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Nanoscale Sensors pp 55–86Cite as

BioFET-SIM: A Tool for the Analysis and Prediction of Signal Changes in Nanowire-Based Field Effect Transistor Biosensors

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Part of the book series: Lecture Notes in Nanoscale Science and Technology ((LNNST,volume 19))

Abstract

Biosensors based on nanowire field effect transistor (FET) have received much attention in recent years as a way to achieve ultra-sensitive and label-free sensing of molecules of biological interest. The BioFET-SIM computer model permits the analysis and interpretation of experimental sensor signals through its web-based interface www.biofetsim.org. The model also allows for predictions of the effects of changes in the experimental setup on the sensor signal. After an introduction to nanowire-based FET biosensors, this chapter reviews the theoretical basis of BioFET-SIM models describing both single and multiple charges on the analyte. Afterwards the usage of the interface and its relative command line version is briefly shown. Finally, possible applications of the BioFET-SIM model are presented. Among the possible uses of the interface, the effects on the predicted signal of pH, buffer ionic strength, analyte concentration, and analyte relative orientation on nanowire surface are illustrated. Wherever possible, a comparison to experimental data available in literature is given, displaying the potential of BioFET-SIM for interpreting experimental results.

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References

  1. Thévenot, D.R., Toth, K., Durst, R.A., Wilson, G.S.: Electrochemical biosensors: recommended definitions and classification. Biosens. Bioelectron. 16(1–2), 121 (2001). DOI 10.1016/S0956-5663(01)00115-4

    Article  Google Scholar 

  2. Hermanson, G.T.: Bioconjugate Techniques. Academic, San Diego (1996)

    Google Scholar 

  3. Stern, E., Klemic, J.F., Routenberg, D.A., Wyrembak, P.N., Turner-Evans, D.B., Hamilton, A.D., LaVan, D.A., Fahmy, T.M., Reed, M.A.: Label-free immunodetection with CMOS-compatible semiconducting nanowires. Nature 445, 519 (2007). DOI 10.1038/nature05498

    Article  Google Scholar 

  4. Vacic, A., Criscione, J.M., Rajan, N.K., Stern, E., Fahmy, T.M., Reed, M.A.: Determination of molecular configuration by Debye length modulation. J. Am. Chem. Soc. 133(35), 13886 (2011). DOI 10.1021/ja205684a

    Article  Google Scholar 

  5. Chen, Y., Wang, X., Erramilli, S., Mohanty, P., Kalinowski, A.: Silicon-based nanoelectronic field-effect pH sensor with local gate control. Appl. Phys. Lett. 89(22), 223512 (2006). DOI 10.1063/1.2392828

    Article  Google Scholar 

  6. Cui, Y., Wei, Q., Park, H., Lieber, C.M.: Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293, 1289 (2001). DOI 10.1126/science.1062711

    Article  Google Scholar 

  7. Gao, X.P., Zheng, G., Lieber, C.M.: Subthreshold regime has the optimal sensitivity for nanowire FET biosensors. Nano Lett. 10(2), 547 (2009). DOI 10.1021/nl9034219

    Article  Google Scholar 

  8. Tian, R., Regonda, S., Gao, J., Liu, Y., Hu, W.: Ultrasensitive protein detection using lithographically defined Si multi-nanowire field effect transistors. Lab Chip 11, 1952 (2011). DOI 10.1039/C0LC00605J

    Article  Google Scholar 

  9. Wong, I.Y., Melosh, N.A.: Directed hybridization and melting of DNA linkers using counterion-screened electric fields. Nano Lett. 9(10), 3521 (2009). DOI 10.1021/ nl901710n

    Article  Google Scholar 

  10. Dorvel, B.R., Reddy, B., Go, J., Duarte Guevara, C., Salm, E., Alam, M.A., Bashir, R.: Silicon nanowires with high-k Hafnium oxide dielectrics for sensitive detection of small nucleic acid oligomers. ACS Nano 6(7), 6150 (2012). DOI 10.1021/nn301495k

    Google Scholar 

  11. Chang, H.K., Ishikawa, F.N., Zhang, R., Datar, R., Cote, R.J., Thompson, M.E., Zhou, C.: Rapid, label-free, electrical whole blood bioassay based on nanobiosensor systems. ACS Nano 5(12), 9883 (2011). DOI 10.1021/nn2035796

    Article  Google Scholar 

  12. Berthing, T., Sørensen, C.B., Nygård, J., Martinez, K.L.: Applications of nanowire arrays in nanomedicine. J. Nanoneurosci. 1(1), 3 (2009). DOI 10.1166/jns.2009.001

    Article  Google Scholar 

  13. Patolsky, F., Zheng, G., Lieber, C.M.: Nanowire-based biosensors. Anal. Chem. 78(13), 4260 (2006). DOI 10.1021/ac069419j

    Google Scholar 

  14. Shinwari, M.W., Deen, M.J., Landheer, D.: Study of the electrolyte-insulator-semiconductor field-effect transistor (EISFET) with applications in biosensor design. Microelectron. Reliab. 47(12), 2025 (2007). DOI 10.1016/j.microrel.2006.10.003

    Article  Google Scholar 

  15. Curreli, M., Zhang, R., Ishikawa, F.N., Chang, H.K., Cote, R.J., Zhou, C., Thompson, M.E.: Real-time, label-free detection of biological entities using nanowire-based FETs. IEEE Trans. Nanotechnol. 7(6), 651 (2008). DOI 10.1109/TNANO.2006.880908

    Article  Google Scholar 

  16. Neizvestny, I.G.: Semiconductor nanowire sensors. Russ. Microelectron. 38(4), 223 (2009). DOI 10.1134/S1063739709040015

    Article  Google Scholar 

  17. Roy, S., Gao, Z.: Nanostructure-based electrical biosensors. Nano Today 4(4), 318 (2009). DOI 10.1016/j.nantod.2009.06.003

    Article  Google Scholar 

  18. Nair, P.R., Alam, M.A.: Performance limits of nanobiosensors. Appl. Phys. Lett. 88(23), 233120 (2006). DOI 10.1063/1.2211310

    Article  Google Scholar 

  19. Nair, P.R., Alam, M.A.: Screening-limited response of nanoBiosensors. Nano Lett. 8(5), 1281 (2008). DOI 10.1021/nl072593i

    Article  Google Scholar 

  20. Nair, P.R., Alam, M.A.: Theory of “Selectivity” of label-free nanobiosensors: A geometro-physical perspective. J. Appl. Phys. 107(6), 064701 (2010). DOI 10.1063/1. 3310531

    Article  Google Scholar 

  21. Heitzinger, C., Klimeck, G.: Computational aspects of the three-dimensional feature-scale simulation of silicon-nanowire field-effect sensors for DNA detection. J. Comput. Electron. 6, 387 (2007). DOI 10.1007/s10825-006-0139-x

    Article  Google Scholar 

  22. Ringhofer, C., Heitzinger, C.: Multi - scale modeling and simulation of field-effect biosensors. ECS Trans. 14(1), 11 (2008). DOI 10.1149/1.2956012

    Google Scholar 

  23. Heitzinger, C., Kennell, R., Klimeck, G., Mauser, N., McLennan, M., Ringhofer, C.: Modeling and simulation of field-effect biosensors (BioFETs) and their deployment on the nanoHUB. J. Phys. Conf. Ser. 107, 012004 (2008). DOI 10.1088/1742-6596/107/ 1/012004

    Google Scholar 

  24. Chen, H., Mukherjee, S., Aluru, N.: Charge distribution on thin semiconducting silicon nanowires. Comput. Methods Appl. Mech. Eng. 197(41–42), 3366 (2008). DOI 10.1016/j.cma.2008.02.007

    Article  Google Scholar 

  25. Heitzinger, C., Mauser, N.J., Ringhofer, C., Liu, Y., Dutton, R.W.: Proceedings of the Simulation of Semiconductor Processes and Devices (SISPAD 2009) (San Diego, CA, USA, 2009), pp. 86–90 (2009). DOI 10.1109/SISPAD.2009.5290244

    Google Scholar 

  26. Heitzinger, C., Mauser, N.J., Ringhofer, C.: Multiscale modeling of planar and nanowire field-effect biosensors. SIAM J. Appl. Math. 70(5), 1634 (2010). DOI 10.1137/080725027

    Article  Google Scholar 

  27. Windbacher, T., Sverdlov, V., Selberherr, S.: Biomedical engineering systems and technologies. In: Fred, A., Filipe, J., Gamboa, H. (eds.) Communications in Computer and Information Science, vol. 52, pp. 85–95. Springer, Berlin (2010). DOI 10.1007/ 978-3-642-11721-3\{∖_\}6

    Google Scholar 

  28. Park, H.H., Zeng, L., Buresh, M., Wang, S., Klimeck, G., Mehrotra, S.R., Heitzinger, C., Haley, B.P.: Nanowire, NanoHUB website (2006). DOI 10254/nanohub-r1307. 8. URL http://nanohub.org/resources/1307. Accessed Mar 2013

  29. Nair, P.R., Go, J., Landells, G.J., Pandit, T.R., Alam, M.A.: BioSensorLab, NanoHUB website (2008). DOI 10254/nanohub-r2929. 5. URL http://nanohub.org/resources/2929. Accessed Mar 2013

  30. Medici: Two Dimensional Device Simulation Program (2003). Synopsis

    Google Scholar 

  31. Sørensen, M.H., Mortensen, N.A., Brandbyge, M.: Screening model for nanowire surface-charge sensors in liquid. Appl. Phys. Lett. 91(10), 102105 (2007). DOI 10.1063/1.2779930

    Article  Google Scholar 

  32. De Vico, L., Sørensen, M.H., Iversen, L., Rogers, D.M., Sørensen, B.S., Brandbyge, M., Nygård, J., Martinez, K.L., Jensen, J.H.: Quantifying signal changes in nano-wire based biosensors. Nanoscale 3, 706 (2011). DOI 10.1039/C0NR00442A

    Google Scholar 

  33. De Vico, L., Iversen, L., Sørensen, M.H., Brandbyge, M., Nygård, J., Martinez, K.L., Jensen, J.H.: Predicting and rationalizing the effect of surface charge distribution and orientation on nano-wire based FET bio-sensors. Nanoscale 3, 3635 (2011). DOI 10.1039/C1NR10316D

    Google Scholar 

  34. Hediger, M.R., Jensen, J.H., De Vico, L.: BioFET-SIM Web Interface: Implementation and Two Applications. PLoS One 7(10), e45379 (2012). DOI 10.1371/ journal.pone.0045379

    Google Scholar 

  35. Punzet, M., Baurecht, D., Varga, F., Karlic, H., Heitzinger, C.: Determination of surface concentrations of individual molecule-layers used in nanoscale biosensors by in situ ATR-FTIR spectroscopy. Nanoscale 4, 2431 (2012). DOI 10.1039/C2NR12038K

    Article  Google Scholar 

  36. Hakim, M.M.A., Lombardini, M., Sun, K., Giustiniano, F., Roach, P.L., Davies, D.E., Howarth, P.H., de Planque, M.R.R., Morgan, H., Ashburn, P.: Thin film polycrystalline silicon nanowire biosensors. Nano Lett. 12(4), 1868 (2012). DOI 10.1021/nl2042276

    Google Scholar 

  37. Duan, X., Li, Y., Rajan, N., Routenberg, D., Modis, Y., Reed, M.: Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors. Nat. Nanotechnol. 7(6), 401 (2012). DOI 10.1038/nnano.2012.82

    Article  Google Scholar 

  38. Elnathan, R., Kwiat, M., Pevzner, A., Engel, Y., Burstein, L., Khatchtourints, A., Lichtenstein, A., Kantaev, R., Patolsky, F.: Biorecognition layer engineering: Overcoming screening limitations of nanowire-based FET devices. Nano Lett. 12(10), 5245 (2012). DOI 10.1021/nl302434w

    Article  Google Scholar 

  39. Lloret, N., Frederiksen, R.S., Møller, T.C., Rieben, N.I., Upadhyay, S., De Vico, L., Jensen, J.H., Nygård, J., Martinez, K.L.: Effects of buffer composition and dilution on nanowire field-effect biosensors. Nanotechnology 24(3), 035501 (2013). DOI 10.1088/0957-4484/24/3/035501

    Google Scholar 

  40. Magliulo, M., Mallardi, A., Mulla, M.Y., Cotrone, S., Pistillo, B.R., Favia, P., Vikholm-Lundin, I., Palazzo, G., Torsi, L.: Electrolyte-gated organic field-effect transistor sensors based on supported biotinylated phospholipid bilayer. Adv. Mater. 25(14), 2090 (2013). DOI 10.1002/adma.201203587

    Article  Google Scholar 

  41. Hammock, M.L., Knopfmacher, O., Naab, B.D., Tok, J.B.H., Bao, Z.: Investigation of protein detection parameters using nanofunctionalized organic field-effect transistors. ACS Nano 7(5), 3970 (2013). DOI 10.1021/nn305903q

    Article  Google Scholar 

  42. Baumgartnerth, S., Heitzinger, C., Vacic, A., Reed, M.A.: Predictive simulations and optimization of nanowire field-effect PSA sensors including screening. Nanotechnology 24(22), 225503 (2013). DOI 10.1088/0957-4484/24/22/225503

    Article  Google Scholar 

  43. Nitzan, A., Galperin, M., Ingold, G.L., Grabert, H.: On the electrostatic potential profile in biased molecular wires. J. Chem. Phys. 117(23), 10837 (2002). DOI 10.1063/1.1522406

    Article  Google Scholar 

  44. Liang, G.C., Ghosh, A.W., Paulsson, M., Datta, S.: Electrostatic potential profiles of molecular conductors. Phys. Rev. B 69, 115302 (2004). DOI 10.1103/PhysRevB.69. 115302

    Article  Google Scholar 

  45. Zhang, X.G., Pantelides, S.T.: Screening in nanowires and nanocontacts: Field emission, adhesion force, and contact resistance. Nano Lett. 9(12), 4306 (2009). DOI 10.1021/nl902533n, pMID: 19845331

    Article  Google Scholar 

  46. Sørensen, M.H.: Nanowires for chemical sensing in a liquid environment. Bachelor Thesis (2007)

    Google Scholar 

  47. Olver, F.W.J.: In: Abramowitz, M., Stegun, I.A. (eds.) Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables, pp. 355–436. Dover, New York (1973)

    Google Scholar 

  48. Ishikawa, F.N., Chang, H.K., Curreli, M., Liao, H.I., Olson, C.A., Chen, P.C., Zhang, R., Roberts, R.W., Sun, R., Cote, R.J., Thompson, M.E., Zhou, C.: Label-free, electrical detection of the SARS virus N-protein with nanowire biosensors utilizing antibody mimics as capture probes. ACS Nano 3(5), 1219 (2009). DOI 10.1021/ nn900086c

    Article  Google Scholar 

  49. Björk, M.T., Schmid, H., Knoch, J., Riel, H., Riess, W.: Donor deactivation in silicon nanostructures. Nat. Nanotechnol. 4(2), 103 (2009). DOI 10.1038/nnano.2008.400

    Article  Google Scholar 

  50. Garnett, E.C., Tseng, Y.C., Khanal, D.R., Wu, J., Bokor, J., Yang, P.: Dopant profiling and surface analysis of silicon nanowires using capacitance–voltage measurements. Nat. Nanotechnol. 4(5), 311 (2009). DOI 10.1038/nnano.2009.43

    Article  Google Scholar 

  51. Stern, E., Wagner, R., Sigworth, F.J., Breaker, R., Fahmy, T.M., Reed, M.A.: Importance of the Debye screening length on nanowire field effect transistor sensors. Nano Lett. 7(11), 3405 (2007). DOI 10.1021/nl071792z

    Article  Google Scholar 

  52. Nair, P.R., Alam, M.A.: Design considerations of silicon nanowire biosensors. IEEE Trans. Electron Devices 54(12), 3400 (2007). DOI 10.1109/TED.2007.909059

    Article  Google Scholar 

  53. Yates, D.E., Levine, S., Healy, T.W.: Site-binding model of the electrical double layer at the oxide/water interface. J. Chem. Soc. Faraday Trans. 1 70, 1807 (1974). DOI 10.1039/F19747001807

    Google Scholar 

  54. Li, H., Robertson, A.D., Jensen, J.H.: Very fast empirical prediction and rationalization of protein pK a values. Proteins Struct. Funct. Bioinforma. 61(4), 704 (2005). DOI 110.1002/prot.20660

    Google Scholar 

  55. Bas, D.C., Rogers, D.M., Jensen, J.H.: Very fast prediction and rationalization of pKa values for protein-ligand complexes. Proteins Struct. Funct. Bioinforma. 73(3), 765 (2008). DOI 10.1002/prot.22102

    Article  Google Scholar 

  56. Olsson, M.H.M., Søndergaard, C.R., Rostkowski, M., Jensen, J.H.: PROPKA3: Consistent treatment of internal and surface residues in empirical pKa predictions. J. Chem. Theory Comput. 7(2), 525 (2011). DOI 10.1021/ct100578z

    Article  Google Scholar 

  57. Ullmann, G.M., Knapp, E.W.: Electrostatic models for computing protonation and redox equilibria in proteins. Eur. Biophys. J. 28, 533 (1999). DOI 10.1007/ s002490050236

    Article  Google Scholar 

  58. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E.: The protein data bank. Nucleic Acids Res. 28(1), 235 (2000). DOI 10.1093/nar/28.1.235

    Article  Google Scholar 

  59. Liu, Y., Rieben, N., Iversen, L., Sørensen, B., Park, J., Nygård, J., Martinez, K.: Specific and reversible immobilization of histidine-tagged proteins on functionalized silicon nanowires. Nanotechnology 21, 245105 (2010). DOI 10.1088/0957-4484/21/24/ 245105

    Article  Google Scholar 

  60. Pugliese, L., Coda, A., Malcovati, M., Bolognesi, M.: Three-dimensional structure of the tetragonal crystal form of egg-white avidin in its functional complex with biotin at 2.7 å resolution. J. Mol. Biol. 231(3), 698 (1993). DOI 10.1006/jmbi.1993.1321

    Google Scholar 

  61. Weber, P., Ohlendorf, D., Wendoloski, J., Salemme, F.: Structural origins of high-affinity biotin binding to streptavidin. Science 243(4887), 85 (1989). DOI 10. 1126/science.2911722

    Google Scholar 

  62. Green, N.M.: Avidin-biotin technology. In: Wilchek, M., Bayer, E.A. (eds.) Methods in Enzymology, vol. 184, pp. 51–67. Academic, London (1990). DOI 10.1016/ 0076-6879(90)84259-J

    Google Scholar 

  63. Hediger, M.R.: A perspective on bionanosensor simulation & computational enzyme engineering. Ph.D. Thesis, Department of Chemistry, University of Copenhagen (2013)

    Google Scholar 

  64. The PyMOL Molecular Graphics System: Version 1.3.0 Schrödinger, LLC

    Google Scholar 

  65. Harris, L.J., Larson, S.B., Hasel, K.W., McPherson, A.: Refined structure of an intact IgG2a monoclonal antibody. Biochemistry 36(7), 1581 (1997). DOI 10.1021/ bi962514+

    Google Scholar 

  66. Macao, B., Johansson, D., Hansson, G., Härd, T.: Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat. Struct. Mol. Biol. 13(1), 71 (2005). DOI 10.1038/nsmb1035

    Article  Google Scholar 

  67. Goodsell, D.S., Morris, G.M., Olson, A.J.: Automated docking of flexible ligands: Applications of autodock. J. Mol. Recognit. 9(1), 1 (1996). DOI 10.1002/(SICI) 1099-1352(199601)9:1⟨1::AID-JMR241⟩3.0.CO;2-6

    Google Scholar 

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Acknowledgements

This work has been partially funded by the Danish Research Council for Technology and Production Sciences (FTP), the Danish Natural Science Research Council (FNU), and by UNIK Synthetic Biology program, funded by the Danish Ministry for Science, Technology and Innovation. The authors acknowledge fruitful discussions with Lars Iversen, Noémie Loret, Rune S. Frederiksen, and Shivendra Upadhyay.

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Authors and Affiliations

  1. Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100, Copenhagen, Denmark

    Martin R. Hediger, Jan H. Jensen & Luca De Vico

  2. Bionanotechnology and Nanomedicine Laboratory, Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100, Copenhagen, Denmark

    Karen L. Martinez

  3. Nano-Science Center, University of Copenhagen, Universitetsparken 5, DK-2100, Copenhagen, Denmark

    Karen L. Martinez & Jesper Nygård

  4. Niels Bohr Institute, Center for Quantum Devices, University of Copenhagen, Universitetsparken 5, DK-2100, Copenhagen, Denmark

    Jesper Nygård

  5. DTU Nanotech, Department of Micro and Nanotechnology, Technical University of Denmark, DTU-Building 345 East, DK-2800, Kongens Lyngby, Denmark

    Mads Brandbyge

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  1. Martin R. Hediger
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Editors and Affiliations

  1. State Key Laboratory of Electronic Thin, University of Electronic Science and Technology of China, Chengdu, People's Republic of China

    Shibin Li

  2. State Key Laboratory of Electronic Thin, University of Electronic Science and Technology of China, Chengdu, People's Republic of China

    Jiang Wu

  3. State Key Laboratory of Electronic, University of Electronic Science and Technology, Chengdu, People's Republic of China

    Zhiming M. Wang

  4. State Key Laboratory of Electronic Thin, University of Electronic Science and Technology of China, Chengdu, People's Republic of China

    Yadong Jiang

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Hediger, M.R., Martinez, K.L., Nygård, J., Brandbyge, M., Jensen, J.H., De Vico, L. (2013). BioFET-SIM: A Tool for the Analysis and Prediction of Signal Changes in Nanowire-Based Field Effect Transistor Biosensors. In: Li, S., Wu, J., Wang, Z., Jiang, Y. (eds) Nanoscale Sensors. Lecture Notes in Nanoscale Science and Technology, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-319-02772-2_3

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