Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 2,534

The DOI matches its Crossref record.

The potential and challenges of nanopore sequencing

Open access
Branton, Daniel, Deamer, David W, Marziali, Andre, Bayley, Hagan, Benner, Steven A, Butler, Thomas, Di Ventra, Massimiliano, Garaj, Slaven, Hibbs, Andrew, Huang, Xiaohua, Jovanovich, Stevan B, Krstic, Predrag S, Lindsay, Stuart, Ling, Xinsheng Sean, Mastrangelo, Carlos H, Meller, Amit, Oliver, John S, Pershin, Yuriy V, Ramsey, J Michael, Riehn, Robert, Soni, Gautam V, Tabard-Cossa, Vincent, Wanunu, Meni, Wiggin, Matthew, Schloss, Jeffery A·2008·Nature Biotechnology
DOI 10.1038/nbt.1495
Open this paper in CoChat — free account

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nbt.1495

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 85

  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). · DOI · Paper page
  2. Braha, O. et al. Designed protein pores as components for biosensors. Chem. Biol. 4, 497–505 (1997). · DOI · Paper page
  3. Kang, X.F., Gu, L.-Q., Cheley, S. & Bayley, H. Single protein pores containing molecular adapters at high temperatures. Angew. Chem. Int. Edn Engl. 44, 1495–1499 (2005). · DOI
  4. 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). · DOI · Paper page
  5. Meller, A., Nivon, L., Brandin, E., Golovchenko, J. & Branton, D. Rapid nanopore discrimination between single oligonucleotide molecules. Proc. Natl. Acad. Sci. USA 97, 1079–1084 (2000). · DOI · Paper page
  6. Meller, A., Nivon, L. & Branton, D. Voltage-driven DNA translocations through a nanopore. Phys. Rev. Lett. 86, 3435–3438 (2001). · DOI · Paper page
  7. Deamer, D.W. & Branton, D. Characterization of nucleic acids by nanopore analysis. Acc. Chem. Res. 35, 817–825 (2002). · DOI · Paper page
  8. Nakane, J.J., Akeson, M. & Marziali, A. Nanopore sensors for nucleic acid analysis. J. Phys. Condens. Matter 15, R1365–R1393 (2003). · doi:10.1088/0953-8984/15/32/203
  9. Healy, K. Nanopore-based single-molecule DNA analysis. Nanomedicine 2, 459–481 (2007). · DOI
  10. Wanunu, M. & Meller, A. Single-molecule analysis of nucleic acids and DNA-protein interactions using nanopores. in Single-Molecule Techniques: A Laboratory Manual (eds. Selvin, P. & Ha, T.J.), p 395–420 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 2008).
  11. Tobkes, N., Wallace, B.A. & Bayley, H. Secondary structure and assembly mechanism of an oligomeric channel protein. Biochemistry 24, 1915–1920 (1985). · DOI · Paper page
  12. Li, J. et al. Ion-beam sculpting at nanometre length scales. Nature 412, 166–169 (2001). · DOI · Paper page
  13. Harrell, C.C. et al. Resistive-pulse DNA detection with a conical nanopore sensor. Langmuir 22, 10837–10843 (2006). · doi:10.1021/la061234k
  14. Schloss, J.A. How to get genomes at one ten-thousandth the cost. Nat. Biotechnol. 26, 1113–1116 (2008). · DOI
  15. Shendure, J. & Hanlee, J. Next-generation DNA sequencing. Nat. Biotechnol. 26, 1135–1145 (2008). · DOI · Paper page
  16. Rothberg, J.M. & Leamon, J. The development and impact of 454 sequencing. Nat. Biotechnol. 26, 1117–1124 (2008). · DOI · Paper page
  17. Mardis, E.R. The impact of next-generation sequencing technology on genetics. Trends Genet. 24, 133–141 (2008). · DOI · Paper page
  18. Meller, A. & Branton, D. Single molecule measurements of DNA transport through a nanopore. Electrophoresis 23, 2583–2591 (2002). · DOI · Paper page
  19. Ashkenasy, N., Sanchez-Quesada, J., Bayley, H. & Ghadiri, M.R. Recognizing a single base in an individual DNA strand: a step toward DNA sequencing in nanopores. Angew. Chem. Int. Ed. 44, 1401–1404 (2005). · DOI
  20. Aksimentiev, A., Heng, J.B., Timp, G. & Schulten, K. Microscopic kinetics of DNA translocation through synthetic nanopores. Biophys. J. 87, 2086–2097 (2004). · DOI · Paper page
