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Partial sequencing of a single DNA molecule with a scanning tunnelling microscope


The scanning tunnelling microscope is capable of the real-space imaging and spectroscopy of molecules on an atomic scale. Numerous attempts have been made to use the scanning tunnelling microscope to sequence single DNA molecules, but difficulties in preparing samples of long-chain DNA molecules on surfaces, and problems in reproducing results have limited these experiments1,2,3,4,5,6. Here, we report single-molecule DNA sequencing with a scanning tunnelling microscope by using an oblique pulse-injection method to deposit the molecules onto a copper surface. First, we show that guanine bases have a distinct electronic state that allows them to be distinguished from the other nucleic acid bases. Then, by comparing data on M13mp18, a single-stranded phage DNA, with a known base sequence7, the ‘electronic fingerprint’ of guanine bases in the DNA molecule is identified. These results show that it is possible to sequence individual guanine bases in real long-chain DNA molecules with high-resolution scanning tunnelling microscope imaging and spectroscopy.

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Figure 1: STM imaging and spectroscopy of single-stranded peptide nucleic acid (ssPNA) and DNA adsorbed on a Cu(111) surface.
Figure 2: Deposition and STM analysis of single-stranded M13mp18 DNA molecules on a Cu(111) surface.
Figure 3: STM imaging of M13mp18 DNA extended and fixed on a Cu(111) surface.
Figure 4: Partial topographic image, dI/dV map and dI/dV spectra of M13mp18 DNA.
Figure 5: Bias voltage dependence on the STM imaging of M13mp18 DNA on a Cu(111) surface.


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The authors thank A. V. Balatsky and S. Kilina for valuable comments and correction of the manuscript, and H. Sakamoto and K. Suzuki for their technical assistance. This work was financially supported by CREST, JST (Japan Science and Technology Agency) and NEDO (the New Energy and Industrial Technology Development Organization). H.T. is grateful for a Grant-in-Aid for Scientific Research for the Encouragement of Young Scientists (B) (no.14750236) from the Japan Society for the Promotion of Science (JSPS).

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H.T. and T.K. conceived and designed the experiments. H.T. performed the experiments and analysed the data. H.T. wrote the paper. H.T. and T.K. discussed the results.

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Correspondence to Hiroyuki Tanaka or Tomoji Kawai.

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Tanaka, H., Kawai, T. Partial sequencing of a single DNA molecule with a scanning tunnelling microscope. Nature Nanotech 4, 518–522 (2009).

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