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Achieving homogeneous tumour heating is one of the most long-standing challenges in magnetic hyperthermia for cancer therapy. Clinical studies must meet strict safety regulations that require knowledge and control over the physical properties of the chosen magnetic nanoparticles [1]. Whereas it is well-established that the heat released by magnetic nanostructures is influenced by interparticle interactions, as of today there is no method to analyze heat exchange at single-particle level in interacting systems at nonzero temperature. This gap needs to be bridged so to harness nanoparticle magnetization dynamics for the sake of biomedical applications.&lt;br/&gt;&lt;br/&gt;Building on previous theoretical work [2], we present an equation to estimate the heat dissipation of individual, interacting particles at nonzero temperature that perform both field-induced and thermal switching. After validating this equation, we use the macrospin simulation tool Vinamax [3], to investigate a system of interacting particles with different anisotropies, as we showed in this contribution [4]. Our preliminary results indicate (see figure) that the generated heat becomes more homogeneously distributed at larger fields. We believe that this homogenization of the particle heating will help to achieve a more homogenized heating of tumors during hyperthermia treatments.&lt;br/&gt;&lt;br/&gt;The use of the proposed equation would simplify the selection process of optimum nanoparticle distributions leading to optimal tumour heating. Its simplicity and flexibility also allow it to be integrated into multi-scale, multi-physics simulations to accurately assess the magnetic hyperthermia therapy without impacting the overall computational time.

![](https://assets.underline.io/uploads/markdown_image/1/image/cd66b63a757f78697365ef1ca41b5bd1.jpg)

Figure: Heat generated in a system consisting of two interacting nanoparticles with different anisotropies. Both particles show switching behavior as soon as the excitation field amplitude overcomes their anisotropy barrier. The heat generation tends to become more uniform with increasing excitation fields.

2022 Joint MMM-INTERMAG

Homogenization of Heating in Magnetic Hyperthermia Through Exploitation of Magnetisation Dynamics of Interacting Particles

ENDO 2021

ENDO is the leading meeting for endocrinology research and clinical care worldwide. 

Achieving homogeneous tumour heating is one of the most long-standing challenges in magnetic hyperthermia for cancer therapy. Clinical studies must meet strict safety regulations that require knowledge and control over the physical properties of the chosen magnetic nanoparticles [1]. Whereas it is well-established that the heat released by magnetic nanostructures is influenced by interparticle interactions, as of today there is no method to analyze heat exchange at single-particle level in interacting systems at nonzero temperature. This gap needs to be bridged so to harness nanoparticle magnetization dynamics for the sake of biomedical applications. Building on previous theoretical work [2], we present an equation to estimate the heat dissipation of individual, interacting particles at nonzero temperature that perform both field-induced and thermal switching. After validating this equation, we use the macrospin simulation tool Vinamax [3], to investigate a system of interacting particles with different anisotropies, as we showed in this contribution [4]. Our preliminary results indicate (see figure) that the generated heat becomes more homogeneously distributed at larger fields. We believe that this homogenization of the particle heating will help to achieve a more homogenized heating of tumors during hyperthermia treatments. The use of the proposed equation would simplify the selection process of optimum nanoparticle distributions leading to optimal tumour heating. Its simplicity and flexibility also allow it to be integrated into multi-scale, multi-physics simulations to accurately assess the magnetic hyperthermia therapy without impacting the overall computational time.

![](https://assets.underline.io/uploads/markdown_image/1/image/cd66b63a757f78697365ef1ca41b5bd1.jpg)

Figure: Heat generated in a system consisting of two interacting nanoparticles with different anisotropies. Both particles show switching behavior as soon as the excitation field amplitude overcomes their anisotropy barrier. The heat generation tends to become more uniform with increasing excitation fields.

technical paper

The 15th Joint MMM-INTERMAG Conference (2022 Joint) is sponsored jointly by AIP Publishing and the IEEE Magnetics Society. Members of the international scientific and engineering communities interested in recent developments in fundamental and applied magnetism are invited to attend and contribute to the technical sessions. The technical program will include invited and contributed papers in oral and poster sessions, invited symposia, a plenary session, and an evening session, with about 1500 presentations overall. This Conference provides an outstanding opportunity for worldwide participants to meet their colleagues and collaborators and discuss developments in all areas of magnetism research.

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This Conference provides an outstanding opportunity for worldwide participants to meet their colleagues and collaborators and discuss developments in all areas of magnetism research.

Fourier transform holography (FTH) is a lensless imaging technique that uses a known reference in the sample to retrieve the object of interest in one single step of calculation (i.e. it does not require an iterative method), overcoming the phase problem inherent to other techniques such as coherent diffraction imaging and ptychography. In the case of an extended reference, a linear differential filter is applied and the object can simply be obtained by calculating the inverse Fourier transform. This approach is known under the name of HERALDO [1]. By exploiting the x-ray magnetic circular dichroism effect, this technique has shown to be useful to image magnetic textures by providing a projection (sometimes two) of the magnetization in 2D layers [2-5]. In this work, we go further and use FTH to image the magnetic structure of a 3D object. To be sensitive to all three components of the magnetization (perpendicular as well as in-plane), we use a sample setup with two perpendicular slits as complementary references (Fig. 1). By tilting the sample around the axes defined by the two slits, we obtain a dual set of projections which gives information about the internal configuration of the sample [6]. We discuss the different problems that can arise in the experiment, such as shadowing effects and a reduced angular range for the tilting of the sample, and how these can be conquered. We test the method in a 1μm thick Fe/Gd multilayer with maze-like magnetic pattern and image a circular window of diameter 5μm. Finally, we use this projection set as input to the tomography algorithm that we developed [7] to reconstruct the vector field structure of the whole object.

![](https://assets.underline.io/uploads/markdown_image/1/image/3d094f6eccc80616b54ad2113433005c.jpg)

Fig. 1: Fourier transform holography: The coherent x-ray beam illuminates the whole sample. A circular window is milled into the gold layer, which masks the magnetic sample, to allow passing through the x-rays. Two slit references are also milled across the mask and the sample. After filtering the diffraction pattern and applying the inverse Fourier transform, the magnetic projection is recovered (magnetic contrast is obtained by x-ray magnetic circular dichroism). Tilting the sample around two axes allows us to probe all three components of the magnetization.

Imaging the Magnetization Vector with Fourier Transform Holography

Magnetic nanoparticles are powerful tools in biomedical applications, where they are employed in both diagnosis and therapy. A prerequisite for the efficiency of these applications are precisely characterized particles. Several magnetic measurement techniques are established, which all have in common that they measure the magnetic response of the particles exposed to an externally applied magnetic field, which may change the magnetic state of the particles [1]. Therefore, Thermal Noise Magnetometry (TNM) has been developed, a magnetic nanoparticle characterization technique that does not rely on an external magnetic excitation [2]. It detects amplitude variations in the net magnetic moment of the sample caused by thermal fluctuations. TNM measurements have been proven to be feasible, and complementary to other characterization techniques due to their diminutive impact on the sample [2, 3]. Two mechanisms are responsible for the directional fluctuations of the magnetic moments. Brownian fluctuations occur if the particles are free to move in the sample, i.e. when they are suspended in a solution. The hydrodynamic size of the particles and the viscosity of the fluid influence the Brownian fluctuation rate. In parallel, the magnetization of each particle can also switch in the frame of the particles themselves, called Néel switching. The Néel switching rate is determined by the volume of the particles’ magnetic core and anisotropy constant. Additionally, the timescales of both mechanisms also depend on the temperature since the fluctuations are induced by the thermal energy in system. TNM experiments are typically performed at room temperature, but the particles are characterized for biomedical applications at body temperature. From preliminary results, a considerable effect of temperature variations in TNM is visible, influencing the particles’ fluctuation rate distributions and noise spectrum. As expected from the theory, the fluctuation rates shift towards higher values for higher temperatures, which leads to a decrease in the noise power in the considered frequency range.

