In-depth magnetometry and EPR analysis of the spin structure of human-liver ferritin: from DC to 9 GHz.

Ferritin, the major iron storage protein in organisms, stores iron in the form of iron oxyhydroxide most likely involving phosphorous as a constituent, the mineral form of which is not well understood. Therefore, the question of how the ca. 2000 iron atoms in the ferritin core are magnetically coupled is still largely open. The ferritin core, with a diameter of 5-8 nm, is encapsulated in a protein shell that also catalyzes the uptake of iron and protects the core from outside interactions. Neurodegenerative disease is associated with iron imbalance, generating specific interest in the magnetic properties of ferritin. Here we present 9 GHz continuous wave EPR and a comprehensive set of magnetometry techniques including isothermal remanent magnetization (IRM) and AC susceptibility to elucidate the magnetic properties of the core of human liver ferritin. For the analysis of the magnetometry data, a new microscopic model of the ferritin-core spin structure is derived, showing that magnetic moment is generated by surface-spin canting, rather than defects. The analysis explicitly includes the distribution of magnetic parameters, such as the distribution of the magnetic moment. This microscopic model explains some of the inconsistencies resulting from previous analysis approaches. The main findings are a mean magnetic moment of 337µB with a standard deviation of 0.947µB. In contrast to previous reports, only a relatively small contribution of paramagnetic and ferrimagnetic phases is found, in the order of maximally 3%. For EPR, the over 30 mT wide signal of the ferritin core is analyzed using the model of the giant spin system [Fittipaldi et al., Phys. Chem. Chem. Phys., 2016, 18, 3591-3597]. Two components are needed minimally, and the broadening of these components suggests a broad distribution of the magnetic resonance parameters, the zero-field splitting, D, and the spin quantum number, S. We compare parameters from EPR and magnetometry and find that EPR is particularly sensitive to the surface spins of the core, revealing the potential to use EPR as a diagnostic for surface-spin disorder.

Performance of a Nonlinear Magnetic Handheld Probe for Intraoperative Sentinel Lymph Node Detection: A Phantom Study.

OBJECTIVE: This study investigates the performance of the DiffMag handheld probe (nonlinear magnetometry), to be used for sentinel lymph node detection. Furthermore, the performance of DiffMag is compared with a gamma probe and a first-order magnetometer (Sentimag®, linear magnetometry). METHODS: The performance of all three probes was evaluated based on longitudinal distance, transverse distance, and resolving power for two tracer volumes. A phantom was developed to investigate the performance of the probes for a clinically relevant situation in the floor of the mouth (FOM). RESULTS: Considering the longitudinal distance, both DiffMag handheld and Sentimag® probe had comparable performance, while the gamma probe was able to detect at least a factor of 10 deeper. Transverse distances of 13, 11, and 51 mm were measured for the small tracer volume by the DiffMag handheld, Sentimag®, and the gamma probe, respectively. For the large tracer volume this was 21, 18, and 55 mm, respectively. The full width at half maximum, at 7 mm probe height from the phantom surface, was 14, 12, and 18 mm for the small tracer volume and 15, 18, and 25 mm for the large tracer volume with the DiffMag handheld, Sentimag®, and gamma probe, respectively. CONCLUSIONS: With a high resolving power but limited longitudinal distance, the DiffMag handheld probe seems suitable for detecting SLNs which are in close proximity to the primary tumor. In this study, comparable results were shown using linear magnetometry. The gamma probe reached 10 times deeper, but has a lower resolving power compared with the DiffMag handheld probe.

Diamond-Based Nanoscale Quantum Relaxometry for Sensing Free Radical Production in Cells.

Diamond magnetometry makes use of fluorescent defects in diamonds to convert magnetic resonance signals into fluorescence. Because optical photons can be detected much more sensitively, this technique currently holds several sensitivity world records for room temperature magnetic measurements. It is orders of magnitude more sensitive than conventional magnetic resonance imaging (MRI) for detecting magnetic resonances. Here, the use of diamond magnetometry to detect free radical production in single living cells with nanometer resolution is experimentally demonstrated. This measuring system is first optimized and calibrated with chemicals at known concentrations. These measurements serve as benchmarks for future experiments. While conventional MRI typically has millimeter resolution, measurements are performed on individual cells to detect nitric oxide signaling at the nanoscale, within 10-20 nm from the internalized particles localized with a diffraction limited optical resolution. This level of detail is inaccessible to the state-of-the-art techniques. Nitric oxide is detected and the dynamics of its production and inhibition in the intra- and extracellular environment are followed.

