The ability of nanoparticles to stabilize oil/water emulsions provides many interesting opportunities for the petroleum industry. Emulsions can be used as a displacing fluid for enhanced oil recovery to improve sweep efficiencies. Emulsions can be used to improve conformance control by effectively blocking thief zones in reservoirs with a high degree of heterogeneity. As shown in this thesis emulsions can be used to deliver fluids that contact and mobilize residual oil. It is imperative to understand emulsion behavior in porous media for design purposes in enhanced or improved oil recovery processes involving emulsions. Nanoparticle-stabilized oil-in-water emulsions were continuously generated by co-injecting aqueous nanoparticle dispersion and oil through a beadpack. There exists a critical shear rate below which a stable emulsion will not be generated. The critical shear rate increased with decreasing bead size. Above the critical shear rate, the droplet size of the generated emulsion was a function of shear rate and decreased with increasing shear rate. The stable emulsions were characterized by their droplet size and rheology. The emulsion viscosity was highly dependent upon droplet size and not the bulk oil viscosity in the emulsion. The emulsions were highly shear thinning and emulsions with smaller droplets were more viscous than emulsions with larger droplets. Highly stable emulsions that were generated by co-injection were collected, separated from excess phase(s) and injected into beadpacks. In most experiments the injected emulsion coalesced into the bulk fluids. Whether the bulk fluids generated a new emulsion in the bead pack depended on the shear rate, bead size, and initial saturation of the beadpack. Different beadpack experiments showed the transition from one flow regime to a second flow regime as the slow movement of a coalescence/regeneration front propagated through the beadpack. Coreflood experiments confirmed the mechanisms hypothesized for the beadpack emulsion injection experiments. When a stable emulsion was injected the effluent emulsion rheology and droplet size were altered solely as a result of being forced through sandstone cores, not because of fluids contacted within the core. The shear rate controlled whether the emulsion coalesced and produced no effluent emulsion, regenerated into an emulsion with larger droplets, or regenerated into an emulsion with smaller droplets. Oil recovery experiments showed that nanoparticle-stabilized oil-in-water emulsion increased the recovery of oil compared to a waterflood for cores with immobile and mobile oil. The mechanism is the coalesced oil droplets form a flowing phase that is miscible with oil present in the core and thus achieves a much more efficient displacement. The possible continuous generation and coalescence of droplets may have increased the apparent viscosity, improving the sweep efficiency of the emulsion injection. A novel oil recovery mechanism was shown in imbibition experiments where nanoparticle dispersion was used to displace oil. Large shear rates coupled with the affinity for nanoparticles at the oil water interface enabled residual oil to be mobilized, or for residual oil blobs to spawn smaller droplets that are stabilized by the nanoparticles and thus can be transported with the dispersion through the core. / text

The intriguing size- and shape dependent properties of nanoparticles have garnered recent attention in many science and engineering areas. When the particle size is in the nanometer size range, the material exhibits very different properties such as surface plasmon resonance (of gold nanoparticles) and superparamagnetism (of iron oxide nanoparticles). The size-dependent properties of quantum dots have made them useful as UV-Vis-NIR sensors and in telecommunications applications. However, the separation and purification of nanoparticles are still challenging due to their size, insolubility in many solvents, and irreversible adsorption to other materials. Membrane filtration is widely used to separate nano-sized biological materials such as proteins, viruses, DNA and RNA. This dissertation presents novel approaches to the use of ultrafiltration and nanofiltration membranes for nanoparticle separation and purification using dead-end and cross-flow filtration techniques. Purification of phosphine-stabilized Au₁₁ (Au₁₁(PPh₃)₈Cl₃, M.W. 4371, d[subscript core]=0.8 nm), produced in a microreactor without recrystallization, was achieved using nanofiltration membranes. The ceramic and polymer nanofiltration membranes were able to purify the Au₁₁ with rejection values higher than 90%. A novel continuous nanofiltration system design was applied and characterized. The continuous synthesis process, coupled with continuous nanofiltration, resulted in a significant reduction in synthesis time while producing higher yield than could be achieved in batch experiments. The diafiltration system was applied towards isolation of Au₁₁, and results were presented