Influence of size, volume concentration and aggregation state on magnetic nanoparticle hyperthermia properties versus excitation conditions.

Treatment planning in magnetic hyperthermia requires a thorough knowledge of specific loss power of magnetic nanoparticles as a function of size and excitation conditions. Moreover, in biological tissues the magnetic nanoparticles can aggregate into clusters, making the evaluation of their heating performance more challenging because of the magnetostatic dipole-dipole interactions. In this paper, we present a comprehensive modelling analysis of 10-40 nm sized spherical magnetite (Fe3O4) nanoparticles, investigating how their heating properties are influenced by magnetic field parameters (peak amplitude and frequency), and by volume concentration and aggregation state. The analysis is performed by means of an in-house micromagnetic numerical model, which solves the Landau-Lifshitz-Gilbert equation under the assumption of single-domain nanoparticles, including thermal effects via a Langevin approach. The obtained results provide insight into how to tune hyperthermia properties by varying magnetic nanoparticle size, under different excitation magnetic fields fulfilling the Hergt-Dutz limit (frequency between 50 kHz and 1 MHz, and peak amplitude between 1 kA m-1 and 50 kA m-1). Special attention is finally paid to the role of volume concentration and aggregation order, putting in evidence the need for models able to account for stochasticity and clustering in spatial distribution, to accurately simulate the contribution of magnetostatic dipole-dipole interactions in real applications.

Dual-responsive magnetic nanodroplets for controlled oxygen release via ultrasound and magnetic stimulation.

Magnetic oxygen-loaded nanodroplets (MOLNDs) are a promising class of nanomaterials dually sensitive to ultrasound and magnetic fields, which can be employed as nanovectors for drug delivery applications, particularly in the field of hypoxic tissue treatment. Previous investigations were primarily focused on the application of these hybrid systems for hyperthermia treatment, exploiting magnetic nanoparticles for heat generation and nanodroplets as carriers and ultrasound contrast agents for treatment progress monitoring. This work places its emphasis on the prospect of obtaining an oxygen delivery system that can be activated by both ultrasound and magnetic fields. To achieve this goal, Fe3O4 nanoparticles were employed to decorate and induce the magnetic vaporization of OLNDs, allowing oxygen release. We present an optimized method for preparing MOLNDs by decorating nanodroplets made of diverse fluorocarbon cores and polymeric coatings. Furthermore, we performed a series of characterizations for better understanding how magnetic decoration can influence the physicochemical properties of OLNDs. Our comprehensive analysis demonstrates the efficacy of magnetic stimulation in promoting oxygen release compared to conventional ultrasound-based methods. We emphasize the critical role of selecting the appropriate fluorocarbon core and polymeric coating to optimize the decoration process and enhance the oxygen release performance of MOLNDs.

Design and Validation of Experimental Setup for Cell Spheroid Radiofrequency-Induced Heating.

While hyperthermia has been shown to induce a variety of cytotoxic and sensitizing effects on cancer tissues, the thermal dose-effect relationship is still not well quantified, and it is still unclear how it can be optimally combined with other treatment modalities. Additionally, it is speculated that different methods of applying hyperthermia, such as water bath heating or electromagnetic energy, may have an effect on the resulting biological mechanisms involved in cell death or in sensitizing tumor cells to other oncological treatments. In order to further quantify and characterize hyperthermia treatments on a cellular level, in vitro experiments shifted towards the use of 3D cell spheroids. These are in fact considered a more representative model of the cell environment when compared to 2D cell cultures. In order to perform radiofrequency (RF)-induced heating in vitro, we have recently developed a dedicated electromagnetic field applicator. In this study, using this applicator, we designed and validated an experimental setup which can heat 3D cell spheroids in a conical polypropylene vial, thus providing a reliable instrument for investigating hyperthermia effects at the cellular scale.

Improvement of Hyperthermia Properties of Iron Oxide Nanoparticles by Surface Coating.

