Amyloid fibrils are a type of protein nanofibres that form when a normally soluble protein aggregates in a regular fashion via self-association. Their organised and repetitive β-sheet structure is thought to be a generic property of all proteins, depending on the environmental conditions. The nanometre size and high stability of these protein nanofibres are attractive features to exploit in bionanomaterials. This thesis aimed to manipulate insulin amyloid fibrils, as a model protein nanofibre system, through investigating the effect of chemical modification on insulin fibril formation in heterogeneous mixtures. Using acetylation, reduction carboxymethylation, reduction pyridylethylation, trypsin digestion and chymotrypsin digestion, it was shown that nanofibres can form in heterogeneous mixtures of modified insulin at variable rates to produce fibrils of distinct morphologies. Distinctively well defined, long, unbranched nanofibres were observed in the crude reduced carboxymethylated insulin mixture after incubation at 60°C (pH 7.4), which formed at a faster rate than native insulin. The crude reduced pyridylethylated insulin revealed the formation of “wavy” fibrils when exposed to 60°C and pH 1.6, compared to the straight native insulin amyloid fibrils. Although, the trypsin digestion inhibited nanofibre formation at 60°C and pH 1.6, chymotrypsin digestion of insulin produced a mixture of long and short nanofibres under the same conditons. Thus chemical modification provides a simple means of manipulating protein nanofibre assembly for use in bionanotechnology. Protein nanofibres were incorporated into a model polymer polyvinylalcohol (PVOH) film in order to assess the impact on material properties. A systematic study involving both insulin and a crude source of crystallin proteins derived from bovine eye lens was undertaken. A protein nanofibre-PVOH nanocomposite was successfully fabricated by a procedure of solution mixing and casting. Dynamic mechanical analysis showed that the addition of insulin fibrils did not change the stiffness of the PVOH. However, an increase in the stiffness of the PVOH-crude bovine eye lens composites was found. Both insulin and bovine eye lens nanofibres reduced the damping properties of the polymer, which suggested a reduction in molecular mobility/slipping. The results revealed that protein nanofibre formation can be controlled through the modification of the protein and that nanofibres may alter polymer properties in a protein specific manner. Employing these findings in the development of novel bionanomaterials that use the protein nanofibres as a form of natural scaffolding offers a fruitful avenue of future research.

Skin wound healing is an urgent problem in clinical treatment, in particular, with a military context. Although significant advances have been made in treating skin wounds, traditional methods face several challenges, e.g., limited donor skin tissue for transplants and inflammation over the period of long term healing. To address these challenges, in this study we present a method to fabricate Poly (ethylene-co-vinyl alcohol) (EVOH) nanofibres encapsulated with the Ag nanoparticle, using the electro-spinning technique. The manufacturing process of nanofibres by electro-spinning is the subject of the present research. Electro-spinning is a process which produces nanofibres through the electrically charged jet of a polymer solution. While the principle has long been understood, the process of forming them still remains difficult to control. In its simplest form, the technique consists of a pipette to hold the polymer solution, two electrodes and a DC voltage supply over a 10 KV range. The polymer dropping from the tip of the pipette is drawn into a jet which is electrically charged and spun into fine fibres by the electronic field. An appropriate combination of the control parameters, such as the charge voltage, density and viscosity of the polymer solution and the travel distance of the jet, etc. will lead to the production of fibres with diameters in the range of 10-7~8 meters. The fibres can then be collected on the surface of a grounded target. regulating three main parameters, namely, a concentrated EVOH solution, the electric voltage and the distance between the injection needle tip (high voltage point) and the fibre collector. Ag was added to the nanofibres to offer long term anti-inflammation properties by the slow release of Ag nanoparticles through the gradual degradation of the EVOH nanofibre. The method developed here could lead to new dressing materials for the treatment of skin wounds. The thin EVOH nanofibre sheets obtained from electro-spinning were tested in uniaxial tension for their mechanical properties, with a view to the possibilities of using them as wound dressings. It was found that the sheets show a mild hardening behaviour with extensive elongation and necking before failure in multiple fractures at random locations. The failure is not simply fibre breakage. Due to the random orientation of the continuing fibres in the sheet, detachment, shear, straightening and twinning. etc., among the fibres all occur at the same time to different extents. The Young’s modulus and the yield stress (at 0.4~0.5% proof strains) are predominately affected by the diameters of the fibres. The latter are largely insensitive to strain rate over the range tested.

