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Electrostatic focusing of unlabelled DNA into nanoscale pores using a salt gradient

Nature Nanotechnology volume 5, pages 160–165 (2010)Cite this article

Abstract

Solid-state nanopores are sensors capable of analysing individual unlabelled DNA molecules in solution. Although the critical information obtained from nanopores (for example, DNA sequence) comes from the signal collected during DNA translocation, the throughput of the method is determined by the rate at which molecules arrive and thread into the pores. Here, we study the process of DNA capture into nanofabricated SiN pores of molecular dimensions. For fixed analyte concentrations we find an increase in capture rate as the DNA length increases from 800 to 8,000 base pairs, a length-independent capture rate for longer molecules, and increasing capture rates when ionic gradients are established across the pore. Furthermore, we show that application of a 20-fold salt gradient allows the detection of picomolar DNA concentrations at high throughput. The salt gradients enhance the electric field, focusing more molecules into the pore, thereby advancing the possibility of analysing unamplified DNA samples using nanopores.

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Figure 1: Biomolecular funnelling into a solid-state nanopore.
Figure 2: Dependence of the specific capture rate RC on DNA length and voltage under symmetric salt conditions.
Figure 3: Capture rate enhancement using a salt gradient across the nanopore.
Figure 4: Picomolar detection of unlabelled DNA under asymmetric salt concentrations.
Figure 5: Measurement of the capture rate from single-molecule ion-current blockades.

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References

  1. 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 

  2. Chen, P. et al. Probing single DNA molecule transport using fabricated nanopores. Nano Lett. 4, 2293–2298 (2004).

    Article  CAS  Google Scholar 

  3. Storm, A. J. et al. Fast DNA translocation through a solid-state nanopore. Nano Lett. 5, 1193–1197 (2005).

    Article  CAS  Google Scholar 

  4. Smeets, R. 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 

  5. Heng, J. B. et al. The electromechanics of DNA in a synthetic nanopore. Biophys. J. 90, 1098–1106 (2006).

    Article  CAS  Google Scholar 

  6. McNally, B., Wanunu, M. & Meller, A. Electro-mechanical unzipping of individual DNA molecules using synthetic sub-2-nm pores. Nano Lett. 8, 3418–3422 (2008).

    Article  CAS  Google Scholar 

  7. Wanunu, M., Sutin, J., McNally, B., Chow, A. & Meller, A. DNA translocation governed by interactions with solid state nanopores. Biophys. J. 95, 4716–4725 (2008).

    Article  CAS  Google Scholar 

  8. Smeets, R. M. M., Kowalczyk, S. W., Hall, A. R., Dekker, N. H. & Dekker, C. Translocation of recA-coated double-stranded DNA through solid-state nanopores. Nano Lett. 9, 3089–3095 (2009).

    Article  CAS  Google Scholar 

  9. Wanunu, M., Sutin, J. & Meller, A. DNA profiling using solid-state nanopores: detection of DNA-binding molecules. Nano Lett. 9, 3498–3502 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Henrickson, S. E., Misakian, M., Robertson, B. & Kasianowicz, J. J. Driven DNA transport into an asymmetric nanometer scale pore. Phys. Rev. Lett. 85, 3057–3060 (2000).

    Article  CAS  Google Scholar 

  13. Meller, A. & Branton, D. Single molecule measurements of DNA transport through a nanopore. Electrophoresis 23, 2583–2591 (2002).

    Article  CAS  Google Scholar 

  14. Meller, A. Dynamics of polynucleotide transport through nanometre-scale pores. J. Phys. Condens. Matter 15, R581–R607 (2003).

    Article  CAS  Google Scholar 

  15. Zhang, J. & Shklovskii, B. I. Effective charge and free energy of DNA inside an ion channel. Phys. Rev. E 75, 021906 (2007).

    Article  Google Scholar 

  16. Gershow, M. & Golovchenko, J. A. Recapturing and trapping single molecules with a solid-state nanopore. Nature Nanotech. 2, 775–779 (2007).

