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Carbon nanotube transistors for biosensing applications

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Abstract

Electronic detection of biomolecules, although still in its early stages, is gradually emerging as an effective alternative to optical detection methods. We describe field effect transistor devices with carbon nanotube conducting channels that have been developed and used for biosensing and biodetection. Both transistors with single carbon nanotube conducting channels and devices with nanotube network conducting channels have been fabricated and their electronic characteristics examined. The devices readily respond to changes in the environment, and such effects have been examined using gas molecules and coatings with specific properties. Device operation in (conducting) buffer and in a dry environment—after buffer removal—is also discussed. Applications in the biosensing area are illustrated with three examples: the investigation of the interaction between devices and biomolecules, the electronic monitoring of biomolecular processes, and attempts to integrate cell membranes with active electronic devices.

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Notes

  1. Comment on 20, Balavoine et al (1999) Angew Chem Int Edit 38:1912 (Helical crystallization of proteins on carbon nanotubes: a first step towards the development of new biosensors): Of course, proteins are easily immobilized on other surfaces, including the silicon substrate onto which the nanotube conducting channels are deposited. The presence of biomolecules on a surface that does not participate in the conduction process will, however, not influence the device’s characteristics.

  2. Comment on 29, Bradley et al (2004) Nano Lett 4:253 (Charge transfer from adsorbed proteins): The number of amine groups can also be estimated using a simple model in which roughly spherical proteins cover the top half of the cylindrical nanotube. The proteins are assumed to coat the available nanotube surface with amine groups proportional to the surface area in contact. The nanotube under consideration here has a diameter of 24 nm (as reflected in the small bandgap observed in Fig. 7a), so that the surface area in contact with each 5 nm protein is π/2×2.4×5 nm2. Each protein surface contains 100 amine groups distributed over the 5 nm sphere, so that on average each protein contacts the nanotube with 20 amine groups. Since the proteins are 5 nm in diameter, we assume that 200 proteins are adsorbed on the 1 mm nanotube. Thus the monolayer of adsorbed protein contacts the nanotube with 4000 adsorbed amine groups, again in good agreement with what one finds by examining the transistor charge characteristics

  3. Detailed experiments performed by us (M. Briman and G. Gruner, to be published) using a setup similar to described in [41, 42] demonstrate that conduction through the buffer leads to negligible effect. The transistor characteristics, however, depend on the pH, and such dependence has to be taken into account when the effect of biomolecules on the transistor characteristics is evaluated.

  4. This asymmetry is reflected in the large amount of charge induced in mixed-orientation devices, since without an asymmetry, the charge induced by equal amounts of cytoplasmic-oriented and extracellular-oriented PM should cancel.

  5. The background charge due to the phosphate heads of the lipids is 0.2 electrons per square nanometer [25], which is too weak to explain the charge induced in our devices.

  6. For example, biotin–streptavidin binding has been measured using nanowire-based [81] and carbon nanotube-based [82] devices. While a few percent change is observed using nanowires, the binding leads to an order of magnitude change when carbon nanotube-based transistors are used.

References

  1. Robers M, Rensink IJAM, Hack CE, Aarden CE, Reutelingsperger CPM, Glatz JFC, Hermens WT (1999) A new principle for rapid immunoassay of proteins based on in situ precipitate-enhanced ellipsometry. Biophys J 76:2769

    PubMed  CAS  Google Scholar 

  2. McNeil CJ, Athey D, Wah OH (1995) Direct electron transfer bioelectronic interfaces application to clinical analysis. Biosens Bioelectron 10:75

    Article  PubMed  CAS  Google Scholar 

  3. Willner I (2002) Bioelectronics biomaterials for sensors, fuel cells, and circuitry. Science 298:2407

    Article  PubMed  CAS  Google Scholar 

  4. Hu H, Ni Y, Montana V, Haddon RC, Parpura V (2004) Chemically functionalized carbon nanotubes as substrates for neuronal growth. Nano Lett 4:507

    Article  CAS  Google Scholar 

  5. Pantarotto D, Partidos CD, Graff R, Hoebeke J, Briand J-P, Prato M, Bianco A (2003) Synthesis structural characterization and immunological properties of carbon nanotubes functionalized with peptides. J Am Chem Soc 125:6160

    Article  PubMed  CAS  Google Scholar 

  6. Zheng M, Jagota A, Strano MS, Santos AP, Barone P, Chou SG, Diner BA, Dresselhaus MS, Mclean RS, Onoa GB, Samsonidze GG, Semke ED, Usrey M, Walls DJ (2003) Structure-based carbon nanotube sorting by sequence-dependent DNA assembly. Science 302:1545

