (% EE)). A desirability function was applied to identify the optimum parameters to formulate nanogels in the CFR with ideal characteristics. Nanogels prepared using the optimal parameters were successfully produced in the nanoparticle range at 84 ± 4 nm, showing a high encapsulation efficiency of 94.6 ± 2.9% and a high monodispersity of 0.26 ± 0.01. The lysis activity of the protein lysozyme was significantly enhanced in the nanogels at 157.6% in comparison to lysozyme alone. Overall, the study has demonstrated that the CFR is a viable method for the synthesis of functional nanogels containing bioactive molecules.

Stable Iron Oxide Nanoflowers with Exceptional Magnetic Heating Efficiency: Simple and Fast Polyol Synthesis.

Magnetically induced hyperthermia has reached a milestone in medical nanoscience and in phase III clinical trials for cancer treatment. As it relies on the heat generated by magnetic nanoparticles (NPs) when exposed to an external alternating magnetic field, the heating ability of these NPs is of paramount importance, so is their synthesis. We present a simple and fast method to produce iron oxide nanostructures with excellent heating ability that are colloidally stable in water. A polyol process yielded biocompatible single core nanoparticles and nanoflowers. The effect of parameters such as the precursor concentration, polyol molecular weight as well as reaction time was studied, aiming to produce NPs with the highest possible heating rates. Polyacrylic acid facilitated the formation of excellent nanoheating agents iron oxide nanoflowers (IONFs) within 30 min. The progressive increase of the size of the NFs through applying a seeded growth approach resulted in outstanding enhancement of their heating efficiency with intrinsic loss parameter up to 8.49 nH m2 kgFe-1. The colloidal stability of the NFs was maintained when transferring to an aqueous solution via a simple ligand exchange protocol, replacing polyol ligands with biocompatible sodium tripolyphosphate to secure the IONPs long-term colloidal stabilization.

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.

Small iron oxide nanoparticles as MRI T1 contrast agent: scalable inexpensive water-based synthesis using a flow reactor.

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.

Continuous Single-Phase Synthesis of [Au25(Cys)18] Nanoclusters and their Photobactericidal Enhancement.

Thiolate-gold nanoclusters have various applications. However, most of the synthesis methods require prolonged synthesis times from several hours to days. In the present study, we report a rapid synthesis method for [Au25(Cys)18] nanoclusters and their application for photobactericidal enhancement. For [Au25(Cys)18] synthesis, we employed a tube-in-tube membrane reactor using CO as a reducing agent at elevated temperatures. This approach allows continuous generation of high-quality [Au25(Cys)18] within 3 min. Photobactericidal tests against Staphylococcus aureus showed that crystal violet-treated polymer did not have photobactericidal activity, but addition of [Au25(Cys)18] in the treated polymer demonstrated a potent photobactericidal activity at a low white light flux, resulting in >4.29 log reduction in viable bacteria numbers. Steady-state and time-resolved photoluminescence spectroscopies demonstrated that after light irradiation, photoexcited electrons in crystal violet flowed to [Au25(Cys)18] in the silicone, suggesting that redox reaction from [Au25(Cys)18] enhanced the photobactericidal activity. Stability tests revealed that leaching of crystal violet and [Au25(Cys)18] from the treated silicone was negligible and cyclic testing showed that the silicone maintained a strong photobactericidal activity after repeated use.

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.

Rapid Millifluidic Synthesis of Stable High Magnetic Moment FexCy Nanoparticles for Hyperthermia.

A millifluidic reactor with a 0.76 mm internal diameter was utilized for the synthesis of monodisperse, high magnetic moment, iron carbide (FexCy) nanoparticles by thermal decomposition of iron pentacarbonyl (Fe(CO)5) in 1-octadecene in the presence of oleylamine at 22 min nominal residence time. The effect of reaction conditions (temperature and pressure) on the size, morphology, crystal structure, and magnetic properties of the nanoparticles was investigated. The system developed facilitated the thermal decomposition of precursor at reaction conditions (up to 265 °C and 4 bar) that cannot be easily achieved in conventional batch reactors. The degree of carbidization was enhanced by operating at elevated temperature and pressure. The nanoparticles synthesized in the flow reactor had size 9-18 nm and demonstrated high saturation magnetization (up to 164 emu/gFe). They further showed good stability against oxidation after 2 months of exposure in air, retaining good saturation magnetization values with a change of no more than 10% of the initial value. The heating ability of the nanoparticles in an alternating magnetic field was comparable with other ferrites reported in the literature, having intrinsic loss power values up to 1.52 nHm2 kg-1.