![](https://assets.underline.io/uploads/markdown_image/1/image/cb671696c9bc121f01d6d3494d47ebc4.jpg)

Power spectrum densities for Perimag® particles at different temperatures.

The Effect of Temperature Variations in Thermal Noise Magnetometry

Since the discovery of monolayer graphene in 2004, immense exploration of 2D materials with the main goal of minimizing electronic devices towards atomic level is in progress. The 2D materials family includes a huge range of materials- from insulators, semiconductors, metals to superconductors. In 2017, two independent groups demonstrated stable magnetic ordering in 2D materials (CrI3 and Cr2Ge2Te6) 1,2 bringing ferromagnetic materials into the 2D family. Since then, 2D magnetism has been discovered in various vdW materials, for example CrX3 (X= Cl, Br, I) 3,4 among which CrBr3 is the most air stable in the CrX3 family. Magnetic and optical properties of bulk CrBr3 have been studied since the 1960s. Based on the various optical measurements, it is believed that CrBr3 has an energy gap in the range of 1.68 – 2.1 eV5,6. These controversial results have indicated that the electronic properties of CrBr3 are not well explored. In this poster, I will present the STM/S result of both thin and thick CrBr3 flakes with the density fluctuation theory (DFT) calculations to reveal a small energy gap to be 0.57 eV ± 0.04 eV7. This uncovering of the small energy gap will solve the controversy and is the key to better understand the electronic properties of CrBr3.

Scanning Tunneling Microscopy and Spectroscopy (STM/S) Reveals Small Energy Gap in CrBr3

Magnetic van der Waals (vdW) materials have emerged as promising candidates for spintronics applications, especially after the discovery of intrinsic ferromagnetism in monolayer vdW materials. Here, we report a real-space imaging study of itinerant ferromagnet Fe3GeTe2 and the enhancement of its Curie temperature well above ambient temperature [1]. We later found implanting Ga into Fe3GeTe2 could greatly enhance the Fe3GeTe2 Curie temperature by almost 100% [2]. Magnetic skyrmions are topological spin textures, which usually exist in noncentrosymmetric materials where the crystal inversion symmetry breaking generates the so-called Dzyaloshinskii-Moriya interaction. Using photoemission electron microscopy and Lorentz transmission electron microscopy, we investigated and stabilized Néel-type magnetic skyrmion in vdW ferromagnetic Fe3GeTe2 on top of (Co/Pd)n without the need of an external magnetic field.

Magnetic Domains in 2D van der Waals Material Fe3GeTe2

We report on the imaging domain wall structure of amorphous Fe/Gd multilayer thin films with dendritic stripe domains. Micromagnetic calculations suggest in both stripe and skyrmion phases the domain walls have a hybrid structure where the center of the domain wall is Bloch-like with random helicity transitioning to Néel-like walls at the surfaces with fixed helicity. To experimentally probe the domain structure we combine transmission electron microscopy in Lorentz mode (L-TEM) and scanning electron microscopy with polarization analysis (SEMPA). L-TEM images are processed to show the magnetic induction through the bulk of the sample, while SEMPA images show magnetization at the top surface of the sample. In this way, 3-dimensional reconstructions of the surface magnetization can be realized[1]. The SEMPA instrument, based on an Auger microscope, leverages spin-polarized secondary electrons scattered from the top few nanometers of a sample[2]. These secondaries are accelerated through the column and Mott scattered from a gold target in order to reveal the left-right and up-down polarization for both in-plane and out-of-plane electrons. We observe and characterize the the chirality of Néel-like domains closure caps at the surface of Fe/Gd following the convention established by Chen et al[3]. The z-components of magnetization for several domains are shown in Fig. 1. A comparison of the average magnetization vectors in the plane of the sample is shown in Fig. 2, where the difference in L-TEM and SEMPA observations indicate an out-of-plane, twisting component. We have thus confirmed Bloch wall formation in the bulk topped with Néel caps at the surface.