that indicate increased yield and enhanced product purity. Organic-solvent resistant nanofiltration and ultrafiltration membranes were applied for purification and size-based separation of lead sulfide nanoparticles and gold nanoparticles that were initially synthesized with a 2-8nm size distribution. The nanofiltration membranes achieved rejection values greater than 95% for each of the nanoparticle samples and retained most of the nanoparticles on the membranes. The nanofiltration membranes also exhibited high permeability, which translates to a reduced purification time. Ultrafiltration membranes were screened and successfully applied to the size fractionation of lead sulfide nanoparticles and gold nanoparticles. A templated silsesquioxane (ssq) membrane was synthesized within the pore space of an alumina support membrane and used for the separation and purification of nano-sized materials such as nanoparticles and macromolecules. The ssq membrane was fabricated by polycondensation of a silsesquioxane monomer solution in the presence of a surfactant within the macroporous space of an Anodisc alumina membrane (Whatman, CO. Ltd, Maidstone, UK). The novel ssq membranes were successfully applied for size exclusion separations of organic soluble 5-8 nm gold nanoparticles (protected with dodecanethiol). A ssq membrane also proved useful for the separation of biological macromolecules such as bovine serum albumin and myoglobin. / Graduation date: 2012

As of 2010, cancer remains the leading cause of death in Canada, and second in the United States of America. This is despite decades of research into development of chemotherapeutics and diagnostics. A number of major challenges have prevented new discoveries from translating into a reduction in mortality rates. One challenge is the poor efficiency with which anti-cancer agents (diagnostic contrast agents and therapeutics) reach deregulated cells in the body. Therefore, development of new methods and technologies for improving efficiency of delivery has been a focus of research. Nanoparticles are leading candidates for improving the efficiency of delivery because they can act as payload vehicles for anti-cancer agents, because it is possible to mediate their interaction with biological systems and thus their pharmaockinetics, and because they can exploit inherent vulnerabilities of tumours. This thesis describes the results from a series of research projects designed to progress our understanding of how nanoparticles behave in vivo, and how their design can be optimized to improve tumour targeting.

This thesis presents experimental work with the primary aim of developing new approaches for the detection and characterisation of nanoparticles via electrochemical methods. The first chapter introduces the fundamental aspects of electrochemistry while the second chapter discusses the need for nanoparticle detection methods and the nonelectrochemical and electrochemical techniques that are currently used in the measurement of nanoparticles. A novel way to quantify silver nanoparticles in aqueous solution is proposed via nanoparticle-electrode impact experiments. In this technique a suitably potentiostatted electrode is immersed in a nanoparticle solution so as to bring about the oxidation or reduction of a single nanoparticle upon its collision with the electrode surface. This “direct” nanoparticle impact technique is then employed to detect laboratory synthesised silver nanoparticles in seawater. It is further shown that this method is capable of sizing silver nanoparticles contained in a commercially available cleaning product. Commercial silver nanoparticles are subsequently monitored via a sticking and stripping technique where homemade gold electrodes fabricated from CDs are immersed in a seawater sample spiked with nanoparticles prior to stripping voltammetry. The reduction of hydrogen peroxide on the surface of silver nanoparticles impacting upon an electrode is also examined. This “indirect” nanoparticle detection method is shown to provide an accurate route to nanoparticle sizing. A Fickian model is subsequently proposed to describe nanoparticle transport to the substrate electrode in both direct and indirect nanoparticle detection techniques. The importance of determining the proportion of nanoparticles which adhere to the electrode surface upon impact is highlighted and the sticking coefficient of a gold nanoparticle at a carbon surface determined. This technique to monitor nanoparticle sticking is optimised by chemical modification of the substrate electrode in order to achieve a “sticky” surface improving the rate of silver nanoparticle sticking. Finally, the nanoparticle collision method is shown to be applicable to C₆₀ nanoparticles where their detection and sizing is achieved in non-aqueous conditions. The methods developed in this thesis make a significant contribution to the promising application of electrochemical techniques in the detection and characterisation of single nanoparticles.

A study was done to examine the effect of surface orientation as well as heterogeneous epitaxy at an interface between two materials with a large lattice mismatch. Silver nanoparticles of different diameters were grown in an effort to study methods of preferentially orienting the geometry of metal nanoparticles. Arrays of calcium fluoride nanorods were grown on silicon substrates using oblique angle thermal vapor deposition. The chamber operated at an ultra high vacuum pressure of 10^-10 Torr during the deposition of the rods and an oblique angle of 75° was kept between the silicon substrate normal and the direction of incident flux. A method was then developed to grow silver nanoparticles exclusively on the (111) facet of the calcium fluoride tips. This was accomplished by once again using oblique angle deposition with an angle of 75° along with the larger size of the (111) calcium fluoride tip facet. Cross sectional scanning electron microscopy and transmission electron microscopy imaging was used to verify that the nanoparticles adhered exclusively to the desired facet of the tip. Using selected area diffraction, (SAED) and dark field in the TEM, it was shown that the nanoparticles did grow at a (111) orientation at the interface between them and the calcium fluoride rods. Different thicknesses and diameters of nanoparticles were then grown to determine what an ideal size was to achieve the most (111) orientation of the nanoparticles. Thicknesses of the particles varied between 5 nanometers and 15 nanometers. Through characterization it was shown that all three of the different thicknesses grown exhibited (111) orientation of the silver nanoparticles, both at the interface and in the overall nanoparticle as well with the 10 nanometer sample being the most ideal in terms of the desired result. Lattice straining of the silver nanoparticles was also observed by characterization through diffraction and SAED.

In this work, an experimental method is developed to study the effects of particle size, flow rate, pulsation, particle/substrate material, and temperature on the short-term reentrainment of submicron particles. The particles tested are in the size range of 10-900 nm and are deposited by wetting the inside of capillary tubes with a liquid suspension. The tubes are then dried in a desiccator. The particles are reentrained under turbulent dry air flow conditions and a condensation particle counter is used to measure the number of entrained particles.There has been very limited work done with nanoscale particles in general and no previous experimental work has reported about this particular parameter set. In order to interpret the data, a bimodal lognormal probability density for the ratio of adhesion force to removal forces is suggested. The majority of particles is attached to the surface by strong forces and cannot be entrained. However, a small fraction of particles, called loose particles, is attached to the surface by much smaller forces. Based on experimental data, an analytical equation for the fraction of loose particles in terms of a dimensionless force is developed. This dimensionless force is a function of particle size and gas flow rate. The temporal variations of fraction of deposited particles are calculated by incorporating the fraction of loose particles with the model of Wen and Kasper (1989).The experimental data confirmed the theoretical expectation that entrainment strongly depends on particle size and decreases as the size of the particle decreases. Both higher flow rates and pulsation of the flow increase the entrainment. Pulsation causes the distribution of forces to broaden. It is shown that the effect of particle/substrate material on entrainment can be predicted by the compound Hamaker constant provided that the morphology and the roughness of the system remain the same. Otherwise, the effect of roughness or morphology may override the effect of Hamaker constant.