Photobactericidal activity activated by thiolated gold nanoclusters at low flux levels of white light.

The emergence of antibiotic resistant bacteria is a major threat to the practice of modern medicine. Photobactericidal agents have obtained significant attention as promising candidates to kill bacteria, and they have been extensively studied. However, to obtain photobactericidal activity, an intense white light source or UV-activation is usually required. Here we report a photobactericidal polymer containing crystal violet (CV) and thiolated gold nanocluster ([Au25(Cys)18]) activated at a low flux levels of white light. It was shown that the polymer encapsulated with CV do not have photobactericidal activity under white light illumination of an average 312 lux. However, encapsulation of [Au25(Cys)18] and CV into the polymer activates potent photobactericidal activity. The study of the photobactericidal mechanism shows that additional encapsulation of [Au25(Cys)18] into the CV treated polymer promotes redox reactions through generation of alternative electron transfer pathways, while it reduces photochemical reaction type-ІІ pathways resulting in promotion of hydrogen peroxide (H2O2) production.

Unravelling the growth mechanism of the co-precipitation of iron oxide nanoparticles with the aid of synchrotron X-Ray diffraction in solution.

Co-precipitation is the most ubiquitous method for forming iron oxide nanoparticles. For a typical co-precipitation synthesis, the pH of a ferrous and/or ferric ion solution is increased via the addition of a base. The latter can be added either slowly (a steady addition over either minutes or hours) or fast (a one-time addition) resulting in an abrupt increase in the pH. However, understanding the mechanism of particle formation is still lacking, which limits the reproducibility of the co-precipitation reaction due to intermediate phases still being present in the final product. In this work, we study in detail a co-precipitation synthesis with an abrupt increase in pH via the addition of sodium carbonate. Fast and reproducible mixing at defined precursor and base solution temperatures was achieved utilising a flow reactor. Transmission electron microscopy, electron diffraction and room temperature 57Fe Mössbauer spectroscopy showed a distinct transition from an amorphous ferrihydrite phase to a mixture of magnetite-maghemite (Fe3O4/γ-Fe2O3). Synchrotron X-ray diffraction revealed the initial formation of crystalline iron hydroxide carbonate (green rust) plates occurring before the Fe3O4/γ-Fe2O3 appeared. The ferrihydrite particles increase in size over time as the proportion of iron hydroxide carbonate plates are re-dissolved into solution, until the ferrihydrite particles crystallise into Fe3O4/γ-Fe2O3.

Effects of bovine serum albumin on light activated antimicrobial surfaces.

Bovine serum albumin (BSA) is currently recommended as an interfering substance to emulate organic soiling, in evaluating the efficacy of disinfectants. The European Standard recommends 0.03% BSA to test clean conditions and 0.3% for dirty conditions. Reactive oxygen species are known to exert excellent antimicrobial activity with low specificity against a broad range of pathogens. Herein, we present our data from the first study of the effects of the addition of BSA on the antibacterial activity of light activated antimicrobial surfaces. Light activated antimicrobial surfaces were made from polyurethane swell-encapsulated with gold nanoparticles (AuNPs) coated with the light active triarylmethane dye, crystal violet (PU-AuNP-CV). The antibacterial efficacy of the antimicrobial substrates was tested against two strains of Staphylococcus aureus 8325-4, a well-characterised laboratory strain and MRSA 4742, a recent clinical isolate, in the presence of 0.1% to 1% BSA by irradiating the substrates with a fluorescent lamp (300 lux). After 6 hours of irradiation, the number of surviving bacteria was determined. The results showed that BSA reduced the antibacterial efficacy of all the PU-AuNP-CV surfaces with increasing BSA concentrations resulting in a progressive reduction in antibacterial activity towards the bacteria tested. However, the light activated surfaces did perform well at 0.1 and 0.25% BSA levels, showing they may have potential for real world environments with low levels of organic soiling.

Recommendations for clinical translation of nanoparticle-enhanced radiotherapy.

