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Analytical and Bioanalytical Chemistry

, Volume 402, Issue 1, pp 209–230 | Cite as

Natural and artificial ion channels for biosensing platforms

  • L. StellerEmail author
  • M. Kreir
  • R. Salzer
Review

Abstract

The single-molecule selectivity and specificity of the binding process together with the expected intrinsic gain factor obtained when utilizing flow through a channel have attracted the attention of analytical chemists for two decades. Sensitive and selective ion channel biosensors for high-throughput screening are having an increasing impact on modern medical care, drug screening, environmental monitoring, food safety, and biowarefare control. Even virus antigens can be detected by ion channel biosensors. The study of ion channels and other transmembrane proteins is expected to lead to the development of new medications and therapies for a wide range of illnesses. From the first attempts to use membrane proteins as the receptive part of a sensor, ion channels have been engineered as chemical sensors. Several other types of peptidic or nonpeptidic channels have been investigated. Various gating mechanisms have been implemented in their pores. Three technical problems had to be solved to achieve practical biosensors based on ion channels: the fabrication of stable lipid bilayer membranes, the incorporation of a receptor into such a structure, and the marriage of the modified membrane to a transducer. The current status of these three areas of research, together with typical applications of ion-channel biosensors, are discussed in this review.

Keywords

Biosensor Ion channel Lipid membrane Planar patch clamp High throughput Drug sensing 

Notes

Acknowledgment

We would like to acknowledge the financial support provided by the German Federal Ministry of Education and Research (BMBF 13N10969; BMBF 03IP610).

References

  1. 1.
    The Royal Swedish Academy of Sciences (2003) The Nobel Prize in Chemistry 2003: Peter Agre, Roderick MacKinnon. http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html. Accessed 4 July 2011
  2. 2.
    Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544Google Scholar
  3. 3.
    Hille B, Armstrong CM, MacKinnon R (1999) Ion channels: from idea to reality. Nat Med 5:1105–1109CrossRefGoogle Scholar
  4. 4.
    Cornell BA, Braach-Maksvytis VLB, King LG, Osman PDJ, Raguse B, Wieczorek L, Pace RJ (1997) A biosensor that uses ion-channel switches. Nature (London) 387(6633):580–583CrossRefGoogle Scholar
  5. 5.
    Curran ME, Splawski I, Timothy KW, Vincen GM, Green ED, Keating MT (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80:795–803CrossRefGoogle Scholar
  6. 6.
    Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT (1995) SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80:805–811CrossRefGoogle Scholar
  7. 7.
    Waxman SG (2007) Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nat Neurosci 10:405–409CrossRefGoogle Scholar
  8. 8.
    Sigworth FJ, Klemic KG (2005) Microchip technology in ion-channel research. IEEE Trans Nanobiosci 4(1):121–127CrossRefGoogle Scholar
  9. 9.
    Banik SSR, Doranz BJD (2009) Antibody strategies for membrane protein targets. Drug Discovery Dev 12(9):14–17Google Scholar
  10. 10.
    Cannon SC (2006) Pathomechanisms in channelopathies of skeletal muscle and brain. Annu Rev Neurosci 29:387–415Google Scholar
  11. 11.
    Lindsay MA (2003) Target discovery. Nat Rev Drug Discovery 2:831–838CrossRefGoogle Scholar
  12. 12.
    Bally M, Bailey K, Sugihara K, Grieshaber D, Vörös J, Städtler B (2010) Liposome and bilayer arrays towards biosensing applications. Small 6(22):2481–2497CrossRefGoogle Scholar
  13. 13.
    Conte Camerino D, Desaphy JF (2010) Grand challenge for ion channels: an underexploited resource for therapeutics. Front Pharmacol 1:113. doi: 10.3389/fphar.2010.00113
  14. 14.
    Liu A, Qitao Z, Guan X (2010) Stochastic nanopore sensors for the detection of terrorist agents: current status and challenges. Anal Chim Acta 675:106–115Google Scholar
  15. 15.
    Phung T, Zhang Y, Dunlop J, Dalziel J (2011) Bilayer lipid membranes supported on Teflon filters: a functional environment for ion channels. Biosens Bioelectron 26:3127–3135CrossRefGoogle Scholar
  16. 16.
    Lee SK, Cascao-Pereira LG, Sala RF, Holmes SP, Ryan KJ, Becker T (2005) Ion channel switch array. A biosensor for detecting multiple pathogens. Ind Biotechnol 1(1):26–31CrossRefGoogle Scholar
  17. 17.
    Turner APF (1997) Switching channels makes sense. Nature 387:555–557CrossRefGoogle Scholar
  18. 18.
    Nielsen CH (2009) Biomimetic membranes for sensor and separation applications. Anal Bioanal Chem 395:697–718CrossRefGoogle Scholar
  19. 19.
    Simon R (2008) The use of genomics in clinical trial design. Clin Cancer Res 14(19):5984–5993CrossRefGoogle Scholar
  20. 20.
    Ramachandran N, Srivastava S, LaBaer J (2008) Applications of protein microarrays for biomarker discovery. Proteomics Clin Appl 2:1444–1459CrossRefGoogle Scholar
  21. 21.
    Janshoff A, Steinem C (2006) Transport across artificial membranes—an analytical perspective. Anal Bioanal Chem 385:433–451Google Scholar
  22. 22.
    Suzuki H, Takeuchi S (2008) Microtechnologies for membrane protein studies. Anal Bioanal Chem 391:2695–2702CrossRefGoogle Scholar
  23. 23.
    Miller C, Racker E (1976) Ca++-induced fusion of fragmented sarcoplasmic reticulum with artificial planar bilayers. J Membr Biol 30:283–300Google Scholar
  24. 24.
    Le Pioufle B, Suzuki H, Tabata KV, Noji H, Takeuchi S (2008) Lipid bilayer microarray for parallel recording of transmembrane ion currents. Anal Chem 80:328–332CrossRefGoogle Scholar
  25. 25.
    Maurer JA, White VE, Dougherty DA, Nadeau JL (2007) Reconstitution of ion channels in agarose-supported silicon orifices. Biosens Bioelectron 22:2577–2584CrossRefGoogle Scholar
  26. 26.
