1,491 research outputs found

    Ruthenium metallotherapeutics: a targeted approach to combatting multidrug resistant pathogens

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    The discovery of antibiotics revolutionised healthcare practice. However due to overuse, inappropriate use, widespread prophylaxis therapy and the lack of new developments, the threat of antimicrobial resistance is now a major global threat to health. By 2050, it is estimated that mortality due to antimicrobial resistant infections will exceed 10 million people per annum, superseding cancer as the leading cause of global mortality. The use of drug repurposing to identify potential therapies which combat antimicrobial resistance is one potential solution. Metals have been used as antimicrobial agents throughout the history of medicine for a broad range of applications, including the use of Silver as an antimicrobial agent which dates back to antiquity. More recently, Ruthenium metallotherapeutic complexes have been shown to exhibit highly active antimicrobial properties by targeting a range of bacterial species, and in contrast to traditional antibiotics, these compounds are thought to elicit antibacterial activity at multiple sites within the bacterial cell, which may reduce the possibility of resistance evolution. This study aimed to evaluate the antimicrobial activity of a series of Ruthenium metallotherapeutic complexes against multidrug-resistant bacterial pathogens, with a focus on use within wound care applications. Antimicrobial susceptibility assays identified two lead candidates, Hexaammineruthenium (III) chloride and [Chlorido(η6-p-cymene)(N-(4-chlorophenyl)pyridine-2-carbothioamide) ruthenium (II)] chloride which demonstrated activity against Pseudomonas aeruginosa and Staphylococcus aureus respectively with MIC values ranging between 4 μg mL-1 and 16 μg mL-1. Furthermore, Hexaammineruthenium (III) chloride demonstrated antibiofilm activity in both a time and concentration-dependent manner. Synergy studies combining lead complexes with antibiotics demonstrated the potential for use as resistance breakers. Subsequent in vitro infection modelling using scratch assays with skin cell lines, coupled with a 3D full thickness skin wound infection model was used to determine potential applied applications of Hexaammineruthenium (III) chloride for use as topical antimicrobial agent against P. aeruginosa infections. Antimicrobial mechanistic studies demonstrated that Hexaammineruthenium (III) chloride targeted the bacterial cell ultrastructure of P. aeruginosa strain PAO1 as cell perturbations were observed when treated cells were analysed by scanning electron microscopy. Furthermore, exposure of P. aeruginosa PAO1 to Hexaammineruthenium (III) chloride also resulted in a concentration dependent membrane depolarisation, which further supported the antimicrobial mechanistic role. Finally, global changes in gene expression following exposure of P. aeruginosa strain PAO1 to Hexaammineruthenium (III) chloride were explored by RNA sequencing. Genes involved in ribosome function, cofactor biosynthesis and membrane fusion were downregulated, which provided a further insight into the wider mechanisms of antibacterial activity. The research conducted in the present study indicated the potential use of Hexaammineruthenium (III) chloride (and derivatives) as a potential treatment option for chronic wounds infected with P. aeruginosa, which could be applied as either a direct treatment or used within antimicrobial wound care applications

    Mechanical characterization, constitutive modeling and applications of ultra-soft magnetorheological elastomers

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    Mención Internacional en el título de doctorSmart materials are bringing sweeping changes in the way humans interact with engineering devices. A myriad of state-of-the-art applications are based on novel ways to actuate on structures that respond under different types of stimuli. Among them, materials that respond to magnetic fields allow to remotely modify their mechanical properties and macroscopic shape. Ultra-soft magnetorheological elastomers (MREs) are composed of a highly stretchable soft elastomeric matrix in the order of 1 kPa and magnetic particles embedded in it. This combination allows large deformations with small external actuations. The type of the magnetic particles plays a crucial role as it defines the reversibility or remanence of the material magnetization. According to the fillers used, MREs are referred to as soft-magnetic magnetorheological elastomers (sMREs) and hard-magnetic magnetorheological elastomers (hMREs). sMREs exhibit strong changes in their mechanical properties when an external magnetic field is applied, whereas hMREs allow sustained magnetic effects along time and complex shape-morphing capabilities. In this regard, end-of-pipe applications of MREs in the literature are based on two major characteristics: the modification of their mechanical properties and macrostructural shape changes. For instance, smart actuators, sensors and soft robots for bioengineering applications are remotely actuated to perform functional deformations and autonomous locomotion. In addition, hMREs have been used for industrial applications, such as damping systems and electrical machines. From the analysis of the current state of the art, we identified some impediments to advance in certain research fields that may be overcome with new solutions based on ultrasoft MREs. On the mechanobiology area, we found no available experimental methodologies to transmit complex and dynamic heterogeneous strain patterns to biological systems in a reversible manner. To remedy this shortcoming, this doctoral research proposes a new mechanobiology experimental setup based on responsive ultra-soft MRE biological substrates. Such an endeavor requires deeper insights into the magneto-viscoelastic and microstructural mechanisms of ultra-soft MREs. In addition, there is still a lack of guidance for the selection of the magnetic fillers to be used for MREs and the final properties provided to the structure. Eventually, the great advances on both sMREs and hMREs to date pose a timely question on whether the combination of both types of particles in a hybrid MRE may optimize the multifunctional response of these active structures. To overcome these roadblocks, this thesis provides an extensive and comprehensive experimental characterization of ultra-soft sMREs, hMREs and hybrid MREs. The experimental methodology uncovers magneto-mechanical rate dependences under numerous loading and manufacturing conditions. Then, a set of modeling frameworks allows to delve into such mechanisms and develop three ground-breaking applications. Therefore, the thesis has lead to three main contributions. First and motivated on mechanobiology research, a computational framework guides a sMRE substrate to transmit complex strain patterns in vitro to biological systems. Second, we demonstrate the ability of remanent magnetic fields in hMREs to arrest cracks propagations and improve fracture toughness. Finally, the combination of soft- and hard-magnetic particles is proved to enhance the magnetorheological and magnetostrictive effects, providing promising results for soft robotics.Los materiales inteligentes están generando cambios radicales en la forma que los humanos interactúan con dispositivos ingenieriles. Distintas aplicaciones punteras se basan en formas novedosas de actuar sobre materiales que responden a diferentes estímulos. Entre ellos, las estructuras que responden a campos magnéticos permiten la modificación de manera remota tanto de sus propiedades mecánicas como de su forma. Los elastómeros magnetorreológicos (MREs) ultra blandos están compuestos por una matriz elastomérica con gran ductilidad y una rigidez en torno a 1 kPa, reforzada con partículas magnéticas. Esta combinación permite inducir grandes deformaciones en el material mediante la aplicación de campos magnéticos pequeños. La naturaleza de las partículas magnéticas define la reversibilidad o remanencia de la magnetización del material compuesto. De esta manera, según el tipo de partículas que contengan, los MREs pueden presentar magnetización débil (sMRE) o magnetización fuerte (hMRE). Los sMREs experimentan grandes cambios en sus propiedades mecánicas al aplicar un campo magnético externo, mientras que los hMREs permiten efectos magneto-mecánicos sostenidos a lo largo del tiempo, así como programar cambios de forma complejos. En este sentido, las aplicaciones de los MREs se basan en dos características principales: la modificación de sus propiedades mecánicas y los cambios de forma macroestructurales. Por ejemplo, los campos magnéticos pueden emplearse para inducir deformaciones funcionales en actuadores y sensores inteligentes, o en robótica blanda para bioingeniería. Los hMREs también se han aplicado en el ámbito industrial en sistemas de amortiguación y máquinas eléctricas. A partir del análisis del estado del arte, se identifican algunas limitaciones que impiden el avance en ciertos campos de investigación y que podrían resolverse con nuevas soluciones basadas en MREs ultra blandos. En el área de la mecanobiología, no existen metodologías experimentales para transmitir patrones de deformación complejos y dinámicos a sistemas biológicos de manera reversible. En esta investigación doctoral se propone una configuración experimental novedosa basada en sustratos biológicos fabricados con MREs ultra blandos. Dicha solución requiere la identificación de los mecanismos magneto-viscoelásticos y microestructurales de estos materiales, según el tipo de partículas magnéticas, y las consiguientes propiedades macroscópicas del material. Además, investigaciones recientes en sMREs y hMREs plantean la pregunta sobre si la combinación de distintos tipos de partículas magnéticas en un MRE híbrido puede optimizar su respuesta multifuncional. Para superar estos obstáculos, la presente tesis proporciona una caracterización experimental completa de sMREs, hMREs y MREs híbridos ultra blandos. Estos resultados muestran las dependencias del comportamiento multifuncional del material con la velocidad de aplicación de cargas magneto-mecánicas. El desarrollo de un conjunto de modelos teórico-computacionales permite profundizar en dichos mecanismos y desarrollar aplicaciones innovadoras. De este modo, la tesis doctoral ha dado lugar a tres bloques de aportaciones principales. En primer lugar, este trabajo proporciona un marco computacional para guiar el diseño de sustratos basados en sMREs para transmitir patrones de deformación complejos in vitro a sistemas biológicos. En segundo lugar, se demuestra la capacidad de los campos magnéticos remanentes en los hMRE para detener la propagación de grietas y mejorar la tenacidad a la fractura. Finalmente, se establece que la combinación de partículas magnéticas de magnetización débil y fuerte mejora el efecto magnetorreológico y magnetoestrictivo, abriendo nuevas posibilidades para el diseño de robots blandos.I want to acknowledge the support from the Ministerio de Ciencia, Innovación y Universidades, Spain (FPU19/03874), and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 947723, project: 4D-BIOMAP).Programa de Doctorado en Ingeniería Mecánica y de Organización Industrial por la Universidad Carlos III de MadridPresidente: Ramón Eulalio Zaera Polo.- Secretario: Abdón Pena Francesch.- Vocal: Laura de Lorenzi