Accurate magnetic field imaging using nanodiamond quantum sensors enhanced by machine learning.

Nanodiamonds can be excellent quantum sensors for local magnetic field measurements. We demonstrate magnetic field imaging with high accuracy of 1.8 [Formula: see text]T combining nanodiamond ensemble (NDE) and machine learning without any physical models. We discover the dependence of the NDE signal on the field direction, suggesting the application of NDE for vector magnetometry and the improvement of the existing model. Our method enhances the NDE performance sufficiently to visualize nano-magnetism and mesoscopic current and expands the applicability of NDE in arbitrarily shaped materials, including living organisms. This accomplishment bridges machine learning to quantum sensing for accurate measurements.

Occurrence of south- and north-seeking multicellular magnetotactic prokaryotes in a coastal lagoon in the South Hemisphere / Presencia de procariotatos magnetotácticos multicelulares que buscan el sur y el norte en una laguna costera del hemisferio sur

Magnetotactic bacteria (MTB) response to the magnetic field can be classified into north-seeking (NS) and south-seeking (SS), which usually depends on their inhabiting site in the North and South Hemisphere, respectively. However, uncommon inverted polarity was observed on both hemispheres. Here, we studied magnetotactic multicellular prokaryotes (MMPs) from a coastal lagoon in Brazil collected in April and August 2014. MMPs from the first sampling period presented both magnetotactic behaviors, while MMPs collected in August/2014 were only SS. Phylogenetic analysis based on the 16S rRNA coding gene showed that these organisms belong to the Deltaproteobacteria class. The 16S rRNA gene sequences varied among MMPs regardless of the sampling period, and similarity values were not related to the type of magnetotactic response presented by the microorganisms. Therefore, differences in the magnetotactic behavior might result from the physiological state of MMPs, the availability of resources, or the instability of the chemical gradient in the environment. This is the first report of NS magnetotactic behavior on MMPs from the South Hemisphere.(AU)

Accurate optically pumped magnetometer based on Ramsey-style interrogation.

Light-atom interactions during spin preparation and readout in optically pumped magnetometers can lead to inaccuracies. We demonstrate a novel, to the best of our knowledge, detection strategy that exploits an interrogation sequence in the pulsed free-induction-decay modality to suppress these systematic errors. The technique is predicated on monitoring the dynamics of preoriented atomic spins as they evolve unperturbed during a dark interval, by subsequently applying a time-delayed optical pulse to infer the spin state's phase. This detection mode reduced light shift inaccuracies to within 0.6 nT, and could be employed in a wide variety of high-precision atomic magnetometry experiments.

Triaxial detection of the neuromagnetic field using optically-pumped magnetometry: feasibility and application in children.

Optically-pumped magnetometers (OPMs) are an established alternative to superconducting sensors for magnetoencephalography (MEG), offering significant advantages including flexibility to accommodate any head size, uniform coverage, free movement during scanning, better data quality and lower cost. However, OPM sensor technology remains under development; there is flexibility regarding OPM design and it is not yet clear which variant will prove most effective for MEG. Most OPM-MEG implementations have either used single-axis (equivalent to conventional MEG) or dual-axis magnetic field measurements. Here we demonstrate use of a triaxial OPM formulation, able to characterise the full 3D neuromagnetic field vector. We show that this novel sensor is able to characterise magnetic fields with high accuracy and sensitivity that matches conventional (dual-axis) OPMs. We show practicality via measurement of biomagnetic fields from both the heart and the brain. Using simulations, we demonstrate how triaxial measurement offers improved cortical coverage, especially in infants. Finally, we introduce a new 3D-printed child-friendly OPM-helmet and demonstrate feasibility of triaxial measurement in a five-year-old. In sum, the data presented demonstrate that triaxial OPMs offer a significant improvement over dual-axis variants and are likely to become the sensor of choice for future MEG systems, particularly for deployment in paediatric populations.

Following Polymer Degradation with Nanodiamond Magnetometry.