    Knoll W, Köper I, Naumann R, Sinner EK (2008) Tethered bimolecular lipid membranes—a novel model membrane platform. Electrochim Acta 53:6680–6689Google Scholar
  27. 27.
    Kepplinger C, Höfer I, Steinem C (2009) Impedance analysis of valinomycin activity in nano-BLMs. Chem Physics Lipids 160:109–113CrossRefGoogle Scholar
  28. 28.
    Brueggemann A, George M, Klau M, Beckler M, Steindl J, Behrends JC, Fertig N (2002) Ion channel drug discovery and research: the automated nano-patch-clamp technology. Biophys J 82(6):3056–3062CrossRefGoogle Scholar
  29. 29.
    Urisu T, Asano T, Zhang Z, Uno H, Tero R, Junkyu H, Hiroko I, Arima Y, Iwata H, Shibasaki K, Tominaga M (2008) Incubation type Si-based planar ion channel biosensor. Anal Bioanal Chem 391:2703–2709CrossRefGoogle Scholar
  30. 30.
    Leifert WR, Glatz RV, Bailey K, Cooper T, Bally M, Stadler BM, Reimhult E, Shapter JG (2010) Nanoscale biosensors and biochips. Ann Rev Nano Res 3:1–82Google Scholar
  31. 31.
    Schmidt J (2005) Stochastic sensors. J Mater Chem 15(8):831–840CrossRefGoogle Scholar
  32. 32.
    Capone R, Blake S, Restrepo MR, Yang J, Mayer M (2007) Designing nanosensors based on charged derivatives of gramicidin A. J Am Chem Soc 129:9737–9745Google Scholar
  33. 33.
    Futaki S, Zhang Y, Kiwada T, Nakase I, Yagami T, Oiki S, Sugiura Y (2003) Gramicidin-based channel systems for the detection of protein–ligand interaction. Bioorg Med Chem 12:1343–1350CrossRefGoogle Scholar
  34. 34.
    Husaru L, Schulze R, Steiner G, Wolff T, Habicher WD, Salzer R (2005) Potential analytical applications of gated artificial ion channels. Anal Bioanal Chem 382:1882–1888CrossRefGoogle Scholar
  35. 35.
    Zimmerer CA, Braun HG, Kitsche M, Steiner G, Friedrich ST, Salzer R (2003) Optical biosensor array based on natural ion channels. Proc SPIE 5047:403–409Google Scholar
  36. 36.
    Grutter T, Prado de Carvalho L, Dufresne V, Taly A, Fischer M, Changeux JP (2005) A chimera encoding the fusion of an acetylcholine-binding protein to an ion channel is stabilized in a state close to the desensitized form of ligand-gated ion channels. CR Biologies 328:223–234CrossRefGoogle Scholar
  37. 37.
    Bartlett S, Bonci A, Haass-Koffler C, Naeemuddin M (2011) Construction of chimeric ion channel compositions and their uses in therapeutic and diagnostic products. PCT Int Appl WO 2011035045 A1 20110324Google Scholar
  38. 38.
    Haga T (1995) In: Meyers RA (ed) Molecular biology and biotechnology. A comprehensive desk reference. Wiley-VCH, New YorkGoogle Scholar
  39. 39.
    Hucho F, Weise C (2001) Ligand-gated ion channels. Angew Chem Int Ed 40:3100–3116Google Scholar
  40. 40.
    Arnadottir J, Chalfie M (2010) Eukaryotic mechanosensitive channels. Annu Rev Biophys 39:111–139CrossRefGoogle Scholar
  41. 41.
    Lipscombe D (2005) Ion channels. In: eLS. Wiley, ChichesterGoogle Scholar
  42. 42.
    Brunton L, Buxton I, Blumenthal D, Parker K (2007) Goodman and Gilman’s manual of pharmacology and therapeutics. McGraw-Hill, New YorkGoogle Scholar
  43. 43.
    Maelicke A (1997) Chemie heute: das Wissenschaftsmagazin des Fonds der Chemischen Industrie. Fons der chemischen Industrie, Frankfurt am Main, pp 90–95Google Scholar
  44. 44.
    Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JO, White LE (2008) Neuroscience, 4th edn. Sinauer Associates, SunderlandGoogle Scholar
  45. 45.
    Salzer R, Li J, Rautenberg C, Friedrich S (2001) Integration of ion channel proteins into a polymer matrix—investigation by the patch-clamp technique. Macromol Symp 164:239–245Google Scholar
  46. 46.
    Poulos JL, Jeon TJ, Damoiseaux R, Gillespie EJ, Bradley KA, Schmidt JJ (2009) Ion channel and toxin measurement using a high throughput lipid membrane platform. Biosens Bioelectron 24:1806–1810CrossRefGoogle Scholar
  47. 47.
    Kawano R, Osaki T, Sasaki H, Takinoue M, Yoshizawa S, Takeuchi S (2011) Rapid detection of a cocaine-binding aptamer using biological nanopores on a chip. J Am Chem Soc 133(22):8474–8477. doi: 10.1021/ja2026085 CrossRefGoogle Scholar
  48. 48.
    Aksimentiev A, Schulten K (2005) Imaging α-hemolysin with molecular dynamics: ionic conductance, osmotic permeability and the electrostatic potential map. Biophys J 88:3745–3761Google Scholar
  49. 49.
    Yin P, Burns CJ, Osman PDJ, Cornell BA (2003) A tethered bilayer sensor containing alamethicin channels and its detection of amiloride based inhibitors. Biosens Bioelectron 18:389–397CrossRefGoogle Scholar
  50. 50.
    Sawyer DB, Koeppe RE, Andemen OS (1989) Induction of conductance heterogeneity in gramicidin channels. Biochemistry 28:6571–6583CrossRefGoogle Scholar
  51. 51.
    Woodhouse G, King L, Wieczorek L, Osman P, Cornell B (1999) The ion channel switch biosensor. J Mol Recognit 12:328–334CrossRefGoogle Scholar
  52. 52.
    Coldrick Z, Penezic A, Gasparovic B, Steenson P, Merrifield J, Nelson A (2011) High throughput systems for screening biomembrane interactions on fabricated mercury film electrodes. J Appl Electrochem 41:939–949CrossRefGoogle Scholar
  53. 53.
    Anslyn EV (2007) Supramolecular analytical chemistry. J Org Chem 72:687–699Google Scholar
  54. 54.
