The microscopic distribution of microspheres and the resulting radiation dose deposition patterns in human liver following hepatic arterial infusion of 90Y labelled microspheres have been investigated. Tissue samples from normal liver, the tumour periphery and tumour centre were taken from a patient following infusion of 3 GBq of 32 pm diameter resin microspheres labelled with 90Y as treatment for an 80 millimetre diameter metastatic liver tumour. Microspheres were found to deposit inhomogeneously in tissues, preferentially lodging in a region approximately 6 mm wide around the periphery of the tumour. A relative concentration of microspheres of 50 to 70 times that of normal hepatic parenchyma and 65 to 94 times that in the tumour centre was measured in this region. The deposition of microspheres in the tumour periphery was not uniform, and cluster analysis showed that the spheres could be classified into clusters. The number of microspheres in a cluster was skewed towards low numbers and cluster sizes varied from 20 pm to 1500 pm. Microsphere deposition in normal liver was demonstrated to be non-uniform, there being significant variations in concentration over distances on the order of 3 to 4 millimetres. The observed microsphere distributions in three dimensions were used to calculate radiation dose patterns, and the results showed that heterogeneous doses were delivered to all tissues. Within the tumour periphery average doses ranged from 200 Gy to 600 Gy with minimum doses between 70 Gy and 190 Gy. The maximum and minimum doses for the tumour centre sample were 920 Gy and 3.7 Gy respectively, the median dose was 5.8 Gy. In the normal liver sample the median dose was 7.3 Gy with maximum and minimum doses of 753 Gy and 5 Gy respectively. Less than 1% of the normal liver tissue volume received more than 30 GY, the level above which complications have resulted for ++ / whole liver exposure using external beam radiotherapy. These calculations suggest that preferential deposition of microspheres in the well vascularised periphery of large tumours will lead to a high proportion of the tumour volume receiving a therapeutic dose, with most of the normal liver tissue being spared substantial damage.

No description available.

Porous Wall Hollow Glass Microspheres (PWHGMs) were developed by the Savannah River National Laboratory. What makes these microspheres unique is the interconnected porosity spread throughout their wall allowing various materials to travel from the surface to the hollow interior. With their characteristic porosity, the PWHGMs are a great tool for encapsulating or filtrating different materials. Unfortunately, there is little information available on the mechanical properties of PWHGMs. The main goal of this research was to develop a method to crush individual microspheres and statistically analyze the results. One objective towards completing this goal was to measure the microsphere diameter distribution. Microsphere diameter is a major factor affecting strength as well as the Weibull parameters. Two different methods, microscopy counting and laser light scattering, used in the research yielded similar distributions. The main objective of this research was to analyze the crush strength of individual microspheres. Using nanoindentation, data were collected to analyze the crush strength of PWHGMs in uniaxial compression. Nanoindentation data were used to analyze how the strength of the PWHGMs changes through the different stages of production and at different diameter ranges. Data for 3M commercial microspheres were compared to ARC microspheres. Most data were analyzed using a statistical technique known as the two parameter Weibull analysis. The data indicated that the strength generally decreased as the microsphere diameter increased. Scattering in the data was nearly the same across all sample sets tested. Results indicated that the PWHGMs were weaker than the ARC hollow glass microspheres (HGMs). This is primarily due to the addition of wall porosity in the PWHGM. / Master of Science