    Article  PubMed  CAS  Google Scholar 

  7. Richard C, Balavoine F, Schultz P, Ebbesen TW, Mioskowski C (2003) Supramolecular self-assembly of lipid derivatives on carbon nanotubes. Science 300:775

    Article  PubMed  CAS  Google Scholar 

  8. Fritz J, Cooper EB, Gaudet S, Sorger PK, Manalis SR (2002) Electronic detection of DNA by its intrinsic molecular charge. Proc Natl Acad Sci USA 99:14142

    Article  PubMed  CAS  Google Scholar 

  9. Zayats M, Raitman OA, Chegel VI, Kharitonov AB, Willner I (2002) Probing antigen-antibody binding processes by impedance measurements on ion-sensitive field-effect transistor devices and complementary surface plasmon resonance analyses: development of cholera toxin sensors. Anal Chem 74:4763

    Article  PubMed  CAS  Google Scholar 

  10. Kharitonov AB, Zayats M, Lichtenstein A, Katz E, Willner I (2000) Enzyme monolayer-functionalized field-effect transistors for biosensor applications. Sens Actuat B Chem 70:222

    Article  Google Scholar 

  11. Pouthas F, Gentil C, Côte D, Bockelmann U (2004) DNA detection on transistor arrays following mutation-specific enzymatic amplification. Appl Phys Lett 84:1594

    Article  CAS  Google Scholar 

  12. Li Z, Chen Y, Li X, Kamins TI, Nauka K, Williams RS (2004) Sequence-specific label-free DNA sensors based on silicon nanowires. Nano Lett 4:245

    Article  CAS  Google Scholar 

  13. Wang WU, Chen C, Lin K-H, Fang Y, Lieber CM (2005) Label-free detection of small-molecule–protein interactions by using nanowire nanosensors. Proc Natl Acad Sci USA 102:3213

    Article  PubMed  CAS  Google Scholar 

  14. Hahm JI, Lieber CM (2003) Direct ultrasensitive electrical detection of DNA and DNA sequence variations using nanowire nanosensors. Nano Lett 4:51

    Article  CAS  Google Scholar 

  15. Saito R, Dresselhaus G, Dresselhaus MS (1998) Physical properties of carbon nanotubes. Imperial College Press, London

  16. Shim M, Shi Kam NW, Chen RJ, Li Y, Dai H (2002) Functionalization of carbon nanotubes for biocompatibility and biomolecular recognition. Nano Lett 2:285

    Article  CAS  Google Scholar 

  17. Huang W, Taylor S, Fu K, Lin Y, Zhang D, Hanks TW, Rao AM, Sun Y-P (2002) Attaching proteins to carbon nanotubes via diimide-activated amidation. Nano Lett 2:311

    Article  CAS  Google Scholar 

  18. Chen RJ, Zhang Y, Wang D, Dai H (2001) Noncovalent sidewall functionalization of single-walled carbon nanotubes for protein immobilization. J Am Chem Soc 123:3838

    Article  PubMed  CAS  Google Scholar 

  19. Davis JJ, Green MLH, Allen H, Hill O, Leung YC, Sadler PJ, Sloan J, Xavier AV, Tsang SC (1998) The immobilisation of proteins in carbon nanotubes. Inorg Chim Acta 272:261

    Article  CAS  Google Scholar 

  20. Balavoine F, Schultz P, Richard C, Mallouh V, Ebbesen TW, Mioskowski C (1999) Helical crystallization of proteins on carbon nanotubes: a first step towards the development of new biosensors. Angew Chem Int Edit 38:1912

    Article  CAS  Google Scholar 

  21. Dieckmann GR, Dalton AB, Johnson PA, Razal J, Chen J, Giordano GM, Munoz E, Musselman IH, Baughman RH, Draper RK (2003) Controlled assembly of carbon nanotubes by designed amphiphilic peptide helices. J Am Chem Soc 125:1770

    Article  PubMed  CAS  Google Scholar 

  22. Martel R, Schmidt T, Shea HR, Hertel T, Avouris Ph (1998) Single- and multi-wall carbon nanotube field-effect transistors. Appl Phys Lett 73:2447

    Article  CAS  Google Scholar 

  23. Bachtold A, Hadley P, Nakanishi T, Dekker C (2001) Logic circuits with carbon nanotube transistors. Science 294:1317

    Article  PubMed  CAS  Google Scholar 

  24. Collins PG, Bradley K, Ishigami M, Zettl A (2000) Extreme oxygen sensitivity of electronic properties of carbon nanotubes. Science 287:1801