  21. Aksimentiev, A. & Schulten, K. Imaging α-hemolysin with molecular dynamics: ionic conductance, osmotic permeability, and the electrostatic potential map. Biophys. J. 88, 3745–3761 (2005). · DOI · Paper page
  22. Muthukumar, M. & Kong, C.Y. Simulation of polymer translocation through protein channels. Proc. Natl. Acad. Sci. USA 103, 5273–5278 (2006). · DOI
  23. Liu, H., Qian, S. & Bau, H.H. The effect of translocating cylindrical particles on the ionic current through a nanopore. Biophys. J. 92, 1164–1177 (2007). · DOI
  24. Drmanac, R. et al. Sequencing by hybridization (SBH): advantages, achievements, and opportunities. Adv. Biochem. Eng. Biotechnol. 77, 75–101 (2002).
  25. Fologea, D. et al. Detecting single stranded DNA with a solid state nanopore. Nano Lett. 5, 1905–1909 (2005). · doi:10.1021/nl051199m
  26. Jett, J.H. et al. High-speed DNA sequencing: an approach based upon fluorescence detection of single molecules. J. Biomol. Struct. Dyn. 7, 301–309 (1989). · DOI
  27. Astier, Y., Braha, O. & Bayley, H. Toward single molecule DNA sequencing: direct identification of ribonucleoside and deoxyribonucleoside 5′-monophosphates by using an engineered protein nanopore equipped with a molecular adapter. J. Am. Chem. Soc. 128, 1705–1710 (2006). · DOI · Paper page
  28. Wu, H.-C., Astier, Y., Maglia, G., Mikhailova, E. & Bayley, H. Protein nanopores with covalently attached molecular adapters. J. Am. Chem. Soc. 129, 16142–16148 (2007). · doi:10.1021/ja0761840
  29. Soni, G.V. & Meller, A. Progress toward ultrafast DNA sequencing using solid-state nanopores. Clin. Chem. 53, 1996–2001 (2007). · DOI
  30. Lee, J.W. & Meller, A. Rapid DNA sequencing by direct nanoscale reading of nucleotide bases on individual DNA chains. in Perspectives in Bioanalysis vol. 2, (ed. Mitchelson, K.), 245–263 (Elsevier, Oxford, UK, 2007).
  31. Sauer-Budge, A.F., Nyamwanda, J.A., Lubensky, D.K. & Branton, D. Unzipping kinetics of double-stranded DNA in a nanopore. Phys. Rev. Lett. 90, 2381011–2381014 (2003). · DOI · Paper page
  32. 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). · doi:10.1002/adma.200601191
  33. Zwolak, M. & Di Ventra, M. Electronic signature of DNA nucleotides via transverse transport. Nano Lett. 5, 421–424 (2005). · DOI · Paper page
  34. Zikic, R. et al. Characterization of the tunneling conductance across DNA bases. Phys. Rev. E 74, 011919 (2006). · doi:10.1103/physreve.74.011919
  35. Meunier, V. & Krstic, P.S. Enhancement of the transverse conductance in DNA nucleotides. J. Chem. Phys. 128, 041103 (2008). · doi:10.1063/1.2835350
  36. Lagerqvist, J., Zwolak, M. & Di Ventra, M. Fast DNA sequencing via transverse electronic transport. Nano Lett. 6, 779–782 (2006). · DOI · Paper page
  37. Zhang, X.-G., Krstic, P.S., Zikic, R., Wells, J.C. & Fuentes-Cabrera, M. First-principles transversal DNA conductance deconstructed. Biophys. J. 91, L04–L06 (2006). · doi:10.1529/biophysj.106.085548
  38. Lagerqvist, J., Zwolak, M. & Di Ventra, M. Influence of the environment and probes on rapid DNA sequencing via transverse electronic transport. Biophys. J. 93, 2384–2390 (2007). · DOI
  39. Meng, S., Maragakis, P., Papaloukas, C. & Kaxiras, E. DNA nucleoside interaction and identification with carbon nanotubes. Nano Lett. 47, 45–50 (2007). · DOI · Paper page
  40. Xu, M., Endres, R.G. & Arakawa, Y. The electronic properties of DNA bases. Small 3, 1539–1543 (2007). · doi:10.1002/smll.200600732
  41. Zwolak, M. & DiVentra, M. Physical approaches to DNA sequencing and detection. Rev. Mod. Phys. 80, 141–165 (2008). · DOI · Paper page
  42. Golovchenko, J. The tunneling microscope: a new look at the atomic world. Science 232, 48–53 (1986). · doi:10.1126/science.232.4746.48