![](https://assets.underline.io/uploads/markdown_image/1/image/2f064e2fb92d0b646f15fbcf73cf3382.jpg)

Fig. 1: Hybrid domains in amorphous Fe/Gd with arrows showing reconstructed in-plane and colors showing in- (blue) and out-of-plane (red) magnetization.

![](https://assets.underline.io/uploads/markdown_image/1/image/6ef24c67176adf710147a1a02e566c08.jpg).

Fig. 2: Angle of in-plane magnetization relative to increasing out-of-plane magnetization (α) showing expected π/2 radians average from L-TEM, indicating Bloch walls, and larger deviations averaging 3π/4 radians from SEMPA, indicating Néel caps.

Characterization of Hybrid Domain Wall Structure and Surface Chirality for Amorphous Fe/Gd Thin Films

Magnetic nanowires can be engineered using composition and shape, and by modulating both of these along their axes (10nm-100um) or their diameters (10-200nm). This talk will discuss applications of both single nanowires and arrays of vertically aligned nanowires in biomedical fields, such as nano-barcodes [1], and biolabels for cells and exosomes [2,3], nano-heaters for hyperthermia therapy and organ preservation [4], and biocomposites [5]. For most of these applications, the reversal mechanism of magnetization can play a critical role. For example, magnetic coercivity and remanence has been used for contact-free readout of nano-barcode signatures, and the motion of domain walls can limit heating. Magnetic reversal typically occurs by uniform precession and coherent rotation or by domain walls that are transverse or vortices. Here, a novel approach to decoding specific reversal signatures will be described via a fast modification of the first order reversal curve (FORC) technique, called the projection method. In addition to decoding, the method elucidates the mechanisms of reversal which is of interest to the fundamental understanding of nanomagnets and can lead to improved future devices, such as decoding using ferromagnetic resonance (FMR) [6]. By understanding the nanomagnetics, these nanowires have been used individually to isolate biospecies, such as cancer cells [2] and tumor-derived exosomes (TEXs) [3] for fundamental studies in medicine. As nanoscale objects, nanowires have also been suspended in cryopreservation agents to provide the rapid, uniform nanowarming needed to restore preserved tissues and organs [4]. The mechanical properties are also found to change in response to magnetic fields which can impact their applications [7]. Finally, by aligning nanowires vertically in bio-friendly polymers, applications such as internal band-aids can be coded or functionalized for personalized health care. This talk will focus on the measurement methods for each of the biomedical applications mentioned, and will relate these measurements back to the fundamental magnetization engineering of the cylindrical nanowires.

![](https://assets.underline.io/uploads/markdown_image/1/image/a968033564d55218858a02f4df8459f7.jpg)

By controlling the reversal behavior of magnetic nanowires, efficient nanowarming can be achieved. One future application is the uniform and rapid warming of cryopreserved tissues and organs, which will ethically extend the viability between donors and recipients.



Bioapplications of magnetic nanowires: barcodes, heaters, biocomposites

Magnetic fluid hyperthermia is a promising cancer therapy in which magnetic nanoparticles (MNPs) act as heat sources activated by an external AC magnetic field. The MNPs, located near or inside the tumor, absorb energy from the magnetic field and then heat up the cancerous tissues [1]. However, during a hyperthermia treatment, it is crucial to control the temperature of different tissues: the desired therapeutic effect is not achieved with too low temperature. On the contrary, an excessive temperature increment can produce undesired damage [2]. Nevertheless, the current conventional thermometry in magnetic hyperthermia presents some important technical problems. For example, the widely used optical fiber thermometers only provide the temperature in a discrete. Moreover, surgery is required to locate these probes in the correct place. In this scope, we propose here a non-invasive method to measure the temperature of a MNP sample. The approach is based on the thermal dependence of the high order harmonic phases of the MNP dynamic magnetization. The method is non-invasive and it does not need any additional probe or sensor attached to the MNPs. In addition, this method has the potential to be used to map the spatial distribution of the temperature [3]. In the present work, a previously tested lab-made AC magnetometer [4] was used to study the variation with temperature of high order harmonics (3rd , 5th and 7th) from iron oxide MNPs. These MNP samples are identical to those used in a previous work [5]. External AC magnetic fields typical from magnetic hyperthermia were chosen (40-550 kHz). The actual temperature of the sample (30-50 °C) was measured by optical fiber thermometry. I was observed that the high order harmonic phases vary with temperature in an almost linear manner (see figure 1a). Therefore, we propose here the measurement of the harmonic phases as a non-invasive method to obtain the sample temperature. In this scope, the temperature would be obtained via previous calibration of the harmonic phase with temperature. In order to prove this concept an in-vitro experiment has carried out with water dispersed iron oxide MNPs. As it can be observed in figure 2, there is an error less than 0,5 °C.

![](https://assets.underline.io/uploads/markdown_image/1/image/e8e239b2390362d06b2ac387e5d3f1bd.jpg)

![](https://assets.underline.io/uploads/markdown_image/1/image/03c17ce20f966d21290570234dd22127.jpg)

Harmonic Phases of the Nanoparticle Magnetization: an Intrinsic Temperature Probe

Magnetic hyperthermia (MH) is a nanotechnology-driven therapy that seizes the heat release of magnetic nanoparticles when exposed to an alternating magnetic field. It has already been and is currently trialed in clinical settings as adjuvant of chemotherapy and radiotherapy to successfully treat several types of tumors [1, 2]. In silico testing (computer simulations) allows us to mimic several clinical situations and to evaluate the treatment safety in terms of dosimetry and temperature rise, including possible hot spots due to eddy currents, in a cheap and fast way. MH has taken advantages of this virtual testing in its way towards personalized therapy. The versatility of the simulations to evaluate many clinical setups allows us to study the actual risks of the current exclusion criteria [1, 3]. Nowadays, bearing any kind of metallic object, orthopedic implants for example, constitutes a contraindication for the treatment. This is based on the knowledge obtained from MRI related studies, but there is an important lack in the literature about the quantification of these risks in the context of clinical MH. In this work, we use computer simulations to study the actual risks of potential MH patients carrying different orthopedic prosthesis, as well as the influence of the presence of this metallic object in the effective magnetic field reaching the nanoparticles site. We have considered different treatment setups varying tumor locations, implant types and materials to evaluate the temperature increase and the dosimetric values in the major tissue groups. These safety parameters have been included in a multi-criteria decision analysis to asses a risk index for each tissue group in every clinical situation analyzed [4]. Acknowledgements We acknowledge COST Action MyWave (CA 17115), NoCanTher project (grant agreement No 685795), Regional Government of Madrid under contract PEJD-2017-PRE/IND-3663, Spanish Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, Ramón y Cajal RYC2018-025253-I, the “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2016-0686) and the support of NVIDIA Corporation through the GPU Grant Program with the donation of the Quadro P6000 GPU used in this work.