    Article  PubMed  CAS  Google Scholar 

  25. Kong J, Franklin NR, Zhou C, Chapline MG, Peng S, Cho K, Dai H (2000) Nanotube molecular wires as chemical sensors. Science 287:622

    Article  PubMed  CAS  Google Scholar 

  26. Star A, Tzong-Ruhan, Gabriel J-CP, Bradley K, Grüner G (2003) Interaction of aromatic compounds with carbon nanotubes. Nano Lett 3:1421

    Article  CAS  Google Scholar 

  27. Bradley K, Gabriel J-CP, Briman M, Star A, Grüner G (2003) Charge transfer from aqueous ammonia absorbed on nanotube transistors. Phys Rev Lett 91:218301

    Article  PubMed  CAS  Google Scholar 

  28. Cui Y, Wei Q, Park H, Lieber CM (2001) Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293:1289

    Article  PubMed  CAS  Google Scholar 

  29. Bradley K, Briman M, Star A, Grüner G (2004) Charge transfer from adsorbed proteins. Nano Lett 4:253

    Article  CAS  Google Scholar 

  30. Star A, Bradley K, Gabriel J-CP, Grüner G (2003) Nano-electronic sensors: chemical detection using carbon nanotubes. Pol Mater: Sci Eng 89:204

    CAS  Google Scholar 

  31. Bradley K, Gabriel J-CP, Star A, Grüner DG (2003) Short channel effects in contact-passivated nanotube chemical sensors. Appl Phys Lett 83:3821

    Article  CAS  Google Scholar 

  32. Artukovic E, Kaempgen M, Hecht DS, Roth S, Grüner G (2005) Transparent and flexible carbon nanotube transistors. Nano Lett 5:757

    Article  PubMed  CAS  Google Scholar 

  33. Larsen DS, Ohta K, Xu Q, Cyrier M, Fleming GR (2001) Influence of intramolecular vibrations in third-order, time domain resonant spectroscopies: 1. Experiments. J Chem Phys 114:8008

    Article  CAS  Google Scholar 

  34. Xie A, van der Meer AFG, Austin RH (2002) Excited-state lifetimes of far-infrared collective modes in proteins. Phys Rev Lett 88:018102

    Article  PubMed  CAS  Google Scholar 

  35. Arai M, Ikura T, Semisotnov GV, Kihara H, Amemiya Y, Kuwajima K (1998) Kinetic refolding of beta-lactoglobulin studies by synchrotron X-ray scattering, and circular dichroism, absorption and fluorescence spectroscopy. J Mol Biol 275:149

    Article  PubMed  CAS  Google Scholar 

  36. Pollack L, Tate MW, Finnefrock AC, Kalidas C, Trotter S, Darnton NC, Lurio L, Austin RH, Batt CA, Gruner SM, Mochrie SGJ (2001) Time resolved collapse of a folding protein observed with small angle X-ray scattering. Phys Rev Lett 86:4962

    Article  PubMed  CAS  Google Scholar 

  37. Kuwata K, Shastry R, Cheng H, Hoshino M, Batt CA, Goto Y, Roder H (2001) Structural and kinetic characterization of early folding events in beta-lactoglobulin. Nature Struct Biol 8:151

    Article  PubMed  CAS  Google Scholar 

  38. Jones CM, Henry ER, Hu Y, Chan C, Luck SD, Bhuyan A, Roder H, Hofrichter J, Eaton WA (1993) Fast events in protein folding initiated by nanosecond laser photolysis. Proc Natl Acad Sci USA 90:11860

    Article  PubMed  CAS  Google Scholar 

  39. Lim M, Jackson TA, Anfinrud PA (1997) Modulating carbon monoxide binding affinity and kinetics in myoglobin: the roles of the distal histidine and the heme pocket docking site. J Biol Inorg Chem 2:531

    Article  CAS  Google Scholar 

  40. Lipman EA, Schuler B, Bakajin O, Eaton WA (2003) Single molecule measurement of protein folding. Kinetics 310:1233

    Google Scholar 

  41. Rosenblatt S, Yaish Y, Park J, Gore J, Sazonova V, McEuen PL (2002) High performance electrolyte gated carbon nanotube transistors. Nano Lett 2:869

    Article  CAS  Google Scholar 

  42. Krüger M, Buitelaar MR, Nussbaumer T, Schönenberger C, Forró L (2001) Electrochemical carbon nanotube field-effect transistor. Appl Phys Lett 78:1291

    Article  CAS  Google Scholar 

  43. Chang H, Lee JD, Lee SM, Lee YH (2001) Adsorption of NH3 and NO2 molecules on carbon nanotubes. Appl Phys Lett 79:3863

