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.

Master of Science / Department of Chemical Engineering / John Schlup / This study investigated the specular reflectance properties of 6061-T6 aluminum alloy anodized in accordance with military specification MIL-A-8625 as a function of both etch process time and anodization process potential. Both process parameters affect the specular reflectance characteristics when measured using a 660 nm, collimated diode laser source. The etch process time, when varied between 0.5 to 20 minutes, resulted in a decrease in specular reflectivity with increasing time. The anodization process potential was varied between 10 and 21 volts, with a 15 volt condition producing samples with the greatest specular reflectivity. Between the two parameters, the etch time had the greater effect. Additionally, the dependence of the incident beam angle on specular reflectivity was shown not to have a significant effect when compared to the etch process time and process potential.

Master of Science / Department of Chemical Engineering / Larry Erickson / Oxy-fired boilers are receiving increasing focus as a potential response to reduced boiler emissions limits and greenhouse gas legislation. Among the challenges in cleaning boiler gas for sequestration is attaining the necessary purity of the CO[subscript]2. A key component in the oxy-fired cleaning path is high purity SO[subscript]x and NO[subscript]x removal, often through absorption using the lead-chamber or similar process. Aerosol formation has been found to be a source of product contamination in many flue gas absorption processes. A number of authors presented simulation methods to determine the formation of aerosols in gas absorption. But these methods are numerically challenging and not suitable for day-to-day analysis of live processes in the field. The goal of this study is to devise a simple and practical method to predict the potential for and effect of aerosol formation in gas absorption using information from Aspen Plus, a commonly used process simulation tool. The NO[subscript]x absorber in an oxy-fired boiler CO[subscript]2 purification system is used as a basis for this investigation. A comprehensive review of available data suitable for simulating NO[subscript]x absorption in an oxy-fired boiler slipstream is presented. Reaction rates for eight reactions in both liquid and vapor phases are covered. These are entered into an Aspen Plus simulation using a RadFrac block for both rate-based and equilibrium reactions. A detailed description of the simulation format is given. The resulting simulation was compared to a previously published simulation and process data with good agreement. An overall description of the aerosol formation mechanism is presented, along with an estimate of expected aerosol nuclei reaching the NO[subscript]x absorption process. A method to estimate aerosol quantities produced based on inlet gas nuclei concentration and available condensable water vapor is presented. To estimate aerosol composition and emissions, an exit gas slipstream is used to equilibrate with a pure water aerosol using an Aspen Plus Equilibrium Reactor block. Changing the composition of the initial aerosol feed liquid suggests that the location of aerosol formation may influence the final composition and emissions.

Master of Science / Department of Chemical Engineering / John Schlup / In this study, life cycle analysis (LCA) of shea butter biodiesel from Well-to-Pump (WTP) is considered utilizing information gathered from Anuanom Industrial Bio Products Ltd. (AIBP) in Ghana, West Africa. The information presented in this report starts with shea plant cultivation, proceeds through harvesting of shea fruits, extraction of shea butter from shea kernels, and finishes with the production of shea butter biodiesel via homogenous acid–alkali transesterification reactions utilizing methanol. After researching the conversion of shea butter to biodiesel, the GREET software was explored as a tool to perform LCA. Shea butter is an excellent alternative feedstock to produce biodiesel on an industrial scale. Though research into shea plant cultivation and subsequent conversion into biodiesel in Ghana has not received formal attention, it has huge potential in the biodiesel industry. The tree originates in Africa and is tropical and drought-resistant. Although even some basic agronomic characteristics of shea butter are not yet fully understood, the plant enjoys a booming interest, which may hold the risk of unsustainable practice. The GREET software from the Argonne National laboratory of the US Department of Energy (DOE) was used in LCA. The software is a very useful tool specifically designed for LCA focused on energy and emissions of different production processes, including biodiesel production. This software is managed by DOE research laboratory and is made available for public use. The GREET software allow users perform many existing fuel production processes. To perform an LCA on shea butter biodiesel which is a new feedstock to the GREET software, some of the requisite information, and data input has to be sent to the Argonne National Laboratory personnel for input. For a new biodiesel feedstock such as shea butter which is not part of the GREET software database, it is important to work with the Argonne National laboratory to perform the LCA.

