Real-time tracking of delayed-onset cellular apoptosis induced by intracellular magnetic hyperthermia

AIM: To assess cell death pathways in response to magnetic hyperthermia. MATERIALS & METHODS: Human melanoma cells were loaded with citric acid-coated iron-oxide nanoparticles, and subjected to a time-varying magnetic field. Pathways were monitored in vitro in suspensions and in situ in monolayers using fluorophores to report on early-stage apoptosis and late-stage apoptosis and/or necrosis. RESULTS: Delayed-onset effects were observed, with a rate and extent proportional to the thermal-load-per-cell. At moderate loads, membranal internal-to-external lipid exchange preceded rupture and death by a few hours (the timeline varying cell-to-cell), without any measurable change in the local environment temperature. CONCLUSION: Our observations support the proposition that intracellular heating may be a viable, controllable and nonaggressive in vivo treatment for human pathological conditions

Size effects in the magnetic behaviour of TbAl_2 milled alloys

The study of the magnetic properties depending upon mechanical milling of the ferromagnetic polycrystalline TbAl_2 material is reported. The Rietveld analysis of the X-ray diffraction data reveals a decrease of the grain size down to 14 nm and -0.15 % of variation of the lattice parameter, after 300 hours of milling time. Irreversibility in the zero field cooled - field cooled (ZFC-FC) DC-susceptibility and clear peaks in the AC susceptibility between 5 and 300 K show that the long-range ferromagnetic structure is inhibited in favour of a disordered spin arrangement below 45 K. This glassy behaviour is also deduced from the variation of the irreversibility transition with the field (H^{2/3}) and frequency. The magnetization process of the bulk TbAl_2 is governed by domain wall thermal activation processes. By contrast, in the milled samples, cluster-glass properties arise as a result of cooperative interactions due to the substitutional disorder. The interactions are also influenced by the nanograin structure of the milled alloys, showing a variation of coercivity with the grain size, below the crossover between the multi- and single-domain behaviours.Comment: 23 pages, 11 figures, to appear in J. Phys.: Condens. Ma

On the 'centre of gravity' method for measuring the composition of magnetite/maghemite mixtures, or the stoichiometry of magnetite-maghemite solid solutions, via Fe-57 Mossbauer spectroscopy

We evaluate the application of 57Fe Mössbauer spectroscopy to the determination of the composition of magnetite (Fe3O4)/maghemite (γ-Fe2O3) mixtures and the stoichiometry of magnetite-maghemite solid solutions. In particular, we consider a recently proposed model-independent method which does not rely on a priori assumptions regarding the nature of the sample, other than that it is free of other Fe-containing phases. In it a single parameter, δRT—the ‘centre of gravity’, or area weighted mean isomer shift at room temperature, T = 295 ± 5 K—is extracted by curve-fitting a sample’s Mössbauer spectrum, and is correlated to the sample’s composition or stoichiometry. We present data on highpurity magnetite and maghemite powders, and mixtures thereof, as well as comparison literature data from nanoparticulate mixtures and solid solutions, to show that a linear correlation exists between δRT and the numerical proportion of Fe atoms in the magnetite environment: α = Femagnetite/Fetotal = − ( ) δ δ RT o /m, where δo = 0.3206 ± 0.0022mm s−1 and m = 0.2135 ± 0.0076mm s−1 . We also present equations to relate α to the weight percentage w of magnetite in mixed phases, and the magnetite stoichiometry x = Fe2+/Fe3+ in solid solutions. The analytical method is generally applicable, but is most accurate when the absorption profiles are sharp; in some samples this may require spectra to be recorded at reduced temperatures. We consider such cases and provide equations to relate δ ( ) T to the corresponding α value

Precise U-Pb zircon ages and geochemistry of Jurassic granites, Ellsworth-Whitmore terrane, central Antarctica