Os grandes desafios da medicina contemporânea destacam a necessidade de uma intensa pesquisa para desenvolver novos tratamentos para muitas doenças crônicas, tais como as reumáticas, que sejam efetivos, seguros e com qualidade. Uma das novas ferramentas para o desenvolvimento de novos medicamentos é a nanotecnologia, a qual nos últimos anos tem aumentado a sua aplicação na área farmacêutica contemplando um crescente otimismo acerca do seu potencial uso para obter melhores oportunidades de diagnóstico e de terapias mais eficazes. No presente trabalho foram encapsulados dois antiinflamatórios em sistemas nanoparticulados, nanoesferas de acido poli-láctico co-glicólico (PLGA), a técnica utilizada permitiu a encapsulação de compostos hidrofílicos e hidrofóbicos na mesma nanopartícula polimérica, diclofenaco de sódio (DS) e dexametasona (DX), respectivamente, obtendo nanopartículas com potencial para o tratamento de doenças inflamatórias crônicas. Para o desenvolvimento das nanoesferas se utilizou a técnica de emulsão/evaporação do solvente. As nanoesferas foram caraterizadas por microscopia eletrônica de varredura (SEM), microscopia eletrônica de transmissão (TEM), medição do pH, medição do tamanho de partícula, potencial zeta e polidisversividade e espectroscopia vibracional de infravermelho (IR). A eficiência de encapsulação (EE) dos fármacos (diclofenaco de sódio e dexametasona) nas nanoesferas foi realizada pelas técnicas analíticas, cromatografia líquida de alta eficiência (HPLC) e eletroforese capilar (CE), previamente validadas. Na melhor formulação foi obtida encapsulação de 51,4 ± 5,5 % para o diclofenaco e 66,9 ± 8,4 para a dexametasona. / The great challenges of contemporary medicine emphasize the need for intensive research to develop new treatments for many chronic diseases, such as the rheumatic, to be effective, safe and of good quality. One of the new tools for the development of new drugs is the nanotechnology, which in recent years has increased its application in the pharmaceutical area contemplating a growing optimism about its potential use to get better opportunities for diagnosis and more effective therapies. In the present work were encapsulated two anti-inflammatories in nanoparticulate systems, nanospheres poly-lactic co-glycolic acid (PLGA), the technique used allows the encapsulation of hydrophilic and hydrophobic compounds in the same polymer nanoparticle, diclofenac sodium (DS) and dexamethasone (DX), respectively, obtaining nanoparticles with potential for the treatment of chronic inflammatory diseases. For the development of nanospheres the technique used was emulsion / solvent evaporation. The nanospheres were characterized by zeta potential infrared, particle size, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and pH. The encapsulation of the drug (diclofenac sodium and dexamethasone) in the nanospheres was performed by previously validated analytical techniques high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). In the best formulation was achieved encapsulation 51.4 ± 5.5% for diclofenac and 66.9 ± 8.4 for dexamethasone

Doctor of Philosophy / Department of Food, Nutrition, Dietetics and Health / Tonatiuh Melgarejo / Mark Haub / Human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) have an enormous therapeutic potential because of their immunomodulatory and anti-inflammatory properties. However, there are limitations for their therapeutic use due to low cell survival after implantation, the risk of culture-borne pathogens, and the risk of embolism and thrombosis after intravenous infusion. Exosomes, on the other hand, constitute an important part of the MSCs secretome and may play a role in their therapeutic effects. Here, it was demonstrated that HUC-MSC-derived exosomes accumulate in human and mouse osteosarcoma cell lines in vitro and reduce their proliferation. The distribution of HUC-MSCs exosomes was shown in osteosarcoma tumor- bearing mice. Exosome distribution in vivo was observed using Magnetic Resonance Imaging (MRI) of gadolinium-labeled exosomes and by fluorescent imaging after infusion of near infrared dye-labeled exosomes. HUC-MSC exosomes accumulated in the tumor throughout the 48 hours ours post-injection period. In contrast, synthetic lipid nanoparticle accumulate in tumor only for the first 3ours post-injection. These results suggest that labeling with gadolinium or near-infrared dye may affect exosome accumulation within the spleen. In summary, this study showed that HUC-MSCs exosomes can accumulate to osteosarcoma cells in vitro and in vivo, and thus they may be useful for detecting cancer metastasis.