Degradable polymers are widely used in the biomedical fields due to non-toxicity and great biocompatibility and biodegradability, and it is crucial to understand how they degrade. These polymers are exposed to various biochemical media in medical practice. Hence, it is important to precisely follow the degradation of the polymer in real time. In this study, we made use of diamond magnetometry for the first time to track polymer degradation with nanoscale precision. The method is based on a fluorescent defect in nanodiamonds, which changes its optical properties based on its magnetic surrounding. Since optical signals can be read out more sensitively than magnetic signals, this method allows unprecedented sensitivity. We used a specific mode of diamond magnetometry called relaxometry or T1 measurements. These are sensitive to magnetic noise and thus can detect paramagnetic species (gadolinium in this case). Nanodiamonds were incorporated into polylactic acid (PLA) films and PLA nanoparticles in order to follow polymer degradation. However, in principle, they can be incorporated into other polymers too. We found that T1 constants decreased gradually with the erosion of the film exposed to an alkaline condition. In addition, the mobility of nanodiamonds increased, which allows us to estimate polymer viscosity. The degradation rates obtained using this approach were in good agreement with data obtained by quartz crystal microbalance, Fourier-transform infrared spectroscopy, and atomic force microscopy.

Sentinel lymph node localization and staging with a low-dose of superparamagnetic iron oxide (SPIO) enhanced MRI and magnetometer in patients with cutaneous melanoma of the extremity - The MAGMEN feasibility study.

BACKGROUND: In patients with melanoma, sentinel lymph node (SLN) status is pivotal for treatment decisions. Current routine for SLN detection combines Technetium99m (Tc99) lymphoscintigraphy and blue dye (BD). The primary aim of this study was to examine the feasibility of using a low dose of superparamagnetic iron oxide (SPIO) injected intracutaneously to detect and identify the SLN, and the secondary aim was to investigate if a low dose of SPIO would enable a preoperative MRI-evaluation of SLN status. METHODS: Patients with melanoma of the extremities were eligible. Before surgery, a baseline MRI of the nodal basin was followed by an injection of a low dose (0.02-0.5 mL) of SPIO and then a second MRI (SPIO-MRI). Tc99 and BD was used in parallel and all nodes with a superparamagnetic and/or radioactive signal were harvested and analyzed. RESULTS: Fifteen patients were included and the SLNB procedure was successful in all patients (27 SLNs removed). All superparamagnetic SLNs were visualized by MRI corresponding to the same nodes on scintigraphy. Micrometastatic deposits were identified in four SLNs taken from three patients, and SPIO-MRI correctly predicted two of the metastases. There was an association between MRI artefacts in the lymph node and the dose SPIO given. DISCUSSION: It is feasible to detect SLN in patients with melanoma using a low dose of SPIO injected intracutaneously compared with the standard dual technique. A low dose of SPIO reduces the lymph node MRI artefacts, opening up for a non-invasive assessment of SLN status in patients with cancer.

Transforming and comparing data between standard SQUID and OPM-MEG systems.

Optically pumped magnetometers (OPMs) have recently become so sensitive that they are suitable for use in magnetoencephalography (MEG). These sensors solve operational problems of the current standard MEG, where superconducting quantum interference device (SQUID) gradiometers and magnetometers are being used. The main advantage of OPMs is that they do not require cryogenics for cooling. Therefore, they can be placed closer to the scalp and are much easier to use. Here, we measured auditory evoked fields (AEFs) with both SQUID- and OPM-based MEG systems for a group of subjects to better understand the usage of a limited sensor count OPM-MEG. We present a theoretical framework that transforms the within subject data and equivalent simulation data from one MEG system to the other. This approach works on the principle of solving the inverse problem with one system, and then using the forward model to calculate the magnetic fields expected for the other system. For the source reconstruction, we used a minimum norm estimate (MNE) of the current distribution. Two different volume conductor models were compared: the homogeneous conducting sphere and the three-shell model of the head. The transformation results are characterized by a relative error and cross-correlation between the measured and the estimated magnetic field maps of the AEFs. The results for both models are encouraging. Since some commercial OPMs measure multiple components of the magnetic field simultaneously, we additionally analyzed the effect of tangential field components. Overall, our dual-axis OPM-MEG with 15 sensors yields similar information to a 62-channel SQUID-MEG with its field of view restricted to the right hemisphere.

