The potential and challenges of nanopore sequencing

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Abstract

A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of 'third generation' instruments that will sequence a diploid mammalian genome for $1,000 in 24 h.

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Figure 1: Approaches to nanopore sequencing.
Figure 2: A nanopore reader with chemically functionalized probes.

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Correspondence to Daniel Branton.

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Branton, D., Deamer, D., Marziali, A. et al. The potential and challenges of nanopore sequencing. Nat Biotechnol 26, 1146–1153 (2008) doi:10.1038/nbt.1495

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