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.

Transforming carbon dioxide into jet fuel using an organic combustion-synthesized Fe-Mn-K catalyst.

With mounting concerns over climate change, the utilisation or conversion of carbon dioxide into sustainable, synthetic hydrocarbons fuels, most notably for transportation purposes, continues to attract worldwide interest. This is particularly true in the search for sustainable or renewable aviation fuels. These offer considerable potential since, instead of consuming fossil crude oil, the fuels are produced from carbon dioxide using sustainable renewable hydrogen and energy. We report here a synthetic protocol to the fixation of carbon dioxide by converting it directly into aviation jet fuel using novel, inexpensive iron-based catalysts. We prepare the Fe-Mn-K catalyst by the so-called Organic Combustion Method, and the catalyst shows a carbon dioxide conversion through hydrogenation to hydrocarbons in the aviation jet fuel range of 38.2%, with a yield of 17.2%, and a selectivity of 47.8%, and with an attendant low carbon monoxide (5.6%) and methane selectivity (10.4%). The conversion reaction also produces light olefins ethylene, propylene, and butenes, totalling a yield of 8.7%, which are important raw materials for the petrochemical industry and are presently also only obtained from fossil crude oil. As this carbon dioxide is extracted from air, and re-emitted from jet fuels when combusted in flight, the overall effect is a carbon-neutral fuel. This contrasts with jet fuels produced from hydrocarbon fossil sources where the combustion process unlocks the fossil carbon and places it into the atmosphere, in longevity, as aerial carbon - carbon dioxide.

Spin-enhanced nanodiamond biosensing for ultrasensitive diagnostics.

The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity5 and frequency-domain analysis6 to separate the signal from background autofluorescence7, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10-19 molar for a biotin-avidin model, 105 times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.

Decarbonising energy: The developing international activity in hydrogen technologies and fuel cells.

Hydrogen technologies and fuel cells offer an alternative and improved solution for a decarbonised energy future. Fuel cells are electrochemical converters; transforming hydrogen (or energy sources containing hydrogen) and oxygen directly into electricity. The hydrogen fuel cell, invented in 1839, permits the generation of electrical energy with high efficiency through a non-combustion, electrochemical process and, importantly, without the emission of CO2 at its point of use. Hitherto, despite numerous efforts to exploit the obvious attractions of hydrogen technologies and hydrogen fuel cells, various challenges have been encountered, some of which are reviewed here. Now, however, given the exigent need to urgently seek low-carbon paths for humankind's energy future, numerous countries are advancing the deployment of hydrogen technologies and hydrogen fuel cells not only for transport, but also as a means of the storage of excess renewable energy from, for example, wind and solar farms. Furthermore, hydrogen is also being blended into the natural gas supplies used in domestic heating and targeted in the decarbonisation of critical, large-scale industrial processes such as steel making. We briefly review specific examples in countries such as Japan, South Korea and the People's Republic of China, as well as selected examples from Europe and North America in the utilization of hydrogen technologies and hydrogen fuel cells.

Hydrophobin-Encapsulated Quantum Dots.

The phase transfer of quantum dots to water is an important aspect of preparing nanomaterials that are suitable for biological applications, and although numerous reports describe ligand exchange, very few describe efficient ligand encapsulation techniques. In this report, we not only report a new method of phase transferring quantum dots (QDs) using an amphiphilic protein (hydrophobin) but also describe the advantages of using a biological molecule with available functional groups and their use in imaging cancer cells in vivo and other imaging applications.

Probabilistic modelling of prospective environmental concentrations of gold nanoparticles from medical applications as a basis for risk assessment.