    Article  CAS  Google Scholar 

  44. Kong J, Dai H (2001) Full and modulated chemical gating of individual carbon nanotubes by organic amine compounds. J Phys Chem B 105:2890

    Article  CAS  Google Scholar 

  45. Robers M, Rensink IJAM, Hack CE, Aarden LA, CPM Reutelingsperger, JFC Glatz, Hermens WT (1999) A new principle for rapid immunoassay of proteins based on in situ precipitate-enhanced ellipsometry. Biophys J 76:2769

    PubMed  CAS  Google Scholar 

  46. McNeil CJ, Athey D, Ho WO (1995) Direct electron transfer bioelectronic interfaces: application to clinical analysis. Biosens Bioelectron 10:75

    Article  PubMed  CAS  Google Scholar 

  47. Turner DC, Chang CY, Fang K, Brandow SL, Murphy DB (1995) Selective adhesion of functional microtubules to patterned silane surfaces. Biophys J 69:2782

    PubMed  CAS  Google Scholar 

  48. Wadu-Mesthrige K, Amro NA, Garno JC, Xu S, Liu G-Y (2001) Fabrication of nanometer-sized protein patterns using atomic force microscopy and selective immobilization. Biophys J 80:1891

    PubMed  CAS  Google Scholar 

  49. Nicolau DV, Taguchi T, Taniguchi H, Yoshikawa S (1998) Micron-sized protein patterning on diazonaphthoquinone/novolak thin polymeric films. Langmuir 14:1927

    Article  CAS  Google Scholar 

  50. Pompa PP, Blasi L, Longo L, Cingolani R, Ciccarella G, Vasapollo G, Rinaldi R, Rizzello A, Storelli C, Maffia M (2003) Phys Rev E 67:41902

    Article  CAS  Google Scholar 

  51. Sagvolden G (1999) Protein adhesion force dynamics and single adhesion events. Biophys J 77:526–532

    PubMed  CAS  Google Scholar 

  52. Weber PC, Wendoloski JJ, Pantoliano MW, Salemme FR (1992) Crystallographic and thermodynamic comparison of natural and synthetic ligands bound to streptavidin. J Am Chem Soc 114:3197

    Article  CAS  Google Scholar 

  53. Athappilly FK, Hendrickson WA (1997) Crystallographic analysis of the pH-dependent binding of iminobiotin by streptavidin. Protein Sci 6:1338

    PubMed  CAS  Google Scholar 

  54. Yatcilla MT, Robertson CR, Gast AP (1998) Influence of pH on two-dimensional streptavidin crystals. Langmuir 14:497

    Article  CAS  Google Scholar 

  55. Wang S-W, Robertson CR, Gast AP (2000) Role of N- and C-terminal amino acids in two-dimensional streptavidin crystal form. Langmuir 16:5199

    Article  CAS  Google Scholar 

  56. Frey W, Schief WR Jr, Pack DW, Chen C-T, Chilkoti A, Stayton P, Vogel V, Arnold FA (1996) Two-dimensional protein crystallization via metal-ion coordination by naturally occurring surface histidines. Proc Natl Acad Sci USA 93:4937

    Article  PubMed  CAS  Google Scholar 

  57. Star A, Gabriel J-CP, Bradley K, Grüner G (2003) Electronic detection of specific protein binding using nanotube FET devices. Nano Lett 3:459

    Article  CAS  Google Scholar 

  58. Chen RJ, Bangsaruntip S, Drouvalakis KA, Wong Shi Kam N, Shim M, Li Y, Kim W, Utz PJ, Dai H (2003) Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors. Proc Natl Acad Sci USA 100:4984

    Article  PubMed  CAS  Google Scholar 

  59. Besteman K, Lee J-O, Wiertz FGM, Heering HA, Dekker C (2003) Enzyme-coated carbon nanotubes as single-molecule biosensors. Nano Lett 3:727

    Article  CAS  Google Scholar 

  60. Schnabel W (1981) Polymer degradation. Henser International, Berlin, Ch 6

  61. Wool RP, Raghavan D, Wagner GC, Billieux SJ (2000) Biodegradation dynamics of polymer-starch composites. Appl Polym Sci 77:1643

    Article  CAS  Google Scholar 

  62. Moreno-Chulim MV, Barahona-Perez F, Canche-Escamilla G (2003) Biodegradation of starch and acrylic-grafted starch by Aspergillus niger. Appl Polym Sci 89:2764

    Article  CAS  Google Scholar 

  63. Star A, Joshi V, Han T-R, Altoe MVP, Gruner G, Stoddart JF (2004) Electronic detection of the enzymatic degradation of starch. Org Lett 6:2089