A novel magnetophoretic-based device for magnetometry and separation of single magnetic particles and magnetized cells.

The use of magnetic micro- and nanoparticles in medicine and biology is expanding. One important example is the transport of magnetic microparticles and magnetized cells in lab-on-a-chip systems. The magnetic susceptibility of the particles is a key factor in determining their response to the externally applied magnetic field. Typically, to measure this parameter, their magnetophoretic mobility is studied. However, the particle tracking system for accurately determining the traveled distance in a certain time may be too complicated. Here, we introduce a lithographically fabricated chip composed of an array of thin magnetic micro-disks for evaluating the magnetic susceptibility of numerous individual magnetic particles simultaneously. The proposed novel magnetometer works based on the phase change in the trajectory of microparticles circulating around the disks in a rotating in-plane magnetic field. We explain that the easily detectable transition between the "phase-locked" and the "phase-slipping" regimes and the frequency at which it happens are appropriate parameters for measuring the magnetic susceptibility of the magnetic particles at the single-particle level. We show that this high-throughput (i.e., ∼ten thousand particles on a 1 cm2 area) single-particle magnetometry method has various crucial applications, including i) magnetic characterization of magnetic beads as well as magnetically labeled living cells, ii) determining the magnetization rate of the cells taking up magnetic nanoparticles with respect to time, iii) evaluating the rate of degradation of magnetic nanoparticles in cells over time, iv) detecting the number of target cells in a sample, and v) separating particles based on their size and magnetic susceptibility.

Cross-Axis projection error in optically pumped magnetometers and its implication for magnetoencephalography systems.

Optically pumped magnetometers (OPMs) developed for magnetoencephalography (MEG) typically operate in the spin-exchange-relaxation-free (SERF) regime and measure a magnetic field component perpendicular to the propagation axis of the optical-pumping photons. The most common type of OPM for MEG employs alkali atoms, e.g. 87Rb, as the sensing element and one or more lasers for preparation and interrogation of the magnetically sensitive states of the alkali atoms ensemble. The sensitivity of the OPM can be greatly enhanced by operating it in the SERF regime, where the alkali atoms' spin exchange rate is much faster than the Larmor precession frequency. The SERF regime accommodates remnant static magnetic fields up to ±5 nT. However, in the presented work, through simulation and experiment, we demonstrate that multi-axis magnetic signals in the presence of small remnant static magnetic fields, not violating the SERF criteria, can introduce significant error terms in OPM's output signal. We call these deterministic errors cross-axis projection errors (CAPE), where magnetic field components of the MEG signal perpendicular to the nominal sensing axis contribute to the OPM signal giving rise to substantial amplitude and phase errors. Furthermore, through simulation, we have discovered that CAPE can degrade localization and calibration accuracy of OPM-based magnetoencephalography (OPM-MEG) systems.

Laparoscopic Probe for Sentinel Lymph Node Harvesting Using Magnetic Nanoparticles.

OBJECTIVE: Sentinel lymph node harvesting is an essential step in the surgical treatment of a growing number of malignancies. Various techniques are available to facilitate this purpose. The present study reports a new laparoscopic technique for lymph node harvesting using magnetic nanoparticles containing a superparamagnetic iron-oxide core and dextran coating. This study assesses the clinical relevance of the prototype and provides input for further technological development on the way to clinical implementation. METHODS: A laparoscopic differential magnetometer prototype was built, utilizing a nonlinear detection principle (differential magnetometry) for magnetic identification of lymph nodes. The iron content sensitivity, depth & spatial sensitivity, and angular sensitivity were analyzed to investigate clinical options. RESULTS: The minimum detectable amount of iron was 9.8 µg at a distance of 1 mm. The detection depth was 5, 8, and 10 mm for samples containing 126, 252, and 504 µg iron, respectively. The maximum lateral detection distance was 5, 7, and 8 mm for samples containing 126, 252, and 504 µg iron, respectively. A sample containing 504 µg iron was detectable at all angulations assessed (0°, 30°, 60° and 90°). CONCLUSION: The laparoscopic differential magnetometer demonstrates promising results for further investigation and development towards laparoscopic lymph node harvesting using magnetic nanoparticles. SIGNIFICANCE: The laparoscopic differential magnetometer facilitates a novel method for sentinel lymph node harvesting, which helps to determine prognosis and treatment of cancer patients.