    Terrettaz S, Follonier S, Makohliso S, Vogel H (2009) A synthetic membrane protein in tethered lipid bilayers for immunosensing in whole blood. J Struct Biol 168:177–182CrossRefGoogle Scholar
  55. 55.
    Bayley H, Cremer PS (2001) Stochastic sensors inspired by biology. Nature 413(6852):226–230. doi: 10.1038/35093038 CrossRefGoogle Scholar
  56. 56.
    Clarke J, Wu HC, Jayasinghe L, Patel A, Reid S, Bayley H (2009) Continuous base identification for single-molecule nanopore DNA sequencing. Nat Nanotechnol 4:265–270CrossRefGoogle Scholar
  57. 57.
    Kobuke Y, Ueda K, Sokabe M (1992) Artificial non-peptide single ion channels. J Am Chem Soc 114:7618–7622CrossRefGoogle Scholar
  58. 58.
    Bayley H, Jayasinghe L (2004) Functional engineered channels and pores (review). Mol Membr Biol 21(4):209–220. doi: 10.1080/09687680410001716853 Google Scholar
  59. 59.
    Moreau CJ, Dupuis JP, Revilloud J, Arumugam K, Vivaudou M (2008) Coupling ion channels to receptors for biomolecule sensing. Nat Nanotechnol 3:620–625CrossRefGoogle Scholar
  60. 60.
    Gu LQ, Shim JW (2010) Single molecule sensing by nanopores and nanopore devices. Analyst 135:441–451CrossRefGoogle Scholar
  61. 61.
    Gardeniers HJGE (2009) Chemistry in nanochannel confinement. Anal Bioanal Chem 394:385–397CrossRefGoogle Scholar
  62. 62.
    Menon SK, Modi NR, Patel B, Patel MB (2011) Azo calix[4]arene based neodymium(III)-selective PVC membrane sensor. Talanta 83:1329–1334CrossRefGoogle Scholar
  63. 63.
    Husaru L, Gruner M, Wolff T, Habicher WD, Reiner Salzer R (2005) Photoresponsive upper-rim azobenzene substituted calix[4]resorcinarenes. Tetrahedron Lett 46:3377–3379Google Scholar
  64. 64.
    Ali M, Tahir MN, Siwy Z, Neumann R, Tremel W, Ensinger W (2011) Hydrogen peroxide sensing with horseradish peroxidase-modified polymer single conical nanochannels. Anal Chem 83:1673–1680Google Scholar
  65. 65.
    Miller C (1986) Ion channel reconstitution. Plenum, New YorkGoogle Scholar
  66. 66.
    Plant AL, Brigham-Burke M, Petrella EC, O’Shannessy DJ (1995) Phospholipid/alkanethiol bilayers for cell-surface receptor studies by surface plasmon resonance. Anal Biochem 226(2):342–348CrossRefGoogle Scholar
  67. 67.
    Yang T, Jung S, Mao H, Cremer PS (2001) Fabrication of phospholipid bilayer-coated microchannels for on-chip immunoassays. Anal Chem 73(2):165–169CrossRefGoogle Scholar
  68. 68.
    Korlach J, Schwille P, Webb WW, Feigenson GW (1999) Characterization of lipid bilayer phases by confocal microscopy and fluorescence correlation spectroscopy. Proc Natl Acad Sci USA 96(15):8461–8466Google Scholar
  69. 69.
    Kahya N, Scherfeld D, Bacia K, Poolman B, Schwille P (2003) Probing lipid mobility of raft-exhibiting model membranes by fluorescence correlation spectroscopy. J Biol Chem 278:28109–28115CrossRefGoogle Scholar
  70. 70.
    Angelova M, Soleau S, Meleard P, Faucon J, Bothorel P (1992) Preparation of giant vesicles by external AC fields. Kinetics and application. Progr Colloid Polymer Sci 89:127–131Google Scholar
  71. 71.
    Angelova MI, Hristova N, Tsoneva I (1999) DNA-induced endocytosis upon local microinjection to giant unilamellar cationic vesicles. Eur Biophys J 28:142–150Google Scholar
  72. 72.
    Mueller P, Chien TF, Rudy B (1983) Formation and properties of cell-size lipid bilayer vesicles. Biophys J 44:375–381CrossRefGoogle Scholar
  73. 73.
    Montal M, Darszon A, Schindler HG (1981) Functional reassembly of membrane proteins in planar lipid bilayers. Q Rev Biophys 14:1–79CrossRefGoogle Scholar
  74. 74.
    Bean RC, Shepherd WC, Chan H, Eichner J (1969) Discrete conductance fluctuations in lipid bilayer protein membranes. J Gen Physiol 53(6):741–757CrossRefGoogle Scholar
  75. 75.
    Kagawa Y, Racker E (1971) Partial resolution of the enzymes catalyzing oxidative phosphorylation. XXV. Reconstitution of particles catalyzing 32Pi-adenosine triphosphate exchange. J Biol Chem 246:5477–5487Google Scholar
  76. 76.
    Hinkle PC, Kim JJ, Racker E (1972) Ion transport and respiratory control in vesicles formed from cytochrome oxidase and phospholipids. J Biol Chem 247(4):1338–1339Google Scholar
  77. 77.
    Racker E (1972) Reconstitution of a calcium pump with phospholipids and a purified Ca++−adenosine triphosphatase from sacroplasmic reticulum. J Biol Chem 247(24):8198–8200Google Scholar
  78. 78.
    Montal M, Mueller P (1972) Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proc Natl Acad Sci USA 69(12):3561–3566Google Scholar
  79. 79.
    Wilmsen U, Methfessel C, Hanke W, Boheim G (1983) Channel current fluctuations studies with solvent free lipid bilayers using Neher–Sakmannpipetts. In: Troyanowsky C (ed) Physical chemistry of transmembrane ion motions. Elsevier, AmsterdamGoogle Scholar
  80. 80.
    Mueller P, Rudin DO, Tien HT, Wescott WC (1962) Reconstitution of cell membrane structure in vitro and its transformation into an excitable system. Nature 194:979–980CrossRefGoogle Scholar
  81. 81.
    Schindler H, Quast U (1980) Formation of planar membranes from natural liposomes. Application to acetylcholine receptor from Torpedo. Ann N Y Acad Sci 358:361CrossRefGoogle Scholar
  82. 82.
