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Electrochemical DNA analysis comes of age

Nature Biotechnology volume 18, pages 1042–1043 (2000)Cite this article

For the past 30 years, fluorescence methods have dominated instrumentation for DNA analysis. However, this era, ushered in by the pioneering work of Leroy Hood and colleagues at Cal Tech in the late 1970s, may soon be brought to an end by high-density, high-throughput microarray systems1. Ever since Arnold Beckman developed the pH electrode in 1935, electrochemical methods have held considerable promise for measuring chemical species. A perfect example of their versatility and sensitivity is shown in this issue, where Barton and coworkers have used electrocatalysis to detect single-base mismatches in double-stranded DNA (dsDNA) immobilized on an electrode surface2. This work demonstrates some of the unique properties of electrochemical methods that can be exploited to create modern instrumentation for genetic analysis.

In recent years a number of formats have been developed for this purpose—namely, direct detection of DNA in solution, detection of electrical signals after sample DNA hybridization to surface-immobilized probes, and detection of alterations in the electrical properties of DNA through charge transfer reactions. Barton and coworkers have exploited the latter approach, one that does not rely solely on hybridization to detect whether a DNA in the sample can pair with a single-stranded probe. Instead, they immobilized dsDNA to a gold electrode surface by means of a thiol tether, and detected charge transport through the DNA duplex as it shuttles from a redox-active DNA intercalator (methylene blue) to a redox species (ferricyanide)2. They report that when the surface-immobilized dsDNA is perfectly matched, charge transport through the π-stacked helix occurs readily. However, this charge transport is disrupted by the presence of a single-base mismatch or a damaged DNA base, thereby blocking redox catalysis by the DNA film. In the other extreme, when only single-stranded DNA (ssDNA) is immobilized to the surface, electron transfer to the redox mediator is not blocked by the DNA film, and redox catalysis occurs as if no DNA were present. Using this method, they could easily differentiate single-base mismatches from the fully paired complement in synthetic oligonucleotides corresponding to sequences from the human p53 gene.

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  1. Department of Chemistry, University of California, Riverside, 92521, CA

    Werner G. Kuhr

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Kuhr, W. Electrochemical DNA analysis comes of age. Nat Biotechnol 18, 1042–1043 (2000). https://doi.org/10.1038/80229

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