Advanced transmission electron microscopy on nanostructured magnetic materials

This doctoral work is focused on the study of nanostructured magnetic materials by advanced transmission electron microscopy (TEM) techniques, with emphasis on Ni2MnGa shape memory alloy thin films and magnetite nanoparticles for biomedical applications. The combination of high-resolution transmission electron microscopy and electron diffraction to characterize morphology and crystalline structure, with Lorentz microscopy and Electron Holography, permits to achieve a deep insight in the structural and magnetic nano-characterization of magnetic nanostructured materials. The work, carried out at the CNR-IMEM institute of Parma and partially at the LMA-INA institute of Zaragoza in the framework of the Erasmus Placement, produced remarkable results concerning the correlation between the microstructure of these systems and their magnetic/functional properties, from nano-to micro-to macro scale. In detail, the main topics treated are: 1) The use of Lorentz microscopy to investigate the role of dipolar interaction on hyperthermia of magnetic nanoparticles. Magnetic nanoparticles (NPs) in the superparamagnetic state are suitable for both diagnostic and therapeutic approaches. In particular, the magnetic hyperthermia, performed applying radiofrequency magnetic fields, can be effectively employed to locally induce cancer cell death. In real systems, clusters of magnetic nanoparticles with different size can form and the dipolar interactions that arise among nanoparticles can strongly influence the heating ability of the colloidal suspension. The role of the dipolar interactions in the hyperthermic behaviour of the system, however, is still not completely understood. About this topic, an investigation about magnetite nanoparticles with different degrees of interaction was carried out by Lorentz microscopy in a TEM. With this technique, it was possible to visualize and map the inter-particle interactions and to develop reliable models on the power losses mechanisms for different nanoparticles aggregates. As a result, a deeper understanding of the interactions effects on the performance of different nanoparticles suspensions as hyperthermic mediators was obtained. All the TEM results were supported and complemented by conventional o macroscopic (?) magnetic characterization. 2) Employment of advanced TEM techniques to study the effect of epitaxial strain and film thickness in the twin variants formation in Ni2MnGa martensitic thin films In martensitic thin films, the martensitic phase transition gives rise to a poly-twinned system characterized by a complex microstructure in which two families of twin variants can be displayed, with different magnetic anisotropies. Both the use of different substrates and film thickness can significantly modify the twin variants formation and consequently alter their functional properties. High-resolution TEM (HRTEM), Selected Area Electron Diffraction (SAED) and Electron Holography was employed to fully characterize Ni2MnGa thin films in plan and cross section geometries, by variyng film thicknesses in the range 50-100 nm and substrate type (MgO, MgO/Cr buffer layer). The structural and magnetic properties at the nano-micro scale were obtained by comparing TEM analysis with the morphological, structural and magnetic properties on a larger scale (by atomic force microscopy(AFM) , X-ray diffraction (XRD) and magnetic force microscopy (MFM)). A model for the twin variants selective formation, based on the stress states induced by the different substrates and film thicknesses, is moreover proposed. The model represents a powerful tool to selectively control the twin variants formation in martensitic films with low thicknesses and to tailor their magnetic domains structure. 3) An in depth TEM characterization to study the role of microstructure on magnetically induced reorientation of twin variants in Ni2MnGa 200 nm thin films In Ni2MnGa alloys, giant strains, one order of magnitude higher than the typical magnetostriction and state-of-the-art piezoelectric values, can be obtained by a magnetomechanical effect based on twin variants reorientation induced by magnetic field (MIR). Therefore, the possibility of exploiting the martensitic distortions to create tiny machines while keeping simple design, and high actuation frequencies makes these materials particularly appealing for the integration in active microsystems. However, very limited MIR effects were found in thin films and a full