Magnetic hyperthermia is an oncological therapy that exploits magnetic nanoparticles activated by radiofrequency magnetic fields to produce a controlled temperature increase in a diseased tissue. The specific loss power (SLP) of magnetic nanoparticles or the capability to release heat can be improved using surface treatments, which can reduce agglomeration effects, thus impacting on local magnetostatic interactions. In this work, Fe3O4 nanoparticles are synthesized via a coprecipitation reaction and fully characterized in terms of structural, morphological, dimensional, magnetic, and hyperthermia properties (under the Hergt-Dutz limit). Different types of surface coatings are tested, comparing their impact on the heating efficacy and colloidal stability, resulting that sodium citrate leads to a doubling of the SLP with a substantial improvement in dispersion and stability in solution over time; an SLP value of around 170 W/g is obtained in this case for a 100 kHz and 48 kA/m magnetic field.

Application of Magnonic Crystals in Magnetic Bead Detection.

This paper aims at studying a sensor concept for possible integration in magnetic field-based lab-on-chip devices that exploit ferromagnetic resonance (FMR) phenomena in magnonic crystals. The focus is on 2D magnetic antidot arrays, i.e., magnetic thin films with periodic non-magnetic inclusions (holes), recently proposed as magnetic field sensor elements operating in the gigahertz (GHz) range. The sensing mechanism is here demonstrated for magnetic nano/microbeads adsorbed on the surface of permalloy (Ni80Fe20) antidot arrays with a rhomboid lattice structure and variable hole size. Through extensive micromagnetic modelling analysis, it is shown that the antidot arrays can be used as both bead traps and high-sensitivity detectors, with performance that can be tuned as a function of bead size and magnetic moment. A key parameter for the detection mechanism is the antidot array hole size, which affects the FMR frequency shifts associated with the interaction between the magnetization configuration in the nanostructured film and the bead stray field. Possible applications of the proposed device concept include magnetic immunoassays, using magnetic nano/microbeads as probes for biomarker detection, and biomaterial manipulation.

In silico evaluation of adverse eddy current effects in preclinical tests of magnetic hyperthermia.

BACKGROUND AND OBJECTIVE: Magnetic hyperthermia is an oncological therapy that employs magnetic nanoparticles activated by alternating current (AC) magnetic fields with frequencies between 50 kHz and 1 MHz, to release heat in a diseased tissue and produce a local temperature increase of about 5 °C. To assess the treatment efficacy, in vivo tests on murine models (mice and rats) are typically performed. However, these are often carried out without satisfying the biophysical constraints on the electromagnetic (EM) field exposure, with consequent generation of hot spots and undesirable heating of healthy tissues. Here, we investigate possible adverse eddy current effects, to estimate AC magnetic field parameters (frequency and amplitude) that can potentially guarantee safe animal tests of magnetic hyperthermia. METHODS: The analysis is performed through in silico modelling by means of finite element simulation tools, specifically developed to study eddy current effects in computational animal models, during magnetic hyperthermia treatments. The numerical tools enable us to locally evaluate the specific absorption rate (SAR) and the produced temperature increase, under different field exposure conditions. RESULTS: The simulation outcomes demonstrate that in mice with weight lower than 30 g the thermal effects induced by AC magnetic fields are very weak, also when slightly overcoming the Hergt-Dutz limit, that is the product of the magnetic field amplitude and frequency should be lower than 5·109 A/(m·s). Conversely, we observe significant temperature increases in 500 g rats, amplified when the field is applied transversally to the body longitudinal axis. A strong mitigation of side-effects can be achieved by introducing water boluses or by applying focused fields. CONCLUSIONS: The developed physics-based modelling approach has proved to be a useful predictive tool for the optimization of preclinical tests of magnetic hyperthermia, allowing the identification of proper EM field conditions and the design of setups that guarantee safe levels of field exposure during animal treatments. In such contest, the obtained results can be considered as valid indicators to assess reference levels for animal testing of biomedical techniques that involve EM fields, like magnetic hyperthermia, thus complying with the Directive 2010/63/EU on the protection of animals used for scientific purposes.

