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Perfuorocarboxylate Isomer Aanalysis as a Tool for Source ElucidationDe Silva, Amila 31 July 2008 (has links)
Perfluorocarboxylates (PFCAs) are a class of anthropogenic compounds ubiquitously
found in the environment. PFCAs and their precursors are largely manufactured by
electrochemical fluorination (ECF) or telomerization. ECF products are mixtures of isomers with linear (70-80%) and branched perfluoroalkyl moiety. Telomerization does not produce
isomer mixtures and is predominantly n-perfluorocarbons. This thesis examined the
environmental fate and disposition of PFCAs from a relevant and novel perspective of industrial isomer signature. Potential influences of physical and biological properties of isomers on the
environmental PFCA isomer pattern were investigated. Branched isomers were more water soluble than n-isomer, however, KOW did not indicate any appreciable differences among isomers. It is possible that the similarity in KOW is due to a balancing effect between elevated
activity coefficients in both water and n-octanol. In fish and rats, the major branched isomers of ECF PFOA were eliminated faster than n-isomer. In comparison, PFOS isomer pharmacokinetics were indistinguishable. These findings highlight the need to understand
underlying mechanisms mediating PFCA and PFOS isomer pharmacokinetics which may
constrain extrapolation from animal-based models to humans. Environmental monitoring
revealed PFCA isomers in both abiotic and biotic environment, in temperate regions and remote Arctic. Branched PFOA isomers were consistent with ECF production. In temperate regions, industrially produced ECF PFOA was expected to be a major source of these isomers, given its legacy and volume of production. In the Arctic, PFOA isomers consistent with an ECF signature
were attributed to ECF perfluorooctylsulfonamides which likely undergo long range atmospheric transport and atmospheric reactions. The major difference in ECF signature between remote and temperate regions is the presence of ECF PFNA isomers compared to their absence in the Arctic. ECF PFNA is an impurity in ECF PFOA, comprising 0.2%. Input from a linear source, such as fluorotelomer compounds, was also suggestive as both PFOA and PFNA were >95% linear, much more than in technical ECF. Furthermore, longer chain ECF impurities do not account for the PFNA, PFDA, PFUnA, etc. in the Arctic.
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Exploring Sources of Human and Environmental Fluorochemical ContaminationD'eon, Jessica C. 05 September 2012 (has links)
Perfluorinated carboxylates (PFCAs) and perfluorinated sulfonates (PFSAs) are found almost ubiquitously in the environment, however their direct production and use is limited. The focus of this thesis was to explore connections between observed contamination with the manufacture and/or use of commercial fluorochemical materials. Perfluorinated sulfonamides (PFSAms) are semi-volatile materials used in the manufacture of commercial fluorochemicals. Investigations into the atmospheric fate of a model PFSAm found atmospheric lifetimes that allow transport to remote environments, potentially through a novel N–dealkylation product. A suite of PFCAs, as well as the PFSA from loss of the amide moiety, were also observed. This investigation demonstrated that PFSAm atmospheric oxidation will contribute to PFCA and PFSA contamination in remote locations, including the Arctic.
The perfluorinated phosphonates (PFPAs) were used as defoaming additives in pesticide formulations. Using novel extraction and analysis methods, widespread PFPA contamination was detected in Canadian surface waters and wastewater treatment plant (WWTP) effluent. As fully fluorinated acids, the PFPAs are a new class of perfluorinated acid discovered in the environment. Uptake and elimination parameters determined in the rat demonstrate the potential for human PFPA exposure, as these chemicals are bioavailable.
Processes governing the pharmacokinetics and disposition of perfluorinated acids in the body are poorly understood. Novel heteronuclear nuclear magnetic resonance experiments identified human serum albumin as the major site of interaction. Competitive binding experiments found the PFCAs displaced the endogenous human serum albumin ligand, 13C1-oleic acid, at lower concentrations than established ligands. The strong association observed between the PFCAs and human serum albumin may inform observed human toxic endpoints and long elimination half-lives.
The polyfluoroalkyl phosphates (PAPs) are used in food-contact paper packaging. High PAP concentrations were discovered in human sera, waste paper fibres and WWTP sludge, establishing human exposure to these chemicals. Biotransformation from PAP to PFCA was investigated in a rat model. The serum kinetics and PFCA products observed, suggest PAP exposure may be a significant source of human PFCA contamination.
The concerted approach of environmental monitoring with investigations of atmospheric and biological fate allowed strong associations to be made between commercial fluorochemical sources and observed contamination.
