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Identifying single bases in a DNA oligomer with electron tunnelling

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Abstract

It has been proposed that single molecules of DNA could be sequenced by measuring the physical properties of the bases as they pass through a nanopore1,2. Theoretical calculations suggest that electron tunnelling can identify bases in single-stranded DNA without enzymatic processing3,4,5, and it was recently experimentally shown that tunnelling can sense individual nucleotides6 and nucleosides7. Here, we report that tunnelling electrodes functionalized with recognition reagents can identify a single base flanked by other bases in short DNA oligomers. The residence time of a single base in a recognition junction is on the order of a second, but pulling the DNA through the junction with a force of tens of piconewtons would yield reading speeds of tens of bases per second.

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Figure 1: Reading a single base within a heteropolymer.
Figure 2: Tunnelling signals from nucleotides trapped in a functionalized tunnel gap.
Figure 3: Tunnelling signal distributions from oligomers resemble those of the constituent nucleotides.
Figure 4: The lifetime of the reading complex is on the order of a second at zero force.

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Acknowledgements

The authors acknowledge useful discussions with O. Sankey, P. Krstic and B. Gyarfus. P. Collins made helpful comments on an earlier version of this manuscript. H. Liu composed the graphic for Fig. 1a. This work was supported by a grant from the Sequencing Technology Program of the National Human Genome Research Institute (HG004378). R.R. and A.F. were supported by a grant from the National Cancer Institute (U54CA143682).

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S.H., S.C. and J.H. carried out tunnelling measurements and characterized the samples. P.Z., F.L. and Sq. L. designed, synthesized and characterized reagents. M.T. prepared tunnelling probes. A.F. and R.R. carried out force spectroscopy. S.L. designed experiments, analysed data and wrote the paper.

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Correspondence to Stuart Lindsay.

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S.L., P.Z. and J.H. are named as inventors in patent applications.

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Huang, S., He, J., Chang, S. et al. Identifying single bases in a DNA oligomer with electron tunnelling. Nature Nanotech 5, 868–873 (2010). https://doi.org/10.1038/nnano.2010.213

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