Tissue engineered blood vessels (TEBVs) have great potential as tools for disease modeling and drug screening. However, existing methods for fabricating TEBVs create homogenous tissue tubes, which may not be conducive to modeling focal vascular diseases such as intimal hyperplasia or aneurysm. In contrast, our lab has a unique modular system for fabricating TEBVs. Smooth muscle cells (SMCs) are seeded into an annular agarose mold, where they aggregate into vascular tissue rings, which can be stacked and fused into small diameter TEBVs. Our goal is to create a platform technology that may be used for fabricating focal vascular disease models, such as intimal hyperplasia. Because tubes are fabricated from individual ring units, each ring can potentially be customized, enabling the creation of focal changes or regions of disease along the tube length. In these studies, we first demonstrated our ability to modulate cell phenotype within individual SMC ring units using incorporated growth factor-loaded degradable gelatin microspheres. Next, we evaluated fusion of ring subunits to form composite tissue tubes, and demonstrated that cells retain their spatial positioning within individual rings during fusion. By incorporating electrospun polycaprolactone cannulation cuffs at each end, tubes were mounted on bioreactors after only 7 days of fusion to impart luminal medium flow for 7 days at a physiological shear stress of 12 dyne/cm2. We then created focal heterogeneities along the tube length by fusing microsphere-containing rings in the central region of the tube between rings without microspheres. In the future, microspheres may be used to deliver growth factors to this localized region of microsphere incorporation and induce disease phenotypes. Due to the challenges of working with primary human SMCs, we next evaluated human mesenchymal stem cells (hMSCs) as an alternative cell source to generate vascular SMCs. We evaluated the effects of microsphere-mediated platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor beta-1 (TGF-β1) delivery on ring thickness, proliferation, and contractile protein expression over a 14 day period. Finally, we created a structurally distinct region of smooth muscle within tissue tubes by fusing human aortic SMCs in a central region between hMSC rings. In summary, we developed a platform technology for creating modular tubular tissues that may be further developed into an in vitro intimal hyperplasia model. It may also be modified to model other focal vascular diseases, such as aneurysm, or to create other types of multi-tissue tubular structures, such as trachea.

For cavity quantum electrodynamics systems (cavity-QED) to play a role in quantum information processing applications and in quantum networks, they must be robust and scalable in addition to having a suitable method for the generation, processing and storage of quantum bits. One solution is to develop a composite system that couples a nitrogen vacancy (NV) center in diamond to a whispering gallery mode supported by a fused silica microsphere. Such a system is motivated by the optical and electron-spin properties of the NV center. The NV center is the leading spin-qubit and exhibits atomic like linewidths at cryogenic temperatures and has spin coherence times greater than milliseconds at room temperature. These long coherence times, coupled with nanosecond scale spin readout and manipulation times, allow for millions of quantum operations to be processed. Silica whispering gallery resonators are the only class of microresonators with quality factor high enough to reach the strong coupling regime, which is necessary for some quantum information processing applications. Integrating these two components into a system that could position a diamond nanopillar near the surface of a deformed-double stemmed microsphere system, with nanometer precision, at 10 K was a major achievement of this research. Cavity resonances in deformed microspheres can be excited with a free-space coupling technique which simplifies their integration into cryogenic environments. In these intentionally deformed resonators, an enhanced evanescent field decay length was observed at specific locations along the ray orbit. The double-stem arrangement enables the cavity resonance to be tuned over 450 GHz, with sub-10 MHz resolution, at 10 K. These two features, the enhanced decay length and broad range tuning with high resolution, are indispensible tools for cavity-QED studies with silica microspheres. Diamond nanopillars were fabricated from single crystal diamond with diameters as small as 140 nm in order to maintain a high quality factor. Studies were conducted on NV centers in nanopillars and bulk diamond to determine their suitability for cavity-QED applications. In an attempt to increase the light-matter interaction between NV centers and whispering gallery modes, diamond substrates were optically characterized that were irradiated with nitrogen ions.

Chronic total occlusions are a common problem in patients with coronary artery disease. The primary barrier to successful percutaneous coronary intervention is inability to cross the lesion with a guidewire. We seek to characterize polymer microspheres as a controlled delivery mechanism for collagenase and VEGF, novel intralesional therapies being investigated to alter CTO structural properties. Release profiles for protein-loaded PLGA [poly(lactic-co-glycolic acid)] microspheres showed sustained BSA and VEGF release over eight and 48 hours respectively. Polymer degradation products had no impact on endothelial cell growth and protein bioactivity was maintained post-release. In vivo localization of microsphere-released collagenase was not possible due to low concentrations remaining at the site. Histology confirmed microspheres remained in the collagen-dense, proximal 15 mm of the lesion, likely altering the structural integrity of the plaque.

Chronic total occlusions are a common problem in patients with coronary artery disease. The primary barrier to successful percutaneous coronary intervention is inability to cross the lesion with a guidewire. We seek to characterize polymer microspheres as a controlled delivery mechanism for collagenase and VEGF, novel intralesional therapies being investigated to alter CTO structural properties. Release profiles for protein-loaded PLGA [poly(lactic-co-glycolic acid)] microspheres showed sustained BSA and VEGF release over eight and 48 hours respectively. Polymer degradation products had no impact on endothelial cell growth and protein bioactivity was maintained post-release. In vivo localization of microsphere-released collagenase was not possible due to low concentrations remaining at the site. Histology confirmed microspheres remained in the collagen-dense, proximal 15 mm of the lesion, likely altering the structural integrity of the plaque.