    Engineered polysaccharide, Alpha-1,3 Glucan, as a Functional Filler of Rubber Composites

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    Rubber products represent an essential and highly functional class of performance materials required in many daily applications. However, the increasing interest in enhancing the overall material sustainability of rubber products has accelerated the focus on compatible, lightweight, and environmentally sustainable fillers. As part of the effort to design sustainable rubber composites, enzymatic polymerization-derived polysaccharide fillers, alpha-1,3 glucan, with designed fibrids, platelet and spherical morphology and high crystallinity was employed as a novel sustainable filler system in natural rubber (NR) films. The alpha-1,3 glucan is supplied by International Fragrances and Flavors (IFF), former E.I. DuPont Industrial Biosciences. Initially, lightly crosslinked NR films reinforced with 0 – 10 phr MCG were fabricated using dipping and casting processes. The effect of MCG on the physicochemical properties, chemical stability, and thermo-mechanical properties of the composite films was investigated. In the subsequent project, colloidal alpha-1,3 glucan with spherical morphology was employed as a functional filler of NR coating films. Coating formulations containing NR latex and 10 – 100 phr colloidal alpha-1,3 glucan were prepared and applied to paper substrates at three different thicknesses. The effect of various coating formulations on the barrier properties against water vapor, oxygen, oil as well as on dry and wet mechanical properties were investigated. In order to study the impact of alpha,1-3 glucan’s morphology on the barrier properties of the paper coating, the following studies were conducted. This study employed enzymatically polymerized microcrystalline glucan (MCG) as a functional additive in natural rubber (NR)-based coating formulations. Typically, NR coating formulations containing 0–50 wt. % MCG were fabricated at a constant coating thickness with a constant solid content. The influence of MCG on the wet and dry strength, rheology, adhesion strength, and barrier properties such as moisture, oxygen, and grease barrier of the formulated coatings was investigated. Also, further study on the effect of solid content and low crosslinking on the barrier properties was conducted. The last stage of the study involved a solvent-free, batch mixer-based reactive process to carry out the reaction of ENR with glucan. In order to enhance the degree of dispersion and bonding of polar filler in a nonpolar natural rubber matrix, in situ melt grafting of epoxidized natural rubber (ENR) onto the polysaccharide was employed to achieve enhanced material properties. The process of temperature and shear-mediated melt grafting, in the presence of two catalysts (sodium hydroxide (NaOH) and dicumyl peroxide (DCP)), was investigated. Analytical characterization techniques, including Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and solvent swelling, were employed to confirm the formation of covalent bonds between alpha1,3-glucan and ENR. The selected ENR-glucan masterbatch samples were then subjected to melt-mixing with NR formulations to produce NR composites. Overall, this study aimed to develop a sustainable rubber composite with the incorporation of alpha-1,3 glucan as a functional filler targeting dipped rubber, packaging, and footwear applications and indicating the potential of this study in alleviating the environmental pollution induced by traditional polymers

    Selected problems of materials science. Vol. 2. Nano-dielectrics metals in electronics. Mеtamaterials. Multiferroics. Nano-magnetics

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    The textbook examines physical foundations and practical application of current electronics materials. Modern theories are presented, more important experimental data and specifications of basic materials necessary for practical application are given. Contemporary research in the field of microelectronics and nanophysics is taken into account, while special attention is paid to the influence of the internal structure on the physical properties of materials and the prospects for their use. English-language lectures and other classes on the subject of the book are held at Igor Sikorsky Kyiv Polytechnic Institute at the departments of “Applied Physics” and “Microelectronics” on the subject of materials science, which is necessary for students of higher educational institutions when performing scientific works. For master’s degree applicants in specialty 105 “Applied physics and nanomaterials”.Розглянуто фізичні основи та практичне застосування актуальних матеріалів електроніки. Подано сучасні теорії, наведено найважливіші експериментальні дані та специфікації основних матеріалів, які потрібні для практичного застосування. Враховано сучасні дослідження у галузі мікроелектроніки та нанофізики, при цьому особливу увагу приділено впливу внутрішньої структури на фізичні властивості матеріалів і на перспективи їх використання. Англомовні лекції та інші види занять за тематикою книги проводяться в КПІ ім. Ігоря Сікорського на кафедрах «Прикладна фізика» та «Мікро-електроніка» за напрямом матеріалознавство, що необхідно студентам вищих навчальних закладів при виконанні наукових робіт. Для здобувачів магістратури за спеціальністю 105 «Прикладна фізика та наноматеріали»

    Development of 3D printed enzymatic biofuel cells for powering implantable biomedical devices

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    The drive toward device miniaturisation in the field of enzyme-based bioelectronics established a need for multi-dimensional geometrically structured and highly effective microelectrodes, which are difficult to implement and manufacture in devices such as biofuel cells and sensors. Additive manufacturing coupled with electroless metal plating enables the production of three-dimensional (3D) conductive microarchitectures with high surface area for potential applications in such devices. However, interfacial delamination between the metal layer and the polymer structure is a major reliability concern, which results in device performance degradation and eventually device failure. This thesis demonstrates a method to produce a highly conductive and robust metal layer on a 3D printed polymer microstructure with strong adhesion by introducing an interfacial adhesion layer. Prior to 3D printing, multifunctional acrylate monomers with alkoxysilane (-Si-(OCH3)3) were synthesised via the Thiol-Michael addition reaction between pentaerythritol tetraacrylate (PETA) and 3-mercaptopropyltrimethoxysilane (MPTMS) with a 1:1 stoichiometric ratio. Alkoxysilane functionality remains intact during photopolymerisation in a projection micro-stereolithography (PµSLA) system and is utilised for the sol-gel reaction with MPTMS post-functionalisation of the 3D printed microstructure to build an interfacial adhesion layer. This functionalisation leads to the implementation of abundant thiol functional groups on the surface of the 3D printed microstructure, which can act as a strong binding site for gold during electroless plating to improve interfacial adhesion. The 3D conductive microelectrode prepared by this technique exhibited excellent conductivity of 2.2×107 S/m (53% of bulk gold) with strong adhesion between a gold layer and a polymer structure even after harsh sonication and adhesion tape test, which offers potential to build a robust 3D conductive microarchitecture for applications such as biosensors and biofuel cells. As a proof-of-concept, the microelectrode with gold-coated complex lattice geometry was employed as an enzymatic glucose anode, which showed a significant increase in the current output compared to the one in the simple cube form. As the first approach, glucose oxidase was used as an enzyme. To find the optimal protocol for the enzyme immobilisation, the enzyme was first immobilised on agarose to achieve the enzyme’s highest activity and stability. Then, this immobilisation protocol was applied to immobilise the enzyme on the gold electrode surface. Preliminary studies on the preparation of 3D gold diamond lattice microelectrode modified with cysteamine and glucose oxidase as a bioanode for single cell enzymatic biofuel cell (EFC) application were performed, which demonstrated high current density of 0.38 μA cm–2 at 0.35 V in glucose solutions. This method for fabrication of 3D conductive microelectrodes offers potential for several biological applications. Instead of using a thiol, the surface of the 3D-printed part can be functionalised with different other functional groups to create an appropriate surface for biomolecules and cell adhesion. Furthermore, the surface of thiol functionalised printed parts can be perfect for additional metal coatings, opening the door to the creation of highly efficient and customised implantable energy harvesters and biosensors

