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DNA molecules and configurations in a solid-state nanopore microscope

Abstract

A nanometre-scale pore in a solid-state membrane provides a new way of electronically probing the structure of single linear polymers, including those of biological interest in their native environments. Previous work with biological protein pores wide enough to let through and sense single-stranded DNA molecules demonstrates the power of using nanopores, but many future tasks and applications call for a robust solid-state pore whose nanometre-scale dimensions and properties may be selected, as one selects the lenses of a microscope. Here we demonstrate a solid-state nanopore microscope capable of observing individual molecules of double-stranded DNA and their folding behaviour. We discuss extensions of the nanopore microscope concept to alternative probing mechanisms and applications, including the study of molecular structure and sequencing.

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Figure 1: Details of the experimental setup.
Figure 2: Distribution of events as a function of td and <ΔIb> for 10-kb dsDNA.
Figure 3
Figure 4: Density of events over td and <ΔIb> for 10-kb dsDNA passing through a 10-nm pore.
Figure 5: Instantaneous time distribution of blockade current ΔIb over all events.

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Acknowledgements

We acknowledge discussion and criticism of this work by D. Branton, M. Muthukumar and M. Aziz. Dr H. Wang prepared the 3-kb DNA used in the work. A. Kavcic, M. Burns, A. Huang and J. Gu assisted with software analysis. Q. Cai assisted with nanopore preparation and C. Russo provided assistance during preparation of this manuscript. Support for this research has been provided by DARPA, NSF, DOE, AFOSR and Agilent Technologies.

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Correspondence to J. A. Golovchenko.

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Li, J., Gershow, M., Stein, D. et al. DNA molecules and configurations in a solid-state nanopore microscope. Nature Mater 2, 611–615 (2003). https://doi.org/10.1038/nmat965

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