Over the last decade in North America, an increasing number of microbiological drinking water regulations have been used to manage groundwater resources that are potentially influenced by surface water. Regulations such as the Ontario Ministry of Environment Regulation 505, which requires at least a 60 day groundwater travel time between surface waters and drinking water wells, have been created with limited understanding of subsurface pathogen transport processes. Groundwater Under Direct Influence studies (GUDI or GWUDI in USA) are conducted to assess the need to treat well water at an extraction point. Currently, there is a lack of knowledge regarding factors that affect the transport of pathogens through porous media at the surface water-groundwater interface. Such information is required to supply sufficient quantities of drinking water in a cost effective and safe manner. <br /><br /> Factors that affect pathogen transport through porous media include: properties of the pathogen (i. e. surface charge, size, and morphology), properties of the granular media (i. e. mineralogy, size, texture, angularity) and properties of the water (i. e. pH, ionic strength and content, and natural organic matter). This study examines the effects of ionic strength, grain size and influent virus concentrations on pathogen transport in porous media. Fourteen column tests were conducted using the bacteriophage MS2 and 1. 5 µm microspheres; two commonly used non-pathogenic surrogates representative of human viruses and bacteria, respectively. Two size distributions of crushed silica sand, with median grain diameters of 0. 7 and 0. 34 mm, and two ionic strengths of 8 and 95 mmol/L were used. A 2² partial factorial design was used with a minimum of two replicates of each combination of the parameters. <br /><br /> The results show that complete breakthrough of both viruses and microspheres occurred in medium sand at low ionic strength. It was found that increasing ionic strength by Ca²⁺ addition precluded breakthrough of MS2 in both the medium and fine sands. This represents a greater than 8 log reduction in peak effluent concentration and essentially complete attenuation. <br /><br /> In fine sand, with low ionic strength water, a 5 log reduction in peak MS2 concentrations was observed. In the same sand at high ionic strength, no MS2 broke through the column, corresponding to a greater than 8 log removal. Since complete attenuation occurred in both grain sizes at high ionic strength, the effect of higher ionic strength in the fine sand was indistinguishable from the effect observed from raising the ionic strength in the medium sand. <br /><br /> In contrast to the viruses, microsphere transport was essentially unaffected by increasing ionic strength under the conditions investigated. A 1 log reduction in peak concentration was observed in the high ionic strength water in the medium sand. In spite of this, grain size had a profound effect on the attenuation of microspheres. There was no evidence of microsphere breakthrough in any of the fine sand columns at the low or high ionic strengths, yielding a greater than 5 log reduction in microsphere concentration associated with grain size alone. The effect of varying virus concentration was also investigated. It was found that varying the concentration of viruses between 10⁵ and 10⁷ pfu/ml had no discernable effect on their observed transport characteristics; normalised peak breakthrough concentration, percent attenuation and retardation relative to a bromide tracer. <br /><br /> Based on the results from this Thesis, in a riverbank filtration environment, there is reason to expect that, at comparable water qualities and in similar porous media, multiple logarithmic reductions of viruses and bacteria would occur over the much longer (than column length) flowpaths associated with RBF. There is also reason to expect this attenuation capability to vary based on riverbank grain size and water chemistry.

Over the last decade in North America, an increasing number of microbiological drinking water regulations have been used to manage groundwater resources that are potentially influenced by surface water. Regulations such as the Ontario Ministry of Environment Regulation 505, which requires at least a 60 day groundwater travel time between surface waters and drinking water wells, have been created with limited understanding of subsurface pathogen transport processes. Groundwater Under Direct Influence studies (GUDI or GWUDI in USA) are conducted to assess the need to treat well water at an extraction point. Currently, there is a lack of knowledge regarding factors that affect the transport of pathogens through porous media at the surface water-groundwater interface. Such information is required to supply sufficient quantities of drinking water in a cost effective and safe manner. <br /><br /> Factors that affect pathogen transport through porous media include: properties of the pathogen (i. e. surface charge, size, and morphology), properties of the granular media (i. e. mineralogy, size, texture, angularity) and properties of the water (i. e. pH, ionic strength and content, and natural organic matter). This study examines the effects of ionic strength, grain size and influent virus concentrations on pathogen transport in porous media. Fourteen column tests were conducted using the bacteriophage MS2 and 1. 5 µm microspheres; two commonly used non-pathogenic surrogates representative of human viruses and bacteria, respectively. Two size distributions of crushed silica sand, with median grain diameters of 0. 7 and 0. 34 mm, and two ionic strengths of 8 and 95 mmol/L were used. A 2² partial factorial design was used with a minimum of two replicates of each combination of the parameters. <br /><br /> The results show that complete breakthrough of both viruses and microspheres occurred in medium sand at low ionic strength. It was found that increasing ionic strength by Ca²⁺ addition precluded breakthrough of MS2 in both the medium and fine sands. This represents a greater than 8 log reduction in peak effluent concentration and essentially complete attenuation. <br /><br /> In fine sand, with low ionic strength water, a 5 log reduction in peak MS2 concentrations was observed. In the same sand at high ionic strength, no MS2 broke through the column, corresponding to a greater than 8 log removal. Since complete attenuation occurred in both grain sizes at high ionic strength, the effect of higher ionic strength in the fine sand was indistinguishable from the effect observed from raising the ionic strength in the medium sand. <br /><br /> In contrast to the viruses, microsphere transport was essentially unaffected by increasing ionic strength under the conditions investigated. A 1 log reduction in peak concentration was observed in the high ionic strength water in the medium sand. In spite of this, grain size had a profound effect on the attenuation of microspheres. There was no evidence of microsphere breakthrough in any of the fine sand columns at the low or high ionic strengths, yielding a greater than 5 log reduction in microsphere concentration associated with grain size alone. The effect of varying virus concentration was also investigated. It was found that varying the concentration of viruses between 10⁵ and 10⁷ pfu/ml had no discernable effect on their observed transport characteristics; normalised peak breakthrough concentration, percent attenuation and retardation relative to a bromide tracer. <br /><br /> Based on the results from this Thesis, in a riverbank filtration environment, there is reason to expect that, at comparable water qualities and in similar porous media, multiple logarithmic reductions of viruses and bacteria would occur over the much longer (than column length) flowpaths associated with RBF. There is also reason to expect this attenuation capability to vary based on riverbank grain size and water chemistry.

Pulp from recycled paper products contains various waxes, glues, adhesives, filler, and inorganics that are collectively referred to as contaminants. Contaminants that are not drained out during the forming process are trapped in the sheet and carried down the paper machine. These contaminant particles and contaminants in solution can become deposited on the dryer cylinders. The contaminants which deposit on the dryer cylinders lead to reduced quality and production of paper on the machine. The process by which contaminants are deposited on a dryer cylinder has not been explored at a fundamental level. Rather, quick industrial fixes have been tested to try and eliminate the contaminant deposition and only reductions in deposition have been achieved. The literature reviewed does not relate the flow of particle suspensions through porous media to the heat transfer and fluid dynamics processes associated with drying paper. The experiments in the literature showed the general trends of particle and dye distributions across the thicknesses of different porous media during forming or filtration processes. Filler and fines distribution were not able to be changed by flows induced by pressing a sheet. The mechanisms for how particles move through porous media found in the literature were a basis for what kind of phenomena would be expected in the particle flow experiments. A means of completely eliminating sticky deposits could be found by examining the parameters which contribute to the deposition process. The hypothesis proposed in this thesis is that contaminant particles and liquid containing contaminants are transported to the dryer can surface by liquid flows induced by the drying process. By performing particle flow experiments during drying, bounds for the particle size, initial drying surface temperature, drying time, and initial solids content will be determined for which the hypothesis is true. The particle and dye transport studies performed showed an array of processes at work simultaneously. The results from the particle and dye transport studies show that a particle diameter of ~1.0 and #956;m or less, handsheet solids content of less than 30%, open sheet structure and a high surface drying temperature (200C) were needed to create a significant change in filler and dye distribution across the thickness of a handsheet.