    Article  CAS  Google Scholar 

  17. 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 

  18. Schmidt, C., Mayer, M. & Vogel, H. A chip-based biosensor for the functional analysis of single ion channels. Angew Chem. Int. Ed. 39, 3137–3140 (2000).

    Article  CAS  Google Scholar 

  19. Long, D., Viovy, J.-L. & Ajdari, A. Simultaneous action of electric fields and nonelectric forces on a polyelectrolyte: motion and deformation. Phys. Rev. Lett. 76, 3858–3861 (1996).

    Article  CAS  Google Scholar 

  20. Nkodo, A. E. et al. Diffusion coefficient of DNA molecules during free solution electrophoresis. Electrophoresis 22, 2424–2432 (2001).

    Article  CAS  Google Scholar 

  21. Olivera, B. M., Baine, P. & Davidson, N. Electrophoresis of the nucleic acids. Biopolymers 2, 245–257 (1964).

    Article  CAS  Google Scholar 

  22. Wong, C. T. A. & Muthukumar, M. Polymer capture by electro-osmotic flow of oppositely charged nanopores. J. Chem. Phys. 126, 164903 (2007).

    Article  CAS  Google Scholar 

  23. Chou, T. Enhancement of charged macromolecule capture by nanopores in a salt gradient. J. Chem. Phys. 131, 034703 (2009).

    Article  Google Scholar 

  24. Luan, B. & Aksimentiev, A. Electro-osmotic screening of the DNA charge in a nanopore. Phys. Rev. E 78, 021912 (2008).

    Article  Google Scholar 

  25. Dorp, S. V., Keyser, U. F., Dekker, N. H., Dekker, C. & Lemay, S. G. Origin of the electrophoretic force on DNA in solid-state nanopores. Nature Phys. 5, 347–351 (2009).

    Article  Google Scholar 

  26. Wanunu, M. & Meller, A. Chemically-modified solid-state nanopores. Nano Lett. 7, 1580–1585 (2007).

    Article  CAS  Google Scholar 

  27. Wanunu, M. & Meller, A. Single Molecule Analysis of Nucleic Acids and DNA–Protein Interactions using Nanopores (Cold Spring Harbor Press, 2008).

    Google Scholar 

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Acknowledgements

The authors would like to thank B. McNally for help in data acquisition, and support from Harvard's Center for Nanoscale Systems (CNS). We are grateful for stimulating and fruitful discussions with M. Frank-Kamenetskii, A. Kolomeisky, O. Krichevsky, G. Lakatos, D.R. Nelson, A. Parsegian and B. Shklovskii. A.M. acknowledges support from National Institutes of Health award HG-004128 and National Science Foundation award PHY-0646637. Y.R. and A.G. acknowledge support by the US–Israel Binational Science Foundation. Y.R. acknowledges a grant from the Israeli Science Foundation and the hospitality of the NYU Department of Physics.

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Authors and Affiliations

  1. Department of Biomedical Engineering and Department of Physics, Boston University, Boston, 02215, Massachusetts, USA

    Meni Wanunu, Will Morrison & Amit Meller

  2. Department of Physics, Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 52900, Israel

    Yitzhak Rabin

  3. Department of Physics, New York University, New York, 10003, New York, USA

    Alexander Y. Grosberg

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  1. Meni Wanunu
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  2. Will Morrison
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Contributions

A.M. and M.W. designed the experiments. M.W. performed all experiments and analysed the data. W.M. performed finite element simulations. Y.R. and A.G. developed the theoretical model. M.W., W.M., Y.R., A.G. and A.M. co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Amit Meller.

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Wanunu, M., Morrison, W., Rabin, Y. et al. Electrostatic focusing of unlabelled DNA into nanoscale pores using a salt gradient. Nature Nanotech 5, 160–165 (2010). https://doi.org/10.1038/nnano.2009.379

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