The Ellsworth-Whitmore Mountain terrane of central Antarctica was part of the early Paleozoic amalgamation of Gondwana, including a 13,000 m section of Cambrian–Permian sediments in the Ellsworth Mountains deposited on Grenville-age crust. The Jurassic breakup of Gondwana involved a regional, bimodal magmatic event during which the Ellsworth-Whitmore terrane was intruded by intraplate granites before translation of the terrane to its present location in central Antarctica. Five widely separated granitic plutons in the Ellsworth-Whitmore terrane were analyzed for their whole-rock geochemistry (X-ray fluorescence), Sr, Nd, and Pb isotopic compositions, and U-Pb zircon ages to investigate the origins of the terrane magmas and their relationships to mafic magmatism of the 183 Ma Karoo-Ferrar large igneous province (LIP). We report high-precision (±0.1 m.y.) isotope dilution–thermal ionization mass spectrometry (ID-TIMS) U-Pb zircon ages from granitic rocks from the Whitmore Mountains (208.0 Ma), Nash Hills (177.4–177.3 Ma), Linck Nunatak (175.3 Ma), Pagano Nunatak (174.8 Ma), and the Pirrit Hills (174.3–173.9 Ma), and U-Pb sensitive high-resolution ion microprobe (SHRIMP) ages from the Whitmore Mountains (200 ± 5 Ma), Linck Nunatak (180 ± 4 Ma), Pagano Nunatak (174 ± 4 Ma), and the Pirrit Hills (168 ± 4 Ma). We then compared these results with existing K-Ar ages and Nd model ages, and used initial Sr, Nd, and Pb isotope ratios, combined with xenocrystic zircon U-Pb inheritance, to infer characteristics of the source(s) of the parent magmas. We conclude that the Jurassic plutons were not derived exclusively from crustal melts, but rather they are hybridized magmas composed of convecting mantle, subcontinental lithospheric mantle, and lower continental crustal contributions. The mantle contributions to the granites share isotopic similarities to the sources of other Jurassic LIP mafic magmas, including radiogenic 87Sr/86Sr (0.706–0.708), unradiogenic 143Nd/144Nd (εNd < –5), and Pb isotopes consistent with a low-µ source (where μ = 238U/204Pb). Isotopes and zircon xenocrysts point toward a crustal end member of predominantly Proterozoic provenance (0.5–1.0 Ga; Grenville crust), extending the trends illustrated by Ferrar mafic intrusive rocks, but contrasting with the inferred Archean crustal and/or lithospheric mantle contributions to some basalts of the Karoo sector of the LIP. The Ellsworth-Whitmore terrane granites are the result of mafic rocks underplating the hydrous crust, causing crustal melting, hybridization, and fractionation to produce granitic magmas that were eventually emplaced as post-Ferrar, within-plate melts at higher crustal levels as the Ellsworth-Whitmore terrane rifted off Gondwana (47°S) before migrating to its current position (82°S) in central Antarctica

Elucidating the morphological and structural evolution of iron oxide nanoparticles formed by sodium carbonate in aqueous medium

Ferrimagnetic iron oxides are the common choice for many current technologies, especially those with application in biology and medicine. Despite the comprehensive knowledge accumulated about their chemistry in the bulk state, the sequence of changes taking place during the precipitation of iron oxide nanoparticles in aqueous media is much less extensive. We show that using sodium carbonate as a co-precipitating agent for the synthesis of uncoated iron oxide nanoparticles, the reaction proceeds sufficiently slowly to enable a detailed study of both the reaction pathway and products. The effect of pH, temperature and reaction time on particle size, morphology, crystalline phase and its magnetic properties was investigated. The obtained nanoparticles showed an increase in average particle size of about 10 nm per pH unit for the magnetite phase leading to 6.9 ± 0.4 nm, 18 ± 3 nm and 28 ± 5 nm for pH 8, 9 and 10 respectively. Goethite was initially formed by an olation mechanism at room temperature, followed by a slow transformation into magnetite over a 24 h period, as tracked by X-ray diffraction. In another set of experiments where the reaction temperatures were varied, magnetite was obtained directly by the oxolation mechanism at temperatures above 45 °C. The optimization of the experimental parameters led to superparamagnetic nanoparticles with a high saturation magnetization of 82 A m2 kg−1 at 300 K when synthesized at pH 9

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

Systematic first-principles study of impurity hybridization in NiAl

We have performed a systematic first-principles computational study of the effects of impurity atoms (boron, carbon, nitrogen, oxygen, silicon, phosporus, and sulfur) on the orbital hybridization and bonding properties in the intermetallic alloy NiAl using a full-potential linear muffin-tin orbital method. The matrix elements in momentum space were used to calculate real-space properties: onsite parameters, partial densities of states, and local charges. In impurity atoms that are empirically known to be embrittler (N and O) we found that the 2s orbital is bound to the impurity and therefore does not participate in the covalent bonding. In contrast, the corresponding 2s orbital is found to be delocalized in the cohesion enhancers (B and C). Each of these impurity atoms is found to acquire a net negative local charge in NiAl irrespective of whether they sit in the Ni or Al site. The embrittler therefore reduces the total number of electrons available for covalent bonding by removing some of the electrons from the neighboring Ni or Al atoms and localizing them at the impurity site. We show that these correlations also hold for silicon, phosporus, and sulfur.Comment: Revtex, 8 pages, 7 eps figures, to appear in Phys. Rev.

Safety Implications of High-Field MRI: Actuation of Endogenous Magnetic Iron Oxides in the Human Body

Background: Magnetic Resonance Imaging scanners have become ubiquitous in hospitals and high-field systems (greater than 3 Tesla) are becoming increasingly common. In light of recent European Union moves to limit high-field exposure for those working with MRI scanners, we have evaluated the potential for detrimental cellular effects via nanomagnetic actuation of endogenous iron oxides in the body.Methodology: Theoretical models and experimental data on the composition and magnetic properties of endogenous iron oxides in human tissue were used to analyze the forces on iron oxide particles.Principal Finding and Conclusions: Results show that, even at 9.4 Tesla, forces on these particles are unlikely to disrupt normal cellular function via nanomagnetic actuation