Modelling optically pumped magnetometer interference in MEG as a spatially homogeneous magnetic field.

Here we propose that much of the magnetic interference observed when using optically pumped magnetometers for MEG experiments can be modeled as a spatially homogeneous magnetic field. We show that this approximation reduces sensor level variance and substantially improves statistical power. This model does not require knowledge of the underlying neuroanatomy nor the sensor positions. It only needs information about the sensor orientation. Due to the model's low rank there is little risk of removing substantial neural signal. However, we provide a framework to assess this risk for any sensor number, design or subject neuroanatomy. We find that the risk of unintentionally removing neural signal is reduced when multi-axis recordings are performed. We validated the method using a binaural auditory evoked response paradigm and demonstrated that removing the homogeneous magnetic field increases sensor level SNR by a factor of 3. Considering the model's simplicity and efficacy, we suggest that this homogeneous field correction can be a powerful preprocessing step for arrays of optically pumped magnetometers.

Precision magnetic field modelling and control for wearable magnetoencephalography.

Optically-pumped magnetometers (OPMs) are highly sensitive, compact magnetic field sensors, which offer a viable alternative to cryogenic sensors (superconducting quantum interference devices - SQUIDs) for magnetoencephalography (MEG). With the promise of a wearable system that offers lifespan compliance, enables movement during scanning, and provides higher quality data, OPMs could drive a step change in MEG instrumentation. However, this potential can only be realised if background magnetic fields are appropriately controlled, via a combination of optimised passive magnetic screening (i.e. enclosing the system in layers of high-permeability materials), and electromagnetic coils to further null the remnant magnetic field. In this work, we show that even in an OPM-optimised passive shield with extremely low (<2 nT) remnant magnetic field, head movement generates significant artefacts in MEG data that manifest as low-frequency interference. To counter this effect we introduce a magnetic field mapping technique, in which the participant moves their head to sample the background magnetic field using a wearable sensor array; resulting data are compared to a model to derive coefficients representing three uniform magnetic field components and five magnetic field gradient components inside the passive shield. We show that this technique accurately reconstructs the magnitude of known magnetic fields. Moreover, by feeding the obtained coefficients into a bi-planar electromagnetic coil system, we were able to reduce the uniform magnetic field experienced by the array from a magnitude of 1.3±0.3 nT to 0.29±0.07 nT. Most importantly, we show that this field compensation generates a five-fold reduction in motion artefact at 0‒2 Hz, in a visual steady-state evoked response experiment using 6 Hz stimulation. We suggest that this technique could be used in future OPM-MEG experiments to improve the quality of data, especially in paradigms seeking to measure low-frequency oscillations, or in experiments where head movement is encouraged.

Optically pumped magnetometers reveal fasciculations non-invasively.

OBJECTIVE: This proof-of-principle-study evaluated the extent to which spontaneous activity (SA) of the muscle can be detected via non-invasive magnetomyography (MMG) with optically pumped magnetometers (OPM). METHODS: Five patients, who together exhibited all forms of SA (fibrillations, positive sharp waves, fasciculations, myotonic discharges, complex-repetitive discharges) with conventional needle electromyography (EMG), were studied by OPM-MMG and simultaneous surface EMG (sEMG) while at rest, during light muscle activation, and when a muscle stretch reflex was elicited. Three healthy subjects were measured as controls. SA was considered apparent in the OPM-MMG if a signal could be visually detected that corresponded in shape and frequency to the SA in the respective needle EMG. RESULTS: SA in the context of fasciculations could be detected in 2 of 5 patients by simultaneous OPM-MMG/sEMG. Other forms of SA could not be detected at rest, during light muscle activation, or after provocation of a muscle stretch reflex. CONCLUSIONS: Results show that fasciculations could be detected non-invasively via a new method (OPM). SIGNIFICANCE: We show that other forms of SA are not detectable with current OPM and propose necessary technical solutions to overcome this circumstance. Our results motivate to pursue OPM-MMG as a new clinical neurophysiological diagnostic.