Factors that may govern diesel particulate matter (DPM) oxidation at low temperatures (~200°C) were studied using reactivity and TP-ToFSIMS analysis. Best-case scenarios that give maximum gasification rates were determined for DPM impregnated with KOH and non-catalyzed DPM using temperature programmed oxidation and isothermal experiments. Conditions of intimate catalyst-carbon contact (K/C molar ratio=1/50) and high NO2 concentrations (1%) to improve the reactivity of the carbon reactive sites were unable to meet the steady state gasification rate needed for particulate filter regeneration for a modern diesel engine at 200°C. Oxygen-free thermal annealing (>500°C) caused reactivity losses of a maximum of 40% that correspond to changes to surface morphology and/or concentration of oxygen-containing functional groups. TP-ToFSIMS identified surface functional group changes with temperature on non-dosed and NOX pre-dosed (1.5%NO, 1%NO2, 4.5%O2, balance helium) diesel soot and sucrose char. Detailed analysis of the NOX dosed sucrose char spectra using both inspection and principal component analysis techniques revealed that the 1200 ion fragments created could be reduced to five sets of ions that are chemically and kinetically distinct. These sets presumably represent surface functional groups on the carbon. For example, Set IV may represent carboxylic acid, lactone, or carboxylic anhydride functional groups. Based on these results a mechanism for the surface reaction of NO2 with carbon under vacuum conditions was postulated. At temperatures less than 200°C the ion fragments contain primarily carbon-NO2 type ions. As temperature increases between 200 and 400°C the ion fragments are primarily carbon-NO and carbon-N type fragments. At higher temperatures (>500°C) the surface is enriched with nitrogen containing functional groups. A surface reaction mechanism is proposed where NO2 is bonded to an armchair site and with increasing temperatures and molecular rearrangements the N is incorporated into the carbon ring. The initial surface composition of NOx containing functional groups changes within the area of relevance of low temperature soot regeneration (i.e. between 25° and 200°C). Further studies are needed to understand the effect of N-incorporation on carbon reactivity. No rate processes either in reactor studies or based on surface functional groups met the rate criteria for low temperature DPM oxidation.

A microencapsulation-based technology platform for effective delivery of multiple micronutrients for food fortification has been developed. The technology, consisting of extrusion agglomeration followed by encapsulation through surface coating, has been successfully tested on three size scales in typical staple foods: as a surface treatment on salt and sugar, on 20-100µm scale; in salt on a 300-1200 μm scale; and on reconstituted rice on the 5-10 mm scale. The process results in effective delivery systems for one or more active ingredients with organoleptic properties that are unnoticeable to the average consumer. Particularly, salt double fortified with iodine and iron using the microencapsulated ferrous fumarate premix made by the extrusion-based agglomeration process had acceptable sensory properties and stability when stored at 40oC and 60% relative humidity (RH) for up to a year. In these tests >85% of iodine and >90% of ferrous iron were retained. Reconstituted Ultra Rice® grains made by extrusion stabilized by internal gelation has resulted in improved grain integrity and a much simplified process, compared to the original, patented surface crosslinking technique. The most effective internal gelation system is composed of alginate, calcium sulphate (CaSO4), and sodium tripolyphosphate (STPP) at a best ratio of 3%:3%:0.6% (w/w). It is feasible to incorporate folic acid into the existing fortification programs using the technology platform developed in this study. The results indicate that the potential interactions of folic acid with other added micronutrients or with the food vehicles could be prevented by incorporating folic acid as a premix made by the extrusion-based technology. Virtually no folic acid was lost after 9 months storage at 40oC and 60% RH when the folic acid premix was added into salt or sugar samples. The technical feasibility of the microencapsulation-based technology platform has been successfully demonstrated for micronutrient delivery in food vehicles of different size ranges, resulting in fortified staple foods with desired physical, chemical, nutritional, and organoleptic properties. The technology should be adaptable to formulating customized delivery systems of active ingredients for broader applications, and promises to bring immediate benefits in combatting micronutrient deficiencies, that will have far reaching effects in health and social development.