Thesis in theoretical part provides an overview of oral drugs in the biopharmaceutical point of view. It describes the main difficulties of this application route and presents selected facts about new approaches to improve the bioavailability of poorly absorbable substances. These approaches, in recent years, also use nanofiber membranes. The experimental part focuses on the in vitro evaluation of diamine delivery from nanofiber membranes in vehicle buffered at pH 7.4. The tested membranes contain the active substance in three graduated concentrations (20%, 30% and 40%), and specifically differ in basic weight. To evaluate the delivery the fluxes of diamine witin the first linear section of delivery are used, the percentage of substance released within 60 minutes was used to the evaluation of releasable proportion of diamine. Determination of diamine was performed by HPLC. The release of nearly all releasable diamine amounts were always obtained in 15 minutes from the beginning of release. The release rate of the diamine from nanofiber membranes is high. Important, however, is the finding that the rate of drug release is not probably significantly dependent on the drug concentration in the nanofiber membrane, but it is significantly influenced by the basic weight of membranes. The variability...

A theoretical part of the diploma thesis describes solubility, classification of solubility and ways of influencing of solubility, and it gives a detailed summary of naproxen as the drug further used and evaluated in in vitro experiments for drug release. An experimental section is focused to in vitro release of naproxen from nanofibre membranes produced by electrospinning with regard to the possibility of the use of layering. At both layered and non-layered nanofibre membranes of three different naproxen concentrations (e.g. 5%, 15% and 30% by weight) the drug release amounts within 5 minutes were from 10 to 90 percent of total amounts. An overal percentage of naproxen released in 60 minutes was always about 100 % of the total drug loaded in the nanomembranes. The nanofibre membranes layered with the glycerol and propylene glycol were of the same profiles as with non-layered membranes.

The performance of peristaltic pumps is mainly governed by their tubing or hose materials. Research and development in this area is therefore very important for peristaltic pump manufacturers to keep in front of the competition and to open up new applications to enable further market penetration. Another aspect of this is of course price; performance and cost have to be in balance. As an approach to fabricate a new tube material, the field of negative Poisson's ratio (or: auxetic) materials is explored. The combined deformations of tensile, compression and shear in a peristaltic pump tube may well benefit from the specific characteristics of auxetic materials. Materials can be designed to keep their dimensions constant in directions perpendicular to an applied load. This is referred to as “auxetic balancing”. Finite element modelling shows that lowering the Poisson's ratio will rapidly decrease the maximum stresses in the cross-section of an occluded tube. Optimum values for the Poisson's ratio are found to be between −0.1 and +0.1, preferentially being 0. The re-entrant honeycomb structure is selected for initial trials, but manufacturing of this structure at the desired dimension proved to be too difficult at this time. Instead, electrospun nanofibre membranes are selected as the reinforcement structure. A liquid silicone elastomer is used as the matrix material. Key characteristics for the new material are derived from baseline test results on existing tubing. Laminates are manufactured from electrospun nylon6 nanofibre membranes coated with a liquid silicone rubber. Compression moulding is used to cure the nylon6-silicone rubber laminate, to give two effects: it ensures impregnation of the membrane and the compression deforms the nanofibre structure in such a way that it will become auxetic through-the-thickness. Flat sheet laminates of 2 mm thickness are manufactured with 14 layers of reinforcement. A reinforcing effect and substantial lowering of the through-the-thickness Poisson's ratio is observed for the laminates at low strains. At higher strains (>50%) the effect of the reinforcement diminishes and the Poisson's ratio of the laminate and pure silicone rubber equalises. Finally, tubular laminates are manufactured and the resulting tubes are tested in a peristaltic pump with some promising results (>1 million occlusions before failure). Tube performance is not yet at the required level, but with further optimisation of the laminating process, mould design and (post-)curing large steps forward can be made.

