The billion dollar pharmaceutical research and development pipeline suffers greatly from high attrition rates of novel therapeutic compounds within pre-clinical and clinical trials. Poor bioavailability in many new drugs, originating in the various methodologies of high throughput screening, may explain part of these growing failure rates. One interpretation of this phenomenon relies on bioavailability's correlation with aqueous solubility; much modern processing allows chemicals to fully develop without touching water, yielding upwards of 90% of new chemical entities practically insoluble in aqueous media. Thus, one approach to alleviating bioavailability and potentially clinical attrition rates necessitates augmented aqueous solubility. The amorphous nanoparticle presents the largest boost in aqueous solubility of a chemical through processing alone. In this contribution, we propose electrospray as a novel, competitive candidate to produce pharmaceutical amorphous nanoparticles with the intent of augmenting solubility. Electrospray represents an idyllic nominee for three reasons: repeatability, flexibility, and scalability. Electrospray offers low batch to batch variation with less than 30% relative standard deviation between various droplets. This triumphs over the several orders of magnitude in variation in pneumatic sprays. Electrospray's flexibility draws from its ability to attain diameters over several orders of magnitude, ranging from hundreds of microns to several nanometers; in this contribution droplets are produced between 500 nm and 1[micro]m. Finally, electrospray displays scalability to any industrial requirement; though a single nozzle operates at mere microliters per hour, a single multiplexed array of emitters may increase this throughput by several orders of magnitude. This exploration, utilizing Indomethacin as a model low solubility chemical, verifies electrospray as a compatible processing tool for the pharmaceutical industry. Scanning electron microscopy coupled with the image analysis software ImageJ gleans the size and shape of emitted (and dried) particles. Amorphicity verification of particles employs grazing angle x-ray diffraction. Finally, ultraviolet and visual spectrum spectroscopy evaluates the solubility advantage of particles.

Στην παρούσα διπλωματική εργασία μελετάται η καταβύθιση του αντιφλεγμονώδους φαρμάκου ναπροξένης, παρουσία του πολυμερούς PVP. Βρέθηκε ότι η παρουσία του PVP, επηρεάζει το μέγεθος και το σχήμα των κρυστάλλων της ναπροξένης. Μελετήθηκαν οι συνθήκες καταβύθισης όπως η θερμοκρασία, το pH του διαλύματος καθώς και ο συνδυασμός αυτών των δυο. Βρέθηκε ότι σε ορισμένες περιοχές pH και θερμοκρασίας επηρεάζεται το μέγεθος και το σχήμα των κρυστάλλων. Λήφθησαν φωτογραφίες από το ηλεκτρονικό μικροσκόπιο σάρωσης (SEM) για κάθε πείραμα που πραγματοποιήθηκε και έγινε στατιστική επεξεργασία των αποτελεσμάτων. / In the present work was studied the precipitation of naproxen in the presence of the polymer PVP. It was found that the presence of PVP, influents the size and the form of naproxen’s crystals. Were studied the conditions of precipitation such as the temperature, pH of the solution as well as the combination of both. It was found that in some areas of pH and temperature influence significantly the size and the form of crystals. It was taken images from scanning electron microscopy (SEM) for each experiment was carried out and it was made statistical analysis of the results.

Highly monodisperse droplets are attracting great attention both in many research areas, such as aerosol science, combustion, and Nano-manufacturing. This thesis invents a novel aerosol generator: “Periodic Electro Hydro-dynamic Chopper” termed as “PEHD chopper”, and develops a new method to directly print micro-patterns with monodisperse droplets. The principle of the PEHD chopper is to use the fringe electric field of a capacitor to introduce controlled perturbation on a liquid jet. We first derived the governing equations for a circular inviscid liquid jet under transverse electric fields. The electric fields were obtained through numerical simulation. Then we used a high speed camera (up to one million frames per second) to visualize the jet break-up as well as the droplets’ size and shape. The experiments show that the PEHD chopper can effectively “chop” a neutral micro-jet and generate highly monodisperse micro-droplets, which diameter range from 100 µm to 500 µm. To reduce the droplet size, PEHD chopper with a butterfly design is applied on a typical single electrospray. In this configuration, the jet swings at long wavelengths (>R), where R is the Rayleigh wave length, but breaks up into highly monodisperse droplets near 2R and R without satellite droplets. The butterfly configuration combined with electrified jet expands the diameter range into 20 µm to 100 µm. iv Finally, we demonstrate the electrospray printing of Polymer Derived Ceramics (PDC) for sensor applications in harsh environment. A modified single ES with an additional driving electric field is used to directly print PDC precursor without mask, we achieved 1D feature as narrow as 35 µm and a micro pentagram pattern. Moreover, after pyrolysis of PDC at 1100 °C in nitrogen, amorphous alloys of silicon, carbon and nitrogen (SiCN) are obtained. The samples exhibit excellent good integrity and adhesion to the substrate.

