Recapturing and trapping single molecules with a solid-state nanopore

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Abstract

The development of solid-state nanopores1,2,3,4,5,6,7, inspired by their biological counterparts8,9,10,11,12,13,14,15, shows great potential for the study of single macromolecules16,17,18,19,20,21. Applications such as DNA sequencing6,22,23 and the exploration of protein folding6 require control of the dynamics of the molecule's interaction with the pore, but DNA capture by a solid-state nanopore is not well understood24,25,26. By recapturing individual molecules soon after they pass through a nanopore, we reveal the mechanism by which double-stranded DNA enters the pore. The observed recapture rates and times agree with solutions of a drift-diffusion model. Electric forces draw DNA to the pore over micrometer-scale distances, and upon arrival at the pore, molecules begin translocation almost immediately. Repeated translocation of the same molecule improves measurement accuracy, offers a way to probe the chemical transformations and internal dynamics of macromolecules on sub-millisecond time and sub-micrometre length scales, and demonstrates the ability to trap, study and manipulate individual macromolecules in solution.

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Figure 1: Overview of the recapture experiment.
Figure 2: Capture rates and recapture probabilities.
Figure 3: Capture time histograms for returning molecules for different delays before voltage reversal.
Figure 4: Current versus time traces from a single-molecule trapping experiment.

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Acknowledgements

This work was supported by NIH/NGRI grant no. 5 R01 HG00370302. Some fabrication was carried out at Harvard University's Center for Nanoscale Systems, with the assistance of D. Bell, Yuan Lu and J.D. Deng. We thank E. Brandin for preparing the molecules for the trapping experiment, S. Coutreau and P. Testa for machining assistance, Jiali Li, D. Branton, S. Bezrukov, D. Hoogerheide and D. Vlassarev for useful discussions, and M. Biercuk for valuable suggestions regarding the manuscript.

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Correspondence to J. A. Golovchenko.

Supplementary information

Supplementary Information

Supplementary experimental methods and supplementary figures S1–S3 (PDF 409 kb)

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Gershow, M., Golovchenko, J. Recapturing and trapping single molecules with a solid-state nanopore. Nature Nanotech 2, 775–779 (2007) doi:10.1038/nnano.2007.381

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