BACKGROUND: The use of gold nanoparticles (Au-NP) based medical applications is rising due to their unique physical and chemical properties. Diagnostic devices based on Au-NP are already available in the market or are in clinical trials and Au-NP based therapeutics and theranostics (combined diagnostic and treatment modality) are in the research and development phase. Currently, no information on Au-NP consumption, material flows to and concentrations in the environment are available. Therefore, we estimated prospective maximal consumption of Au-NP from medical applications in the UK and US. We then modelled the Au-NP flows post-use and predicted their environmental concentrations. Furthermore, we assessed the environment risks of Au-NP by comparing the predicted environmental concentrations (PECs) with ecological threshold (PNEC) values. RESULTS: The mean annual estimated consumption of Au-NP from medical applications is 540 kg for the UK and 2700 kg for the US. Among the modelled concentrations of Au-NP in environmental compartments, the mean annual PEC of Au-NP in sludge for both the UK and US was estimated at 124 and 145 µg kg(-1), respectively. The mean PEC in surface water was estimated at 468 and 4.7 pg L(-1), respectively for the UK and US. The NOEC value for the water compartment ranged from 0.12 up to 26,800 µg L(-1), with most values in the range of 1000 µg L(-1). CONCLUSION: The results using the current set of data indicate that the environmental risk from Au-NP used in nanomedicine in surface waters and from agricultural use of biosolids is minimal in the near future, especially because we have used a worst-case use assessment. More Au-NP toxicity studies are needed for the soil compartment.

Comparison of ESC and NICE guidelines for patients with suspected coronary artery disease: evaluation of the pre-test probability risk scores in clinical practice.

The European Society of Cardiology (ESC) and UK National Institute for Health and Care Excellence (NICE) have recently published guidelines for investigating patients with suspected coronary artery disease (CAD). Both provide a risk score (RS) to assess the pre-test probability for CAD to guide clinicians to undertake the most effective investigation. The aim of the study was to establish whether there is a difference between the two RS models. We retrospectively reviewed records of 479 patients who presented to a UK district general hospital with chest pain between August 2011 and April 2013. The RS was calculated using ESC and NICE guidelines and compared. From the 479 patients, 277 (58%) were male and the mean age was 60 years. The mean RS was greater using NICE guidelines compared with ESC (66.3 vs 47.9%, 18.4% difference; p<0.0001). The difference in mean RS was smaller in patients with typical chest pain (13.0%). When we divided the cohort based on NICE criteria into 'high'- and 'low'-risk groups, the difference in the mean RS was 24.3% in the 'high'-risk group (p<0.001) compared with 2.8% in the 'low'-risk group. The UK NICE risk score model overestimates risk compared with the ESC model.

Potential environmental implications of nano-enabled medical applications: critical review.

The application of nanotechnology and nanoscience for medical purposes is anticipated to make significant contributions to enhance human health in the coming decades. However, the possible future mass production and use of these medical innovations exhibiting novel and multifunctional properties will very likely lead to discharges into the environment giving rise to potentially new environmental hazards and risks. To date, the sources, the release form and environmental fate and exposure of nano-enabled medical products have not been investigated and little or no data exists, although there are a small number of currently approved medical applications and a number in clinical trials. This paper discusses the current technological and regulatory landscape and potential hazards and risks to the environment of nano-enabled medical products, data gaps and gives tentative suggestions relating to possible environmental hotspots.

In vivo demonstration of enhanced radiotherapy using rare earth doped titania nanoparticles.

Radiation therapy is often limited by damage to healthy tissue and associated side-effects; restricting radiation to ineffective doses. Preferential incorporation of materials into tumour tissue can enhance the effect of radiation. Titania has precedent for use in photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon photoexcitation, but is limited by the penetration depth of UV light. Optimization of a nanomaterial for interaction with X-rays could be used for deep tumour treatment. As such, titania nanoparticles were doped with gadolinium to optimize the localized energy absorption from a conventional medical X-ray, and further optimized by the addition of other rare earth (RE) elements. These elements were selected due to their large X-ray photon interaction cross-section, and potential for integration into the titania crystal structure. Specific activation of the nanoparticles by X-ray can result in generation of ROS leading to cell death in a tumour-localized manner. We show here that intratumoural injection of RE doped titania nanoparticles can enhance the efficacy of radiotherapy in vivo.

Synthesis of semiconductor nanoparticles.

Here, we describe typical methods and provide detailed experimental protocols for synthesizing and processing various semiconductor nanoparticles which have potential application in biology and medicine. These include synthesis of binary semiconductor nanoparticles; core@shell nanoparticles and alloyed nanoparticles; size-selective precipitation to obtain monodisperse nanoparticles; and strategies for phase transfer of nanoparticles from organic solution to aqueous media.