A semi-analytical solution and AI-based reconstruction algorithms for magnetic particle tracking.

Magnetic particle tracking is a recently developed technology that can measure the translation and rotation of a particle in an opaque environment like a turbidity flow and fluidized-bed flow. The trajectory reconstruction usually relies on numerical optimization or filtering, which involve artificial parameters or thresholds. Existing analytical reconstruction algorithms have certain limitations and usually depend on the gradient of the magnetic field, which is not easy to measure accurately in many applications. This paper discusses a new semi-analytical solution and the related reconstruction algorithm. The new method can be used for an arbitrary sensor arrangement. To reduce the measurement uncertainty in practical applications, deep neural network (DNN)-based models are developed to denoise the reconstructed trajectory. Compared to traditional approaches such as wavelet-based filtering, the DNN-based denoisers are more accurate in the position reconstruction. However, they often over-smooth the velocity signal, and a hybrid method that combines the wavelet and DNN model provides a more accurate velocity reconstruction. All the DNN-based and wavelet methods perform well in the orientation reconstruction.

Optimal design of on-scalp electromagnetic sensor arrays for brain source localisation.

Optically pumped magnetometers (OPMs) are quickly widening the scopes of noninvasive neurophysiological imaging. The possibility of placing these magnetic field sensors on the scalp allows not only to acquire signals from people in movement, but also to reduce the distance between the sensors and the brain, with a consequent gain in the signal-to-noise ratio. These advantages make the technique particularly attractive to characterise sources of brain activity in demanding populations, such as children and patients with epilepsy. However, the technology is currently in an early stage, presenting new design challenges around the optimal sensor arrangement and their complementarity with other techniques as electroencephalography (EEG). In this article, we present an optimal array design strategy focussed on minimising the brain source localisation error. The methodology is based on the Cramér-Rao bound, which provides lower error bounds on the estimation of source parameters regardless of the algorithm used. We utilise this framework to compare whole head OPM arrays with commercially available electro/magnetoencephalography (E/MEG) systems for localising brain signal generators. In addition, we study the complementarity between EEG and OPM-based MEG, and design optimal whole head systems based on OPMs only and a combination of OPMs and EEG electrodes for characterising deep and superficial sources alike. Finally, we show the usefulness of the approach to find the nearly optimal sensor positions minimising the estimation error bound in a given cortical region when a limited number of OPMs are available. This is of special interest for maximising the performance of small scale systems to ad hoc neurophysiological experiments, a common situation arising in most OPM labs.

Evolution of MEG: A first MEG-feasible fluxgate magnetometer.

In the current article, we present the first solid-state sensor feasible for magnetoencephalography (MEG) that works at room temperature. The sensor is a fluxgate magnetometer based on yttrium-iron garnet films (YIGM). In this feasibility study, we prove the concept of usage of the YIGM in terms of MEG by registering a simple brain induced field-the human alpha rhythm. All the experiments and results are validated with usage of another kind of high-sensitive magnetometers-optically pumped magnetometer, which currently appears to be well-established in terms of MEG.

New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives with MI-Crobicidal and Antibiofilm Activity Enhanced by Combination with Iron Oxide Nanoparticles.

Antimicrobial resistance is one of the major public health threats at the global level, urging the search for new antimicrobial molecules. The fluorene nucleus is a component of different bioactive compounds, exhibiting diverse pharmacological actions. The present work describes the synthesis, chemical structure elucidation, and bioactivity of new O-aryl-carbamoyl-oxymino-fluorene derivatives and the contribution of iron oxide nanoparticles to enhance the desired biological activity. The antimicrobial activity assessed against three bacterial and fungal strains, in suspension and biofilm growth state, using a quantitative assay, revealed that the nature of substituents on the aryl moiety are determinant for both the spectrum and intensity of the inhibitory effect. The electron-withdrawing inductive effect of chlorine atoms enhanced the activity against planktonic and adhered Staphylococcus aureus, while the +I effect of the methyl group enhanced the anti-fungal activity against Candida albicans strain. The magnetite nanoparticles have substantially improved the antimicrobial activity of the new compounds against planktonic microorganisms. The obtained compounds, as well as the magnetic core@shell nanostructures loaded with these compounds have a promising potential for the development of novel antimicrobial strategies.