Miniaturized electrochemical cells for applications in drug screening and protein cleavage

    Research output: ThesisPhD Thesis - Research UT, graduation UT

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    Abstract

    This thesis describes the design of a small flow-through electrochemical cell in a lab-on-chip format. This cell contains a complete, integrated 3-electrode setup with platinum working and counter electrodes and a palladium or iridiumoxide pseudo-reference electrode. The cell has sub-microliter internal volumes and is aimed for high turnover rates of the introduced chemical species. Using this cell, the turnover rate of small and fast reacting ions is studied and found to be near to 100%. Also, the cell is used to mimic the oxidative metabolism of the enzyme CYP450. Although direct oxidation can not be compared directly to enzymatic oxidation, it can be used to screen drugs at an early stage of development. The direct oxidation of procainamide and amodiaquine is studied in this thesis. Procainamide is a known antiarrythmic drug, while procainamide is a known antimalarial agent. The electrochemical cell on-chip was able to generate the main metabolites of both drugs. The thesis also describes preliminary work of tyrosine specific electrochemical cleavage of proteins as alternative to tryptic digestion. Some cleavage of the tripeptide Leucine-Tyrosine-Leucine is observed, although future work requires a redesign of the chip and the surrounding equipment for this specific task to get sufficient cleavage efficiency. In the final chapter, redox cycling is investigated as a tool to measure electrochemical compounds with a high selectivity and high sensitivity. Using this phenomena, a new measurement method named differential cyclic voltammetry (DCV) is proposed. This method provides easy and simultaneous detection of concentrations of redox cyling compounds with a high selectivity. The method is investigated both theoretically using finite element computer simulations and experimentally using an interdigitated array electrode.
    Original languageUndefined
    Awarding Institution
    • University of Twente
    Supervisors/Advisors
    • van den Berg, Albert , Supervisor
    • Olthuis, Wouter , Advisor
    Thesis sponsors
    Award date4 Mar 2011
    Place of PublicationZuthphen
    Publisher
    Print ISBNs978-90-365-3143-6
    DOIs
    Publication statusPublished - 4 Mar 2011

    Keywords

    • METIS-277713
    • EWI-20327
    • IR-76123

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