    Laser Micromachining: An Enabling Technology for Functional Surfaces and Materials

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    L'abstract è presente nell'allegato / the abstract is in the attachmen

    Applications of a fast multiple-overtone quartz crystal microbalance (QCM) in electrochemistry and beyond

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    Akustische Sensoren haben in der Grenzflächenanalytik und insbesondere in der Elektrochemie enorm an Bedeutung gewonnen. Der wichtigste Vertreter dieser Geräteklasse ist die Schwingquarzmikrowaage (quartz crystal microbalance, QCM). Wird eine elektrochemische Schwingquarzmikrowaage (EQCM) mit einem flüssigen Elektrolyten beladen und das Potential der Vorderelektrode variiert, ändern sich die Schwingungseigenschaften des Resonators. Die Verschiebung der Resonanzfrequenz, "Δf" , und der halben Bandbreite, "ΔΓ" , gehen sowohl auf elektrochemischen Ladungstransport an der Elektrode als auch auf die Umladung der Doppelschicht zurück. Die Einzelheiten dieser Zusammenhänge sind eine Schlüsselfrage in dieser Dissertation. Im Fall einer Elektroabscheidung ist f weitgehend proportional zur abgeschiedenen Masse, während unverändert bleibt. Eine darüberhinausgehende Modellbildung im Hinblick auf Rauigkeit-, Viskosität- und Viskoelastizität erfordert die Messung von "Δf" und "ΔΓ" auf mehreren Obertönen. Wenn intermediäre Spezies oder Submonolagen untersucht werden, liegen "Δf" und "ΔΓ" nur knapp über der Rauschgrenze. Zudem erfolgen die Änderungen in "Δf" und "ΔΓ" im Zeitraum von Millisekunden, sodass aktuelle QCMs, die auf Impedanzanalyse oder Ring-Down basieren, an ihr technisches Limit stoßen. Diese Geräte erreichen bestenfalls Zeitauflösungen im Bereich von 20 ms (Messung eines Obertons) und eine Frequenzgenauigkeit von 20 mHz (bei kleiner Datenrate). Um die Zeitauflösung zu verbessern, wird hier auf Multifrequenz Lockin Verstärkung (MLA) zurückgegriffen. Das Ausleseverfahren ist mit der Impedanzanalyse verwandt. Es wird jedoch der Frequenzsweep durch einen Kamm von bis zu 32 gleichmäßig verteilten Frequenzen ersetzt (comb drive). Dabei werden nur 6 Frequenzen benötigt, um einen einzelnen Oberton zu erfassen. Die verbleibenden Frequenzen können über weitere Obertöne verteilt werden. Die Resonanzkurven werden somit als Single-Shot erhalten. Die Zeitauflösung entspricht dem inversen Frequenzabstand im Kamm. Typische Werte sind 1 10 ms. Bei Bedarf kann die Zeitauflösung durch Ansteuern der QCM mit einer festen Frequenz (fixed-frequency drive) auf 100 µs verbessert werden. Darüber hinaus konnte die Frequenzauflösung durch Modulation des Elektrodenpotentials und Akkumulation von "Δf" und "ΔΓ" über viele Zyklen auf unter 10 mHz verbessert werden. Für die Gestalt der Potentialmodulation haben sich Stufen, lineare Rampen, und Treppen als geeignet erwiesen. Die Vorteile dieses neuen Instruments werden anhand der kapazitiven Doppelschicht-umladung, der Unterpotentialabscheidung von Kupfer in Gegenwart von Additiven sowie der reversiblen Oxidation/Reduktion der Redoxmediatoren Methylviologenchlorid (MVC) und Flavinadenindinukleotid (FAD) vorgestellt. Andere Experimente, in denen Modulation weder möglich noch notwendig ist, behandeln Trocknungsprozesse. Diese Experimente zeigen, dass auch ohne Modulation die schnelle QCM dynamische Prozesse, wie z. B. den tropfenbasierten