Design and Characterization of an RF Applicator for In Vitro Tests of Electromagnetic Hyperthermia.

The evaluation of the biological effects of therapeutic hyperthermia in oncology and the precise quantification of thermal dose, when heating is coupled with radiotherapy or chemotherapy, are active fields of research. The reliable measurement of hyperthermia effects on cells and tissues requires a strong control of the delivered power and of the induced temperature rise. To this aim, we have developed a radiofrequency (RF) electromagnetic applicator operating at 434 MHz, specifically engineered for in vitro tests on 3D cell cultures. The applicator has been designed with the aid of an extensive modelling analysis, which combines electromagnetic and thermal simulations. The heating performance of the built prototype has been validated by means of temperature measurements carried out on tissue-mimicking phantoms and aimed at monitoring both spatial and temporal temperature variations. The experimental results demonstrate the capability of the RF applicator to produce a well-focused heating, with the possibility of modulating the duration of the heating transient and controlling the temperature rise in a specific target region, by simply tuning the effectively supplied power.

Experimental and Modelling Analysis of the Hyperthermia Properties of Iron Oxide Nanocubes.

The ability of magnetic nanoparticles (MNPs) to transform electromagnetic energy into heat is widely exploited in well-known thermal cancer therapies, such as magnetic hyperthermia, which proves useful in enhancing the radio- and chemo-sensitivity of human tumor cells. Since the heat release is ruled by the complex magnetic behavior of MNPs, a careful investigation is needed to understand the role of their intrinsic (composition, size and shape) and collective (aggregation state) properties. Here, the influence of geometrical parameters and aggregation on the specific loss power (SLP) is analyzed through in-depth structural, morphological, magnetic and thermometric characterizations supported by micromagnetic and heat transfer simulations. To this aim, different samples of cubic Fe3O4 NPs with an average size between 15 nm and 160 nm are prepared via hydrothermal route. For the analyzed samples, the magnetic behavior and heating properties result to be basically determined by the magnetic single- or multi-domain configuration and by the competition between magnetocrystalline and shape anisotropies. This is clarified by micromagnetic simulations, which enable us to also elucidate the role of magnetostatic interactions associated with locally strong aggregation.

Modal Frustration and Periodicity Breaking in Artificial Spin Ice.

Here, an artificial spin ice lattice is introduced that exhibits unique Ising and non-Ising behavior under specific field switching protocols because of the inclusion of coupled nanomagnets into the unit cell. In the Ising regime, a magnetic switching mechanism that generates a uni- or bimodal distribution of states dependent on the alignment of the field is demonstrated with respect to the lattice unit cell. In addition, a method for generating a plethora of randomly distributed energy states across the lattice, consisting of Ising and Landau states, is investigated through magnetic force microscopy and micromagnetic modeling. It is demonstrated that the dispersed energy distribution across the lattice is a result of the intrinsic design and can be finely tuned through control of the incident angle of a critical field. The present manuscript explores a complex frustrated environment beyond the 16-vertex Ising model for the development of novel logic-based technologies.

Comparison and Validation of Different Magnetic Force Microscopy Calibration Schemes.

The future of consumer electronics depends on the capability to reliably fabricate nanostructures with given physical properties. Therefore, techniques to characterize materials and devices with nanoscale resolution are crucial. Among these is magnetic force microscopy (MFM), which transduces the magnetic force between the sample and a magnetic oscillating probe into a phase shift, enabling the locally resolved study of magnetic field patterns down to 10 nm. Here, the progress done toward making quantitative MFM a common tool in nanocharacterization laboratories is shown. The reliability and ease of use of the calibration method based on a magnetic reference sample, with a calculable stray field, and a deconvolution algorithm is demonstrated. This is achieved by comparing two calibration approaches combined with numerical modeling as a quantitative link: measuring the probe's effect on the voltage signal when scanning above a nanosized graphene Hall sensor, and recording the MFM phase shift signal when the probe scans across magnetic fields produced by metallic microcoils. Furthermore, in the case of the deconvolution algorithm, it is shown how it can be applied using the open-source software package Gwyddion. The estimated magnetic dipole approximation for the most common probes currently in the market is also reported.