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Towards a Microfluidic Toolbox for Proteomics: Novel Sample Pre-processing and Separation TechniquesWatson, Michael 15 September 2011 (has links)
Microfluidics was introduced in the early 1990’s and was posited to usher in a new age of integrated analysis systems in the form of labs-on-a-chip. To date, numerous embodiments of microfluidic technologies including fully integrated analysis systems have been described for various applications. Microfluidics can be sub-divided into two paradigms based on fluid manipulation in streams or droplets. In the former, streams of fluids flow through micron-dimension channels, and typical volumes manipulated are in the pico-liter to nano-litre range. These devices are mainly employed for rapid, high efficiency chemical separations, among other applications. In the latter, droplets are manipulated on a dielectric-coated array of microelectrodes in a process called digital microfluidics (DMF). In DMF each droplet is individually addressable, giving superior spatial control over fluid droplets with volumes in the pico-liter to micro-litre range. Independently addressable droplets make DMF amenable to carrying out sequential reactions. This thesis presents methods towards the integration of these two microfluidic paradigms into “hybrid microfluidic” platforms. Hybrid devices contain a DMF array for sample preparation and a microfluidic channel network for on-line analysis by chemical separation. Sample transfer between the platforms is made by way of a digital-channel interface, which has been fabricated in two geometries: side-on and vertical. Chemical separations on hybrid devices are performed in various open-channel and chromatographic modes. In open-channel methods analytes are separated by microchannel zone electrophoresis (MZE) or micellar electrokinetic chromatography (MEKC). In chromatographic separations porous polymer monolithic (PPM) columns were created in situ by UV-initiated polymerization of acrylate monomers. Prior to integration into hybrid microfluidic devices PPMs were optimized for use in gradient elution microchannel electrochromatography (MEC) of peptides. It is anticipated that hybrid microfluidic devices will bridge a large bottleneck for myriad analyses by combining sample preparation with on-line analysis by chemical separation.
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Development and Utilization of Shear Mode Acoustic Wave Biosensors for the Detection of Ovarian CancerSaoud, Marwan 28 July 2010 (has links)
Recent proteome studies have discovered the presence of heat shock protein 10 (HSP-10) as an immunosuppressant in ovarian cancer patients. Due to the severity of ovarian cancer, the development of highly sensitive techniques for the early detection of this cancer is well in demand. In this manuscript, the thickness shear mode (TSM) acoustic wave biosensor will be used for the real-time and label-free detection of HSP-10 in buffer. The TSM sensitivity for HSP-10 is evaluated based on resonance frequency shifts generated by the biosensor. A nucleic acid aptamer, which is specifically engineered by in vitro selection to target HSP-10, is employed as the biosensing element of the biosensor. Alkylthiol-based self-assembling monolayers (SAMs), composed of various linker/diluent molar ratios, are used to immobilize the aptamer onto gold-coated piezoelectric quartz substrates. The TSM biosensing properties for avidin-biotin interactions are also evaluated in order to assess the biosensor response to HSP-10 protein-aptamer interaction.
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Innovative Approaches for the Electrochemical Detection of Acetylcholinesterase InhibitorsDounin, Vladimir 31 December 2010 (has links)
This document describes research conducted during 2009-2010 in the Kerman Group laboratory at the University of Toronto Scarborough to investigate the application of electrochemical techniques for the detection of acetylcholinesterase inhibitors in aqueous samples. Two main projects were completed and are discussed herein. The first project demonstrated that the new unmodified, nanostructured gold disposable electrochemical printed (DEP) chips produced by BioDevice Technology can compete with surface-modified electrode configurations to detect trace concentrations of insecticides. This was achieved through the measurement of acetylcholinesterase-catalyzed production of thiocholine after incubation of the enzyme with low concentrations of paraoxon (10 ppb) and carbofuran (8 ppb). The second project featured the novel application of a glassy carbon (GC) electrode to monitor the changes in availability of Thioflavin T (ThT) for oxidation at the electrode surface, which is non-linearly modulated by the presence of acetylcholinesterase and the enzyme’s pre-treatment with trace concentrations of paraoxon and carbachol.