    Hanke W, Breer H (1986) Channel properties of an insect neuronal acetylcholine receptor protein reconstituted in planar lipid bilayers. Nature 321(6066):171–174. doi: 10.1038/321171a0 CrossRefGoogle Scholar
  83. 83.
    Finkelstein A, Zimmerberg J, Cohen FS (1986) Osmotic swelling of vesicles: its role in the fusion of vesicles with planar phospholipid bilayer membranes and its possible role in exocytosis. Annu Rev Physiol 48:163–174. doi: 10.1146/annurev.ph.48.030186.001115 CrossRefGoogle Scholar
  84. 84.
    Miller C (1983) Integral membrane channels: studies in model membranes. Physiol Rev 63:1209–1242Google Scholar
  85. 85.
    Coronado R (1986) Recent advances in planar phospholipid bilayer techniques for monitoring ion channels. Annu Rev Biophys Biophys Chem 15:259–277CrossRefGoogle Scholar
  86. 86.
    Evans WH (1990) Organelles and membranes of animal cells. In: Findlay JBC, Evans WH (eds) Biological membranes: a practical approach. IRL, Oxford, pp 1–35Google Scholar
  87. 87.
    Levitski A (1985) Reconstitution of membrane receptor systems. Biochim Biophys Acta 822:127–153Google Scholar
  88. 88.
    Catterall WA, Seagar MJ, Takahashi M, Nunoki K (1989) Molecular properties of dihydropyridine-sensitive calcium channels. Ann NY Acad Sci 560:1–14CrossRefGoogle Scholar
  89. 89.
    Jones OT, Earnest JP, McNamee MG (1990) Solubilization and reconstitution of membrane proteins. In: Findlay JBC, Evans WH (eds) Biological membranes: a practical approach. IRL, Oxford, pp 139–177Google Scholar
  90. 90.
    Montal M (1987) Reconstitution of channel proteins from excitable cells in planar lipid bilayer membranes. J Membr Biol 98:101–115CrossRefGoogle Scholar
  91. 91.
    Silvius JR (1992) Solubilization and functional reconstitution of biomembrane components. Annu Rev Biophys 21:323–348CrossRefGoogle Scholar
  92. 92.
    Hanke W, Methfessel C, Wilmsen HU, Katz E, Jung G, Boheim G (1983) Melittin and a chemically modified trichotoxin form alamethicin-type multi-state pores. Biochim Biophys Acta 727(1):108–114CrossRefGoogle Scholar
  93. 93.
    Hanke W, Boheim G, Barhanin J, Pauron D, Lazdunski M (1984) Reconstitution of highly purified saxitoxin-sensitive Na+-channels into planar lipid bilayers. EMBO J 3(3):509–515Google Scholar
  94. 94.
    Hanke W, Kaupp UB (1984) Incorporation of ion channels from bovine rod outer segments into planar lipid bilayers. Biophys J 46(5):587–595. doi: 10.1016/S0006-3495(84)84057-6 CrossRefGoogle Scholar
  95. 95.
    Montal M, Anhoil R, Labarca P (1986) The reconstituted acetylcholine receptor. In: Miller C (ed) lon channel reconstitution. Plenum, New York, pp 157–204 .ISBN 0-306-42136-4Google Scholar
  96. 96.
    Coronado R, Latorre R (1983) Phospholipid bilayers made from monolayers on patch-clamp pipettes. Biophys J 43(2):231–236. doi: 10.1016/S0006-3495(83)84343-4 CrossRefGoogle Scholar
  97. 97.
    Suarez-Isla BA, Wan K, Lindstrom J, Montal M (1983) Single-channel recordings from purified acetylcholine receptors reconstituted in bilayers formed at the tip of patch pipets. Biochemistry 22(10):2319–2323CrossRefGoogle Scholar
  98. 98.
    Mueller P, Rudin DO (1963) Induced excitability in reconstituted cell membrane structure. J Theor Biol 4(3):268–280CrossRefGoogle Scholar
  99. 99.
    Schindler H (1980) Formation of planar bilayers from artificial or native membrane vesicles. FEBS Lett 122(1):77–79. doi: 0014-5793(80)80405-4 CrossRefGoogle Scholar
  100. 100.
    Schindler H, Rosenbusch JP, Quast U (1980) A novel concept of membrane reconstitution applied to acetylcholine receptor from Torpedo and matrix protein from Escherichia coli. Neurochem Int 2C:291–298Google Scholar
  101. 101.
    Van Gelder P, Dumas F, Winterhalter M (2000) Understanding the function of bacterial outer membrane channels by reconstitution into black lipid membranes. Biophys Chem 85(2–3):153–167CrossRefGoogle Scholar
  102. 102.
    Gomez-Lagunas F, Pena A, Lievano A, Darszon A (1989) Incorporation of ionic channels from yeast plasma membranes into black lipid membranes. Biophys J 56(1):115–119. doi: 10.1016/S0006-3495(89)82656-6 CrossRefGoogle Scholar
  103. 103.
    Bamberg E, Alpes H, Apell HJ, Bradley R, Harter B, Quelle MJ, Urry DW (1979) Formation of ionic channels in black lipid membranes by succinic derivatives of gramicidin A. J Membr Biol 50(3–4):257–270Google Scholar
  104. 104.
    Bayley H (1999) Designed membrane channels and pores. Curr Opin Biotechnol 10(1):94–103CrossRefGoogle Scholar
  105. 105.
    Cornell BA, Krishna G, Osman PD, Pace RD, Wieczorek L (2001) Tethered-bilayer lipid membranes as a support for membrane-active peptides. Biochem Soc Trans 29(Pt 4):613–617CrossRefGoogle Scholar
  106. 106.
    Peggion C, Moretto V, Formaggio F, Crisma M, Toniolo C, Kamphuis J, Kaptein B, Broxterman QB (2001) Partial [alphaMe]Aun scan of [l-Leu11-OMe]-trichogin GA IV, a membrane active synthetic precursor of the natural lipopeptaibol. J Pept Res 58(4):317–324Google Scholar
  107. 107.
    Baumgart T, Kreiter M, Lauer H, Naumann R, Jung G, Jonczyk A, Offenhausser A, Knoll W (2003) Fusion of small unilamellar vesicles onto laterally mixed self-assembled monolayers of thiolipopeptides. J Colloid Interface Sci 258(2):298–309CrossRefGoogle Scholar
  108. 108.