![](https://assets.underline.io/uploads/markdown_image/1/image/5b88302d4b166afa56c0e9833b44c1ec.jpg)

In Silico Safety Analysis of Magnetic Hyperthermia Treatments of Implant-Bearing Patients

Magnetic metal nanoparticles dispersed in non-magnetic (carbon) matrix are
of great importance both from a scientific point of view and in connection
with numerous applications in biomedicine, spintronics, catalysis, sensors,
etc. [1-3]. Especially promising are synthesis of novel functional nanoparticles with a core-shell architecture for improving their working magnetic
characteristics due to the possibility of combining materials with different
magnetic properties based on these magnetic nanoparticles [4-5]. The
magnetic interactions between the core and the shell provide an additional
degree of freedom for tuning the magnetic characteristics [6]. Nanoparticles
based on iron and iron oxide with a core-shell architecture are effective
intermediaries for heat transfer in an AC magnetic field [7-8]. In current
work, Fe-Fe3O4 core-shell nanoparticles were synthesized by solid-phase
pyrolysis of iron phthalocyanine (FePc), followed by annealing in an oxygen
atmosphere. Changing the pyrolysis conditions, it is possible to vary sizes of
nanoparticles from 5 to 100 nm and core-shell ratio. The quantitative composition of the core-shell was controlled also by changing the concentration of
oxygen. Complex structural analyses of these materials are obtained using
HRTEM, STEM, XRD and Raman spectroscopies. Magnetic properties of
synthesized materials have been studied with a Quantum Design MPMS XL
SQUID magnetometer. To study the structure of the obtained nanoparticles, HAADF-STEM images were taken, confirming the Fe-Fe3O4 core-shell
architecture of the nanoparticles. Figures 1, and 2 show a HAADF-STEM
image with elemental mapping of a single chosen nanoparticle and XRD
pathern of the (Fe-Fe3O4)@C sample obtained by synchrotron radiation
(λ = 0.98782 Å) correspondingly. This work was supported by European
Union’s Horizon 2020 research and innovation program under grant No
857502 (MaNaCa). The work at CSULA supported by NSF CREST Grant
#HRD-1547723. M. Farle acknowledges support by government of the RF
(No 075-15-2019-1886)



Synthesis and Characterization of Fe-Fe3O4 Core-Shell Nanoparticles Dispersed in Carbon Matrix

Magnetorelaxometry imaging (MRXI) [1] enables a quantitative and specific localization of magnetic nanoparticles (MNPs) inside living organisms [2] which is required by several novel therapeutic approaches such as magnetic hyperthermia therapy and magnetic drug targeting. MRXI involves aligning the MNPs’ magnetic moments using electromagnetic coils and subsequently recording their decaying net magnetization (relaxation). The recorded signals are connected to the MNP iron masses inside the discretized region of interest (ROI) via a system of linear equations [3]. The MNP distribution is recovered by solving the corresponding ill-posed inverse problem. However, the ROI discretization is limited to rather large voxel sizes. Finer voxel grids increase the number of unknowns and aggravate accurate reconstructions of MNP distributions. To date, finer voxel resolutions with reliable reconstruction accuracies are still necessary to obtain clinically relevant MRXI reconstructions. Standard MRXI provides only information about the MNP distributions and every voxel can contain MNPs with equal probability. Obviously, this is not realistic in clinical practice due to the different anatomical structures inside a human body. Accompanying traditional medical imaging techniques such as CT are necessary to gain anatomical information about the ROI. Here, we develop a multimodal reconstruction using CT data as prior for MRXI reconstructions, enabling a distinction between voxels with impossible, improbable and probable MNP occurrences. We test the approach on a cylindrical ROI (see Fig. 1) containing objects that produce different radiographic density (meat, wood, water, etc.) as well as MNPs. CT and MRXI measurements were conducted and the incorporation of the CT data allows us to reconstruct MNP distributions more accurately with half the voxel edge lengths than with mere MRXI (see Fig. 2). Our multimodal approach demonstrates that resolution and quantification accuracy of MRXI substantially benefits from anatomical data provided by alternative techniques such as CT or MRI.

Homogenization of Heating in Magnetic Hyperthermia Through Exploitation of Magnetisation Dynamics of Interacting Particles

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Homogenization of Heating in Magnetic Hyperthermia Through Exploitation of Magnetisation Dynamics of Interacting Particles

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Imaging the Magnetization Vector with Fourier Transform Holography

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