Magnetic nanoparticles (MNPs) have been widely used for various applications such as biomedicine and industry. A consistent metrology infrastructure for MNPs and reliable quality control of the key magnetic characteristics of MNPs such as magnetic moments are required for their successful applications as well as for the development of new technologies. In this work, the metrological traceability of magnetic moment measurements using a commercial magnetometer device will be discussed by use of reference materials for magnetic moments and magnetic susceptibility as they are provided by NIST.

AbstractBackgroundMagnetorelaxometry imaging is an experimental imaging technique capable of reconstructing magnetic nanoparticle distributions inside a volume noninvasively and with high specificity. Thus, magnetorelaxometry imaging is a promising candidate for monitoring a number of therapeutical approaches that employ magnetic nanoparticles, such as magnetic drug targeting and magnetic hyperthermia, to guarantee their safety and efficacy. Prior to a potential clinical application of this imaging modality, it is necessary to optimize magnetorelaxometry imaging systems to produce reliable imaging results and to maximize the reconstruction accuracy of the magnetic nanoparticle distributions. Multiple optimization approaches were already applied throughout a number of simulation studies, all of which yielded increased imaging qualities compared to intuitively designed measurement setups.PurposeNone of these simulative approaches was conducted in practice such that it still remains unclear if the theoretical results are achievable in an experimental setting. In this study, we demonstrate the technical feasibility and the increased reconstruction accuracy of optimized coil configurations in two distinct magnetorelaxometry setups.MethodsThe electromagnetic coil positions and radii of a cuboidal as well as a cylindrical magnetorelaxometry imaging setup are optimized by minimizing the system matrix condition numbers of their corresponding linear forward models. The optimized coil configurations are manufactured alongside with two regular coil grids. Magnetorelaxometry measurements of three cuboidal and four cylindrical magnetic nanoparticle phantoms are conducted, and the resulting reconstruction qualities of the optimized and the regular coil configurations are compared.ResultsThe computed condition numbers of the optimized coil configurations are approximately one order of magnitude lower compared to the regular coil grids. The reconstruction results show that for both setups, every phantom is recovered more accurately by the optimized coil configurations compared to the regular coil grids. Additionally, the optimized coil configurations yield better signal qualities.ConclusionsThe presented experimental study provides a proof of the practicality and the efficacy of optimizing magnetorelaxometry imaging systems with respect to the condition numbers of their system matrices, previously only demonstrated in simulations. From the promising results of our study, we infer that the minimization of the system matrix condition number will also enable the practical optimization of other design parameters of magnetorelaxometry imaging setups (e.g., sensor configuration, coil currents, etc.) in order to improve the achievable reconstruction qualities even further, eventually paving the way towards clinical application of this imaging modality.

Abstract Purpose The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields – a process known as magnetic field hyperthermia (MFH) – can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating – characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg – is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements. Materials and Methods An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing. Results The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources. Conclusion We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology.

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.

These files contain the raw measurement data reported for the Radiomag interlaboratory comparison of magnetic hyperthermia characterisation measurements. Each heating curve for samples containing magnetic nanoparticles is presented in a separate excel file detailing the corrected-slope technique (CST) recalculation of the specific loss power and intrinsic loss power for that measurement as described in the manuscript. The measurements are organised into separate folders for Rounds 1 and 2 of the interlaboratory study, with further subfolders dividing the results for samples 1 and 2. Round 2 also includes the results for the “blank” pure water sample which was included in this Round. For each laboratory there is 3 repeated measurements of each sample during each round the study.

Magnetorelaxometry imaging is a highly sensitive technique enabling noninvasive, quantitative detection of magnetic nanoparticles. Electromagnetic coils are sequentially energized, aligning the nanoparticles’ magnetic moments. Relaxation signals are recorded after turning off the coils. The forward model describing this measurement process is reformulated into a severely ill-posed inverse problem that is solved for estimating the particle distribution. Typically, many activation sequences employing different magnetic fields are required to obtain reasonable imaging quality. We seek to improve the imaging quality and accelerate the imaging process using fewer activation sequences by optimizing the applied magnetic fields. Minimizing the Frobenius condition number of the system matrix, we stabilize the inverse problem solution toward model uncertainties and measurement noise. Furthermore, our sensitivity-weighted reconstruction algorithms improve imaging quality in lowly sensitive areas. The optimization approach is employed to real measurement data and yields improved reconstructions with fewer activation sequences compared to non-optimized measurements.

•Magnetic particle spectroscopy (MPS) study of nanoparticles in gelatin.•MPS excitation amplitude shown to influence gelatin melting temperature.•Gelatin sample in MPS is too dilute to show macroscopic heating during MPS.•Field-modulated melting suggests microscopic effects.•Evidence for non-negligible particle-matrix interaction during MPS.

Magnetic nanoparticles have many applications in biomedicine and other technical areas. Despite their huge economic impact, there are no standardised procedures available to measure their basic magnetic properties. The International Organization for Standardization is working on a series of documents on the definition of characteristics of magnetic nanomaterials. We review previous and ongoing European research projects on characteristics of magnetic nanoparticles and present results of an online survey among European researchers.

Magnetic particle imaging (MPI) is an imaging modality capable of quantitatively determining the 3D distribution of a magnetic nanoparticle (MNP) ensemble. In this work, we present a method for reducing the MNP limit of detection by employing a new receive-only coil (Rx-coil) for signal acquisition. The new signal detector is designed to improve the sensitivity and thus quality of reconstructed images. We present characterization measurements conducted with the prototype Rx-coil installed in a preclinical MPI scanner. The gradiometric design of the Rx-coil attenuates the unwanted signal contributions arising from the excitation field, leading to a 17 dB lower background level compared to the conventional dual-purpose coil (TxRx-coil), which is crucial for detecting low amounts of MNP. Network analyzer measurements of the frequency-dependent coil sensitivity, as well as spectral analysis of recorded MPI data demonstrate an overall increase of the coil sensitivity of about  +12 dB for the Rx-coil. Comparisons of the sensitivity distributions revealed no significant degradations in terms of homogeneity for the Rx-coil compared to the TxRx-coil in an imaging volume of 6  ×  3  ×  3 cm3. Finally, the limit of detection was determined experimentally for each coil type using a serial dilution of MNPs, resulting in values of 133 ng of iron for the conventional TxRx-coil and 20 ng for the new Rx-coil, using an acquisition time of 2 s. A linear relationship between the reconstructed signal intensities and the iron mass in the samples was observed with coefficients of determination (R2) of above 99% in the range of the limit of detection to 3 103ng(Fe). These results open the way for improved image quality and faster acquisition time in pre-clinical MPI scanners.

Text Magnetic nanoparticles have appealing properties for many biomedical applications like the emerging cancer treatment magnetic particle hyperthermia. Alternatively, when equipped with a suitable coating, they can be used as drug carriers or disease detectors. The combination of their small sizes and a large magnetic moment also makes them excellent candidates for use in imaging applications. However, for all these applications to work reliably, the nanoparticle properties should be well known and their dynamic behavior should be fully understood.

Research towards the present and future biomedical applications of magnetic nanoparticles (MNP) is steadily increasing in the last two decades.Many approaches take advantage of the fact that due to superparamagnetism, ultrasmall MNPs show non-aggregating behaviour in the absence of external fields, while under field influence they can readily be manipulated.This way, superparamagnetic nanoparticles based on iron oxides are ideal candidates for the separation of cells and molecules, as drug carriers, as contrast agents in imaging, and in simple bioassays.However, the spectra of prospective fields of use of MNP in medicine can be extended to biodiagnostics based on magnetic relaxation, advanced imaging methods, and particle diffusitivity by tailoring their magnetic anisotropy.This way, the characteristic relaxation time is adjustable, and we can take advantage of magnetodynamics for therapeutic or diagnostic means.In the case of thermally fully blocked MNP, these particles can be treated as permanent dipoles and therefor enable direct magnetomechanical coupling.In addition, MNP with shape anisotropy and multi-component particles are available that are of interest as nanoactuators and bioinspired swimming objects.The talk will summarize some of these actual developments from our lab and from others.The pros and cons of these particle systems in comparison to superparamagnetic cores in different areas of application such as magnetic heating, imaging, tissue engineering, addressable implants and nanotransportation with be discussed, and future directions highlighted.

Liquid suspensions of magnetic nanoparticles play a crucial role in current biomedical research and applications. While their magnetic characteristics are of importance for their utilization, no measurement standard exists and an uncertainty budget for static magnetisations measurements of MNP is lacking. Here we present the structure of the uncertainty budget for static magnetisation measurements by stratifying the measurement process and data analysis into seven levels of rising complexity. The main uncertainty contributions of each level are stated and briefly described. This paves the way towards a reliable quantitative uncertainty budget that could be used for interlaboratory comparisons as well as for the development of a measurement standard.

Magnetorelaxometry (MRX) is a well-known measurement technique which allows the retrieval of magnetic nanoparticle (MNP) characteristics such as size distribution and clustering behavior. This technique also enables the non-invasive reconstruction of the spatial MNP distribution by solving an inverse problem, referred to as MRX imaging. Although MRX allows the imaging of a broad range of MNP types, little research has been done on imaging different MNP types simultaneously. Biomedical applications can benefit significantly from a measurement technique that allows the separation of the resulting measurement signal into its components originating from different MNP types. In this paper, we present a theoretical procedure and experimental validation to show the feasibility of MRX imaging in reconstructing multiple MNP types simultaneously. Because each particle type has its own characteristic MRX signal, it is possible to take this a priori information into account while solving the inverse problem. This way each particle type's signal can be separated and its spatial distribution reconstructed. By assigning a unique color code and intensity to each particle type's signal, an image can be obtained in which each spatial distribution is depicted in the resulting color and with the intensity measuring the amount of particles of that type, hence the name multi-color MNP imaging. The theoretical procedure is validated by reconstructing six phantoms, with different spatial arrangements of multiple MNP types, using MRX imaging. It is observed that MRX imaging easily allows up to four particle types to be separated simultaneously, meaning their quantitative spatial distributions can be obtained.

Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation, spanning a large number of industry sectors from imaging and actuation based applications in biomedicine and biotechnology, through large-scale environmental remediation uses such as water purification, to engineering-based applications such as position-controlled lubricants and soaps. Continuous advances in their manufacture have produced an ever-growing range of products, each with their own unique properties. At the same time, the characterisation of magnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpret the measurement data. In many cases, the stringent requirements of the end-user technologies dictate that magnetic nanoparticle products should be clearly defined, well characterised, consistent and safe; or to put it another way-standardised. The aims of this document are to outline the concepts and terminology necessary for discussion of magnetic nanoparticles, to examine the current state-of-the-art in characterisation methods necessary for the most prominent applications of magnetic nanoparticle suspensions, to suggest a possible structure for the future development of standardisation within the field, and to identify areas and topics which deserve to be the focus of future work items. We discuss potential roadmaps for the future standardisation of this developing industry, and the likely challenges to be encountered along the way.

Magnetorelaxometry and thermal magnetic noise spectroscopy are two magnetic characterization techniques enabling one to estimate the magnetic nanoparticle hydrodynamic size distribution. Both techniques are based on the same physical principle, i.e. the thermal fluctuations of the magnetic moment. In the case of magnetorelaxometry these fluctuations give rise to a relaxing magnetic moment after an externally applied magnetic field is switched off, whereas thermal magnetic noise spectra are measured in the absence of any external excitation. Hence, thermal magnetic noise spectroscopy is an equilibrium measurement technique. Here, we compare the similarity and complementarity of both methods and conclude that, for particles within both methods' sensitivity range, they give the same estimate for the size distribution. For small particles (or samples with low viscosities), the used setup is not sufficiently sensitive to accurately estimate the size distribution from the relaxometry signal whereas this is still possible with thermal magnetic noise spectroscopy. For larger particles, however, magnetorelaxometry is the preferred method because of its higher signal to noise ratio and faster measurement time.

Single-core iron-oxide nanoparticles with nominal core diameters of 14nm and 19nm were analyzed with a variety of non-magnetic and magnetic analysis techniques, including transmission electron microscopy (TEM), dynamic light scattering (DLS), static magnetization vs. magnetic field (M-H) measurements, ac susceptibility (ACS) and magnetorelaxometry (MRX). From the experimental data, distributions of core and hydrodynamic sizes are derived. Except for TEM where a number-weighted distribution is directly obtained, models have to be applied in order to determine size distributions from the measurand. It was found that the mean core diameters determined from TEM, M-H, ACS and MRX measurements agree well although they are based on different models (Langevin function, Brownian and Néel relaxation times). Especially for the sample with large cores, particle interaction effects come into play, causing agglomerates which were detected in DLS, ACS and MRX measurements. We observed that the number and size of agglomerates can be minimized by sufficiently strong diluting the suspension.

A three-step aqueous approach to obtain large (> 50 nm) magnetite single-core particles has been developed. The steps are a) synthesis of antiferromagnetic nanoparticles, b) particle coating and c) subsequent reduction of the core material to magnetite. By variation of precursor material and process conditions, the synthesis yielded rhombohedra, discs or needles below 200 nm. A combination of X-ray diffraction, Fe-57 Mossbauer spectroscopy and infrared spectroscopy confirmed magnetite to be the dominant final core material. From transmission electron microscopy, we identified porous structures after the reduction. Magnetic characterization of the different magnetic nanopaticles revealed strikingly different magnetic behaviour depending on their shape, internal structure and reduction process. We conclude that each of these parameters have to be considered in further characterization of large magnetite nanoparticles. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Magnetic Particle Imaging (MPI) is a quantitative imaging modality with promising features for several biomedical applications. Here, we study quantitatively the raw data obtained during MPI measurements. We present a method for the calibration of the MPI scanner output using measurements from a magnetic particle spectrometer (MPS) to yield data in units of magnetic moments. The calibration technique is validated in a simplified MPI mode with a 1D excitation field. Using the calibrated results from MPS and MPI, we determine and compare the detection limits for each system. The detection limits were found to be 5·10-12 Am2 for MPS and 3.6·10-10 Am2 for MPI. Finally, the quantitative information contained in a standard MPI measurement with a 3D excitation is analyzed and compared to the previous results, showing a decrease in signal amplitudes of the odd harmonics related to the case of 1D excitation. We propose physical explanations for all acquired results; and discuss the possible benefits for the improvement of MPI technology.

Magnetic nanoparticles in colloidal dispersions are important for biomedical applications like magnetic drug targeting, magnetic particle hyperthermia, and several imaging applications. For a physical understanding of these applications, the particles' hydrodynamic size distribution should be well characterized. Magnetorelaxometry is a fast method to determine this property, but until now had the drawback that a priori information, like a functional form of the expected size distribution, was necessary. Following recent advances, where Kaczmarz' algorithm was used to determine the core size distribution from static magnetization curves without any such assumptions, we present a similar study for the determination of the hydrodynamic size distribution. Here, the performance of several implementations of Kaczmarz' algorithm are investigated for both simulated and measured magnetorelaxometry data. Our results show that this method is able to determine the hydrodynamic size distribution in agreement with either the known input distribution, in the case of simulated data, or other size estimates determined with different methods such as thermal magnetic noise spectroscopy and dynamic light scattering in the case of measured data.