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Indirect electrochemical detection of DNA hybridization based on catalytic oxidation of cobalt(II) and concentration gradient formation in redox conducting polymers

Date

2008

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Abstract

Since the new concept was introduced back in 1993, efforts to develop electrochemical methods for detecting nucleic acid hybridization (e.g., DNA) have mushroomed. Compared with nearly all other analytical techniques, electrochemical instrumentation is inexpensive, robust, and relatively simple to operate. The first part of the dissertation (Chapter 1 to Chapter 4) describes the development of a novel electrochemical DNA sensor based on catalytic oxidation of a cobalt bipyridine "mediator molecule" on an ITO electrode. Interaction of the surface bound DNA probe with the DNA target results in formation of hybrid duplex, which subsequently brings redox catalyst molecules from solution to the electrode surface. The mode of selective catalyst binding is intercalation between base pairs of ds-DNA. This surface-bound catalyst "turns on" the redox chemistry of the mediator molecule which is otherwise kinetically inert to oxidation on ITO. With this approach, we demonstrate detection of a 20-mer DNA target oligonucleotide at picomolar concentrations with outstanding signal-to-noise. The second part of our research (Chapter 5) mainly concerns redox polymer films containing permanently locked concentration gradients. Upon redox gradient formation, the conducting polymer displays interesting properties, such as solid diode behavior and electroluminescence. Previous methods explored drying and/or cooling the film to physically immobilize its gradient. Unfortunately, this preservation was temporary, and underwent degradation over time. Our work is aimed to overcome this limitation by covalently attaching counterions to the polymer backbone and thus permanently locking the redox gradients. Both parts of this dissertation utilize heteroleptic metal complexes possessing redox potentials close to zero (vs SSCE). Compounds with highly negative potentials are strongly reducing and highly positive potentials means strong oxidizing capabilities, which exerts strict requirements on supporting electrolytes and solvents, including high impurity, broad potential window as well as exclusion of environmental interference. Thus, the closer the potential to zero (vs SSCE), the more stable (electrochemically) the complex and the easier the electrochemical measurements.

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Subject

catalytic oxidation
cobalt(II)
conducting polymers
DNA hybridization
DNA sensors
electrochemical detection
analytical chemistry
biochemistry

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