  43. Ohshiro, T. & Umezawa, Y. Complementary base-pair-facilitated electron tunneling for electrically pinpointing complementary nucleobases. Proc. Natl. Acad. Sci. USA 103, 10–14 (2006). · DOI
  44. He, J., Lin, L., Zhang, P. & Lindsay, S. Identification of DNA base-pairing via tunnel-current decay. Nano Lett. 7, 3854–3858 (2007). · doi:10.1021/nl0726205
  45. Michel, B., Novotny, L. & Durig, U. Low-temperature compatible I–V converter. Ultramicroscopy 42–44, 1647–1652 (1992). · doi:10.1016/0304-3991(92)90499-a
  46. Hughes, M.E., Brandin, E. & Golovchenko, J.A. Optical absorption of DNA-carbon nanotube structures. Nano Lett. 7, 1191–1194 (2007). · DOI
  47. Heng, J.B. et al. Beyond the gene chip. Bell Labs Tech. J. 10, 5–22 (2005). · DOI
  48. Gracheva, M.E. et al. Simulation of the electric response of DNA translocation through a semiconductor nanopore-capacitor. Nanotechnology 17, 622–633 (2006). · DOI
  49. Sigalov, G., Comer, J., Timp, G. & Aksimentiev, A. Detection of DNA sequences using an alternating electric field in a nanopore capacitor. Nano Lett. 8, 56–63 (2008). · DOI · Paper page
  50. Storm, A.J. et al. Fast DNA translocation through a solid-state nanopore. Nano Lett. 7, 1193–1197 (2005). · DOI · Paper page
  51. Gracheva, M.E., Aksimentiev, A. & Leburton, J.-P. Electrical signatures of single-stranded DNA with single base mutations in a nanopore capacitor. Nanotechnology 17, 3160–3165 (2006). · doi:10.1088/0957-4484/17/13/014
  52. Fologea, D., Brandin, E., Uplinger, J., Branton, D. & Li, J. DNA conformation and base number simultaneously determined in a nanopore. Electrophoresis 28, 3186–3192 (2007). · doi:10.1002/elps.200700047
  53. Mathe, J., Visram, H., Viasnoff, V., Rabin, Y. & Meller, A. Nanopore unzipping of individual DNA hairpin molecules. Biophys. J. 87, 3205–3212 (2004). · DOI · Paper page
  54. Li, J., Gershow, M., Stein, D., Brandin, E. & Golovchenko, J. DNA molecules and configurations in a solid-state nanopore microscope. Nat. Mater. 2, 611–615 (2003). · DOI · Paper page
  55. Gershow, M. & Golovchenko, J.A. Recapturing and trapping single molecules with a solid state nanopore. Nature Nanotechnology 2, 775–779 (2007). · DOI
  56. Chen, P. et al. Probing single DNA molecule transport using fabricated nanopores. Nano Lett. 4, 2293–2298 (2004). · DOI · Paper page
  57. Smeets, R.M.M. et al. Salt dependence of ion transport and DNA translocation through solid-state nanopores. Nano Lett. 6, 89–95 (2006). · DOI
  58. Meller, A. Dynamics of polynucleotide transport through nanometer-scale pores. J. Phys. Condens. Matt. 15, R581–R607 (2003). · doi:10.1088/0953-8984/15/17/202
  59. Heng, J.B. et al. Sizing DNA using a nanometer-diameter pore. Biophys. J. 87, 2905–2911 (2004). · DOI · Paper page
  60. Lubensky, D.K. & Nelson, D.R. Driven polymer translocation through a narrow pore. Biophys. J. 77, 1824–1838 (1999). · DOI
  61. Chern, S.S., Cardenas, A.E. & Coalson, R.D. Three-dimensional dynamic Monte Carlo simulations of driven polymer transport through a hole in a wall. J. Chem. Phys. 115, 7772–7782 (2001). · doi:10.1063/1.1392367
  62. Loebl, H.C., Randel, R., Goodwin, S.P. & Matthai, C.C. Simulation studies of polymer translocation through a channel. Phys. Rev. E. 67, 041913–041911 - 041913–041915 (2003). · doi:10.1103/physreve.67.041913
  63. Matysiak, S., Montesi, A., Pasquali, M., Kolomeisky, A.B. & Clementi, C. Dynamics of polymer translocation through nanopores. Theory meets experiment. Phys. Rev. Lett. 96, 118103 (2006). · DOI
  64. Huopaniemi, I., Luo, K., Ala-Nissila, T. & Ying, S.C. Langevin dynamics simulations of polymer translocation through nanopores. J. Chem. Phys. 125, 124901 (2006). · doi:10.1063/1.2357118
  65. Chen, P. & Li, C.M. Nanopore unstacking of single-stranded DNA helices. Small 3, 1204–1208 (2007). · doi:10.1002/smll.200700049
  66. Zhao, X., Payne, C.M., Cummings, P. & Lee, J.W. Single stranded DNA molecules translocation through nanoelectrode gaps. Nanotechnology 18, 424018 (2007). · doi:10.1088/0957-4484/18/42/424018
  67. Cheikh, C. & Koper, G. Influence of the stick-slip transition on the electrokinetic behavior of nanoporous material. Physica A 373, 21–28 (2007). · doi:10.1016/j.physa.2006.08.068
  68. Nakane, J., Wiggin, M. & Marziali, A. A nanosensor for transmembrane capture and identification of single nucleic acid molecules. Biophys. J. 87, 615–621 (2004). · DOI
  69. Tropini, C. & Marziali, A. Multi-nanopore force spectroscopy for DNA analysis. Biophys. J. 92, 1632–1637 (2007). · doi:10.1529/biophysj.106.094060
  70. Wanunu, M., Chakrabarti, B., Mathe, J., Nelson, D.R. & Meller, A. Orientation-dependent interactions of DNA with an α-hemolysin channel. Phys. Rev. E 77, 031904 (2008). · doi:10.1103/physreve.77.031904
  71. Mathe, J., Aksimentiev, A., Nelson, D.R., Schulten, K. & Meller, A. Orientation discrimination of single-stranded DNA inside the α-hemolysin membrane channel. Proc. Natl. Acad. Sci. USA 102, 12377–12382 (2005). · DOI · Paper page
  72. Fologea, D., Uplinger, J., Thomas, B., McNabb, D.S. & Li, J. Slowing DNA translocation in a solid-state nanopore. Nano Lett. 5, 1734–1737 (2005). · DOI · Paper page
  73. Payne, C.M., Zhao, X., Vlcek, L. & Cummings, P. Molecular dynamics simulation of ss-DNA translocation between copper nanoelectrodes incorporating electrode charge dynamics. J. Phys. Chem. B 112, 1712–1717 (2008). · DOI
  74. Hornblower, B. et al. Single-molecule analysis of DNA-protein complexes using nanopores. Nat. Methods 4, 315–317 (2007). · DOI
  75. Benner, S. et al. Sequence-specific detection of individual DNA polymerase complexes in real time using a nanopore. Nat. Nanotechnol. 2, 718–724 (2007). · DOI
  76. Cockroft, S.L., Chu, J., Amorin, M. & Ghadiri, M.R. A single-molecule nanopore device detects DNA polymerase activity with single-nucleotide resolution. J. Am. Chem. Soc. 130, 818–820 (2008). · DOI
  77. Joyce, C.M. & Steitz, T.A. Function and structure relationships in DNA-polymerases. Annu. Rev. Biochem. 63, 777–822 (1994). · DOI · Paper page
  78. Wanunu, M. & Meller, A. Chemically-modified solid-state nanopores. Nano Lett. 7, 1580–1585 (2007). · DOI
  79. Chen, P. et al. Atomic layer deposition to fine-tune the surface properties and diameters of fabricated nanopores. Nano Lett. 4, 1333–1337 (2004). · doi:10.1021/nl0494001
  80. Tabard-Cossa, V., Trivedi, D., Wiggin, M., Jetha, N.N. & Marziali, A. Noise analysis and reduction in solid-state nanopores. Nanotechnology 18, 305505–305510 (2007). · DOI · Paper page
  81. Kang, X.F., Cheley, S., Rice-Ficht, A.C. & Bayley, H. A storable encapsulated bilayer chip containing a single protein nanopore. J. Am. Chem. Soc. 129, 4701–4705 (2007). · doi:10.1021/ja068654g
  82. Holden, M.A. & Bayley, H. Direct introduction of single protein channels and pores into lipid bilayers. J. Am. Chem. Soc. 127, 6502–6503 (2005). · DOI
  83. Holden, M.A., Jayasinghe, L., Daltrop, O., Mason, A. & Bayley, H. Direct transfer of membrane proteins from bacteria to planar bilayers for rapid screening by single-channel recording. Nat. Chem. Biol. 2, 314–318 (2006). · doi:10.1038/nchembio793
  84. White, R.J. et al. Single ion-channel recordings using glass nanopore membranes. J. Am. Chem. Soc. 129, 11766–11775 (2007). · DOI
  85. Storm, A.J., Chen, J.H., Ling, X.S., Zandbergen, H.W. & Dekker, C. Fabrication of solid-state nanopores with single-nanometre precision. Nat. Mater. 2, 537–541 (2003). · DOI · Paper page