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Towards a Surface Microarray based Multiplexed Immunoassay on a Digital Microfluidics PlatformUddayasankar, Uvaraj 12 January 2011 (has links)
The use of digital microfluidics (DMF) for sample handling in a microarray immunoassay was investigated. A two plate DMF device was used, with the top plate being used for the immobilization of antibodies for a sandwich immunoassay. A patterning procedure was developed for the top plate to expose patches of glass that were chemically modified, using silane chemistry, to allow for the covalent immobilization of antibodies. For creating microarrays, a set of parallel microchannels were used for the high density patterning of proteins onto the functionalized surface of the top plate. This patterning procedure was optimized to ensure the reproducibility of the immobilization and the physical integrity of the top plate. Preliminary work for a multiplexed immunoassay such as verification of cross-reactivity and detection schemes was also conducted. This work represents the initial efforts towards a microarray immunoassay on DMF, which has the potential to improve high throughput analysis.
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Miniaturized Electrochemical Immunosensors for the Detection of Growth HormoneLi, Qi 21 March 2012 (has links)
The first part of this research involves the development of a gold-nanoparticle based sandwich type immunosensor to identify trace amounts of human chorionic gonadotropin hormone based on the direct electrochemical detection of Au nanoparticles. The second part of this research is to design a biosensor that can be easily handled, has higher specificity, sensitivity, low-cost, and rapid response and has a better detection of growth hormone (GH). Current bioanalytical techniques have reported the difficulty to detect GH doping. This research aims to address the issue of measuring GH in small volumes, which has been challenging the limits of analytical detection systems. The electrochemical measurements utilize the redox activity of ferro/ferricyanide in cyclic voltammetry and impedance spectroscopy. The detection limit 10 pg/mL was observed for GH in 20 μL sample volume, which indicated that this versatile platform can be easily adapted for decentralized electrochemical immunosensing of clinically important proteins.
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Development and Utilization of Shear Mode Acoustic Wave Biosensors for the Detection of Ovarian CancerSaoud, Marwan 28 July 2010 (has links)
Recent proteome studies have discovered the presence of heat shock protein 10 (HSP-10) as an immunosuppressant in ovarian cancer patients. Due to the severity of ovarian cancer, the development of highly sensitive techniques for the early detection of this cancer is well in demand. In this manuscript, the thickness shear mode (TSM) acoustic wave biosensor will be used for the real-time and label-free detection of HSP-10 in buffer. The TSM sensitivity for HSP-10 is evaluated based on resonance frequency shifts generated by the biosensor. A nucleic acid aptamer, which is specifically engineered by in vitro selection to target HSP-10, is employed as the biosensing element of the biosensor. Alkylthiol-based self-assembling monolayers (SAMs), composed of various linker/diluent molar ratios, are used to immobilize the aptamer onto gold-coated piezoelectric quartz substrates. The TSM biosensing properties for avidin-biotin interactions are also evaluated in order to assess the biosensor response to HSP-10 protein-aptamer interaction.
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Innovative Approaches for the Electrochemical Detection of Acetylcholinesterase InhibitorsDounin, Vladimir 31 December 2010 (has links)
This document describes research conducted during 2009-2010 in the Kerman Group laboratory at the University of Toronto Scarborough to investigate the application of electrochemical techniques for the detection of acetylcholinesterase inhibitors in aqueous samples. Two main projects were completed and are discussed herein. The first project demonstrated that the new unmodified, nanostructured gold disposable electrochemical printed (DEP) chips produced by BioDevice Technology can compete with surface-modified electrode configurations to detect trace concentrations of insecticides. This was achieved through the measurement of acetylcholinesterase-catalyzed production of thiocholine after incubation of the enzyme with low concentrations of paraoxon (10 ppb) and carbofuran (8 ppb). The second project featured the novel application of a glassy carbon (GC) electrode to monitor the changes in availability of Thioflavin T (ThT) for oxidation at the electrode surface, which is non-linearly modulated by the presence of acetylcholinesterase and the enzyme’s pre-treatment with trace concentrations of paraoxon and carbachol.
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Towards a Surface Microarray based Multiplexed Immunoassay on a Digital Microfluidics PlatformUddayasankar, Uvaraj 12 January 2011 (has links)
The use of digital microfluidics (DMF) for sample handling in a microarray immunoassay was investigated. A two plate DMF device was used, with the top plate being used for the immobilization of antibodies for a sandwich immunoassay. A patterning procedure was developed for the top plate to expose patches of glass that were chemically modified, using silane chemistry, to allow for the covalent immobilization of antibodies. For creating microarrays, a set of parallel microchannels were used for the high density patterning of proteins onto the functionalized surface of the top plate. This patterning procedure was optimized to ensure the reproducibility of the immobilization and the physical integrity of the top plate. Preliminary work for a multiplexed immunoassay such as verification of cross-reactivity and detection schemes was also conducted. This work represents the initial efforts towards a microarray immunoassay on DMF, which has the potential to improve high throughput analysis.
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