Neste trabalho, desenvolvemos um gerador de nanopartículas (NPs) como uma adaptação para um sistema de magnetron sputtering. Com ele, somos capazes de produzir NPs de materiais diversos e codepositá-las em matrizes dielétricas ou metálicas. A adaptação consiste em incluir uma região de alta pressão relativa de Ar no caminho do vapor atômico removido do alvo. A aglomeração ocorre termodinamicamente devido a diminuição da energia cinética após colisões com o gás. Desenvolvemos também, uma metodologia para colimar o fluxo de NPs dentro da região de alta pressão. A deposição é feita no substrato na forma de uma mancha com alguns milímetros de diâmetro e o tempo de preparação da amostra é significativamente curto. Desenvolvemos um modelo fenomenológico para explicar a condensação e a colimação do nosso sistema. Este, apesar de não sofisticado, explica bem ambos os fenômenos e consegue prever o diâmetro das nanopartículas para certas condições. Em paralelo ao desenvolvimento, produzimos e caracterizamos nanopartículas de cobalto. Da caracterização morfológica, através de microscopia eletrônica, concluímos que as NPs produzidas tem diâmetros médios de 10 nm com uma dispersão de 13 %. Através de análises de retro espalhamento Rutherford estudamos a distribuição do material sobre o substrato e observamos que este segue uma distribuição Gaussiana de espessuras. Além disso, devido a colimação, observamos que as taxas de deposição são da ordem de 50 vezes maiores que as taxas usuais de um sistema de sputtering. Estudos estruturais através de difração de raios X mostraram que as nanopartículas são nanocristalinas e imagens em alta magnificação de microscopia eletrônica de transmissão comprovaram esta hipótese. Finalmente, estudos magnéticos mostraram que as NPs não possuem eixos preferenciais de magnetização. Desenvolvemos condições padrões de operação e estabilizamos o sistema que atualmente produz amostras confiáveis e reprodutíveis. Além do Co, nanopartículas de Cu e SmCo foram produzidas em condições parecidas. A morfologia destas partículas foi investigadas por microscopia eletrônica e seus tamanhos se mostraram próximos dos das NPs de Co. Estes resultados ilustraram a universalidade do nosso sistema de deposição de nanopartículas. / We have developed a nanoparticle (NP) generator by adapting one of the sputtering guns on a magnetron sputtering system. With it, we are able to produce nanoparticles with different types of material. The adaptation consists of including a high-pressure region in the path of the atomic vapor removed from the sputtering target. The condensation happens thermodynamically through the loss of kinetic energy that the atomic vapor suffers after collisions with the gas. We have also developed a methodology to collimate the flow of nanoparticles inside the high pressure region. The deposition on the substrate is in the form of a stain with a few millimeters in diameter. The sample preparation time is also relatively short. We created a phenomenological model to explain both the condensation and collimation phenomena in our system. Despite being relatively simple, this model explain both quite well. In parallel to the development of the system, we produced and characterized cobalt nanoparticles. From a morphological analysis, carried out using electron microscopy, we determined that the nanoparticles mean diameter is of about 10 nm with a dispersion of 13 %. Through Rutherford back-scattering analysis, we studied the thickness distribution of the sample along the substrate. We observed that it follows a Gaussian distribution. Also, because of the collimation of the material, the deposition rates are about 50 times higher than in a regular sputtering system. Using X ray diffraction we were able to determine that the NPs are nano-crystalline which is corroborated with high resolution transmission electron microscopy images. Finally, magnetic measurements showed that the nanoparticles do not have any preferential magnetization axis. We developed standards of operations and stabilized the system. The samples we produce are trustworthy and reproducible. Besides Co, Cu and SmCo NPs were produced using this system with conditions similar to the ones used on the Co NPs. Through morphological analysis, we determined that their sizes are also similar. These results illustrate the universality of our system.

