Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Local electrical potential detection of DNA by nanowire–nanopore sensors

Nature Nanotechnology volume 7, pages 119–125 (2012)Cite this article

Subjects

Abstract

Nanopores could potentially be used to perform single-molecule DNA sequencing at low cost and with high throughput1,2,3,4. Although single base resolution and differentiation have been demonstrated with nanopores using ionic current measurements5,6,7, direct sequencing has not been achieved because of the difficulties in recording very small (∼pA) ionic currents at a bandwidth consistent with fast translocation speeds1,2,3. Here, we show that solid-state nanopores can be combined with silicon nanowire field-effect transistors to create sensors in which detection is localized and self-aligned at the nanopore. Well-defined field-effect transistor signals associated with DNA translocation are recorded when an ionic strength gradient is imposed across the nanopores. Measurements and modelling show that field-effect transistor signals are generated by highly localized changes in the electrical potential during DNA translocation, and that nanowire–nanopore sensors could enable large-scale integration with a high intrinsic bandwidth.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Nanowire–nanopore transistor.
Figure 2: Single-channel nanowire–nanopore FET detection of DNA translocation.
Figure 3: Nanowire–nanopore sensing mechanism.
Figure 4: Multi-channel recording of DNA translocation with three nanowire–nanopore FET sensors.

Similar content being viewed by others

References

  1. Branton, D. et al. The potential and challenges of nanopore sequencing. Nature Biotechnol. 26, 1146–1153 (2008).

    Article  CAS  Google Scholar 

  2. Venkatesan, B. M. & Bashir, R. Nanopore sensors for nucleic acid analysis. Nature Nanotech. 6, 615–624 (2011).

    Article  CAS  Google Scholar 

  3. Zwolak, M. & Ventra, M. D. Colloquium: physical approaches to DNA sequencing and detection. Rev. Mod. Phys. 80, 141–163 (2008).

    Article  Google Scholar 

  4. Dekker, C. Solid-state nanopores. Nature Nanotech. 2, 209–215 (2007).

    Article  CAS  Google Scholar 

  5. Clarke, J. et al. Continuous base identification for single-molecule nanopore DNA sequencing. Nature Nanotech. 4, 265–270 (2009).

    Article  CAS  Google Scholar 

  6. Derrington, I. M. et al. Nanopore DNA sequencing with MspA. Proc. Natl Acad. Sci. USA 107, 16060–16065 (2010).

    Article  CAS  Google Scholar 

  7. Garaj, S. et al. Graphene as a subnanometre trans-electrode membrane. Nature 467, 190–193 (2010).

    Article  CAS  Google Scholar 

  8. Merchant, C. A. et al. DNA translocation through graphene nanopores. Nano Lett. 10, 2915–2921 (2010).

    Article  CAS  Google Scholar 

  9. Schneider, G. F. et al. DNA translocation through graphene nanopores. Nano Lett. 10, 3163–3167 (2010).

    Article  CAS  Google Scholar 

  10. Fologea, D., Uplinger, J., Thomas, B., McNabb, D. S. & Li, J. Slowing DNA translocation in a solid-state nanopore. Nano Lett. 5, 1734–1737 (2005).

    Article  CAS  Google Scholar 

  11. Peng, H. & Ling, X. S. Reverse DNA translocation through a solid-state nanopore by magnetic tweezers. Nanotechnology 20, 185101 (2009).

    Article  Google Scholar 

  12. Olasagasti, F. et al. Replication of individual DNA molecules under electronic control using a protein nanopore. Nature Nanotech. 5, 798–806 (2010).

    Article  CAS  Google Scholar 

  13. Luan, B. et al. Base-by-base ratcheting of single stranded DNA through a solid-state nanopore. Phys. Rev. Lett. 104, 238103 (2010).

    Article  Google Scholar 

  14. Gracheva, M. E. et al. Simulation of the electric response of DNA translocation through a semiconductor nanopore-capacitor. Nanotechnology 17, 622–633 (2006).

    Article  CAS  Google Scholar 

  15. King, G. M. & Golovchenko, J. A. Probing nanotube–nanopore interactions. Phys. Rev. Lett. 95, 216103 (2005).

    Article  CAS  Google Scholar 

  16. Lagerqvist, J., Zwolak, M. & Ventra, M. D. Fast DNA sequencing via transverse electronic transport. Nano Lett. 6, 779–782 (2006).

