Nanoproteomics pp 223-237

Part of the Methods in Molecular Biology book series (MIMB, volume 790)

Nanowire Biosensors for Label-Free, Real-Time, Ultrasensitive Protein Detection



Sensitive and quantitative analysis of proteins is central to disease diagnosis, drug screening, and proteomic studies. Among recent research advances exploiting new nanomaterials for biomolecule analysis, silicon nanowires (SiNWs), which are configured as field-effect transistors (FETs), have emerged as one of the most promising and powerful platforms for label-free, real-time, and highly sensitive electrical detection of proteins as well as many other biological species. Here, we describe a detailed protocol for realizing SiNW biosensors for protein detection that includes SiNW synthesis, FET device fabrication, surface receptor functionalization, and electrical sensing measurements. Moreover, incorporating both p-type and n-type SiNWs in the same sensor array provides a unique means of internal control for sensing signal verification.

Key words

Nanowire Chemical vapor deposition FET Surface modification Cancer marker Isoelectric point 


  1. 1.
    Morales, A.M., Lieber, C.M. (1998) A laser ablation method for the synthesis of crystalline semiconductor nanowires. Science 279, 208–211.Google Scholar
  2. 2.
    Lieber, C.M., Wang, Z.L. (2007) Functional nanowires. MRS Bull 32, 99–108.Google Scholar
  3. 3.
    Patolsky, F., Timko, B.P., Zheng, G., et al. (2007) Nanowire-based nanoelectronic devices in the life sciences. MRS Bull 32, 142–149.Google Scholar
  4. 4.
    Cui, Y., Wei, Q., Park, H., et al. (2001) Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293, 1289–1292.Google Scholar
  5. 5.
    Zheng, G., Patolsky, F., Cui, Y., et al. (2005) Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol 23, 1294–1301.Google Scholar
  6. 6.
    Stern, E., Klemic, J.F., Routenberg, D.A., et al. (2007) Label-free immunodetection with CMOS-compatible semiconducting nanowires. Nature 445, 519–522.Google Scholar
  7. 7.
    McAlpine, M.C., Ahmad, H., Wang, D.W., et al. (2007) Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors. Nat Mater 6, 379–384.Google Scholar
  8. 8.
    Park, I., Li Z., Pisano, A.P., et al. (2010) Top-down fabricated silicon nanowire sensors for real-time chemical detection. Nanotechnol 21, 015501.Google Scholar
  9. 9.
    Domansky, K., Janata, J. (1993) Present state of fabrication of chemically sensitive field-effect transistors. Analyst 118, 335–340.Google Scholar
  10. 10.
    Janata, J. (1994) 20 Years of ion-selective field-effect transistors. Analyst 119, 2275–2278.Google Scholar
  11. 11.
    Sze, S.M., Ng., K.K. (1981) Physics of Semiconductor Devices, 2nd ed. Wiley, New York.Google Scholar
  12. 12.
    Srinivas, P.R., Kramer, B.S., Srivastava, S. (2001) Trends in biomarker research for cancer detection. Lancet Oncol 2, 698–704.Google Scholar
  13. 13.
    Etzioni, R. Urban, N., Ramsey, S., et al. (2003) The case for early detection. Nat Rev Cancer 3, 243–252.Google Scholar
  14. 14.
    Ward, A.M., Catto, J.W.F., Hamdy, F.C. (2001) Prostate specific antigen: biology, biochemistry and available commercial assays. Ann Clin Biochem 38, 633–651.Google Scholar
  15. 15.
    Patolsky, F., Zheng, G., Lieber, C.M. (2006) Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species. Nat Protocol 1, 1711–1724.Google Scholar
  16. 16.
    Whitesides, G.M., Ostuni, E., Takayama, S. et al. (2001) Soft lithography in biology and biochemistry. Annu Rev Biomed Eng 3, 335.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Laboratory of Advanced Materials, Department of ChemistryFudan UniversityShanghaiChina
  2. 2.Department of Chemistry and Chemical Biology and Division of Engineering and Applied ScienceHarvard UniversityCambridgeUSA

Personalised recommendations