Tintenstrahldruck oder das Elektrosprayen, zugänglich macht. Die Beispiele oben demonstrieren die entscheidende Rolle der kinetischen Information. Neben der verbesserten Empfindlichkeit ist insbesondere die Zeitauflösung wegweisend und wird in Zukunft neue Experimente ermöglichen.Acoustic sensors have achieved immense importance in interfacial analysis and especially in electrochemistry. The most important instrument in this class of devices is the quartz crystal microbalance (QCM). When an electrochemical quartz crystal microbalance (EQCM) is immersed in a liquid electrolyte and the potential of the front electrode is varied, the resonator’s resonance properties change. The shifts in resonance frequency, Δf, and half bandwidth, ΔΓ, are caused by electrochemical charge transfer at the electrode and double layer recharging. The details of this correlation are a key question in this dissertation. In the case of electrodeposition, f is largely proportional to the deposited mass, while ΔΓ remains unchanged. Modeling beyond gravimetry in terms of roughness, viscosity, and viscoelasticity requires the measurement of Δf and ΔΓ on multiple overtones. When intermediate species or submonolayers are studied, Δf and ΔΓ are only slightly above the noise level. Moreover, the changes in Δf and ΔΓ occur on a millisecond timescale, so that current QCMs based on either impedance analysis or ring-down reach their technical limit. At best, these devices achieve time resolutions in the range of 20 ms (measuring one overtone) and a frequency sensitivity of 20 mHz (at low data acquisition rate). To improve the time resolution, multifrequency lockin amplification (MLA) is employed. This interrogation scheme is related to impedance analysis but the frequency sweep is replaced by a comb of up to 32 equally spaced frequencies (comb drive). Only 6 frequencies are needed to robustly acquire one single overtone. The remaining frequencies can be distributed to further overtones. Thus, the resonance curves are obtained in a single shot. The time resolution in this mode is equal to the inverse frequency spacing in the comb. Typical values are 1 10 ms. If required, the time resolution can be improved down to 100 µs by driving the QCM with a fixed frequency (fixed-frequency drive). In addition, the frequency resolution can be improved to below 10 mHz in the liquid phase by employing modulation of the electrode potential and accumulation of Δf and ΔΓ over many cycles. Steps, linear ramps, and stairs are suitable shapes for potential modulation. The advantages of this new technique, fast modulation EQCM, are demonstrated by employing capacitive double layer recharging, underpotential deposition of copper in the presence of additives, and reversible oxidation/reduction of the redox mediators methyl viologen chloride (MVC) and flavin adenine dinucleotide (FAD). Other experiments in which modulation is neither possible nor necessary deal with drying processes. Even without modulation, these experiments show that dynamic processes, such as droplet-based inkjet printing or electrospraying, are accessible to the fast QCM. The examples above emphasize the essential role of kinetic information. In addition to the improved sensitivity, the time resolution is groundbreaking and will enable new experiments in the future
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