Cited by

See all 2,534

Metadata

Authors
Branton, D., Deamer, D. W., Marziali, A., Bayley, H., Benner, S. A., Butler, T., Di Ventra, M., Garaj, S., Hibbs, A., Huang, X., Jovanovich, S. B., Krstic, P. S., Lindsay, S., Ling, X. S., Mastrangelo, C. H., Meller, A., Oliver, J. S., Pershin, Y. V., Ramsey, J. M., Riehn, R., Soni, G. V., Tabard-Cossa, V., Wanunu, M., Wiggin, M., & Schloss, J. A.
Venue
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2008-10
Volume
26
Issue
10
Pages
1146-1153
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
DOI
10.1038/nbt.1495
OpenAlex
W2025583382
Cited by
2,534
References
0
FWCI
78.66
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: The potential and challenges of nanopore sequencing. https://app.cochat.ai/papers/10.1038/nbt.1495
The paper
Branton, D., Deamer, D. W., Marziali, A., Bayley, H., Benner, S. A., Butler, T., Di Ventra, M., Garaj, S., Hibbs, A., Huang, X., Jovanovich, S. B., Krstic, P. S., Lindsay, S., Ling, X. S., Mastrangelo, C. H., Meller, A., Oliver, J. S., Pershin, Y. V., Ramsey, J. M., . . . Schloss, J. A. (2008). The potential and challenges of nanopore sequencing. Nature Biotechnology. https://doi.org/10.1038/nbt.1495

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.