    Schiller SM, Naumann R, Lovejoy K, Kunz H, Knoll W (2003) Archaea analogue thiolipids for tethered bilayer lipid membranes on ultrasmooth gold surfaces. Angew Chem Int Ed 42(2):208–211. doi: 10.1002/anie.200390080 Google Scholar
  109. 109.
    Bearinger JP, Terrettaz S, Michel R, Tirelli N, Vogel H, Textor M, Hubbell JA (2003) Chemisorbed poly(propylene sulphide)-based copolymers resist biomolecular interactions. Nat Mater 2(4):259–264. doi: 10.1038/nmat851 CrossRefGoogle Scholar
  110. 110.
    Schmidt EK, Liebermann T, Kreiter M, Jonczyk A, Naumann R, Offenhausser A, Neumann E, Kukol A, Maelicke A, Knoll W (1998) Incorporation of the acetylcholine receptor dimer from Torpedo californica in a peptide supported lipid membrane investigated by surface plasmon and fluorescence spectroscopy. Biosens Bioelectron 13(6):585–591Google Scholar
  111. 111.
    Naumann R, Baumgart T, Graber P, Jonczyk A, Offenhausser A, Knoll W (2002) Proton transport through a peptide-tethered bilayer lipid membrane by the H(+)-ATP synthase from chloroplasts measured by impedance spectroscopy. Biosens Bioelectron 17(1–2):25–34CrossRefGoogle Scholar
  112. 112.
    Becucci L, Moncelli MR, Guidelli R (2002) Thallous ion movements through gramicidin channels incorporated in lipid monolayers supported by mercury. Biophys J 82(2):852–864CrossRefGoogle Scholar
  113. 113.
    McGillivray DJ, Vanderah DJ, Febo-Ayala W, Woodward JT, Heinrich F, Kasianowicz JJ, Lösche M (2007) Molecular-scale structural and functional characterization of sparsely tethered bilayer lipid membranes. Biointerphases 2(1):21–33. doi: 10.1116/1.2709308 CrossRefGoogle Scholar
  114. 114.
    Woodhouse GE, King LG, Wieczorek L, Cornell BA (1998) Kinetics of the competitive response of receptors immobilised to ion-channels which have been incorporated into a tethered bilayer. Faraday Discuss 111:247–258, discussion 331–243Google Scholar
  115. 115.
    Castellana ET, Kataoka S, Albertorio F, Cremer PS (2006) Direct writing of metal nanoparticle films inside sealed microfluidic channels. Anal Chem 78(1):107–112. doi: 10.1021/ac051288j CrossRefGoogle Scholar
  116. 116.
    Mager MD, Almquist B, Melosh NA (2008) Formation and characterization of fluid lipid bilayers on alumina. Langmuir 24(22):12734–12737. doi: 10.1021/la802726u Google Scholar
  117. 117.
    Florin EL, Gaub HE (1993) Painted supported lipid membranes. Biophys J 64(2):375–383CrossRefGoogle Scholar
  118. 118.
    Plant AL, Gueguetchkeri M, Yap W (1994) Supported phospholipid/alkanethiol biomimetic membranes: insulating properties. Biophys J 67(3):1126–1133. doi: 10.1016/S0006-3495(94)80579-X CrossRefGoogle Scholar
  119. 119.
    McConnell HM, Watts TH, Weis RM, Brian AA (1986) Supported planar membranes in studies of cell-cell recognition in the immune system. Biochim Biophys Acta 864(1):95–106Google Scholar
  120. 120.
    Kalb E, Frey S, Tamm LK (1992) Formation of supported planar bilayers by fusion of vesicles to supported phospholipid monolayers. Biochim Biophys Acta 1103(2):307–316CrossRefGoogle Scholar
  121. 121.
    Steltenkamp S, Muller MM, Deserno M, Hennesthal C, Steinem C, Janshoff A (2006) Mechanical properties of pore-spanning lipid bilayers probed by atomic force microscopy. Biophys J 91(1):217–226. doi: 10.1529/biophysj.106.081398 CrossRefGoogle Scholar
  122. 122.
    Csucs G, Ramsden JJ (1998) Solubilization of planar bilayers with detergent. Biochim Biophys Acta 1369(2):304–308CrossRefGoogle Scholar
  123. 123.
    Csucs G, Ramsden JJ (1998) Interaction of phospholipid vesicles with smooth metal-oxide surfaces. Biochim Biophys Acta 1369(1):61–70CrossRefGoogle Scholar
  124. 124.
    Mimms LT, Zampighi G, Nozaki Y, Tanford C, Reynolds JA (1981) Phospholipid vesicle formation and transmembrane protein incorporation using octylglucoside. Biochemistry 20:833CrossRefGoogle Scholar
  125. 125.
    Roessner CA, Struck DK, Ihler GM (1983) Injection of DNA into liposomes by bacteriophage lambda. J Biol Chem 258(1):643–648Google Scholar
  126. 126.
    Hamai C, Yang T, Kataoka S, Cremer PS, Musser SM (2006) Effect of average phospholipid curvature on supported bilayer formation on glass by vesicle fusion. Biophys J 90(4):1241–1248CrossRefGoogle Scholar
  127. 127.
    Funakoshi K, Suzuki H, Takeuchi S (2006) Lipid bilayer formation by contacting monolayers in a microfluidic device for membrane protein analysis. Anal Chem 78(24):8169–8174. doi: 10.1021/ac0613479 CrossRefGoogle Scholar
  128. 128.
    Holden MA, Jayasinghe L, Daltrop O, Mason A, Bayley H (2006) Direct transfer of membrane proteins from bacteria to planar bilayers for rapid screening by single-channel recording. Nat Chem Biol 2(6):314–318. doi: 10.1038/nchembio793 CrossRefGoogle Scholar
  129. 129.
    Bayley H, Cronin B, Heron A, Holden MA, Hwang WL, Syeda R, Thompson J, Wallace M (2008) Droplet interface bilayers. Mol Biosyst 4(12):1191–1208. doi: 10.1039/b808893d CrossRefGoogle Scholar
  130. 130.