The emergence of novel electronic, optical and magnetic properties in ordered two-dimensional (2D) nanoparticle ensembles, due to collective dipolar interactions of surface plasmons or excitons or magnetic moments have motivated intense research efforts into fabricating functional nanostructure assemblies. Such functional assemblies (i.e., highly-integrated and addressable) have great potential in terms of device performance and cost benefits. Presently, there is a paradigm shift from lithography based top-down approaches to bottom-up approaches that use self-assembly to engineer addressable architectures from nanoscale building blocks. The objective of this dissertation was to develop appropriate processing tools that can overcome the common challenges faced in fabricating floating gate memory devices using self-assembled 2D metal nanoparticle arrays as charge storage nodes. The salient challenges being to synthesize monodisperse nanoparticles, develop large scale guided self-assembly processes and to integrate with Complementary Metal Oxide Semiconductor (CMOS) memory device fabrication processes, thereby, meeting the targets of International Technology Roadmap for Semiconductors (ITRS) – 2017, for non-volatile memory devices. In the first part of the thesis, a simple and robust process for the formation of wafer-scale, ordered arrays using dodecanethiol capped gold nanoparticles is reported. Next, the results of ellipsometric measurements to analyze the effect of excess ligand on the self-assembly of dodecanethiol coated gold nanoparticles at the air-water interface are discussed. In a similar vein, the technique of drop-casting colloidal solution is extended for tuning the interparticle spacing in the sub-20 nm regime, by altering the ligand length, through thiol-functionalized polystyrene molecules of different molecular weights. The results of characterization, using the complementary techniques of Atomic Force Microscopy (AFM) and Field-Emission Scanning Electron Microscopy (FESEM), of nanoparticle arrays formed by polystyrene thiol (average molecular weight 20,000 g/mol) grafted gold nanoparticles (7 nm diameter) on three different substrates and also using different solvents is then reported. The substrate interactions were found to affect the interparticle spacing in arrays, changing from 20 nm on silicon to 10 nm on a water surface; whereas, the height of the resultant thin film was found to be independent of substrate used and to correlate only with the hydrodynamic diameter of the polymer grafted nanoparticle in solution. Also, the mechanical properties of the nanoparticle thin films were found to be significantly altered by such compression of the polymer ligands. Based on the experimental data, the interparticle spacing and packing structure in these 2D arrays, were found to be controlled by the substrate, through modulation of the disjoining pressure in the evaporating thin film (van der Waals interaction); and by the solvent used for drop casting, through modulation of the hydrodynamic diameter. This is the first report on the ability to vary interparticle spacing of metal nanoparticle arrays by tuning substrate interactions alone, while maintaining the same ligand structure. A process to fabricate arrays with square packing based on convective shearing at a liquid surface induced by miscibility of colloidal solution with the substrate is proposed. This obviates the need for complex ligands with spatially directed molecular binding properties. Fabrication of 3D aggregates of polymer-nanoparticle composite by manipulating solvent-ligand interactions is also presented. In flash memory devices, charges are stored in a floating gate separated by a tunneling oxide layer from the channel, and the tunneling oxide thickness is scaled down to minimize power consumption. However, reduction in tunneling oxide thickness has reached a stage where data loss can occur due to random defects in the oxide. Using metal nanoparticles as charge-trapping nodes will minimize the data loss and enhance reliability by compartmentalizing the charge storage. In the second part of the thesis, a scalable and CMOS compatible process for fabricating next-generation, non-volatile, flash memory devices using the self-assembled 2D arrays of gold nanoparticles as charge storage nodes were developed. The salient features of the fabricated devices include: (a) reproducible threshold voltage shifts measured from devices spread over cm2 area, (b) excellent retention (>10 years) and endurance characteristics (>10000 Program/Erase cycles). The removal of ligands coating the metal nanoparticles using mild RF plasma etching was found, based on FESEM characterization as well as electrical measurements, to be critical in maintaining both the ordering of the nanoparticles and charge storage capacity. Results of Electrostatic Force Microscope (EFM) measurements are presented, corroborating the need for ligand removal in obtaining reproducible memory characteristics and reducing vertical charge leakage. The effect of interparticle spacing on the memory characteristics of the devices was also studied. Interestingly, the arrays with interparticle spacing of the order of nanoparticle diameter (7 nm) gave rise to the largest memory window, in comparison with arrays with smaller (2 nm) or larger interparticle spacing (20 nm). The effect of interparticle spacing and ligand removal on memory characteristics was found to be independent of different top-oxide deposition processes employed in device fabrication, namely, Radio-frequency magnetron sputtering (RF sputtering), Atomic Layer Deposition (ALD) and electron-beam evaporation. In the final part of the thesis, a facile method for transforming polydisperse citrate capped gold nanoparticles into monodisperse gold nanoparticles through the addition of excess polyethylene glycol (PEG) molecules is presented. A systematic study was conducted in order to understand the role of excess ligand (PEG) in enabling size focusing. The size focusing behavior due to PEG coating of nanoparticles was found to be different for different metals. Unlike the digestive ripening process, the presence of PEG was found to be critical, while the thiol functionalization was not needed. Remarkably, the amount of adsorbed carboxylate-PEG mixture was found to play a key role in this process. The stability of the ordered nanoparticle films under vacuum was also reported. The experimental results of particle ripening draw an analogy with the well-established Pechini process for synthesizing metal oxide nanostructures. The ability to directly self-assemble nanoparticles from the aqueous phase in conjunction with the ability to transfer these arrays to any desired substrate using microcontact printing can foster the development of applications ranging from flexible electronics to sensors. Also, this approach in conjunction with roll-to-roll processing approaches such as doctor-blade casting or convective assembly can aid in realizing the goal of large scale nanostructure fabrication without the utilization of organic solvents.

Existing commercially available microcarriers are very efficient at encouraging cell attachment and proliferation. However, recovery of the cells is problematic as it requires the use of proteolytic enzymes which are damaging to critical cell adhesion proteins. From this perspective, temperature responsive polymers appear to be a valid option. The current innovative study is to produce and engineer microcarriers in terms of particle size, surface coating and properties, as well as thermo-responsiveness for cell release. All these benefits are based on particle production by membrane emulsification to provide a highly controlled particle size. The polymer of choice is poly N-isopropylacrylamide (pNIPAM) because of the sharpness of its phase transition, biocompatibility and transition temperature close to the physiological value. These characteristics make pNIPAM a very attractive material for Tissue Engineering applications. Cells are cultured on the hydrophobic surface at 37??C and can be readily detached without using proteolytic enzymes from the surface by lowering the temperature to room temperature. The Dispersion Cell (MicroPore Technologies Ltd, UK) was successfully employed for the production of W/O emulsions. The generated monomer droplets were additionally solidified by applying a free radical polymerisation to manufacture solid pNIPAM microspheres. Additionally, calcium alginate particles were also generated and further functionalised with amine terminated pNIPAM to form temperature responsive core-shell particles by simply taking advantage of the electrostatic interactions between the carboxyl groups of the alginate and amino groups of the modified pNIPAM. Controlled particle production was achieved by varying process parameters and changing the recipe formulation (e.g. monomer concentration, surfactant concentration, pore size and inter-pore spacing, injection rate, shear stress applied at the membrane s surface). The manufactured particles were then analysed in terms of particle size and size distribution, chemical composition, surface analysis, shrinkage ratio and thermo-responsiveness and further sterilised and used for cell culture and release experiments. Swiss Albino 3T3 fibroblastic cells (ATCC, USA) were utilised to show proof-of-concept for this technology. Cell attachment and proliferation were assessed and successfully demonstrated qualitatively and quantitatively. pNIPAM solid particles, uncoated and with different protein coatings were shown to allow a limited degree of cell attachment and proliferation compared to a commercially available microcarrier. On a different approach, uncoated core-shell structures demonstrated improved capabilities for cell attachment and proliferation, similar to commercially available microcarriers. Having in mind the potential of temperature responsive polymers and the aim of this innovative study, cell detachment from the generated microcarriers was evaluated and compared to a commercially available temperature responsive surface. Necessary time for detachment was recorded and detached cells were recovered and reseeded onto tissue culture plastic surfaces in order to evaluate the replating and reattachment capabilities of the recovered cells. Successful cell detachment was achieved when using the core-shell structures as cell microcarriers, but the necessary time of detachment was of an order higher than that for the commercial temperature responsive surface.

Non-oxidative dehydrogenation of hydrocarbons is an attractive alternative route for the production of CO- and CO2-free hydrogen. It will satisfy a major requirement for successful utilization of polymer electrolyte membrane (PEM) fuel cells (< 10 ppm CO) and sequestering carbon as a potentially valuable by-product, carbon nanotubes (CNTs). Due to the deposition of carbon on the surface of catalyst particles during the reaction, catalyst performance, life-time, and purification of the generated carbon product, are significant issues to solve in order to make the process practically feasible. The scope of this thesis includes: the development of novel Fe, Ni, and Fe-Ni catalysts supported on a Mg(Al)O support to achieve improved catalytic performance with easily-purified CNTs; evaluation of catalysts for ethane/methane dehydrogenation at moderate reaction temperatures; and study of activation and deactivation mechanisms by a variety of characterization techniques including TEM, HRTEM, XRD, Mössbauer spectroscopy, and x-ray absorption fine structure (XAFS) spectroscopy. The Mg(Al)O support was prepared by calcination of synthetic MgAl-hydrotalcite with a Mg to Al ratio of 5. The catalysts were prepared either by conventional incipient wetness method or by a novel nanoparticle impregnation method, where the monodisperse catalyst nanoparticles were prepared in advance by thermal decomposition of a metal-organic complex in an organic-phase solution and then dispersed onto the Mg(Al)O support. Dehydrogenation of undiluted methane was conducted in a fix-bed plug-flow reactor. Before reaction, the catalysts were activated by reduction in hydrogen. Fe-based catalysts exhibit a higher hydrogen yield at temperature above 600ºC compared with monometallic Ni catalyst. FeNi-9 nm/Mg(Al)O, Fe-10 nm/Mg(Al)O and Fe-5 nm/ Mg(Al)O nanoparticle catalysts show much improved performance and longer life-times compared with the corresponding FeNi IW/Mg(Al)O and Fe IW/Mg(Al)O catalysts prepared by incipient wetness. 10 nm is the optimum particle size for methane dehydrogenation. Addition of Ni to Fe forming a bimetallic FeNi alloy catalyst enhances the catalytic performance at the temperatures below 650ºC. Metallic Fe, Ni, FeNi alloy and Fe-Ni-C alloy, unstable iron carbide are all catalytically active components. Catalysts deactivation is due to the carbon encapsulation. The carbon products are in the form of stack-cone CNTs (SCNTs) and multi-walled CNTs (MWNTs), depending on the reaction temperature and catalyst composition. The growth of CNTs follows a tip growth mechanism and the purity of cleaned CNTs is more than 99.5%.

