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Solid-state nanopore channels with DNA selectivity

Nature Nanotechnology volume 2, pages 243–248 (2007)Cite this article

Abstract

Solid-state nanopores have emerged as possible candidates for next-generation DNA sequencing devices. In such a device, the DNA sequence would be determined by measuring how the forces on the DNA molecules, and also the ion currents through the nanopore, change as the molecules pass through the nanopore. Unlike their biological counterparts, solid-state nanopores have the advantage that they can withstand a wide range of analyte solutions and environments. Here we report solid-state nanopore channels that are selective towards single-stranded DNA (ssDNA). Nanopores functionalized with a ‘probe’ of hair-pin loop DNA can, under an applied electrical field, selectively transport short lengths of ‘target’ ssDNA that are complementary to the probe. Even a single base mismatch between the probe and the target results in longer translocation pulses and a significantly reduced number of translocation events. Our single-molecule measurements allow us to measure separately the molecular flux and the pulse duration, providing a tool to gain fundamental insight into the channel–molecule interactions. The results can be explained in the conceptual framework of diffusive molecular transport with particle–channel interactions.

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Figure 1: Details of the functionalized NPC sensors.
Figure 2: Scatter plot of pulse width versus pulse amplitude for electrophoretic transport of 1MM-DNA and PC-DNA through NPC-1.
Figure 3: Scatter plot of pulse width versus pulse amplitude for electrophoretic transport of DNA through NPC-2.
Figure 4: Temporal viability of the NPC-4 with a 1:1 mixture of 1MM-DNA and PC-DNA.
Figure 5: Schematic representation of the potential in the channel.

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References

  1. 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 

  2. Akeson, M., Branton, D., Kasianowicz, J. J., Brandin, E. & Deamer, D. W. Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single RNA molecules. Biophys. J. 77, 3227–3233 (1999).

    Article  CAS  Google Scholar 

  3. Vercoutere, W. A. et al. Discrimination among individual Watson–Crick base pairs at the termini of single DNA hairpin molecules. Nucleic Acids Res. 31, 1311–1318 (2003).

    Article  CAS  Google Scholar 

  4. Mathe, J., Visram, H., Viasnoff, V., Rabin, Y. & Meller, A. Nanopore unzipping of individual DNA hairpin molecules. Biophys. J. 87, 3205–3212 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Storm, A. J., Chen, J. H., Ling, X. S., Zandbergen, H. W. & Dekker, C. Fabrication of solid-state nanopores with single-nanometre precision. Nature Mater. 2, 537–540 (2003).

    Article  CAS  Google Scholar 

  7. Chang, H. et al. Towards integrated micro-machined silicon-based nanopores for characterization of DNA. Hilton Head MEMS conference, Hilton Head, South Carolina (2004).

  8. Li, J., Gershow, M., Stein, D., Brandin, E. & Golovchenko, J. A. DNA molecules and configurations in a solid-state nanopore microscope. Nature Mater. 2, 611–615 (2003).

    Article  CAS  Google Scholar 

  9. Chang, H. et al. DNA-mediated fluctuations in ionic current through silicon oxide nanopore channels. Nano Lett. 4, 1551–1556 (2004).

    Article  CAS  Google Scholar 

  10. Smeets, R. M. M. et al. Salt dependence of ion transport and DNA translocation through solid-state nanopores. Nano Lett. 6, 89–95 (2006).

    Article  CAS  Google Scholar 

  11. Gu, L.-Q., Braha, O., Conlan, S., Cheley, S. & Bayley, H. Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter. Nature 398, 686–690 (1999).

    Article  CAS  Google Scholar 

  12. Meller, A., Nivon, L., Brandin, E., Golovchenko, J. & Branton, D. Rapid nanopore discrimination between single polynucleotide molecules. Proc. Natl Acad. Sci. USA 97, 1079–1084 (2000).

    Article  CAS  Google Scholar 

  13. Howorka, S., Cheley, S. & Bayley, H. Sequence-specific detection of individual DNA strands using engineered nanopores. Nature Biotechnol. 19, 636–639 (2001).

    Article  CAS  Google Scholar 

  14. Siwy, Z. Troffin, L. Kohli, P. Baker, L. A. Trautmann, C. Martin, C. R. Protein biosensors based on biofunctionalized conical gold nanotubes. J. Am. Chem. Soc. 127, 5000–5001 (2005).

    Article  CAS  Google Scholar 

  15. Kohli, P. et al. DNA-functionalized nanotube membranes with single-base mismatch selectivity. Science 305, 984–986 (2004).

    Article  CAS  Google Scholar 

  16. Bauer, W. R. & Nadler, W. Molecular transport through channels and pores: Effects of in-channel interactions and blocking. Proc. Natl Acad. Sci. USA 103, 11446–11451 (2006).

    Article  CAS  Google Scholar 

  17. Noble, R. D., Pellegrino, J. J. & Koval, C.A. Overview of facilitated transport membrane systems. Chem. Eng. Prog. 85, 58–70 (1989).

    CAS  Google Scholar 

  18. Noble, R. D. Generalized microscopic mechanism of facilitated transport in fixed carrier membranes. J. Membr. Sci. 75, 121–129 (1991).

    Article  Google Scholar 

  19. Manning, M., Harvey, S., Galvin, P. & Redmond, G. A versatile multi-platform biochip surface attachment chemistry. Mater. Sci. Eng. C 23, 347–351 (2003).

    Article  Google Scholar 

  20. Nilsson, J., Jonathan R. I. L., Ratto, T. V. & Létant, S. E. Localized functionalization of single nanopores. Adv. Mater. 18, 427–431 (2006).

    Article  CAS  Google Scholar 

  21. Tyagi, S. & Kramer, F. R. Molecular beacons: Probes that fluoresce upon hybridization. Nature Biotechnol. 14, 303–308 (1996).

    Article  CAS  Google Scholar 

  22. Berezhkovskii, A. M. & Bezrukov, S. M. Optimizing transport of metabolites through large channels: Molecular sieves with and without binding. Biophys. J. 88, L17–L19 (2005).

    Article  CAS  Google Scholar 

  23. Gao, Y., Wolf L. K. & Georgiadis, R. M. Secondary structure effects on DNA hybridization kinetics: a solution versus surface comparison. Nucleic Acids Res. 34, 3370–3377 (2006).

    Article  CAS  Google Scholar 

  24. Hamaguchi, N., Ellington A. & Stanton M. Aptamer beacons for the direct detection of proteins. Anal. Biochem. 294, 126–131 (2001).

    Article  CAS  Google Scholar 

  25. Kasianowicz, J. J., Nguyen, T. L. & Stanford, V. M. Enhancing molecular flux through nanopores by means of attractive interactions. Proc. Natl Acad. Sci. USA 103, 11431–11432 (2006).

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge very useful discussions with M.A. Alam, D.E. Bergstrom and G. Balasundaram (Purdue University), P. Kohli (Southern Illinois University, Carbondale), and also C. Martin (University of Florida) for providing critical input to the conceptual discussion. We are thankful to B.M.K. Venkatesan, H. Chang, E.P. Judokusumo, R. Qaseem and P. Bajaj for help in data analysis. We also thank E.J. Basgall at PSU for electron-beam lithography through the NSF-funded National Nanotechnology Infrastructure Network. Partial wafer fabrication was performed in the Nanotechnology Core Facility at University of Illinois at Chicago. This work was initiated with support from NIH/NIBIB Award No. R21RR15118-01, and subsequently supported by the NASA Institute for Nanoelectronics and Computing at Purdue under Award No. NCC 2–1363.

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Authors and Affiliations

  1. Birck Nanotechnology Center, School of Electrical and Computer Engineering, Purdue University, West Lafayette, 47907, Indiana, USA

    Samir M. Iqbal, Demir Akin & Rashid Bashir

  2. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, 47907, Indiana, USA

    Demir Akin & Rashid Bashir

Authors
  1. Samir M. Iqbal
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  2. Demir Akin
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Contributions

S.M.I. developed the DNA attachment protocols, fabricated the devices, carried out the DNA functionalization and characterization of the devices, and led the measurement and analysis of the data. D.A. identified the DNA probe sequence and helped in developing experiments for the optical characterization of the DNA attachment chemistries. S.M.I. and R.B. designed the experiments and developed the conceptual framework and wrote the paper. R.B. supervised all aspects of the project described above.

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Correspondence to Demir Akin or Rashid Bashir.

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The authors declare no competing financial interests.

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Supplementary Information

Supplementary figures S1—S6, Tables S1 and S2 (PDF 577 kb)

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Iqbal, S., Akin, D. & Bashir, R. Solid-state nanopore channels with DNA selectivity. Nature Nanotech 2, 243–248 (2007). https://doi.org/10.1038/nnano.2007.78

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