Skip to main content
SpringerLink
Log in

Stochastic Detection of Terrorist Agents and Biomolecules in a Biological Channel

  • Chapter
  • First Online:
Nanopores

Abstract

Stochastic sensing can detect analytes at the single-molecule level, in which a biological ion channel embedded in a lipid bilayer or a nano-scale sized pore fabricated in a solid-state membrane is used as the sensing element. By monitoring the ionic current modulations induced by the passage of the target analyte through the single pore, both the concentration and the identity of the analyte can be revealed. In this chapter, we highlight recent advances in the stochastic detection of terrorist agents and biomolecules, and in real-world sample analysis using alpha-hemolysin protein ion channels.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bayley, H.; Cremer, P. S. Stochastic sensors inspired by biology. Nature 2001, 413, 226–230.

    Google Scholar 

  2. Schmidt, J. Stochastic sensors, J. Mater. Chem. 2005, 15, 831–840.

    Article  Google Scholar 

  3. Zhao, Q.; Jayawardhana, D. A.; Wang, D.; Guan, X. Study of peptide transport through engineered protein channels. J. Phys. Chem. B 2009, 113, 3572–3578.

    Article  Google Scholar 

  4. Song, L.; Hobaugh, M. R.; Shustak, C.; Cheley, S.; Bayley, H.; Gouaux, J. E. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 1996, 274, 1859–1866.

    Article  Google Scholar 

  5. Conlan, S.; Zhang, Y.; Cheley, S.; Bayley, H. Biochemical and biophysical characterization of OmpG: A monomeric porin. Biochemistry 2000, 39, 11845–11854.

    Article  Google Scholar 

  6. Miles, G.; Cheley, S.; Braha, O.; Bayley, H. The staphylococcal leukocidin bicomponent toxin forms large ionic channels. Biochemistry 2001, 40, 8514–8522.

    Article  Google Scholar 

  7. Braha, O.; Gu, L.-Q.; Zhou, L.; Lu, X.; Cheley, S.; Bayley, H. Simultaneous stochastic sensing of divalent metal ions. Nat. Biotechnol. 2000, 17, 1005–1007.

    Article  Google Scholar 

  8. Braha, O.; Walker, B.; Cheley, S.; Kasianowicz, J. J.; Song, L.; Gouaux, J. E.; Bayley, H. Designed protein pores as components for biosensors. Chem. Biol. 1997, 4, 497–505.

    Article  Google Scholar 

  9. Cheley, S.; Gu, L.-Q.; Bayley, H. Stochastic sensing of nanomolar inositol 1,4,5-trisphosphate with an engineered pore. Chem. Biol. 2002, 9, 829–838.

    Article  Google Scholar 

  10. Gu, L.-Q.; Braha, O.; Conlan, S.; Cheley, S.; Bayley, H. Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter. Nature 1999, 398, 686–690.

    Article  Google Scholar 

  11. Shin, S.-H.; Luchian, T.; Cheley, S.; Braha, O.; Bayley, H. Kinetics of a reversible covalent-bond-forming reaction observed at the single-molecule level. Angew. Chem. Int. Ed. 2002, 41, 3707–3709.

    Article  Google Scholar 

  12. Kang, X. F.; Cheley, S.; Guan, X.; Bayley, H. Stochastic Detection of Enantiomers. J. Am. Chem. Soc. 2006, 128, 10684–10685.

    Article  Google Scholar 

  13. Guan, X.; Gu, L. Q.; Cheley, S.; Braha, O.; Bayley, H. Stochastic sensing of TNT with a genetically engineered pore. ChemBioChem, 2005, 6, 1875–1881.

    Article  Google Scholar 

  14. Jayawardhana, D. A.; Crank, J. A.; Zhao, Q.; Armstrong, D. W.; Guan X. Nanopore stochastic detection of a liquid explosive component and sensitizers using boromycin and an ionic liquid supporting electrolyte. Anal. Chem. 2009, 81, 460–464.

    Article  Google Scholar 

  15. Wang, D.; Zhao, Q.; Guan, X. Detection of nerve agent hydrolytes in an engineered nanopore. Sens. Actuators B Chem. 2009, 139, 440–446.

    Article  Google Scholar 

  16. Wu, H. C.; Bayley, H. Single-molecule detection of nitrogen mustards by covalent reaction within a protein nanopore. J. Am. Chem. Soc. 2008, 130, 6813–6819.

    Article  Google Scholar 

  17. Kasianowicz, J. J.; Brandin, E.; Branton, D.; Deamer, D. Characterization of individual polynucleotide molecules using a membrane channel. Proc. Natl. Acad. Sci. U. S. A. 1996, 93, 13770–13773.

    Google Scholar 

  18. Meller, A.; Nivon, L.; Brandin, E.; Golovchenko, J.; Branton, D. Rapid nanopore discrimination between single polynucleotide molecules. Proc. Natl. Acad. Sci. U.S.A. 2000,97, 1079–1084.

    Article  Google Scholar 

  19. Howorka, S.; Cheley, S.; Bayley, H. Sequence-specific detection of individual DNA strands using engineered nanopores. Nat. Biotechnol. 2001, 19, 636–639.

    Article  Google Scholar 

  20. Sanchez-Quesada, J.; Saghatelian, A.; Cheley, S.; Bayley, H.; Ghadiri, M. R. Single DNA rotaxanes of a transmembrane pore protein. Angew. Chem. Int. Ed. Engl. 2004, 43, 3063–3067.

    Article  Google Scholar 

  21. Maglia, G.; Henricus, M.; Wyss, R.; Li, Q.; Cheley, S.; Bayley, H. DNA strands from denatured duplexes are translocated through engineered protein nanopores at alkaline pH. Nano Lett. 2009, 9, 3831–3836.

    Article  Google Scholar 

  22. Stoddart, D.; Heron, A. J.; Mikhailova, E.; Maglia, G.; Bayley, H. Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 7702–7707.

    Article  Google Scholar 

  23. Clarke, J.; Wu, H. C.; Jayasinghe, L.; Patel, A.; Reid, S.; Bayley, H. Continuous base identification for single-molecule nanopore DNA sequencing. Nat. Nanotechnol. 2009, 4, 265–270.

    Article  Google Scholar 

  24. Maglia, G.; Restrepo, M. R.; Mikhailova, E.; Bayley, H. Enhanced translocation of single DNA molecules through alpha-hemolysin nanopores by manipulation of internal charge. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 19720–19725.

    Article  Google Scholar 

  25. Stefureac, R.; Long, Y. T.; Kraatz, H. B.; Howard, P.; Lee, J. S. Transport of alpha-helical peptides through alpha-hemolysin and aerolysin pores. Biochem. 2006, 45, 9172–9179.

    Article  Google Scholar 

  26. Movileanu, L.; Schmittschmitt, J. P.; Scholtz, J. M.; Bayley, H. Interactions of peptides with a protein pore. Biophys. J. 2005, 89, 1030–1045.

    Article  Google Scholar 

  27. Wolfe, A. J.; Mohammad, M. M.; Cheley, S.; Bayley, H.; Movileanu, L. Catalyzing the translocation of polypeptides through attractive interactions. J. Am. Chem. Soc. 2007, 129, 14034–14041.

    Article  Google Scholar 

  28. Mohammad, M. M.; Movileanu, L. Excursion of a single polypeptide into a protein pore: simple physics, but complicated biology. Eur. Biophys. J. 2008, 37, 913–925.

    Article  Google Scholar 

  29. Movileanu, L.; Howorka, S.; Braha, O.; Bayley, H. Detecting protein analytes that modulate transmembrane movement of a polymer chain within a single protein pore. Nat. Biotechnol. 2000, 18, 1091–1095.

    Article  Google Scholar 

  30. Howorka, S; Nam, J.; Bayley, H.; Kahne, D. Stochastic detection of monovalent and bivalent protein-ligand interactions. Angew. Chem. Int. Ed. Engl. 2004, 43, 842–846.

    Google Scholar 

  31. Xie, H.; Braha, O.; Gu, L.-Q.; Cheley, S.; Bayley, H. Single-molecule observation of the catalytic subunit of cAMP-dependent protein kinase binding to an inhibitor peptide. Chem. Biol. 2005, 12, 109–120.

    Article  Google Scholar 

  32. Cheley, S.; Xie, H.; Bayley, H. A genetically encoded pore for the stochastic detection of a protein kinase. Chembiochem 2006, 7, 1923–1927.

    Article  Google Scholar 

  33. Li, J.; Stein, D.; McMullan, C.; Branton, D.; Aziz, M. J.; Golovchenko, J. A. Ion-beam sculpting at nanometre length scales. Nature 2001, 412, 166–169.

    Article  Google Scholar 

  34. Storm, A. J.; Storm, C.; Chen, J.; Zandbergen, H.; Joanny, J. F.; Dekker, C. Fast DNA translocation through a solid-state nanopore. Nano Lett. 2005, 5, 1193–1197.

    Article  Google Scholar 

  35. 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. 2003, 2, 537–540.

    Article  Google Scholar 

  36. Heins, E. A.; Siwy, Z. S.; Baker, L. A.; Martin, C. R. Detecting single porphyrin molecules in a conically shaped synthetic nanopore. Nano Lett. 2005, 5, 1824–1829.

    Article  Google Scholar 

  37. Siwy, Z.; Apel, P.; Dobrev, D.; Neumann, R.; Spohr, R.; Trautmann, C.; Voss, K. Ion transport through asymmetric nanopores prepared by ion track etching. Nucl. Instrum. Methods Phys. Res., Sect. B 2003,208, 143–148.

    Google Scholar 

  38. Iqbal, S. M.; Akin, D.; Bashir, R. Solid-state nanopore channels with DNA selectivity. Nature Nanotechnol. 2007, 2, 243–248.

    Article  Google Scholar 

  39. Wanunu, M.; Meller, A. Chemically modified solid-state nanopores. Nano Lett. 2007, 7, 1580–1585.

    Google Scholar 

  40. Vlassiouk, I.; Kozel, T. R.; Siwy, Z. S. Biosensing with nanofluidic diodes. J. Am. Chem. Soc. 2009, 131, 8211–8220.

    Article  Google Scholar 

  41. Sun, L.; Crooks, R. M. Single Carbon Nanotube Membranes: A well-defined model for studying mass transport through nanoporous materials. J. Am. Chem. Soc. 2000, 122, 12340–12345.

    Article  Google Scholar 

  42. Yeh, I. C.; Hummer, G. Nucleic acid transport through carbon nanotube membranes. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 12177–12182.

    Article  Google Scholar 

  43. Nardin, C.; Meier, W. Hybrid materials from amphiphilic block copolymers and membrane proteins. J. Biotechnol. 2002, 90, 17–26.

    Google Scholar 

  44. Bayley, H.; Martin, C. R. Resistive-pulse sensing-from microbes to molecules. Chem. Rev. 2000, 100, 2575–2594.

    Article  Google Scholar 

  45. 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. 2007, 129, 4701–4705.

    Article  Google Scholar 

  46. White, R. J.; Ervin, E. N.; Yang, T.; Chen, X.; Daniel, S.; Cremer, P. S.; White, H. S. Single ion-channel recordings using glass nanopore membranes. J. Am. Chem. Soc. 2007, 129, 11766–11775.

    Article  Google Scholar 

  47. Zhao, Q.; Wang, D.; Jayawardhana, D. A.; Guan, X. Stochastic sensing of biomolecules in a nanopore sensor array. Nanotechnology 2008, 19, 505504.

    Article  Google Scholar 

  48. Howorka, S.; Siwy Z. Nanopore analytics: sensing of single molecules. Chem. Soc. Rev. 2009, 38, 2360–2384.

    Article  Google Scholar 

  49. Montal, M.; Mueller, P. Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proc. Natl. Acad. Sci. U.S.A. 1972, 69, 3561–3566.

    Article  Google Scholar 

  50. Matsuno, Y.; Osono, C.; Hirano, A.; Sugawara, M. Single-channel recordings of gramicidin at agarose-supported bilayer lipid membranes formed by the tip-dip and painting methods. Anal. Sci. 2004, 20, 1217–1221.

    Article  Google Scholar 

  51. Gu, L. Q.; Cheley, S.; Bayley, H. Prolonged residence time of a noncovalent molecular adapter, beta-cyclodextrin, within the lumen of mutant alpha-hemolysin pores. J. Gen. Physiol. 2001, 118, 481–494.

    Article  Google Scholar 

  52. Pinnaduwage, L. A.; Gehl, A.; Hedden, D. L.; Muralidharan, G.; Thundat, T.; Lareau, R. T.; Sulchek, T.; Manning, L.; Rogers, B.; Jones, M.; Adams, J. D. Explosives: a microsensor for trinitrotoluene vapour. Nature 2003, 425, 474–474.

    Article  Google Scholar 

  53. Looger, L. L.; Dwyer, M. A.; Smith, J. J.; Hellinga, H. W. Computational design of receptor and sensor proteins with novel functions. Nature 2003, 423, 185–190.

    Article  Google Scholar 

  54. Meagher, R. B. Pink water, green plants, and pink elephants. Nat. Biotechnol. 2001, 19, 1120–1121.

    Article  Google Scholar 

  55. http://www.globalsecurity.org/military/systems/munitions/explosives-liquid.htm.

  56. http://www.howstuffworks.com/liquid-explosives.htm.

  57. Hooijschuur, E. W.; Kientz, C. E.; Brinkman, U. A.Analytical separation techniques for the determination of chemical warfare agents. J. Chromatogr. A 2002, 982, 177–200.