    Article  PubMed  CAS  Google Scholar 

  64. Collins P, Ferrier R (1995) Polysaccharides: their chemistry. Wiley, Chichester, pp 478–523

    Google Scholar 

  65. Lehmann J (1998) Carbohydrates: structure and biology. Georg Thieme, Stuttgart, pp 98–103

  66. Thompson DB (2000) On the non-random nature of amylopectin branching. Carbohydr Polym 43:223

    Article  CAS  Google Scholar 

  67. Yamamoto T (1994) Enzyme chemistry and molecular biology of amylases and related enzymes. CRC, Boca Raton, FL, pp 3–201

  68. Bradley K, Davis A, Gabriel J-CP, Gruner G (2005) Integration of cell membranes and nanotube transistors. Nano Lett 5:841

    Article  PubMed  CAS  Google Scholar 

  69. Oesterhelt D, Stoeckenius W (1973) Functions of a new photoreceptor membrane. Proc Natl Acad Sci USA 70:2853

    Article  PubMed  CAS  Google Scholar 

  70. Steinhoff HJ, Mollaaghababa R, Altenbach C, Hideg K, Krebs M, Khorana HG, Hubbell WL (1994) Time-resolved detection of structural changes during the photocycle of spin-labeled bacteriorhodopsin. Science 266:105–107

    Article  PubMed  CAS  Google Scholar 

  71. Várò G (1981) Dried oriented purple membrane samples. Acta Biol Acad Sci Hung 32:301

    Google Scholar 

  72. Shen Y, Safinya CR, Liang KS, Ruppert AF, Rothschild KJ (1993) Stabilization of the membrane protein bacteriorhodopsin to 140 °C in two-dimensional films. Nature 366:48

    Article  CAS  Google Scholar 

  73. Koyama K, Yamaguchi N, Miyasaka T (1994) Antibody-mediated bacteriorhodopsin orientation for molecular device architectures. Science 265:762

    Article  CAS  Google Scholar 

  74. Tans SJ, Dekker C (2000) Molecular transistors: potential modulations along carbon nanotubes. Nature 404:834

    Article  PubMed  CAS  Google Scholar 

  75. Bradley K, Cumings J, Star A, Gabriel J-CP, Gruner G (2003) Influence of mobile ions on nanotube based FET devices. Nano Lett 3:639

    Article  CAS  Google Scholar 

  76. Freitag M, Radosavljevic M, Zhou Y, Johnson AT, Smith WF (2001) Controlled creation of a carbon nanotube diode by a scanned gate. App Phys Lett 79:3326

    Article  CAS  Google Scholar 

  77. Bockrath M, Cobden DH, McEuen PL, Chopra NG, Zettl A, Thess A, Smalley RE (1997) Single-electron transport in ropes of carbon nanotubes. Science 275:1922

    Article  PubMed  CAS  Google Scholar 

  78. Javey A, Kim H, Brink M, Wang Q, Ural A, Guo J, McIntyre P, McEuen P, Lundstrom M, Dai H (2002) High- dielectrics for advanced carbon-nanotube transistors and logic gates. Nat Mat 1:241

    Article  CAS  Google Scholar 

  79. Star A, Han T-R, Gabriel J-C P, Bradley K, Grüner G (2003) Interaction of aromatic compounds with carbon nanotubes: correlation to the Hammett parameter of the substituent and measured carbon nanotube FET response. Nano Lett 3:1421

    Article  CAS  Google Scholar 

  80. Ehrenberg B, Berezin Y (1984) Surface potential on purple membranes and its sidedness studied by a resonance Raman dye probe. Biophys J 45:663

    Article  PubMed  CAS  Google Scholar 

  81. Cui Y, Wei Q, Park H, Lieber CM (2001) Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293:1289

    Article  PubMed  CAS  Google Scholar 

  82. Star A, Gabriel J-CP, Bradley K, Grüner G (2003) Electronic detection of specific protein binding using nanotube FET devices. Nano Lett 3:459–463

    Article  CAS  Google Scholar 

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Acknowledgements

Many of the experiments reported here were performed by K. Bradley, M. Briman, A. Star, and the devices were fabricated by J.C. Gabriel and D. Hecht. This work was partially supported by the National Science Foundation Grant no. 0415130. Many of the experiments were performed at Nanomix Inc., the company where the author was Chief Scientist.

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    G. Gruner

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Gruner, G. Carbon nanotube transistors for biosensing applications. Anal Bioanal Chem 384, 322–335 (2006). https://doi.org/10.1007/s00216-005-3400-4

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