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DNA computing on surfaces

Nature volume 403, pages 175–179 (2000)Cite this article

Abstract

DNA computing was proposed1 as a means of solving a class of intractable computational problems in which the computing time can grow exponentially with problem size (the ‘NP-complete’ or non-deterministic polynomial time complete problems). The principle of the technique has been demonstrated experimentally for a simple example of the hamiltonian path problem2 (in this case, finding an airline flight path between several cities, such that each city is visited only once3). DNA computational approaches to the solution of other problems have also been investigated4,5,6,7,8,9. One technique10,11,12,13 involves the immobilization and manipulation of combinatorial mixtures of DNA on a support. A set of DNA molecules encoding all candidate solutions to the computational problem of interest is synthesized and attached to the surface. Successive cycles of hybridization operations and exonuclease digestion are used to identify and eliminate those members of the set that are not solutions. Upon completion of all the multi-step cycles, the solution to the computational problem is identified using a polymerase chain reaction to amplify the remaining molecules, which are then hybridized to an addressed array. The advantages of this approach are its scalability and potential to be automated (the use of solid-phase formats simplifies the complex repetitive chemical processes, as has been demonstrated in DNA and protein synthesis14). Here we report the use of this method to solve a NP-complete problem. We consider a small example of the satisfiability problem (SAT)2, in which the values of a set of boolean variables satisfying certain logical constraints are determined.

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Figure 1: Overview of the surface-based approach to DNA computations.
Figure 2: Four cycles of SAT computation.
Figure 3: Three-dimensional plot and histogram of the fluorescence intensities on a 16 element addressed array used for ‘readout’.

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Acknowledgements

We thank S. Gillmor and J. Brockman for help with the preparation of the photopatterned read-out arrays, and M. Lagally for discussions. This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the National Science Foundation.

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Author notes

  1. Qinghua Liu

    Present address: Gen-Probe, Inc., San Diego, California, 92121, USA

  2. Anthony G. Frutos

    Present address: Corning Inc., Corning, New York, 14831, USA

  3. Anne E. Condon

    Present address: Department of Computer Science, University of British Columbia, Vancouver, BC V6T 1Z4, Canada

Authors and Affiliations

  1. Department of Chemistry,

    Qinghua Liu, Liman Wang, Anthony G. Frutos, Robert M. Corn & Lloyd M. Smith

  2. Department of Computer Science, University of Wisconsin, Madison, 53706, Wisconsin, USA

    Anne E. Condon

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Correspondence to Lloyd M. Smith.

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Liu, Q., Wang, L., Frutos, A. et al. DNA computing on surfaces. Nature 403, 175–179 (2000). https://doi.org/10.1038/35003155

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