Influence of shape, size and magnetostatic interactions on the hyperthermia properties of permalloy nanostructures.

We present a detailed study of permalloy (Ni80Fe20) nanostructures with variable shape (disk, cylinder and sphere) for magnetic hyperthermia application, exploiting hysteresis losses for heat release. The study is performed modifying nanostructure aspect ratio and size (up to some hundreds of nanometres), to find the optimal conditions for the maximization of specific heating capabilities. The parameters are also tuned to guarantee negligible magnetic remanence and fulfilment of biophysical limits on applied field amplitude and frequency product, to avoid aggregation phenomena and intolerable resistive heating, respectively. The attention is first focused on disk-shaped nanostructures, with a comparison between micromagnetic simulations and experimental results, obtained on nanodisks still attached on the lithography substrate (2D array form) as well as dispersed in ethanol solution (free-standing). This analysis enables us to investigate the role of magnetostatic interactions between nanodisks and to individuate an optimal concentration for the maximization of heating capabilities. Finally, we study magnetization reversal process and hysteresis properties of nanocylinders (diameter between 150 nm and 600 nm, thickness from 30 nm up to 150 nm) and nanospheres (size between 100 nm and 300 nm), to give instructions on the best combination of geometrical parameters for the design of novel hyperthermia mediators.

Calibration of multi-layered probes with low/high magnetic moments.

We present a comprehensive method for visualisation and quantification of the magnetic stray field of magnetic force microscopy (MFM) probes, applied to the particular case of custom-made multi-layered probes with controllable high/low magnetic moment states. The probes consist of two decoupled magnetic layers separated by a non-magnetic interlayer, which results in four stable magnetic states: ±ferromagnetic (FM) and ±antiferromagnetic (A-FM). Direct visualisation of the stray field surrounding the probe apex using electron holography convincingly demonstrates a striking difference in the spatial distribution and strength of the magnetic flux in FM and A-FM states. In situ MFM studies of reference samples are used to determine the probe switching fields and spatial resolution. Furthermore, quantitative values of the probe magnetic moments are obtained by determining their real space tip transfer function (RSTTF). We also map the local Hall voltage in graphene Hall nanosensors induced by the probes in different states. The measured transport properties of nanosensors and RSTTF outcomes are introduced as an input in a numerical model of Hall devices to verify the probe magnetic moments. The modelling results fully match the experimental measurements, outlining an all-inclusive method for the calibration of complex magnetic probes with a controllable low/high magnetic moment.

Hybrid normal metal/ferromagnetic nanojunctions for domain wall tracking.

Hybrid normal metal/ferromagnetic, gold/permalloy (Au/Py), nanojunctions are used to investigate magnetoresistance effects and track magnetization spatial distribution in L-shaped Py nanostructures. Transversal and longitudinal resistances are measured and compared for both straight and 90° corner sections of the Py nanostructure. Our results demonstrate that the absolute change in resistance is larger in the case of longitudinal measurements. However, due to the small background resistance, the relative change in the transversal resistance along the straight section is several orders of magnitude larger than the analogous longitudinal variation. These results prove that hybrid nanojunctions represent a significant improvement with respect to previously studied all-ferromagnetic crosses, as they also reduce the pinning potential at the junction and allow probing the magnetization locally. In addition, unusual metastable states with longitudinal domain walls along Py straight sections are observed. Micromagnetic simulations in combination with a magnetotransport model allow interpretation of the results and identification of the observed transitions.