In this thesis investigations are carried out on two research topics in context to spray drying. The first research topic is the production of dried particles having uniform characteristics. The second research topic is the development of new applications of the reaction engineering approach which, in recent times, has emerged as an effective tool to formulate drying kinetics models. The reaction engineering approach is also implemented to simulate the drying of monodisperse droplets corresponding to the experimental work in the first research topic. Manufacturing micron- and nano-sized particles having uniform characteristics has recently become a popular research area due to the unique functionalities of these kinds of particles in biomedical, drug delivery, functional foods, nutraceuticals, cosmetics and other valuable applications. Spray drying has been a common and economical route to produce dried particles. A typical characteristic of spray dried products is the existence of a significant variation in particle properties such as size and morphology. One possible idea to restrict this product non-uniformity is to achieve a good control over the droplet’s behaviour and characteristics inside the drying chamber. The current thesis has investigated an innovative spray drying technique, i.e. a single stream drying approach in order to restrict product non-uniformity. In this drying approach, identical sized droplets having vertical trajectories are dried under controlled gas flow conditions. The piezoelectricity-driven monodisperse droplet generator is used as the atomizer to disperse liquid droplets. A prototype single stream dryer was assembled based on the single stream drying approach using various components designed in the laboratory and several parts purchased from the market. Experiments were carried out using aqueous lactose solutions as a model system in order to check the practicability of manufacturing uniform-sized spherical particles. Preliminary results were found to be positive and reported in this thesis. Mathematical models on the drying of monodisperse droplets were developed in order to predict important droplet and gas parameter profiles during single stream drying. These models serve as a platform for design, optimization and scale-up purposes. Several important advantages and drawbacks of single stream drying are also reported. Problems encountered during the experimental work and future recommendations are presented in detail so that a more robust and effective drying research tool can be developed in future. Recently the reaction engineering approach (REA) has emerged as a simple and reliable technique to characterize the drying of various food and dairy materials. In this thesis two new applications of the REA are described for the first time in context to convective drying of aqueous droplets. The REA is used in this study to formulate the drying kinetics model for the drying of aqueous sucrose and maltodextrin (DE6) droplets. The effect of initial moisture content was explicitly demonstrated. The development of a new ‘composite’ REA which aimed to model the drying of aqueous droplets containing multiple solutes has been described. The composite REA was found to be suitable to characterize the drying behaviour of aqueous sucrose-maltodextrin mixtures of different proportions. The second new application of the REA is the development of a procedure to estimate surface properties of aqueous droplets during drying. In literature various droplet characteristics such as surface moisture contents were normally estimated using the diffusion-based drying kinetics model or the receding interface model. Surface moisture content and surface glass transition temperature profiles were evaluated here using a lumped-parameter model (REA) during the drying of aqueous sucrose, maltodextrin (DE6) and their mixtures. The same experimental data used for the development of the composite REA were used to yield predictions. The procedure was found to be useful in estimating surface moisture contents and understanding the stickiness behaviour of sugar droplets during drying. During the formulation of the REA-based drying kinetics model in this thesis, the assumption of uniform temperature within droplets was used. In most studies published in literature the uniform temperature assumption was justified by calculating the heat-transfer Biot numbers at the beginning and end of drying. However, the conventional Biot number concept does not take into account the evaporation effect and therefore would not be suitable to drying scenarios. In this thesis, a new approximation procedure is developed to estimate surface-centre temperature differences within materials following the entire drying process. This new procedure was helpful to check the extent of temperature non-uniformity within skim milk droplets under isothermal laboratory conditions as well as industrial spray drying conditions. Both conventional and drying-based Biot numbers are calculated and compared. Predictions showed that temperature gradients within the droplets were negligible during the drying of suspended droplets under laboratory drying conditions (slow drying), whilst the gradients were small and existed only for a short drying period for small droplets under industrial spray drying conditions (fast drying). Furthermore, it was observed that the maximum temperature gradient within the droplets did not exist at the starting or end points of the drying process, and therefore the estimation of Biot numbers at the starting and end point does not reflect temperature non-uniformity under drying conditions. This is a significant theoretical development in the area.

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Aim of this thesis was to design and prepare polymer-coated monodisperse Fe3O4 nanoparticles as a safe and non-toxic contrast agent for magnetic resonance imaging (MRI) and heat mediator for hyperthermia. Uniform superparamagnetic Fe3O4 nanoparticles were synthesized by thermal decomposition of Fe(III) oleate, mandelate, or glucuronate in high- boiling solvents at temperature >285 řC. Size of the particles was controlled in the range of 8- 27 nm by changing reaction parameters, i.e., temperature, type of iron precursor, and concentration of stabilizer (oleic acid and/or oleylamine), while preserving uniformity of the nanoparticles. Because particles contained hydrophobic stabilizer on the surface, they were dispersible only in organic solvents. To ensure water dispersibility, oleic acid on the particle surface was replaced by hydrophilic and biocompatible methoxy-poly(ethylene glycol) (PEG) and poly(3-O-methacryloyl-α-D-glucopyranose) by ligand exchange. Polymers were previously terminated with anchoring-end groups (hydroxamic or phosphonic) to provide firm bonding to iron atoms on the particle surface. Fe3O4 nanoparticles were also hydrophilized by encapsulation into a silica shell by reverse microemulsion method. Tetramethyl orthosilicate was used to prepare Fe3O4@SiO2 nanoparticles, which were...

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