    Article  Google Scholar 

  58. Rathert, P.; Dhayalan, A.; Murakami, M.; Zhang, X.; Tamas, R.; Jurkowska, R.; Komatsu, Y.; Shinkai, Y.; Cheng, X. D.; Jeltsch, A. Protein lysine methyltransferase G9a acts on non-histone targets. Nat. Chem. Biol. 2008, 4, 344–346.

    Article  Google Scholar 

  59. Asara, J. M.; Schweitzer, M. H.; Freimark, L. M.; Phillips, M.; Cantley, L. C. Protein sequences from mastodon and Tyrannosaurus rex revealed by mass spectrometry. Science 2007, 316, 280–285.

    Article  Google Scholar 

  60. Baker, D.; Sali, A. Protein structure prediction and structural genomics. Science 2001, 294, 93–96.

    Article  Google Scholar 

  61. Zhao, Q.; de Zoysa, R. S.; Wang, D.; Jayawardhana, D. A.; Guan, X. Real-time monitoring of peptide cleavage using a nanopore probe. J. Am. Chem. Soc. 2009, 131, 6324–6325.

    Article  Google Scholar 

  62. National Human Genome Research Institute (2004) Revolutionary Genome Sequencing Technologies—The $1000 Genome. (http://grants1.nih.gov/grants/guide/rfa-files/RFA-HG-04-003.html)

  63. Bayley, H. Sequencing single molecules of DNA. Curr. Opin. Chem. Biol. 2006, 10, 628–637.

    Article  Google Scholar 

  64. 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. The potential and challenges of nanopore sequencing. A. Nat. Biotechnol. 2008, 26, 1146–1153.

    Article  Google Scholar 

  65. Purnell, F. R.; Mehta, K. K.; Schmidt, J. J. Nucleotide identification and orientation discrimination of DNA homopolymers immobilized in a protein nanopore. Nano Lett. 2008, 8, 3029–3034.

    Article  Google Scholar 

  66. 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. 2006, 128, 1705–1710.

    Article  Google Scholar 

  67. Meller, A.; Branton, D. Single molecule measurements of DNA transport through a nanopore. Electrophoresis 2002, 23, 2583–2591.

    Article  Google Scholar 

  68. Meller, A.; Nivon, L.; Branton, D. Voltage-driven DNA translocations through a nanopore. Phys. Rev. Lett. 2001, 86, 3435–3438.

    Article  Google Scholar 

  69. Sigalov, G.; Comer, J.; Timp, G.; Aksimentiev, A. Detection of DNA sequences using an alternating electric field in a nanopore capacitor. Nano Lett. 2008, 8, 56–63.

    Article  Google Scholar 

  70. de Zoysa, R. S.; Jayawardhana, D. A.; Zhao, Q.; Wang, D.; Armstrong, D. W.; Guan, X. Slowing DNA translocation through nanopores using a solution containing organic salts. J. Phys. Chem. B 2009, 113, 13332–13336.

    Article  Google Scholar 

  71. Dickinson, T. A.; White, J.; Kauer, J. S.; Walt, D. R. Current trends in 'artificial-nose' technology. Trends Biotechnol. 1998, 16, 250–258.

    Article  Google Scholar 

  72. Turner, A. P.; Magan, N. Electronic noses and disease diagnostics. Nat. Rev. Microbiol. 2004, 2, 161–166.

    Article  Google Scholar 

  73. Thaler, E. R.; Kennedy, D. W.; Hanson, C. W. Medical applications of electronic nose technology: review of current status. Am. J. Rhinol. 2001, 15, 291–295.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The University of Texas at Arlington, 700 Planetarium Place, Arlington, TX, 76019-0065, USA

    Xiyun Guan

Authors
  1. Xiyun Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ranulu Samanthi S. de Zoysa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dilani A. Jayawardhana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qitao Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiyun Guan .

Editor information

Editors and Affiliations

  1. Department of Electrical Engineering, Nanotechnology Research and Teaching Fac, University of Texas at Arlington, S. Cooper Street, Arlington, 76019-0119, Texas, USA

    Samir M. Iqbal

  2. Department of Electrical and Computer En, University of Illinois at Urbana-Champai, N. Wright Street 208, Urbana, 61820, Illinois, USA

    Rashid Bashir

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Guan, X., de Zoysa, R.S.S., Jayawardhana, D.A., Zhao, Q. (2011). Stochastic Detection of Terrorist Agents and Biomolecules in a Biological Channel. In: Iqbal, S., Bashir, R. (eds) Nanopores. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8252-0_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-8252-0_13

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-8251-3

  • Online ISBN: 978-1-4419-8252-0

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation