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The use of magnetic nanoparticles (MNPs) with appropriate surface functionalization as markers in immunoassays for the detection of specific analytes, such as viruses, proteins, or antibodies, has received increased attention due to the recent pandemic. In combination with magnetic particle spectroscopy (MPS) as an evaluation method, this approach represents a promising alternative to the established testing methods. MPS measures the harmonics of the rotating MNPs, whose dynamics are the characteristics of their binding state. In this article, we discuss the development of the immunoMPS, an immunoassay-optimized as well as cost-effective MPS system, to take a big step toward higher sensitivity. To achieve this, simulations based on the Fokker-Planck equation were performed to optimize the excitation parameters for the used 80-nm-sized Bionized NanoFerrite particle system (BNF80), aiming at the detection of tiny changes in the MNP dynamics. The constructed immunoMPS only has material costs of 350 € in total, and it is mobile and self-contained and, therefore, can be used in S2+ biosafety laboratories. Despite its low price, it can detect down to 40.6-ng iron with BNF80 MNPs. The high performance of the instrument is further illustrated by our magnetic immunoassays (MIAs) with a significantly improved limit of detection (LOD) of $3\times 10^{8}$ viruses/mL (552 fM, 33.1 amole) for the detection of mimic SARS-CoV-2. This is an improvement of about two orders of magnitude compared with previous results reported in this research topic.

Magnetic particle imaging (MPI) is an emerging medical imaging technique that measures the nonlinear magnetization response of magnetic nanoparticles (MNPs). The image reconstruction of MPI is to solve the unknown spatial distribution of MNPs from the measured magnetic response signal, which plays a significant role in MPI. In this study, a sparse-representation-based image reconstruction method is proposed to improve the spatial resolution and reduce the artifacts of MPI images. In the proposed method, the spatial distribution of MNPs is sparsely represented by the Gaussian radial basis functions (GRBFs). The inverse problem in MPI is consequently transformed to obtain the optimal weight coefficient vector of the GRBFs. It helps to reduce the number of unknowns to be reconstructed and improve the robustness of the image reconstruction process. By incorporating the prior knowledge from the preliminary reconstructed images, the center points of the GRBFs are selected densely in the target area and sparsely outside to further reduce the dimension of the system matrix and the artifacts. Numerical simulations are performed to optimize the key parameters in the proposed method. Furthermore, phantom experiments are carried out using a single-harmonic-based narrowband MPI scanner to demonstrate the feasibility of the proposed method. Experimental results show that the proposed method improves the spatial resolution from 0.5 to 0.3 mm and reduces the artifacts compared with the algebraic reconstruction technique (ART) method and the Newton-Raphson method. We envisage that the proposed method is of great significance to biomedical applications for MPI.

This article describes a radio frequency (RF) interconnection for the micro telecommunication computing architecture (MTCA) open standard published by the PCI Industrial Computer Manufacturers Group. The interconnection is capable of transmitting signals with frequencies ranging from dc to 3 GHz from the rear transmission module (RTM) to the advanced mezzanine card (AMC, IEEE1386.1). The existing connection is based on differential connectors and suffers from strong crosstalk between the pairs. The main motivation behind our research is to develop a new connection with high isolation between the ports that can transmit RF signals up to 3 GHz. A new MTCA.4 interconnection class RF1.0 based on two improved single-ended multiport coaxial connectors with up to 12 contacts is introduced. This could open a new field of MTCA-based modular high-frequency instrumentation, e.g., for beam diagnostics in particle accelerators, RF preconditioning in radar systems, or in 5G telecom wireless networks. A sophisticated through-hole technology (THT) and surface-mounted device (SMD) footprint pattern with very-low crosstalk, down to −90 dB between the connector pins, is presented. The new broadband connection between the AMC and the RTM allows the use of modern direct-sampling digitizers [analog-to-digital converter (ADC)] and fast digital-to-analog converters (DACs) on MTCA.4 AMCs, while maintaining the high spectral purity of the converters. This allows omitting large mixer circuits on the RTM, which were needed to reduce the signal frequency due to insufficient isolation of the current differential Zone 3 connector. The RF1.0 interconnection class presented in this article could enable a highly modular instrumentation platform for processing of RF signals.

Immunoassays exploiting magnetization dynamics of magnetic nanoparticles are highly promising for mix-and-measure, quantitative, and point-of-care diagnostics. However, how single-core magnetic nanoparticles can be employed to reduce particle concentration and concomitantly maximize assay sensitivity is not fully understood. Here, we design monodisperse Néel and Brownian relaxing magnetic nanocubes (MNCs) of different sizes and compositions. We provide insights into how to decouple physical properties of these MNCs to achieve ultrahigh sensitivity. We find that tricomponent-based Zn0.06Co0.80Fe2.14O4particles, with out-of-phase to initial magnetic susceptibility χ″/χ0ratio of 0.47 out of 0.50 for magnetically blocked ideal particles, show the ultrahigh magnetic sensitivity by providing a rich magnetic particle spectroscopy (MPS) harmonics spectrum despite bearing lower saturation magnetization than dicomponent Zn0.1Fe2.9O4having high saturation magnetization. The Zn0.06Co0.80Fe2.14O4MNCs, coated with catechol-based poly(ethylene glycol) ligands, measured by our benchtop MPS show 3 orders of magnitude better particle LOD than that of commercial nanoparticles of comparable size.

Magnetic nanoparticles are critical to a broad range of applications from medical diagnostics and therapeutics to biotechnological processes and single-molecule manipulation. To advance these applications, facile and robust routes to synthesize highly magnetic nanoparticles over a wide size range are needed. Here, we demonstrate that changing the degassing temperature of thermal decomposition of metal acetylacetonate precursors from 90 to 25 °C tunes the size of ferrimagnetic ZnxFe3–xO4nanocubes from 25 to 100 nm, respectively. We show that degassing at 90 °C nearly entirely removes acetylacetone ligands from the reaction, which results in an early formation of monomers and a reaction-controlled growth following LaMer’s model toward small nanocubes. In contrast, degassing at 25 °C only partially dissociates acetylacetone ligands from the metal center and triggers a delayed formation of monomers, which leads to intermediate assembled structures made of tiny irregular crystallites and an eventual formation of large nanocubes via a diffusion-controlled growth mechanism. Using complementary techniques, we determine the substitution fraction xof Zn2+to be in the range of 0.35–0.37. Our method reduces the complexity of the thermal decomposition method by narrowing the synthesis parameter space to a single physical parameter and enables fabrication of highly magnetic and uniform zinc ferrite nanocubes over a broad size range. The resulting particles are promising for a range of applications from magnetic fluid hyperthermia to actuation of macromolecules.

A detailed signal generation of the magnetization response of magnetic nanoparticles (MNPs) as a result of externally applied magnetic fields with flux densities of several millitesla is of high interest for biomedical applications such as magnetic resonance imaging or magnetic particle imaging (MPI). Although, MNPs are already frequently used as contrast agents or tracer materials, experimental data are rarely compared to model predictions because of distinct deviations. In this article, we use a customized Brownian-dominated CoFe2O4particle system to compare experimental magnetic particle spectroscopy data with Fokker–Planck simulations considering the Brownian relaxation. The influences of viscosity, size distribution, excitation frequency, and field amplitude are studied. We show that the effective magnetic moment and cluster sizes can be determined using a sample viscosity series. As introduced, such particle systems can serve as model systems to evaluate mathematical expressions and to study dependences on physical influencing factors. Investigations of defined MNP systems and detailed characterizations enable a wide field of improved diagnosis and therapy applications, for example, mobility MPI and magnetic hyperthermia.

Immunoassays with magnetic nanoparticles (MNPs) as markers are a promising approach for the fast and sensitive virus detection. Upon binding of antibody-functionalized MNP on virus proteins, the hydrodynamic diameter increases and a change in the Brownian relaxation time can be measured. In this study, we detect the whole SARS-CoV-2 by mimicking it with streptavidin-coated polystyrene beads with biotinylated spike proteins. Changes of the MNP dynamics are measured by alternating current susceptometry and magnetic particle spectroscopy. Due to the multiple binding sites of MNP and virus, crosslinking enlarges the change of the hydrodynamic diameter. In order to improve the sensitivity and the limit of detection of the assay, the ratio of the virus to the MNP amount RMV/MNPis investigated in detail. High RMV/MNPratios lead to a saturation of the MNPs with viruses, so that the cluster size and therefore the sensitivity decrease again. Additionally, it is found that the smallest virus concentrations can be detected for small MNP concentrations. It is also shown that the RMV/MNPrange that can be used for an unambiguous detection of viruses depends on the virus/MNP concentration; it shifts with increasing MNP concentration to smaller RMV/MNPvalues. For very small virus concentrations, an increase of the Brownian relaxation time is detected implying a decrease of the hydrodynamic diameter. Furthermore, the optimal antibody concentration for MNP functionalization was determined. It is also found that a washing process with a centrifuge improves the sensitivity by reliably removing unbound antibodies and eliminating small MNPs with improper functionalization.

Self-assembled magnetic nanoparticles offer next-generation materials that allow harnessing of their physicochemical properties for many applications. However, how three-dimensional nanoassemblies of magnetic nanoparticles can be synthesized in one-pot synthesis without excessive postsynthesis processes is still a bottleneck. Here, we propose a panel of small organic molecules that glue nanoparticle crystallites during the growth of particles to form large nanoassembled nanoparticles (NANs). We find that both carbonyl and carboxyl functional groups, presenting in benzaldehyde and benzoic acid, respectively, are needed to anchor with metal ions, while aromatic rings are needed to create NANs through π–π stacking. When benzyl alcohol, lacking carbonyl and carboxyl groups, is employed, no NANs are formed. NANs formed by benzoic acid reveal a unique combination of high magnetization and coercivity, whereas NANs formed by benzaldehyde show the largest exchange bias reported in nanoparticles. Surprisingly, our NANs show unconventional colloidal stability due to their unique nanoporous architectures.

We investigated in depth the interrelations among structure, magnetic properties, relaxation dynamics and magnetic hyperthermia performance of magnetic nanoflowers. The nanoflowers are about 39 nm in size, and consist of densely packed iron oxide cores. They display a remanent magnetization, which we explain by the exchange coupling between the cores, but we observe indications for internal spin disorder. By polarized small angle neutron scattering we unambiguously confirm that on average the nanoflowers are preferentially magnetized along one direction. The extracted discrete relaxation time distribution of the colloidally dispersed particles indicates the presence of three distinct relaxation contributions. We can explain the two slower processes by Brownian and classical Néel relaxation, respectively. The additionally observed very fast relaxation contributions are attributed by us to the relaxation of the disordered spins within the nanoflowers. Finally, we show that the intrinsic loss power (ILP, magnetic hyperthermia performance) of the nanoflowers measured in colloidal dispersion at high frequency is comparatively large and independent of the viscosity of the surrounding medium. This concurs with our assumption that the observed relaxation in the high frequency range is primarily a result of internal spin relaxation, and probably connected to the disordered spins within the individual nanoflowers.

By studying the response behavior of ferrofluids of 6–22 nm maghemite nanoparticles in glycerol solution exposed to external magnetic fields, we demonstrate the ability of Mössbauer spectroscopy to access a variety of particle dynamics and static magnetic particle characteristics at the same time, offering an extensive characterization of ferrofluids for in-field applications; field-dependent particle alignment and particle mobility in terms of Brownian motion have been extracted simultaneously from a series of Mössbauer spectra for single-core particles as well as for particle agglomerates. Additionally, information on Néel superspin relaxation and surface spin frustration could be directly inferred from this analysis. Parameters regarding Brownian particle dynamics, as well as Néel-type relaxation behavior, obtained via Mössbauer spectroscopy, have been verified by complementary AC-susceptometry experiments, modulating the AC-field amplitude, and using an extended frequency range of 10–1to 106Hz, while field-dependent particle alignment has been cross-checked via magnetometry.

Herein, by studying a stepwise phase transformation of 23 nm FeO–Fe3O4core–shell nanocubes into Fe3O4, we identify a composition at which the magnetic heating performance of the nanocubes is not affected by the medium viscosity and aggregation. Structural and magnetic characterizations reveal the transformation of the FeO–Fe3O4nanocubes from having stoichiometric phase compositions into Fe2+-deficient Fe3O4phases. The resultant nanocubes contain tiny compressed and randomly distributed FeO subdomains as well as structural defects. This phase transformation causes a 10-fold increase in the magnetic losses of the nanocubes, which remain exceptionally insensitive to the medium viscosity as well as aggregation unlike similarly sized single-phase magnetite nanocubes. We observe that the dominant relaxation mechanism switches from Néel in fresh core–shell nanocubes to Brownian in partially oxidized nanocubes and once again to Néel in completely treated nanocubes. The Fe2+deficiencies and structural defects appear to reduce the magnetic energy barrier and anisotropy field, thereby driving the overall relaxation into Néel process. The magnetic losses of these nanoparticles remain unchanged through a progressive internalization/association to ovarian cancer cells. Moreover, the particles induce a significant cell death after being exposed to hyperthermia treatment. Here, we present the largest heating performance that has been reported to date for 23 nm iron oxide nanoparticles under intracellular conditions. Our findings clearly demonstrate the positive impacts of the Fe2+deficiencies and structural defects in the Fe3O4structure on the heating performance into intracellular environment.

Viele magnetische Sensoren beruhen auf der Interaktion magnetischer Materialien mit einem externen Magnetfeld. Das Magnetisierungsverhalten und die Magnetisierungsdynamik der magnetischen Materialien sind dadurch entscheidende Charakteristiken für die Funktionsfähigkeit dieser Sensoren. Daher wird in der Forschung und generell bei der Optimierung der Sensoren ein besonderer Fokus auf die Materialcharakteristik gelegt. Hier wird ein Messsystem vorgestellt, das diese Charakterisierung sehr empfindlich ermöglicht und zusätzlich auch für verschiedenste Proben eingesetzt werden kann. Beispielsweise zeigen die für Fluxgate-Sensoren verwendeten magnetischen Materialien ein anderes Verhalten als die in MR-Sensoren eingesetzten magnetischen Schichten.

Studying protein interactions is of vital importance both to fundamental biology research and to medical applications. Here, we report on the experimental proof of a universally applicable label-free homogeneous platform for rapid protein analysis. It is based on optically detecting changes in the rotational dynamics of magnetically agitated core–shell nanorods upon their specific interaction with proteins. By adjusting the excitation frequency, we are able to optimize the measurement signal for each analyte protein size. In addition, due to the locking of the optical signal to the magnetic excitation frequency, background signals are suppressed, thus allowing exclusive studies of processes at the nanoprobe surface only. We study target proteins (soluble domain of the human epidermal growth factor receptor 2 - sHER2) specifically binding to antibodies (trastuzumab) immobilized on the surface of our nanoprobes and demonstrate direct deduction of their respective sizes. Additionally, we examine the dependence of our measurement signal on the concentration of the analyte protein, and deduce a minimally detectable sHER2 concentration of 440 pM. For our homogeneous measurement platform, good dispersion stability of the applied nanoprobes under physiological conditions is of vital importance. To that end, we support our measurement data by theoretical modeling of the total particle–particle interaction energies. The successful implementation of our platform offers scope for applications in biomarker-based diagnostics as well as for answering basic biology questions.

IntroductionIn the West Midlands region of the UK, delivery of pre-hospital care has been remodelled through introduction of a 24 h Medical Emergency Response Incident Team (MERIT). Teams including physicians and critical care paramedics (CCP) are deployed to incidents on land-based and helicopter-based platforms. Clinical practice, including delivery of rapid sequence induction of anaesthesia (RSI), is underpinned by standard operating procedures (SOP). This study describes the first 12 months experience of prehospital RSI in the MERIT scheme in the West Midlands.MethodsRetrospective review of the MERIT clinical database for the 12 months following the launch of the scheme. Data was collected relating to the number of RSIs performed; indication for RSI; number of intubation attempts; grade of view on laryngoscopy and the base speciality/grade of the operator performing intubation.ResultsMERIT teams were activated 1619 times, attending scene in 1029 cases. RSI was performed 142 times (13.80% of scene attendances). There was one recorded case of failure to intubate requiring insertion of a supraglottic airway device (0.70%). In over a third of RSI cases, CCPs performed laryngoscopy and intubation (n=53, 37.32%). Proficiency of obtaining Grade I view at laryngoscopy was similar for physicians (74.70%) and CCPs (77.36%). Intubation was successful at the first attempt in over 90% of cases.ConclusionsThis study demonstrates that operation within a system that provides high levels of exposure, underpinned by comprehensive and robust training and governance frameworks, promotes levels of performance in successful prehospital RSI regardless of base speciality or profession.