comprehension and exploitation of the effect is still lacking. An in-depth TEM characterization to correlate the crystal structure to the twin variants configurations and the magnetism inside each domain of the Ni2MnGa alloys is proposed by the combination of different advanced TEM techniques such as High Angle Annular Dark Field (HAADF) imaging, HRTEM with the comparison of the experimental images to the simulated ones, SAED, Electron Holography and magnetic domain analysis by in-situ observation. A model based on TEM results, compared with the findings obtained by XRD, AFM, MFM and magnetization curves, has been finally suggested to explain the anisotropic microstructure formation in a 200 nm thick Ni2MnGa film grown on MgO/Cr, displaying a huge anisotropic MIR. The proposed model is crucial for the engineering of the martensitic microstructure and for achieving substantial values of MIR in constrained films. 4) TEM study of the reduction of dimensionality in martensitic Ni2MnGa systems: from thin films to sub-micrometric disks After gaining a good understanding of the microstructure of two-dimensional NiMnGa martensitic films with relation to their application properties, the last chapter is devoted to test the possibility to obtain new functional properties by scaling down the dimensionality of these systems. To this aim, the in-depth TEM characterization was extended to a novel class of nanostructures, Ni2MnGa nano-disks, to investigate the structural and magnetic properties of the disks and the effect of the lateral confinement on the martensitic phase. By employing HRTEM, Lorentz microscopy and electron diffraction analysis as a function of temperature with heating holder, the actuation mechanisms, which remain active with the dimensionality reduction, can be studied.La presente tesi di dottorato è focalizzata sullo studio di materiali magnetici nanostrutturati tramite tecniche avanzate di microscopia elettronica in trasmissione (TEM), con particolare attenzione su film sottili a base della lega metallica Ni2MnGa, materiale magnetico a memoria di forma, e nanoparticelle di magnetite per applicazioni biomediche. La combinazione delle tecniche di microscopia elettronica in alta risoluzione e di diffrazione elettronica con le tecniche di microscopia di Lorentz e olografia elettronica, permette di ottenere un’approfondita conoscenza delle proprietà magnetico-strutturali di materiali magnetici nanostrutturati. Il presente lavoro, svolto principalmente all’istituto IMEM-CNR di Parma and parzialmente presso il laboratorio LMA-INA di Saragozza, ha prodotto importanti nuovi risultati riguardanti la correlazione tra la microstruttura e le proprietà magnetiche/funzionali di questi sistemi, dalla nanoscala alla micro/macro scala. In dettaglio, i punti più importanti in cui il lavoro è stato articolato sono: 1) Utilizzo della microscopia di Lorentz per l’investigazione riguardante il ruolo delle interazioni dipolari nell’ipertermia magnetica di nanoparticelle di magnetite. Nanoparticelle magnetiche (NPs) nello stato superparamagnetico sono molto promettenti sia nel campo diagnostico, che terapeutico. In particolare, l’ipertermia magnetica, realizzata tramite l’applicazione di un campo magnetico alle radiofrequenze, può essere efficace nell’induzione locale della morte di cellule tumorali. In sistemi di nanoparticelle reali, cluster di nanoparticelle magnetiche con differenti dimensioni possono crearsi grazie alle interazioni dipolari, che possono anche fortemente influenzare la capacità di generazione di calore da parte della sospensione colloidale. Il ruolo delle interazioni dipolari nel comportamento ipertermico del sistema, comunque, non è ancora stato del tutto chiarito. Riguardo questo argomento, uno studio su nanoparticelle di magnetite con differenti gradi di interazioni è stato condotto tramite microscopia elettronica in trasmissione usando la tecnica di microscopia di Lorentz. Con questa tecnica, è possibile visualizzare e mappare le interazioni dipolari tra le particelle e sviluppare modelli attendibili riguardo i meccanismi di perdita di energia per differenti aggregati di nanoparticelle. Come risultato di questo studio, è stata ottenuta una più approfondita comprensione degli effetti indotti dalle interazioni dipolari sulla performance di diversi aggregati di nanoparticelle magnetiche come mediatori ipertermici. Le caratterizzazioni e i risultati conseguiti tramite microscopia TEM sono fortemente supportati dalle caratterizzazioni magnetiche convenzionali. 