The effects of crosslinking on EVA foaming are studied in this thesis. A fundamental approach was applied to describe the influences of crosslinking on EVA/gas viscosities, gas solubility and diffusivity in EVA, EVA foaming nucleation and early stage of bubble growth, which leads to a better understanding of the plastic foaming mechanism. Although crosslinked polyolefin foaming technology has been well applied in industry, more fundamental and thorough studies are demanded to understand the mechanism, which can serve to improve the present technology. The shear and extensional viscosities have been measured for the chemically crosslinked EVA with dissolved gas which could not be found from literature. Furthermore, by controlling the crosslinking agent amount, the polymer melt strength/viscosity can be controlled, so as to obtain optimum foam morphology. The crosslinking also has effects on the diffusivity and solubility of a blowing agent inside EVA. The solubility and the diffusivity of the blowing agent in the EVA decrease with the crosslinking degree increases. The diffusivity decrease makes more gas is utilized for the foaming rather than leak out of the polymer matrix quickly. This thesis also presents the fundamental studies on the effects of crosslinking on cell nucleation and early bubble growth. Theoretical work and in-situ visualization experimental results indicate that partial crosslinking leads to higher cell nucleation density and slower bubble growth, both of which benefit a fine-cell foam morphology generation. Last but not least, an optimized foaming process was conducted to produce chemically crosslinked EVA foams with large expansion ratios in a batch system, using a chemical blowing agent. The results determine that an optimal crosslinking degree is critical for the crosslinked EVA foaming with maximum expansion ratio. Furthermore, all research results not only benefit the foaming of crosslinked EVA, but also serve the better production of other crosslinked polyolefin foams.

This thesis describes the characterization of benzene-degrading denitrifying cultures. Four objectives were pursued. The first objective was to identify conditions that promote or inhibit benzene decomposition and thus, to improve the biodegradation capacity of the cultures. FeS, resazurin, and nitrite had a detrimental impact on benzene degradation, whereas addition of supernatant from an active culture improved the benzene degradation activity by reducing the lag times. The second objective was to determine the microbial community composition in enrichment cultures and to identify the bacterial species that mediate benzene mineralization. Five dominant bacterial Operational Taxonomic Units (OTUs) were identified. The most abundant phylotype was related to the gram-positive Peptococcaceae family. Other bacteria present were closely affiliated with Dechloromonas, Azoarcus, Chlorobi and Anammox species. To correlate the growth of these specific microbes with benzene degradation, the abundance of specific 16S rRNA genes was monitored during mineralization process using quantitative polymerase chain reaction (qPCR). Based on the result of qPCR experiments and information about the metabolisms of the above bacteria, a syntrophic mode of benzene degradation was hypothesized to occur under denitrifying conditions. In this process, Peptococcaceae initiate attack on benzene, and ferment benzene to hydrogen and low molecular weight products such as acetate. These products are then consumed by nitrate-respiring Azoarcus and Dechloromonas or phototrophic Chlorobi. Anammox bacteria recycle and detoxify nitrite, and stabilize the culture. The third objective was to isolate and characterize pure cultures with the ability to mineralize benzene anaerobically. Dechloromonas- and Dechlorosoma-like microorganisms were isolated from several benzene-degrading microcosms. Theses bacteria, however, were not able to metabolize benzene anaerobically. The fourth objective was to investigate the key metabolic steps in the anaerobic benzene degradation pathway and to identify enzymes that are involved in this process. Differential transcription during growth of the culture on benzene versus growth on a metabolite of benzene degradation, i.e. benzoate was examined. Carboxylase-related genes were specifically transcribed in the presence of benzene. Furthermore, mRNA sequences corresponding to the genes that encode different enzymes of the benzoyl-CoA degradation pathway were present in the culture. These findings suggest that mineralization of benzene starts by its activation to benzoate through a carboxylation reaction catalyzed by benzene carboxylase. Benzoate is further metabolized through benzoyl-CoA pathway.