A novel hybrid nano zerovalent iron initiated oxidation--biological degradation approach for remediation of recalcitrant waste metalworking fluids.

Disposal of operationally exhausted metal working fluids (MWF) through a biological route is an attractive option, since it is effective with relatively low energy demands. However, it is enormously challenging since these fluids are chemically complex, including the addition of toxic biocides which are added specifically to retard bio-deterioration whilst the fluids are operational. Nano-sized elemental iron represents a new generation of environmental remediation technologies. Laboratory scale batch studies were performed to test the degradation ability of a semi-synthetic metalworking fluid (MWF) wastewater (which was found to be resistant to initial bacterial treatment in specifically established bioreactors) by employing a novel hybrid approach. The approach was to combine the synergistic effects of nano zerovalent iron (nZVI) induced oxidation, followed by biodegradation, specifically for the remediation of recalcitrant components of MWF effluent. Addition of nZVI particles to oxygenated wastewater resulted in oxidation of organic contaminants present. Our studies confirmed 78% reduction in chemical oxygen demand (COD) by nZVI oxidation at pH 3.0 and 67% reduction in neutral pH (7.5), and 85% concurrent reduction in toxicity. Importantly, this low toxicity made the nZVI treated effluent more amenable for a second stage biological oxidation step. An overall COD reduction of 95.5% was achieved by the novel combined treatment described, demonstrating that nZVI oxidation can be exploited for enhancing the biodegradability of a recalcitrant wastewater in treatment processes.

Nanoparticle augmented radiation treatment decreases cancer cell proliferation.

We report significant and controlled cell death using novel x-ray-activatable titania nanoparticles (NPs) doped with lanthanides. Preferential incorporation of such materials into tumor tissue can enhance the effect of radiation therapy. Herein, the incorporation of gadolinium into the NPs is designed to optimize localized energy absorption from a conventional medical x-ray. This result is further optimized by the addition of other rare earth elements. Upon irradiation, energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species (ROS). FROM THE CLINICAL EDITOR: The authors report significant and controlled cell death using x-ray-activated titania nanoparticles doped with lanthanides as enhancers. Upon irradiation X-ray energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species.

Harmonisation of chemical and biological process in development of a hybrid technology for treatment of recalcitrant metalworking fluid.

Disposal of operationally exhausted metalworking fluids (MWFs) is enormously challenging. In this study the feasibility of employing a sequential Fenton-biological oxidation for the treatment of recalcitrant components of MWF wastewater was investigated. A statistical experimental design was employed to address Fenton reagent (H2O2, Fe²âº) dose optimisation which ensured minimal concentrations of the reagents, thus making the treatment environmentally less toxic to subsequent biological steps and economically viable. This was achieved by employing a five-level-two-variable central composite experimental design. The results demonstrated that Fenton pre-treatment of the MWF effluent greatly improved biodegradability index (BOD5)/COD increased from 0.160 to 0.538) with a synchronous lowering in the toxicity of the wastewater, making the recalcitrant component more amenable to subsequent biological treatment. An overall decrease of 92% and 86% in chemical oxygen demand (COD) and total organic carbon (TOC), respectively, was achieved by the two-step treatment method developed.

Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis.

Cellular microvesicles and nanovesicles (exosomes) are involved in many disease processes and have major potential as biomarkers. However, developments in this area are constrained by limitations in the technology available for their measurement. Here we report on the use of fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles. In this system vesicles are visualized by light scattering using a light microscope. A video is taken, and the NTA software tracks the brownian motion of individual vesicles and calculates their size and total concentration. Using human placental vesicles and plasma, we have demonstrated that NTA can measure cellular vesicles as small as ≈ 50 nm and is far more sensitive than conventional flow cytometry (lower limit ≈ 300 nm). By combining NTA with fluorescence measurement we have demonstrated that vesicles can be labeled with specific antibody-conjugated quantum dots, allowing their phenotype to be determined. FROM THE CLINICAL EDITOR: The authors of this study utilized fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles, demonstrating that NTA is far more sensitive than conventional flow cytometry.