    Hwang WL, Chen M, Cronin B, Holden MA, Bayley H (2008) Asymmetric droplet interface bilayers. J Am Chem Soc 130(18):5878–5879. doi: 10.1021/ja802089s CrossRefGoogle Scholar
  131. 131.
    Fertig N, Meyer C, Blick RH, Trautmann C, Behrends JC (2001) Microstructured glass chip for ion-channel electrophysiology. Phys Rev E 64(4 Pt 1):040901Google Scholar
  132. 132.
    Pantoja R, Sigg D, Blunck R, Bezanilla F, Heath JR (2001) Bilayer reconstitution of voltage-dependent ion channels using a microfabricated silicon chip. Biophys J 81(4):2389–2394. doi: 10.1016/S0006-3495(01)75885-7 CrossRefGoogle Scholar
  133. 133.
    Fertig N, Blick RH, Behrends JC (2002) Whole cell patch clamp recording performed on a planar glass chip. Biophys J 82(6):3056–3062. doi: 10.1016/S0006-3495(02)75646-4 CrossRefGoogle Scholar
  134. 134.
    Fertig N, George M, Klau M, Meyer C, Tilke A, Sobotta C, Blick RH, Behrends JC (2003) Microstructured apertures in planar glass substrates for ion channel research. Receptors Channels 9(1):29–40CrossRefGoogle Scholar
  135. 135.
    Mayer M, Kriebel JK, Tosteson MT, Whitesides GM (2003) Microfabricated teflon membranes for low-noise recordings of ion channels in planar lipid bilayers. Biophys J 85(4):2684–2695. doi: 10.1016/S0006-3495(03)74691-8 CrossRefGoogle Scholar
  136. 136.
    Ionescu-Zanetti C, Shaw RM, Seo J, Jan YN, Jan LY, Lee LP (2005) Mammalian electrophysiology on a microfluidic platform. Proc Natl Acad Sci USA 102(26):9112–9117. doi: 10.1073/pnas.0503418102 Google Scholar
  137. 137.
    Klemic KG, Klemic JF, Sigworth FJ (2005) An air-molding technique for fabricating PDMS planar patch-clamp electrodes. Pflugers Arch 449(6):564–572. doi: 10.1007/s00424-004-1360-8 CrossRefGoogle Scholar
  138. 138.
    Mach T, Chimerel C, Fritz J, Fertig N, Winterhalter M, Futterer C (2008) Miniaturized planar lipid bilayer: increased stability, low electric noise and fast fluid perfusion. Anal Bioanal Chem 390(3):841–846. doi: 10.1007/s00216-007-1647-7 CrossRefGoogle Scholar
  139. 139.
    Kreir M, Farre C, Beckler M, George M, Fertig N (2008) Rapid screening of membrane protein activity: electrophysiological analysis of OmpF reconstituted in proteoliposomes. Lab Chip 8(4):587–595. doi: 10.1039/b713982a Google Scholar
  140. 140.
    Sondermann M, George M, Fertig N, Behrends JC (2006) High-resolution electrophysiology on a chip: transient dynamics of alamethicin channel formation. Biochim Biophys Acta 1758(4):545–551. doi: 10.1016/j.bbamem.2006.03.023 Google Scholar
  141. 141.
    Schmidt C, Mayer M, Vogel H (2000) A chip-based biosensor for the functional analysis of single ion channels. Angew Chem Int Ed 39(17):3137–3140Google Scholar
  142. 142.
    Estes DJ, Mayer M (2005) Giant liposomes in physiological buffer using electroformation in a flow chamber. Biochim Biophys Acta 1712(2):152–160. doi: 10.1016/j.bbamem.2005.03.012 CrossRefGoogle Scholar
  143. 143.
    Estes DJ, Mayer M (2005) Electroformation of giant liposomes from spin-coated films of lipids. Colloids Surfaces B 42(2):115–123. doi: 10.1016/j.colsurfb.2005.01.016 Google Scholar
  144. 144.
    Neher E, Sakmann B (1992) The patch clamp technique. Sci Am 266(3):44–51CrossRefGoogle Scholar
  145. 145.
    Williams AJ (1994) In: Ogden DC (ed) Microelectrode techniques: the Plymouth Workshop handbook, 2nd edn. Company of Biologists, CambridgeGoogle Scholar
  146. 146.
    Borisenko V, Lougheed L, Hesse J, Fuereder-Kitzmueller E, Fertig N, Behrends JC, Woolley GA, Schuetz GJ (2003) Simultaneous optical and electrical recording of single gramicidin channels. Biophys J 84:612–622Google Scholar
  147. 147.
    Fertig N, Tilke A, Blick RH, Kotthaus JP, Behrends JC, ten Bruggencate G (2000) Stable integration of isolated cell membrane patches in a nanomachined aperture. Appl Phys Lett 77:1218Google Scholar
  148. 148.
    Xu J, Guia A, Rothwarf D, Huang M, Sithiphong K, Ouang J, Tao G, Wang X, Wu L (2003) A benchmark study with sealchip planar patch-clamp technology. Assay Drug Dev Technol 1(5):675–684Google Scholar
  149. 149.
    Stett A, Bucher V, Burkhardt C, Weber U, Nisch W (2003) Patch-clamping of primary cardiac cells with micro-openings in polyimide films. Med Biological Eng Computing 41(2):233–240. doi: 10.1007/BF02344895 CrossRefGoogle Scholar
  150. 150.
    Finkel A, Wittel A, Yang N, Handran S, Hughes J, Costantin J (2006) Population patch clamp improves data consistency and success rates in the measurement of ionic currents. J Biomol Screen 11:488. doi: 10.1177/1087057106288050 Google Scholar
  151. 151.
    Yan L, Herrington J, Goldberg E, Dulski PM, Bugianesi RM, Slaughter RS, Banerjee P, Brochu RM, Priest BT, Kaczorowski GJ, Rudy B, Garcia ML (2005) Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels. Mol Pharmacol 67(5):1513–1521. doi: 10.1124/mol.105.011064 Google Scholar
  152. 152.
    Farre C, Stoelzle S, Haarmann C, George M, Bruggemann A, Fertig N (2007) Automated ion channel screening: patch clamping made easy. Expert Opin Ther Targets 11(4):557–565. doi: 10.1517/14728222.11.4.557 Google Scholar
  153. 153.