2) Utilizzo di tecniche avanzate di microscopia elettronica in trasmissione per lo studio degli effetti dovuti a strain epitassiale e spessore del film nella formazione delle varianti di twin in film sottili martensitici di Ni2MnGa. In film sottili martensitici, la transizione di fase martensitica produce una complessa microstruttura rappresentata da un sistema poli-twinnato, in cui due famiglie di varianti di twin con differenti anisotropie magnetiche possono essere comunemente osservate. Sia l’impiego di differenti substrati e/o di buffer-layers come la variazione dello spessore del film, possono pesantemente modificare la formazione delle varianti di twin e conseguentemente alterare le proprietà funzionali dei film stessi. Le tecniche di microscopia elettronica in alta risoluzione (HRTEM), di diffrazione elettronica da area selezionata (SAED) e olografia elettronica sono state impiegate per ottenere una completa caratterizzazione dei film sottili di Ni2MnGa in visione planare ed in sezione trasversale, per film con uno spessore variabile nel range 50-100 nm e con differenti substrati (MgO, MgO/buffer layer di Cr). Le proprietà strutturali e magnetiche alla scala nano-micrometrica sono state ottenute comparano l’analisi TEM con la morfologia e le proprietà strutturali e magnetiche su una scala più ampia (ottenute tramite l’utilizzo di tecniche di: microscopie a scansione di sonda (AFM/MFM), diffrazione di raggi X (XRD). Un modello per la formazione selezione selettiva di varianti di twins, basato sullo stato di stress indotto dai differenti substrati e in funzione dei diversi spessori dei films, è stato inoltre proposto. Questo modello rappresenta un potente strumento per controllare la formazione selettiva delle varianti di twin in film martensitici caratterizzati da bassi spessori e, conseguentemente, permette di controllare la loro struttura a domini magnetici. 3) Caratterizzazione, tramite microscopia elettronica in trasmissione, del ruolo della microstruttura sulla ri-orientazione magnetica delle varianti di twin in film sottili di Ni2MnGa spessi 200 nm. Nelle leghe Ni2MnGa, enormi strain con valori un ordine di grandezza più grandi rispetto a quelli osservati tipicamente nei materiali piezoelettrici, possono essere ottenuti grazie ad un effetto magnetomeccanico basato sulla ri-orientazione delle varianti di twin indotta da un campo magnetico applicato (effetto MIR). Le possibilità di sfruttare la distorsione indotta nella fase martensitica per creare piccoli sistemi di attuazione tenendo un design semplice e di compiere cicli di attuazione ad alte frequenze rendono quindi questi materiali particolarmente attraenti per l’integrazione in microsistemi di attuazione. Tuttavia, effetti MIR molto limitati sono stati osservati in film sottili e una completa comprensione e controllo dell’effetto è tuttora mancante. Una caratterizzazione approfondita per correlare la struttura cristallina alle configurazioni di varianti di twins ed il magnetismo di ogni dominio della lega Ni2MnGa è proposto, tramite l’impiego combinato di differenti tecniche avanzate di microscopia elettronica in trasmissione come imaging con detector anulare ad alto angolo (HAADF), HRTEM con il confronto delle immagini sperimentali a quelle simulate, SAED, olografia elettronica, analisi dei domini magnetici tramite osservazione in-situ. Un modello basato sui risultati ottenuti dalla caratterizzazione TEM, confrontati con i risultati sperimentali ottenuti tramite XRD, AFM, MFM e caratterizzazioni magnetiche, è stato inoltre proposto per spiegare l’orientazione preferenziale della microstruttura in film di Ni2MnGa di 200 nm, cresciuti su MgO/Cr e mostranti un enorme effetto MIR anisotropico. I risultati conseguiti sono di cruciale importanza per l’ingegnerizzazione della microstruttura martensitica e per l’ottenimento di un rilevante effetto MIR in film sottili vincolati al substrato. 4) Studio tramite microscopia elettronica in trasmissione degli effetti della riduzione di dimensionalità in sistemi martensitici Ni2MnGa: dal film sottile al disco sub-micrometrico. Un’approfondita analisi TEM è stata condotta su una nuova classe di materiali nanostrutturati, i nanodischi di Ni2MnGa, per la caratterizzazione delle proprietà strutturali e magnetiche dei dischi e l’effetto del confinamento laterale della fase martensitica. Combinando le tecniche di HRTEM, microscopia di Lorentz e diffrazione elettronica in funzione della temperatura, è possibile scoprire quali sono i meccanismi di attuazione che sopravvivono alla riduzione della dimensionalità

Bottle-brush-shaped heterostructures of NiO-ZnO nanowires: growth study and sensing properties

We present here heterostructured ZnO-NiO nanowires, constituted by a core of single crystalline ZnO nanowires, covered by poly-crystalline NiO nanorods. The bottle-brush shape was investigated by SEM and TEM, confirming that a columnar growth of NiO occurred over the ZnO core, with a preferred orientation of NiO over ZnO nanowires. The heterostructured devices are proposed for gas sensing application. Bare ZnO nanowires and heterostructured sensors with two different thicknesses of NiO poly-crystalline nanorods were analysed for acetone, ethanol, NO2 and H2 detection. All sensors maintained n-type sensing mechanism, with improved sensing performance for lower thickness of NiO, due to high catalytic activity of NiO. The sensing dynamic is also strongly modified by the presence of heterojunction of NiO/ZnO, with a reduction of response and recovery times towards ethanol and acetone at 400°C.

Exploiting magnetic properties of Fe doping in zirconia

In this study we explore, both from theoretical and experimental side, the effect of Fe doping in ZrO2 (ZrO2:Fe). By means of first principles simulation we study the magnetization density and the magnetic interaction between Fe atoms. We also consider how this is affected by the presence of oxygen vacancies and compare our findings with models based on impurity band and carrier mediated magnetic interaction. Experimentally thin films (~ 20 nm) of ZrO2:Fe at high doping concentration are grown by atomic layer deposition. We provide experimental evidence that Fe is uniformly distributed in the ZrO2 by transmission electron microscopy and energy dispersive X-ray mapping, while X-ray diffraction evidences the presence of the fluorite crystal structure. Alternating gradient force magnetometer measurements show magnetic signal at room temperature, however with low magnetic moment per atom. Results from experimental measures and theoretical simulations are compared.Comment: 8 pages, 9 figures. JEMS 201

Fast dynamic control for a boost DC/DC converter in hybrid-electric powertrain with PEM fuel cell and battery pack

When working with hybrid-electric powertrain with a proton exchange membrane fuel cell (PEMFC) along with a battery pack, to increase the life of the PEMFC and avoid a drop of performance it needs to be periodically short circuited. The periodic short circuit of the PEMFC requires the DC/DC converter to be decoupled from the PEMFC. This behaviour leads the converter to undergo several start-up transients, and for an optimal energy management, the converter must reach its reference steady-state condition as quickly as possible. In this frame, this paper presents an innovative dynamic control for current mode operations of a boost DC/DC converter for managing the power exchange between the fuel cell and the battery pack, which could be easily implemented in industrial applications. With the proposed control system, the converter achieves faster step response when turned on, reducing the time required by the controlled current to reach its set point. To support theoretical considerations and simulations results, an experimental validation has been performed with a real system prototype

Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand-based drug design.

Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development. This novel chemical tool, endowed with favourable pharmacological characteristics, was successfully developed, and a preliminary Structure-Activity Relationship investigation was carried out

Discovery of Substituted (2-Aminooxazol-4-yl)Isoxazole-3-carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants

Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of Salmonella thyphimurium serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound 5, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound 5 Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts

Discovery of Substituted (2-Aminooxazol-4-yl)Isoxazole-3-carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants

Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of Salmonella thyphimurium serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound 5, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound 5 Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts

Prevalence and associated factors of COVID-19 across Italian regions: a secondary analysis from a national survey on physiotherapists

Coronavirus disease 2019 (COVID-19) broke out in China in December 2019 and now is a pandemic all around the world. In Italy, Northern regions were hit the hardest during the first wave. We aim to explore the prevalence and the exposure characteristics of physiotherapists (PTs) working in different Italian regions during the first wave of COVID-19

SIAMOC position paper on gait analysis in clinical practice: General requirements, methods and appropriateness. Results of an Italian consensus conference

Gait analysis is recognized as a useful assessment tool in the field of human movement research. However, doubts remain on its real effectiveness as a clinical tool, i.e. on its capability to change the diagnostic-therapeutic practice. In particular, the conditions in which evidence of a favorable cost-benefit ratio is found and the methodology for properly conducting and interpreting the exam are not identified clearly. To provide guidelines for the use of Gait Analysis in the context of rehabilitation medicine, SIAMOC (the Italian Society of Clinical Movement Analysis) promoted a National Consensus Conference which was held in Bologna on September 14th, 2013. The resulting recommendations were the result of a three-stage process entailing i) the preparation of working documents on specific open issues, ii) the holding of the consensus meeting, and iii) the drafting of consensus statements by an external Jury. The statements were formulated based on scientific evidence or experts' opinion, when the quality/quantity of the relevant literature was deemed insufficient. The aim of this work is to disseminate the consensus statements. These are divided into 13 questions grouped in three areas of interest: 1) General requirements and management, 2) Methodological and instrumental issues, and 3) Scientific evidence and clinical appropriateness. SIAMOC hopes that this document will contribute to improve clinical practice and help promoting further research in the field