Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references. Also available on the World Wide Web.

In the first part of this work, magnetized nanoporous silica based microparticles (MMPs) are used for horseradish peroxidase (HRP) immobilization and applied in amperometric peroxidase-based biosensors. A homemade magnetized carbon paste electrode permits the MMPs attraction close to the electrode surface. The resulting original biosensor is applied to the investigation of enzymatic oxidation of model drug compounds namely, clozapine (CLZ) and acetaminophen (APAP) by HRP in the presence of hydrogen peroxide. The biosensor operates at a low applied potential and the signal corresponds to the electro-reduction of electroactive species enzymatically generated. The biosensor allows performing the quantitation of the two drug compounds in the micromolar concentration range. It allows also the study of thiol compounds based on the inhibition of the biosensor response. Interestingly, distinct inhibition results are observed for HRP entrapped in the silica microparticles compared to the soluble HRP. We expect that this type of biosensors holds high promise in quantitative analysis and in biotransformation studies of drug compounds. In the second part of this thesis work, HRP immobilized magnetic nanoparticles are injected on-line and magnetically retained, as a microreactor, in the capillary of a CE setup. The purpose of such a configuration is to develop an analytical tool for studying “in vitro” drug biotransformation. The advantages expected are (i) minimum sample (drug compound) and biocomponent (enzyme) consumption, (ii) high analysis throughput, (iii) selectivity and sensitivity. In order to illustrate the potential of such an instrumental configuration, it has been applied to study acetaminophen as model drug compound. The mechanistic information obtained by the HRP/H2O2 system is in agreement with literature data on acetaminophen metabolization. Horseradish peroxidase kinetic studies are realized by this setup and the apparent Michaelis constant is determined. Capillary electrophoresis permitted the identification of APAP off-line biotransformed products such as N-acetyl-p-benzoquinone imine (NAPQI), the APAP dimer and APAP polymers as inferred from literature data. The formation of the APAP dimer was further confirmed by electrospray ionization mass spectrometry.

Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisor: Dionisios G. Vlachos, Dept. of Chemical Engineering. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 73-79).

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 156-160).

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Thesis (Ph. D.)--Oregon State University, 2009. / Printout. Includes bibliographical references. Also available on the World Wide Web.

More than 1.2 million people worldwide require regular hemodialysis therapy to treat end stage renal failure. In the United States alone, there are 300,000 patients and the National Kidney Foundation predicts that this number will double in the next 10 years. Currently most dialysis patients receive treatment at a dialysis center and need three 4-5 hour treatments each week. While these treatments are useful, more frequent and longer duration dialysis better simulates natural kidney function. Consequently, at-home hemodialysis is expected to provide patients a better quality of life. Current hemodialysis systems are too expensive to support at-home hemodialysis. Cost drivers include the capital costs of the hemodialysis equipment and the raw material costs of expensive hemodialysis membranes. Microchannel hemodialysers have smaller form factors requiring significantly less membrane while enabling reductions in the size and cost of capital equipment. Microchannel devices are typically made by microchannel lamination methods involving the patterning, registration and bonding of thin laminae. Findings in this paper show that membrane utilization is highly dependent on registration accuracy with membrane utilization often dropping below 25%. Efforts here focus on the development of a self-registration method for assembling microchannel hemodialysers capable of supporting registration accuracies below 25 ��m over a 50 mm polycarbonate lamina. Using these methods, registration accuracies below 13 ��m were measured over a 50 mm scale. A mass transfer test article was produced with measured average one dimensional misregistration below 19 ��m with a demonstrated membrane utilization of 44.9% when considering both microchannel and header regions. Mass transfer results suggest that the device performed with a mass transfer area of 90.59 mm��. A design is proposed describing membrane utilization of over 79%. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from 9-17-2012 - 9-17-2013

Thesis (M.S.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 77-78). Also available on the World Wide Web.

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