    Farre C, Haythornthwaite A, Haarmann C, Stoelzle S, Kreir M, George M, Bruggemann A, Fertig N (2009) Port-a-Patch and Patchliner: high fidelity electrophysiology for secondary screening and safety pharmacology. Comb Chem High Throughput Screen 12(1):24–37Google Scholar
  154. 154.
    Farre C, George M, Brueggemann A, Fertig N (2008) Automated ion channel screening: patch clamping made easy. Drug Discov Today 5(1):23–28Google Scholar
  155. 155.
    Sinclair J, Pihl J, Olofsson J, Karlsson M, Jardemark K, Chiu DT, Orwar O (2002) A cell-based bar code reader for high-throughput screening of ion channel-ligand interactions. Anal Chem 74(24):6133–6138CrossRefGoogle Scholar
  156. 156.
    Tao H, Santa Ana D, Guia A, Huang M, Ligutti J, Walker G, Sithiphong K, Chan F, Guoliang T, Zozulya Z, Saya S, Phimmachack R, Sie C, Yuan J, Wu L, Xu J, Ghetti A (2004) Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol 2(5):497–506. doi: 10.1089/adt.2004.2.497 CrossRefGoogle Scholar
  157. 157.
    Mathes C (2006) QPatch: the past, present and future of automated patch clamp. Expert Opin Ther Targets 10(2):319–327. doi: 10.1517/14728222.10.2.319 Google Scholar
  158. 158.
    Kutchinsky J, Friis S, Asmild M, Taboryski R, Pedersen S, Vestergaard RK, Jacobsen RB, Krzywkowski K, Schroder RL, Ljungstrom T, Helix N, Sorensen CB, Bech M, Willumsen NJ (2003) Characterization of potassium channel modulators with QPatch automated patch-clamp technology: system characteristics and performance. Assay Drug Dev Technol 1(5):685–693. doi: 10.1089/154065803770381048 CrossRefGoogle Scholar
  159. 159.
    Li X, Li P (2010) Strategies for the real-time detection of Ca2+ channel events of single cells: recent advances and new possibilities. Expert Rev Clin Pharmacol 3(3):267–280Google Scholar
  160. 160.
    Lepple-Wienhues A, Ferlinz K, Seeger A, Schafer A (2003) Flip the tip: an automated, high quality, cost-effective patch clamp screen. Receptors Channels 9(1):13–17CrossRefGoogle Scholar
  161. 161.
    Zheng W, Spencer RH, Kiss L (2004) High throughput assay technologies for ion channel drug discovery. Assay Drug Dev Technol 2(5):543–552. doi: 10.1089/adt.2004.2.543 CrossRefGoogle Scholar
  162. 162.
    Baxter DF, Kirk M, Garcia AF, Raimondi A, Holmqvist MH, Flint KK, Bojanic D, Distefano PS, Curtis R, Xie Y (2002) A novel membrane potential-sensitive fluorescent dye improves cell-based assays for ion channels. J Biomol Screen 7(79):79–85. doi: 10.1177/108705710200700110 CrossRefGoogle Scholar
  163. 163.
    Cooper MA (2004) Advances in membrane receptor screening and analysis. J Mol Recognit 17(4):286–315. doi: 10.1002/jmr.675 Google Scholar
  164. 164.
    Terrettaz S, Vogel H (2005) Impedance spectroscopy of ion channels in tethered lipid bilayers. J Surface Sci Nanotechnol 3:203–206CrossRefGoogle Scholar
  165. 165.
    Peitz I, Voelker M, Fromherz P (2007) Recombinant serotonin receptor on a transistor as a prototype for cell-based biosensors. Angew Chem Int Ed 46(30):5787–5790. doi: 10.1002/anie.200700726 Google Scholar
  166. 166.
    Ding S, Gao C, Gu LQ (2009) Capturing single molecules of immunoglobulin and ricin with an aptamer-encoded glass nanopore. Anal Chem 81(16):6649–6655. doi: 10.1021/ac9006705 CrossRefGoogle Scholar
  167. 167.
    Mascini M (2009) Aptamers in bioanalysis. Wiley-Blackwell, Oxford, ISBN 9780470148303Google Scholar
  168. 168.
    Strehlitz B, Nikolaus N, Stoltenburg R (2008) Protein detection with aptamer biosensors. Sensors 8:4296–4307. doi: 10.3390/s8074296 Google Scholar
  169. 169.
    Guan X, Gu LQ, Cheley S, Braha O, Bayley H (2005) Stochastic sensing of TNT with a genetically engineered pore. Chembiochem 6(10):1875–1881. doi: 10.1002/cbic.200500064 Google Scholar
  170. 170.
    Castle N, Printzenhoff D, Zellmer S, Antonio B, Wickenden A, Silvia C (2009) Sodium channel inhibitor drug discovery using automated high throughput electrophysiology platforms. Comb Chem High Throughput Screen 12(1):107–122Google Scholar
  171. 171.
    Jentsch TJ, Stein V, Weinreich F, Zdebik AA (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82(2):503–568. doi: 10.1152/physrev.00029.2001 Google Scholar
  172. 172.
    Lynch JW (2004) Molecular structure and function of the glycine receptor chloride channel. Physiol Rev 84(4):1051–1095. doi: 10.1152/physrev.00042.2003 CrossRefGoogle Scholar
  173. 173.
    Galietta LV, Jayaraman S, Verkman AS (2001) Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists. Am J Physiol Cell Physiol 281(5):C1734–C1742Google Scholar
  174. 174.
    Weaver CD, Harden D, Dworetzky SI, Robertson B, Knox RJ (2004) A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells. J Biomol Screen 9(8):671–677. doi: 10.1177/1087057104268749 CrossRefGoogle Scholar
  175. 175.
    Beacham DW, Blackmer T, O’Grady M, Hanson GT (2010) Cell-based potassium ion channel screening using the FluxOR assay. J Biomol Screen 15(4):441–446. doi: 10.1177/1087057109359807 Google Scholar
  176. 176.
    Molokanova E, Savchenko A (2008) Bright future of optical assays for ion channel drug discovery. Drug Discov Today 13(1–2):14–22. doi: 10.1016/j.drudis.2007.11.009 Google Scholar
  177. 177.
    Syeda R, Holden MA, Hwang WL, Bayley H (2008) Screening blockers against a potassium channel with a droplet interface bilayer array. J Am Chem Soc 130(46):15543–15548. doi: 10.1021/ja804968g CrossRefGoogle Scholar
  178. 178.
    Gu LQ, Braha O, Conlan S, Cheley S, Bayley H (1999) Stochastic sensing of organic analytes by a pore-forming protein containing a molecular adapter. Nature 398(6729):686–690. doi: 10.1038/19491 CrossRefGoogle Scholar
  179. 179.
    Sanchez-Quesada J, Saghatelian A, Cheley S, Bayley H, Ghadiri MR (2004) Single DNA rotaxanes of a transmembrane pore protein. Angew Chem Int Ed 43(23):3063–3067. doi: 10.1002/anie.200453907 Google Scholar
  180. 180.
    Braha O, Gu LQ, Zhou L, Lu X, Cheley S, Bayley H (2000) Simultaneous stochastic sensing of divalent metal ions. Nat Biotechnol 18(9):1005–1007. doi: 10.1038/79275 CrossRefGoogle Scholar
  181. 181.
    Kang XF, Cheley S, Guan X, Bayley H (2006) Stochastic detection of enantiomers. J Am Chem Soc 128(33):10684–10685. doi: 10.1021/ja063485l CrossRefGoogle Scholar
  182. 182.
    Matile S, Tanaka H, Litvinchuk S (2007) Analyte sensing across membranes with artificial pores. Top Curr Chem 277:303–309. doi: 10.1007/128_2007_113 Google Scholar
  183. 183.
    Litvinchuk S, Sorde N, Matile S (2005) Sugar sensing with synthetic multifunctional pores. J Am Chem Soc 127(26):9316–9317. doi: 10.1021/ja052134o CrossRefGoogle Scholar
  184. 184.
    Litvinchuk S, Tanaka H, Miyatake T, Pasini D, Tanaka T, Bollot G, Mareda J, Matile S (2007) Synthetic pores with reactive signal amplifiers as artificial tongues. Nat Mater 6(8):576–580. doi: 10.1038/nmat1933 CrossRefGoogle Scholar
  185. 185.
    Razmi H, Heidari H (2009) Nafion/lead nitroprusside nanoparticles modified carbon ceramic electrode as a novel amperometric sensor for L-cysteine. Anal Biochem 388(1):15–22. doi: 10.1016/j.ab.2009.01.036 Google Scholar
  186. 186.
    Shi CG, Xu JJ, Chen HYJ (2007) Electrogenerated chemiluminescence and electrochemical bi-functional sensors for H2O2 based on CdS nanocrystals/hemoglobin multilayers. J Electroanal Chem 610:186–192CrossRefGoogle Scholar
  187. 187.
    Peng Y, Jiang D, Su L, Zhang L, Yan M, Du J, Lu Y, Liu YN, Zhou F (2009) Mixed monolayers of ferrocenylalkanethiol and encapsulated horseradish peroxidase for sensitive and durable electrochemical detection of hydrogen peroxide. Anal Chem 81(24):9985–9992. doi: 10.1021/ac901833s CrossRefGoogle Scholar
  188. 188.
    Lyon JL, Stevenson KJ (2006) Picomolar peroxide detection using a chemically activated redox mediator and square wave voltammetry. Anal Chem 78(24):8518–8525. doi: 10.1021/ac061483d CrossRefGoogle Scholar
  189. 189.
    Oh SY, Cornell B, Smith D, Higgins G, Burrell CJ, Kok TW (2008) Rapid detection of influenza A virus in clinical samples using an ion channel switch biosensor. Biosens Bioelectron 23(7):1161–1165. doi: 10.1016/j.bios.2007.10.011 CrossRefGoogle Scholar
  190. 190.
    VanWiggeren GD, Bynum MA, Ertel JP, Jefferson S, Robotti KM, Thrush EP, Baney DM, Killeen KP (2007) A novel optical method providing for high-sensitivity and high-throughput biomolecular interaction analysis. Sensors Actuat B 127(2):341–349Google Scholar
  191. 191.
    de Boer AR, Hokke CH, Deelder AM, Wuhrer M (2008) Serum antibody screening by surface plasmon resonance using a natural glycan microarray. Glycoconj J 25(1):75–84. doi: 10.1007/s10719-007-9100-x CrossRefGoogle Scholar
  192. 192.
    Stemmler I, Brecht A, Gauglitz G (1999) Compact surface plasmon resonance-transducers with spectral readout for biosensing applications. Sensors Actuat B 54:98–105CrossRefGoogle Scholar
  193. 193.
    Whelan RJ, Wohland T, Neumann L, Huang B, Kobilka BK, Zare RN (2002) Analysis of biomolecular interactions using a miniaturized surface plasmon resonance sensor. Anal Chem 74(17):4570–4576CrossRefGoogle Scholar
  194. 194.
    Grunwald B, Holst G (2004) Fibre optic refractive index microsensor based on white-light SPR excitation. Sensors Actuat 113:174–180CrossRefGoogle Scholar
  195. 195.
    Kasianowicz JJ, Brandin E, Branton D, Deamer DW (1996) Characterization of individual polynucleotide molecules using a membrane channel. Proc Natl Acad Sci USA 93(24):13770–13773Google Scholar
  196. 196.
    Henrickson SE, Misakian M, Robertson B, Kasianowicz JJ (2000) Driven DNA transport into an asymmetric nanometer-scale pore. Phys Rev Lett 85(14):3057–3060CrossRefGoogle Scholar
  197. 197.
    Akeson M, Branton D, Kasianowicz JJ, Brandin E, Deamer DW (1999) Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single RNA molecules. Biophys J 77(6):3227–3233. doi: 10.1016/S0006-3495(99)77153-5 CrossRefGoogle Scholar
  198. 198.
    Vercoutere W, Winters-Hilt S, Olsen H, Deamer D, Haussler D, Akeson M (2001) Rapid discrimination among individual DNA hairpin molecules at single-nucleotide resolution using an ion channel. Nat Biotechnol 19(3):248–252. doi: 10.1038/85696 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Magnetic and Acoustic ResonancesLeibniz Institute for Solid State and Materials Research, DresdenDresdenGermany
  2. 2.Nanion Technologies GmbHMunichGermany
  3. 3.Department of ChemistryDresden University of TechnologyDresdenGermany

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