Catalytic supercritical water gasification (SCWG) is a promising technology for hydrogen and methane production from wet organic feedstocks at relatively low temperatures (e.g. <500 oC). However, in order to make this process technically and economically viable, solid catalyst with enhanced activity and improved hydrogen selectivity should be developed. In this study, different aspects of catalytic SCWG have been investigated. The performance of several supported-nickel catalysts were examined to identify catalysts that lead to high carbon conversion and high hydrogen yields under near-critical conditions (i.e. near 374 oC). Moreover, for the first time, the effects of several parameters which dominated the activity of the supported nickel catalysts have been systematically investigated. Among the several different catalyst supports evaluated at 5% nickel loading, α-Al2O3, carbon nanotube (CNT), and MgO supports resulted in highest carbon conversions, while SiO2, Y2O3, hydrotalcite, yttria-stabilized zirconia (YSZ), and TiO2 showed modest activities. Comparing the XRD patterns for the support materials before and after the exposure to supercritical water, α-Al2O3, YSZ, and TiO2 were found to be hydrothermally stable among the metal oxide supports. Using the same amount of nickel on α-Al2O3, the methane yield decreased by increasing the nickel to support ratio whereas the carbon conversion was only slightly affected. At a given nickel to support ratio, a threefold increase in methane yield was observed by increasing the temperature from 350 to 410 oC. The catalytic activity also increased by the addition small quantity of potassium. The activity of Ni/γ-Al2O3 catalyst varied based on the affinity of the catalyst to form nickel aluminate spinel. This is also the first report on the role of oxidative pretreatment of the carbon nanotubes by nitric acid on the performance of these catalysts for the supercritical water gasification process. Using different lignocellulosic feeds, it was found that the gasification of glucose, fructose, cellulose, xylan and pulp resulted in comparable gas yields (± 10%) after 60 min, whereas alkali lignin was substantially harder to gasify. Interestingly, gasification yield of bark, which had a high lignin content, was comparable to those of cellulose. In summary, the Ni/α-Al2O3 catalyst had a higher hydrogen selectivity and comparable catalytic activity to the best commercially available catalysts for SCWG of carbohydrates.

Treatment of cardiac diseases involves transplantation of donor hearts, since the damaged heart has limited self-regeneration potential. An alternative treatment option has emerged as engineered cardiac tissues, grown in vitro by cultivation of cardiac cells on biomaterials, have comparable properties to native myocardium and can be implanted for cardiac repair. Major current limitations are a viable cell source and adequate vascularization to support cell survival. In this thesis, two proangiogenic biomaterials, a scaffold and a hydrogel, were developed to achieve vascularization in vitro and in vivo for cardiac repair. Scaffold patches are suitable for repairing congestive heart failure or congenital malformations, while injectable biomaterials allow minimally-invasive treatment post-myocardial infarction (MI). In the first aim, a collagen scaffold with covalently immobilized vascular endothelial growth factor (VEGF) was developed, and improved cell mobilization, survival and proliferation when used for free wall repair in adult rats. This increased angiogenesis, which aided in retaining the biomaterial size to allow tissue growth. In the second aim, a collagen-chitosan hydrogel with encapsulated thymosin β4 (Tβ4) was developed to 1) recruit cells from the heart epicardium for repair post-MI in vivo, and 2) guide capillary outgrowths from arteries and veins to form oriented capillary structure for in vitro cardiac tissue engineering. Results showed that the encapsulation of Tβ4 into collagen-chitosan hydrogels led to cell outgrowths from rat or mouse cardiac explants in vitro. A portion of the recruited cells were CD31-positive endothelial cells (ECs) that formed tubes. The hydrogel was injected in vivo to increase vascularization and number of cardiomyocytes within the infarct area post-MI, which improved left ventricular wall thickness. Tβ4-hydrogel also promoted the outgrowth of capillaries from vascular explants that followed the direction of the hydrogel-coated grooves of a micropatterned polydimethylsiloxane (PDMS) substrate. These capillary outgrowths eventually formed a vascular bed for engineering vascularized cardiac tissues. This thesis presents two bioinstructive biomaterials with sustained and localized delivery of angiogenic molecules to be used for in situ cardiac repair based on improved vascularization. The use of cell-free bioactive materials overcomes limitations of cell isolation and expansion as required for cell therapies or implantation of engineered tissues.