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Nucleic Acids Research 2004 32(17):4962-4968; doi:10.1093/nar/gkh817
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Published online 23 September 2004

Nucleic Acids Research, Vol. 32 No. 17 © Oxford University Press 2004; all rights reserved

DNA computing using single-molecule hybridization detection

Kristiane A. Schmidt1,2,*, Christiaan V. Henkel1,2, Grzegorz Rozenberg2,3 and Herman P. Spaink1,2

1 Institute of Biology, Leiden University, Wassenaarseweg 64, 2333 AL Leiden, The Netherlands, 2 Leiden Center for Natural Computing and 3 Leiden Institute of Advanced Computer Science, Leiden University, Niels Bohrweg 1, 2333 CA Leiden, The Netherlands

* To whom correspondence should be addressed at present address: Philips Research, Personal Care Institute, Prof. Holstlaan 4 (WA11), 5656 AA Eindhoven, The Netherlands. Tel: +31 40 27 46773; Fax: +31 40 27 44288; Email: kristiane.schmidt{at}philips.com

Received July 1, 2004; Revised and Accepted August 23, 2004

DNA computing aims at using nucleic acids for computing. Since micromolar DNA solutions can act as billions of parallel nanoprocessors, DNA computers can in theory solve optimization problems that require vast search spaces. However, the actual parallelism currently being achieved is at least a hundred million-fold lower than the number of DNA molecules used. This is due to the quantity of DNA molecules of one species that is required to produce a detectable output to the computations. In order to miniaturize the computation and considerably reduce the amount of DNA needed, we have combined DNA computing with single-molecule detection. Reliable hybridization detection was achieved at the level of single DNA molecules with fluorescence cross-correlation spectroscopy. To illustrate the use of this approach, we implemented a DNA-based computation and solved a 4-variable 4-clause instance of the computationally hard Satisfiability (SAT) problem.


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