Nanofibres are useful in a broad range of applications in areas such as medical science, food science, materials engineering, environmental engineering, and energy and electronics due to their outstanding characteristics: their small size, high surface-to-volume ratio, high porosity, and superior mechanical performance. Recently, controlled drug delivery systems have gained significant attention, especially with respect to the use of polymer nanofibres. For these systems, the ability to control of the length of the polymer nanofibre is important because the amount of drug released depends on the length of the fibre. Electrospinning is the simplest and most cost-effective method of fabricating polymer nanofibres. In the process, a high voltage is used to create an electrified jet which will eventually become a nanofibre. The electrified jet ejects when a high voltage is applied to the electrospinning setup. On the other hand, the jet does not eject when the applied voltage is below the threshold voltage. It is therefore possible to fabricate and chop nanofibres by controlling the values of the voltages applied and a special high-voltage pulsed power supply has been developed for this purpose. In this research, an IGBT-based pulsed power supply has been designed and built to be used for non-continuous-mode electrospinning. The IGBTs are connected in series to deliver high voltage pulse voltages to an electrospinning setup. The IGBT-based pulsed power supply is capable of producing controllable square pulses with a width of a few hundred microseconds to DC and amplitudes up to 10 kV. The technique of non-continuous-mode electrospinning was tested using the pulsed power supply designed in this work. The new system was able to fabricate and chop nanofibres with PEO and alginate/PEO solutions. It was concluded that the minimum pulse width that can initiate an electrified jet is approximately 80 ms for the parameters used in this study. A longer period produces a more constant jet during the pulse-on voltage when the duty ratio is the same value. It is also highly likely that a jet is always ejected during the pulse-on voltage when the duty ratio is more than 40 %.

Nanofibres are useful in a broad range of applications in areas such as medical science, food science, materials engineering, environmental engineering, and energy and electronics due to their outstanding characteristics: their small size, high surface-to-volume ratio, high porosity, and superior mechanical performance. Recently, controlled drug delivery systems have gained significant attention, especially with respect to the use of polymer nanofibres. For these systems, the ability to control of the length of the polymer nanofibre is important because the amount of drug released depends on the length of the fibre. Electrospinning is the simplest and most cost-effective method of fabricating polymer nanofibres. In the process, a high voltage is used to create an electrified jet which will eventually become a nanofibre. The electrified jet ejects when a high voltage is applied to the electrospinning setup. On the other hand, the jet does not eject when the applied voltage is below the threshold voltage. It is therefore possible to fabricate and chop nanofibres by controlling the values of the voltages applied and a special high-voltage pulsed power supply has been developed for this purpose. In this research, an IGBT-based pulsed power supply has been designed and built to be used for non-continuous-mode electrospinning. The IGBTs are connected in series to deliver high voltage pulse voltages to an electrospinning setup. The IGBT-based pulsed power supply is capable of producing controllable square pulses with a width of a few hundred microseconds to DC and amplitudes up to 10 kV. The technique of non-continuous-mode electrospinning was tested using the pulsed power supply designed in this work. The new system was able to fabricate and chop nanofibres with PEO and alginate/PEO solutions. It was concluded that the minimum pulse width that can initiate an electrified jet is approximately 80 ms for the parameters used in this study. A longer period produces a more constant jet during the pulse-on voltage when the duty ratio is the same value. It is also highly likely that a jet is always ejected during the pulse-on voltage when the duty ratio is more than 40 %.

Les travaux de recherche de ce manuscrit s’inscrivent dans le cadre d’une coopération scientifique avec la société STMicroelectronics de Tours concernant les interconnexions des prochaines générations de circuits intégrés. L’intégration de nanotubes de carbone comme connecteurs en microélectronique de puissance, limiterait sévèrement les effets d’échauffements dans les empilements de puces, permettant une meilleure dissipation de la chaleur. Ce travail de thèse avait pour objectif de déterminer un procédé de croissance reproductible de nanotubes de carbone d’au moins 20 dm de long, en tapis perpendiculaire au substrat, peu pollué par du carbone amorphe afin de réaliser un véhicule test permettant de mesurer les propriétés thermiques et électriques du tapis de nanotubes obtenu. Le dispositif expérimental présenté utilise l’ablation laser pour le dépôt de catalyseur (fer) la méthode de CVD assistée par plasma radiofréquence d’éthylène et d’hydrogène pour la croissance de nanotubes de carbone. Des conditions optimales d’obtention des tapis répondant aux critères de réalisation des démonstrateurs, ont été définies à la suite d’une étude paramétrée. Pour les mesures électriques, des plots d’or servant d’électrodes, sont déposés sur les tapis de nanotubes. Lors des tests électriques 4 pointes sur le démonstrateur réalisé, le comportement ohmique des tapis de nanotubes a été mis en évidence. Une puissance de 300 mW/mm2 est déposée sur les plots sans aucun dommage pour les nanotubes, et une résistivité de l’ordre de 10-3 L.m a été estimée. Pour les tests thermiques, une couche mince de titane absorbant l’énergie d’un faisceau laser UV pulsé représentant la source de chaleur, est déposée sur le tapis de nanotubes. Des valeurs de conductivité thermique apparente de 200 – 300 W/m/K et intrinsèque de 660W/m/K ont été déterminées par méthode de pyrométrie infrarouge résolue en temps. / This manuscript presents the research work done in the frame of scientific cooperation with the company STMicroelectronics in Tours concerning the interconnections for the next generation of integrated circuits. The integration of connectors based on carbon nanotubes in microelectronic would severely limits the effects of overheating in the stacks of chips, allowing a better heat dissipation. The aim of this PHD work was the determination of a reproducible carbon nanotubes carpet growth process at least 20 dm long, perpendicular to the substrate, slightly polluted by amorphous carbon in order to achieve a test vehicle for measuring thermal and electrical properties of carbon nanotubes carpet. The experimental device combines laser ablation process for the deposit of catalyst (iron) and RF plasma Enhanced CVD method with a mixture of ethylene and hydrogen gases for the growth of carbon nanotubes. Optimal conditions for obtaining carpet criteria for test vehicle realization have been defined from a parameterized study. For electrical measurements, gold layers as electrodes are deposited on nanotube carpets. Four probes electrical test is achieved and an ohmic behaviour of nanotube carpet is evidenced. A power of 300 mW/mm2 is deposited without any damage for the nanotubes and the carpet resistivity is estimated to be 2,99.10-3 L.m. For thermal testing, a titanium thin film is deposited on the carpet in order to absorb the UV pulsed laser beam representing the heating source. An apparent thermal conductivity value of 200 - 300 W/m/K and an intrinsic value of 660W/m/K were determined by time resolved infrared pyrometry method.

Comme les propriétés physiques d'un matériau à l'échelle nanométrique sont largement dépendantes de la taille et de la forme des nanostructures, il est inutile de synthétiser de nouvelles compositions et morphologies. L'étude avancée de leur structure par les techniques de caractérisation usuelles (MET, MEB, DRX, Raman...) permettra de collecter toutes les informations nécessaires à la compréhension de leurs propriétés physiques (magnétiques, optiques, électriques). Dans ce manuscrit, nous décrirons plusieurs approches d'élaboration de nanostructures 0D, 1D et 2D multifonctionnelles afin de mieux connaître les paramètres qui contrôlent leur composition chimique et leur structure. De plus, ce travail de recherche a abouti à la synthèse de nouveaux matériaux à base d'oxyde et de carbure de fer. Des nanofibres magnétiques ayant des morphologies originales " Ruban " et " tube " ont été élaborées par la technique d'électrospinning en modifiant plusieurs paramètres expérimentaux : concentration de la solution, atmosphères de traitement thermique, température de recuit... De plus, des couches minces guidantes dopées par des nanostructures magnétiques ont été préparées par la technique dip-coating. Nous avons mené une étude complexe et détaillée sur les propriétés structurales de ces matériaux afin de définir les paramètres expérimentaux qui permettront d'obtenir des nano objets de bonne qualité. Dans un but ultime, nous souhaiterons explorer les possibilités d'application de ces matériaux qui présentent à la fois des caractéristiques électriques et magnétiques.

The theoretical part of thesis provides information on the biopharmaceutical classification system of drugs and its context in the research and development of pharmaceuticals. The methods used to increase the solubility and acceleration including electrospinning are presented. The experimental part is the pilot study on the evaluation of conditions suitable for dissolution testing of newly prepared nanofibers made from polyvinylpyrrolidone membranes with a high content (up to 35 per cent) gatrin as a substance poorly soluble in aqueous vehicles. The parameters of determination of gatrin by HPLC using C18 sorbent and a mobile phase of acetonitrile: phosphate buffer pH 8 were preliminarily evaluated as perfectly applicable to vehicle type-phosphate buffer pH 6.0. The same conditions were found to be in a severe collision with a polymer material of nanofibrous membrane during the dissolution evaluation or with acetonitrile in the mobile phase, an accurate determination of gatrin was not obtained in this case. These findings lead to the proposal to change the formulation of the nanofiber membranes using polymer different from polyvinylpyrrolidone (eg. hydroxypropylcellulose) or the replacement of acetonitrile for methanol at the mobile phase for HPLC. However, in all cases, all the analytically...