We present a new approach for homogeneous real-time immunodiagnostics (denoted as “PlasMag”) that can be directly carried out in sample solutions such as serum, thus promising to circumvent the need of sample preparation. It relies on highly sensitive plasmon-optical detection of the relaxation dynamics of magnetic nanoparticles immersed in the sample solution, which changes when target molecules bind to the surfaces of the nanoparticles due to the increase in their hydrodynamic radii. This method requires hybrid nanoparticles that combine both magnetic and optical anisotropic properties. Our model calculations show that core–shell nanorods with a cobalt core diameter of 6 nm, a cobalt core length of 80 nm, and a gold shell thickness of 5 nm are ideally suited as nanoprobes. On the one hand, the spectral position of the longitudinal plasmon resonance of such nanoprobes lies in the near-infrared, where the optical absorption in serum is minimal. On the other hand, the expected change in their relaxation properties on analyte binding is maximal for rotating magnetic fields as excitation in the lower kHz regime. In order to achieve high alignment ratios of the nanoprobes, the strength of the magnetic field should be around 5 mT. While realistic distributions of the nanoprobe properties result in a decrease of their mean optical extinction, the actual relaxation signal change on analyte binding is largely unaffected. These model calculations are supported by measurements on plain cobalt nanorod dispersions, which are the base component of the aspired core–shell nanoprobes currently under development.

AbstractDie Magnetorelaxometrie (MRX) magnetischer Nanoteilchen ist eine sehr aussichtsreiche Methode zur Realisierung von so genannten Magnetorelaxations-Immunoassays (MARIA). Solche Immunoassays haben im Vergleich zu anderen den Vorteil, dass keine Auswaschschritte ungebundener Marker erforderlich sind und die Marker durch magnetische Feldgradienten manipuliert werden können. Wir haben einen Relaxationsmessplatz auf der Grundlage einer differentiellen Fluxgate-Anordnung aufgebaut und verschiedene Magnetit-Ferrofluide auf ihre Eignung für die Realisierung eines MARIA getestet.

We review the progress towards an understanding of the electrodynamics in the vortex-state which arises in response to a magnetic field. B. Experimentally, the goal is to characterize the conductivity of cuprate superconductors in the presence of an applied magnetic field over a broad frequency range from microwave to infrared wavelengths. The theoretical challenge is to understand these measurements with microscopic, as well as phenomenological, models. In describing the experiments to date we will focus on a relatively new technique, coherent terahertz spectroscopy, which is uniquely capable of measuring the complete complex conductivity tensor.

The dependence of the number of clusters,N, and the average size of the clusters, 〈R〉, formed by nucleation and growth in the first stages of first-order phase transformations on the initial supersaturation, χ, is analyzed. The analysis is based on the numerical solution of a system of rate equations of classical nucleation theory describing this process. It is shown that in agreement with von Weimarn's proposal for moderate values of the initial supersaturation these dependencies may be expressed in form of power laws (〈R〉 ∝ χ−p;N∝ χq;p> 0,q> 0). However, considering larger intervals of the initial supersaturation, two distinct regions may be distinguished, characterized by different values of the exponentspandq. The results are of importance both from a theoretical point of view stimulating attempts to reconfirm the results by analytical methods as well as with respect to technological applications of nucleation theory, allowing one to draw conclusions on the initial dispersity of the evolving phase in dependence on the initial supersaturation.

The article explains how with the addition of special emulsified silicone resins has resulted in facade coatings with an improved water vapor permeability. According to the study, to reach an additional water protection special emulsified silicone resins have to be added. This is the most effective protection for buildings.

We investigated the effect of core size distribution on the performance of a magnetic nanoparticle thermometer (MNPT) in circumstances when Neel relaxation dominates the dynamic behavior of particles. Numerical simulations revealed the effects of excitation field strength and core size distribution on the temperature dependence of the amplitude and phase of harmonics. In MNPT, the field dependences of sensitivity deviated significantly from those calculated when the core size distribution was neglected. These simulation results were compared with those from experiments for which reasonable agreement was obtained. These findings must be carefully considered when designing an optimal MNPT system.

A comprehensive quantitative comparison between the measured performance of direct-coupled high Tcsuperconducting quantum interference device (SQUID) magnetometers with 30° bicrystal junctions and a numerical simulation is presented. It is shown that the characteristics of the SQUID magnetometer are considerably affected by resonances due to the large dielectric constant of the SrTiO3substrate. In the realized magnetometer layout, the strip line resonance occurring in the SQUID inductance increases the voltage modulation depth and the output voltage noise of the SQUID, while the flux noise of the SQUID is nearly unchanged. It is also shown that the distortion of the voltage versus flux characteristic is caused by the LCresonance in the pickup loop of the magnetometer in combination with a capacitive feedback. Good agreement between experiment and simulation has been obtained.