A multi-disciplinary cooperative for nanoparticle-enhanced radiotherapy (NERT) has been formed to review the current status of the field and identify key stages towards translation. Supported by the Colorectal Cancer Healthcare Technologies Cooperative, the cooperative comprises a diverse cohort of key contributors along the translation pathway including academics of physics, cancer and radio-biology, chemistry, nanotechnology and clinical trials, clinicians, manufacturers, industry, standards laboratories, policy makers and patients. Our aim was to leverage our combined expertise to devise solutions towards a roadmap for translation and commercialisation of NERT, in order to focus research in the direction of clinical implementation, and streamline the critical pathway from basic science to the clinic. A recent meeting of the group identified barriers to and strategies for accelerated clinical translation. This commentary reports the cooperative's recommendations. Particular emphasis was given to more standardised and cohesive research methods, models and outputs, and reprioritised research drivers including patient quality of life following treatment. Nanoparticle design criteria were outlined to incorporate scalability of manufacture, understanding and optimisation of biological mechanisms of enhancement and in vivo fate of nanoparticles, as well as existing design criteria for physical and chemical enhancement. In addition, the group aims to establish a long-term and widespread international community to disseminate key findings and create a much-needed cohesive body of evidence necessary for commercial and clinical translation.

An engineering approach to synthesis of gold and silver nanoparticles by controlling hydrodynamics and mixing based on a coaxial flow reactor.

In this work we present a detailed study of flow technology approaches that could open up new possibilities for nanoparticle synthesis. The synthesis of gold and silver nanoparticles (NPs) in a flow device based on a coaxial flow reactor (CFR) was investigated. The CFR comprised of an outer glass tube of 2 mm inner diameter (I.D.) and an inner glass tube whose I.D. varied between 0.142 and 0.798 mm. A split and recombine (SAR) mixer and coiled flow inverter (CFI) were further employed to alter the mixing conditions after the CFR. The 'Turkevich' method was used to synthesize gold NPs, with a CFR followed by a CFI. This assembly allows control over nucleation and growth through variation of residence time. Increasing the total flow rate from 0.25 ml min-1 to 3 ml min-1 resulted initially in a constant Au NP size, and beyond 1 ml min-1 to a size increase of Au NPs from 17.9 ± 2.1 nm to 23.9 ± 4.7 nm. The temperature was varied between 60-100 °C and a minimum Au NP size of 17.9 ± 2.1 nm was observed at 80 °C. Silver NPs were synthesized in a CFR followed by a SAR mixer, using sodium borohydride to reduce silver nitrate in the presence of trisodium citrate. The SAR mixer provided an enhancement of the well-controlled laminar mixing in the CFR. Increasing silver nitrate concentration resulted in a decrease in Ag NP size from 5.5 ± 2.4 nm to 3.4 ± 1.4 nm. Different hydrodynamic conditions were studied in the CFR operated in isolation for silver NP synthesis. Increasing the Reynolds number from 132 to 530 in the inner tube created a vortex flow resulting in Ag NPs in the size range between 5.9 ± 1.5 nm to 7.7 ± 3.4 nm. Decreasing the inner tube I.D. from 0.798 mm to 0.142 mm resulted in a decrease in Ag NP size from 10.5 ± 4.0 nm to 4.7 ± 1.4 nm. Thus, changing the thickness of the inner stream enabled control over size of the Ag NPs.

Thiol-Capped Gold Nanoparticles Swell-Encapsulated into Polyurethane as Powerful Antibacterial Surfaces Under Dark and Light Conditions.

A simple procedure to develop antibacterial surfaces using thiol-capped gold nanoparticles (AuNPs) is shown, which effectively kill bacteria under dark and light conditions. The effect of AuNP size and concentration on photo-activated antibacterial surfaces is reported and we show significant size effects, as well as bactericidal activity with crystal violet (CV) coated polyurethane. These materials have been proven to be powerful antibacterial surfaces against both Gram-positive and Gram-negative bacteria. AuNPs of 2, 3 or 5 nm diameter were swell-encapsulated into PU before a coating of CV was applied (known as PU-AuNPs-CV). The antibacterial activity of PU-AuNPs-CV samples was tested against Staphylococcus aureus and Escherichia coli as representative Gram-positive and Gram-negative bacteria under dark and light conditions. All light conditions in this study simulated a typical white-light hospital environment. This work demonstrates that the antibacterial activity of PU-AuNPs-CV samples and the synergistic enhancement of photoactivity of triarylmethane type dyes is highly dependent on nanoparticle size and concentration. The most powerful PU-AuNPs-CV antibacterial surfaces were achieved using 1.0 mg mL-1 swell encapsulation concentrations of 2 nm AuNPs. After two hours, Gram-positive and Gram-negative bacteria were reduced to below the detection limit (>4 log) under dark and light conditions.