Silver nanoparticles (sub 10 nm), supported on, or in, cellulose, have been demonstrated to be well stabilised and immobilised during application in a model continuous reaction: the reduction of 4-nitrophenol (4-NP) to 4-aminophenol with sodium borohydride. The production of these silver nanoparticles (NP), within the cellulose supports, was carried out by either in situ reduction of silver precursors absorbed into the preformed cellulose supports, or, by inclusion of ex situ synthesised NPs (prepared in DMSO solutions) in the dissolution of cellulose and trapping upon subsequent coagulation of cellulose. The effects of NP synthesis method (affecting particle size and agglomeration) and the cellulose morphology and porous structure were examined with respect to the catalytic activity of the materials. The in situ reduction of a silver salt with aqueous NaBH4 solutions (0.03 to 1.0 wt. %) led to tuneable Ag NP sizes with mean diameters of 5 to 11 nm (TEM) and metal loadings of 0.5-1.0 wt. %. The catalytic activity of these samples in the 4-NP reduction reaction (0.05 mM, 0.167 M NaBH4, 30 °C) was demonstrated to increase upon decreasing NP size: TOF values of 22–356 h-1, consistent with a Langmuir-Hinshelwood mechanism. The porous structure of these Ag-cellulose materials (0.2 to 294 m2 g-1) was demonstrated to be variable and dependent on drying treatments of the regenerated cellulose hydrogel. Thermal drying, freeze-drying and critical point drying resulted in materials with different bulk structure and porosity. In turn the different porosities resulted in extremely different catalyst activities, e.g. Ag-cellulose catalyst (0.3 mm disks) thin film, hydrogel and cryogel phases exhibited TOF values of 2, 12 and 178 h-1, respectively. In addition, the NP synthesis could be carried out in either the cellulose hydrogel or cryogel, which led to different extents of Ag NP catalyst stabilisation against agglomeration during the 4-NP reaction and catalyst recovery and recycling. The Ag NPs synthesised in the cryogel cellulose disks were observed to undergo agglomeration (TEM) after use in 4 repeat batch reductions, whilst those NPs synthesised in the hydrogel cellulose, prior to freeze-drying to the final cryogel catalyst material, did not exhibit any agglomeration upon 4 repeat reduction reactions. The ex situ reduction of Ag and Au NPs was carried out by the reduction of AgOAc and Au(OAc)3 by DMSO and variation of the NP synthesis parameters, such as time (10 min – 1h) and temperature (50 – 80 °C), allowed for control of the NP sizes (3 to 6 nm Ag NPs and 4 to 11 nm Au NPs, TEM). It was demonstrated that the addition of the polysaccharide starch (0.42 wt. % in DMSO) allowed for consistent Ag NP size (ca. 4 nm) to be achieved throughout the 8 h synthesis, the starch acting as both the reducing and capping agent, maintaining the small sizes and narrow particle size distributions of the NPs upon aging (72 h). A kinetic model with a bimolecular nucleation step was developed to describe this reduction of the silver acetate by the starch/DMSO system. However, contact of the NPs with solutions of imidazolium ILs, 1-Ethyl-3-methylimidazolium acetate (EmimOAc) and 1-Butyl-3-methylimidazolium chloride (BmimCl) in DMSO, used in the dissolution of cellulose, led to the oxidation of the Ag(0) and Au(0) NPs. Thus, when these NP solutions were mixed in cellulose solutions regeneration by phase inversion with the aim of preparing cellulose/NP composites led to materials with negligible metal loadings (AAS). This oxidation, of the metal NPS, was partially overcome by stabilisation of the starch capped Ag NPs by pre-treatment with cellulose (1:1 mixture of α and MC cellulose). However, the activity of the resulting Ag-cellulose catalyst (0.5 wt. % AAS, 6.7 nm TEM) was much lower than the Ag-cellulose catalysts prepared by in situ reduction of silver in the cellulose hydrogel, despite the comparable NP sizes. This was presumed to be a result of encapsulation of the Ag NPs by the cellulose, leading to a decrease in the accessible surface of the NPs. Finally, the use of Ag NP / cellulose composites, prepared by in situ reduction of silver in cellulose hydrogel beads (0.19 wt. %, 6.4 nm), were demonstrated in the continuous reduction of 4-NP in a packed bed reactor (τ’ 100 g s dm-3). The activation energies of the reactions of 4-NP catalysed by the Ag-cellulose catalyst materials were determined (3.2 to 9.4 kJ mol-1) from Arrhenius plots, which demonstrated that above 20 °C the reaction was likely subject to diffusion limitations in the cellulose beads. The high degree of stabilisation of the Ag NPs against agglomeration imparted by the cellulose support was demonstrated: the rate of reaction was observed to be constant over 120 h, treating 45 L of 4-NP solution, with the catalyst material after use demonstrating no significant leaching of silver, or agglomeration, of NPs (AAS, TEM).