    Article  CAS  Google Scholar 

  17. Ivanov, A. P. et al. DNA tunnelling detector embedded in a nanopore. Nano Lett. 11, 279–285 (2011).

    Article  CAS  Google Scholar 

  18. Chaste, J. et al. Single carbon nanotube transistor at GHz frequency. Nano Lett. 8, 525–528 (2008).

    Article  CAS  Google Scholar 

  19. Hu, Y., Xiang, J., Liang, G., Yan, H. & Lieber, C. M. Sub-100 nanometer channel length Ge/Si nanowire transistors with potential for 2 THz switching speed. Nano Lett. 8, 925–930 (2008).

    Article  CAS  Google Scholar 

  20. Cui, Y., Wei, Q., Park, H. & Lieber, C. M. Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293, 1289–1292 (2001).

    Article  CAS  Google Scholar 

  21. Patolsky, F. et al. Electrical detection of single viruses. Proc. Natl Acad. Sci. USA 101, 14017–14022 (2004).

    Article  CAS  Google Scholar 

  22. Patolsky, F. et al. Detection, stimulation, and inhibition of neuronal signals with high-density nanowire transistor arrays. Science 313, 1100–1104 (2006).

    Article  CAS  Google Scholar 

  23. Kim, M. J., Wanunu, M., Bell, D. C. & Meller, A. Rapid fabrication of uniformly sized nanopores and nanopore arrays for parallel DNA analysis. Adv. Mater. 18, 3149–3153 (2006).

    Article  CAS  Google Scholar 

  24. Kasianowicz, J. J., Brandin, E., Branton, D. & Deamer, D. W. Characterization of individual polynucleotide molecules using a membrane channel. Proc. Natl Acad. Sci. USA 93, 13770–13773 (1996).

    Article  CAS  Google Scholar 

  25. Li, J. et al. Ion-beam sculpting at nanometre length scales. Nature 412, 166–169 (2001).

    Article  CAS  Google Scholar 

  26. Cohen-Karni, T., Timko, B. P., Weiss, L. E. & Lieber, C. M. Flexible electrical recording from cells using nanowire transistor arrays. Proc. Natl Acad. Sci. USA 106, 7309–7313 (2009).

    Article  CAS  Google Scholar 

  27. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localised bioprobes. Science 329, 831–834 (2010).

    Article  Google Scholar 

  28. Osaki, T., Suzuki H., Le Pioutle, B. & Takeuchi, S. Multichannel simultaneous measurements of single-molecule translocation in α-hemolysin nanopore array. Anal. Chem. 81, 9866–9870 (2009).

    Article  CAS  Google Scholar 

  29. Yan, H. et al. Programmable nanowire circuits for nanoprocessors. Nature 470, 240–244 (2011).

    Article  CAS  Google Scholar 

  30. Cui, Y., Zhong, Z., Wang D., Wang, W. & Lieber, C. M. High performance silicon nanowire field effect transistors. Nano Lett. 3, 149–152 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank A. Meller, M. Wanunu, D. Casanova, J. Huang, J. Cahoon and T.J. Kempa for helpful discussions. C.M.L. acknowledges support of this work from a NIH Director's Pioneer Award (5DP1OD003900).

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, 02138, Massachusetts, USA

    Ping Xie, Quan Qing & Charles M. Lieber

  2. Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore

    Qihua Xiong

  3. Division of Microelectronics, School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, 619798, Singapore

    Qihua Xiong

  4. National Center for Nanoscience and Technology, China, Beijing, 100910, PR China

    Ying Fang

  5. School of Engineering and Applied Sciences, Harvard University, Cambridge, 02138, Massachusetts, USA

    Charles M. Lieber

Authors
  1. Ping Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qihua Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Quan Qing
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Charles M. Lieber
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.X., Q.X., Y.F. and C.M.L. designed the experiments. P.X., Q.X. and Y.F. performed the experiments. P.X. performed the modelling and calculation. P.X. and Q.Q. wrote the program for data processing. P.X., Q.X., Y.F., Q.Q. and C.M.L. analysed the data and wrote the manuscript.

Corresponding author

Correspondence to Charles M. Lieber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 3498 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xie, P., Xiong, Q., Fang, Y. et al. Local electrical potential detection of DNA by nanowire–nanopore sensors. Nature Nanotech 7, 119–125 (2012). https://doi.org/10.1038/nnano.2011.217

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2011.217

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing