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Towards a Real-Time, Label-Free, Diamond-Based DNA Sensor

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Hasselt University and Transnationale Universiteit Limburg, School for Life Sciences, Biomedical Research Institute, Agoralaan, Building A, B-3590 Diepenbeek, Belgium, Hasselt University and Transnationale Universiteit Limburg, School for Life Sciences, Institute for Materials Research, Wetenschapspark 1, B-3590 Diepenbeek, Belgium, and IMEC vzw, Division IMOMEC, Wetenschapspark 1, B-3590 Diepenbeek, Belgium
Cite this: Langmuir 2007, 23, 26, 13193–13202
Publication Date (Web):November 16, 2007
Copyright © 2007 American Chemical Society

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    Abstract Image

    Most challenging in the development of DNA sensors is the ability to distinguish between fully complementary target ssDNA (single-strand DNA) and 1-mismatch ssDNA. To deal with this problem, we performed impedance spectroscopy on DNA-functionalized nanocrystalline diamond (NCD) layers during hybridization and denaturation. In both reactions, a difference in behavior was observed for 1-mismatch target DNA and complementary target DNA in real-time. During real-time hybridization, a decrease of the impedance was observed at lower frequencies when the complementary target DNA was added, while the addition of 1-mismatch target ssDNA caused no significant change. Fitting these results to an electrical circuit demonstrates that this is correlated with a decrease of the depletion zone in the space charge region of the diamond. During real-time denaturation, differentiation between 1-mismatch and complementary target DNA was possible at higher frequencies. Denaturation of complementary DNA showed the longest exponential decay time of the impedance, while the decay time during 1-mismatch denaturation was the shortest. The real-time hybridization and denaturation experiments were carried out on different NCD samples in various buffer solutions at temperatures between 20 and 80 °C. It was revealed that the best results were obtained using a Microhyb hybridization buffer at 80 °C and 10× PCR buffer at 30 °C for hybridization and 0.1 M NaOH at temperatures above 40 °C for denaturation. We demonstrate that the combination of real-time hybridization spectra and real-time denaturation spectra yield important information on the type of target. This approach may allow a reliable identification of the mismatch sequence, which is the most biologically relevant.

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     Biomedical Research Institute, Hasselt University and Transnationale Universiteit Limburg.

     These authors contributed equally to this publication.


     Institute for Materials Research, Hasselt University and Transnationale Universiteit Limburg.

     IMEC vzw, Division IMOMEC.


     To whom correspondence should be addressed. E-mail:  luc.michiels@; tel.:  (+32)-11-26-92-31; fax:  (+32)-11-26-92-35.

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