Magnetic vortex chirality determination via local hysteresis loops measurements with magnetic force microscopy.

Magnetic vortex chirality in patterned square dots has been investigated by means of a field-dependent magnetic force microscopy technique that allows to measure local hysteresis loops. The chirality affects the two loop branches independently, giving rise to curves that have different shapes and symmetries as a function of the details of the magnetisation reversal process in the square dot, that is studied both experimentally and through micromagnetic simulations. The tip-sample interaction is taken into account numerically, and exploited experimentally, to influence the side of the square where nucleation of the vortex preferably occurs, therefore providing a way to both measure and drive chirality with the present technique.

Influence of lattice defects on the ferromagnetic resonance behaviour of 2D magnonic crystals.

This paper studies, from a modelling point of view, the influence of randomly distributed lattice defects (non-patterned areas and variable hole size) on the ferromagnetic resonance behaviour and spin wave mode profiles of 2D magnonic crystals based on Ni80Fe20 antidot arrays with hexagonal lattice. A reference sample is first defined via the comparison of experimental and simulated hysteresis loops and magnetoresistive curves of patterned films, prepared by self-assembly of polystyrene nanospheres. Second, a parametric analysis of the dynamic response is performed, investigating how edge, quasi-uniform and localized modes are affected by alterations of the lattice geometry and bias field amplitude. Finally, some results about the possible use of magnetic antidot arrays in frequency-based sensors for magnetic bead detection are presented, highlighting the need for an accurate control of microstructural features.

On-Chip Magnetic Platform for Single-Particle Manipulation with Integrated Electrical Feedback.

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high-throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig-zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1-µm sized beads is demonstrated.

Anisotropic magnetoresistance state space of permalloy nanowires with domain wall pinning geometry.

The domain wall-related change in the anisotropic magnetoresistance in L-shaped permalloy nanowires is measured as a function of the magnitude and orientation of the applied magnetic field. The magnetoresistance curves, compiled into so-called domain wall magnetoresistance state space maps, are used to identify highly reproducible transitions between domain states. Magnetic force microscopy and micromagnetic modelling are correlated with the transport measurements of the devices in order to identify different magnetization states. Analysis allows to determine the optimal working parameters for specific devices, such as the minimal field required to switch magnetization or the most appropriate angle for maximal separation of the pinning/depinning fields. Moreover, the complete state space maps can be used to predict evolution of nanodevices in magnetic field without a need of additional electrical measurements and for repayable initialization of magnetic sensors into a well-specified state.

Visualisation of edge effects in side-gated graphene nanodevices.

Using local scanning electrical techniques we study edge effects in side-gated Hall bar nanodevices made of epitaxial graphene. We demonstrate that lithographically defined edges of the graphene channel exhibit hole conduction within the narrow band of ~60-125 nm width, whereas the bulk of the material is electron doped. The effect is the most pronounced when the influence of atmospheric contamination is minimal. We also show that the electronic properties at the edges can be precisely tuned from hole to electron conduction by using moderate strength electrical fields created by side-gates. However, the central part of the channel remains relatively unaffected by the side-gates and retains the bulk properties of graphene.

Application of the thin-shell formulation to the numerical modeling of Stern layer in biomolecular electrostatics.

In this article, the thin-shell formulation is applied to efficiently modeling the Stern layer within computational algorithms oriented toward the boundary element solution of the linearized Poisson-Boltzmann equation. The attention is focused on the calculation of the electrostatic potential in proximity to a biomolecule immersed in an electrolyte medium. Following the proposed approach, the Stern layer is made to collapse to a zero-thickness region (two-dimensional surface) with interface conditions linking the electrostatic potential over the molecular and the bulk ion accessible surfaces. Advantages lie in the limitation of divergent integral problems and in the halving of the unknown number, with a significant impact on computational time and memory requirements when modeling large biomolecules.