Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species

Nature Protocols volume 1, pages 1711–1724 (2006)Cite this article

Abstract

Detection and quantification of biological and chemical species are central to many areas of healthcare and the life sciences, ranging from diagnosing disease to discovery and screening of new drug molecules. Semiconductor nanowires configured as electronic devices have emerged as a general platform for ultra-sensitive direct electrical detection of biological and chemical species. Here we describe a detailed protocol for realizing nanowire electronic sensors. First, the growth of uniform, single crystal silicon nanowires, and subsequent isolation of the nanowires as stable suspensions are outlined. Second, fabrication of addressable nanowire device arrays is described. Third, covalent modification of the nanowire device surfaces with receptors is described. Fourth, an example modification and measurements of the electrical response from devices are detailed. The silicon nanowire (SiNW) devices have demonstrated applications for label-free, ultrasensitive and highly-selective real-time detection of a wide range of biological and chemical species, including proteins, nucleic acids, small molecules and viruses.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2: Synthesis of semiconductor silicon nanowires.
Figure 3
Figure 4: Photomask pattern for the first photolithography layer.
Figure 5: Nanowire devices and device array fabrication.
Figure 6: Different magnifications of the photomask design pattern for the second photolithography layer.
Figure 7: Transport measurement of SiNW devices in air.
Figure 8: Nanowire FET sensing set-up.
Figure 9: Optical images of device array and transport of SiNW devices in aqueous solution.
Figure 10
Figure 11
Figure 12: Real-time nanowire sensing results.

Similar content being viewed by others

References

  1. Morales, A.M. & Lieber, C.M. A laser ablation method for the synthesis of crystalline semiconductor nanowires. Science 279, 208–211 (1998).

    Article  CAS  Google Scholar 

  2. Lieber, C.M. Nanoscale science and technology: Building a big future from small things. MRS Bull., 28, 486–491 (2003).

    Article  CAS  Google Scholar 

  3. Xiang, J. et al. Ge/Si nanowire heterostructures as high-performance field-effect transistors. Nature 441, 489–493 (2006).

    Article  CAS  Google Scholar 

  4. Cui, Y., Zhong, Z., Wang, D., Wang, W.U. & Lieber, C.M. High performance silicon nanowire field effect transistors. Nano Lett. 3, 149–152 (2003).

    Article  CAS  Google Scholar 

  5. Jin, S. et al. Scalable interconnection and integration of nanowire devices without registration. Nano Lett. 4, 915–919 (2004).

    Article  CAS  Google Scholar 

  6. Patolsky, F. & Lieber, C.M. Nanowire nanosensors. Mater. Today 8, 20–28 (2005).

    Article  CAS  Google Scholar 

  7. Cui, Y., Wei, Q., Park, H. & Lieber, C.M. Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 293, 1289–1292 (2001).

    Article  CAS  Google Scholar 

  8. Sze, S.M. Physics of Semiconductor Devices Edn. 2 p. 481 (John Wiley & Sons, New York, 1981).

    Google Scholar 

  9. Domansky, K. & Janata, J. Present state of fabrication of chemically sensitive field-effect transistors. Analyst 118, 335–340 (1993).

    Article  CAS  Google Scholar 

  10. Janata, J. 20 Years of ion-selective field-effect transistors. Analyst 119, 2275–2278 (1994).

    Article  CAS  Google Scholar 

  11. Hahm, J. & Lieber, C.M. Direct ultrasensitive electrical detection of DNA and DNA sequence variations using nanowire nanosensors. Nano Lett. 4, 51–54 (2004).

    Article  CAS  Google Scholar 

  12. Wang, W.U., Chen, C., Lin, K.H., Fang, Y. & Lieber, C.M. Label-free detection of small-molecule-protein interactions by using nanowire nanosensors. Proc. Natl. Acad. Sci. USA 102, 3208–3212 (2005).

    Article  CAS  Google Scholar 

  13. Patolsky, F. et al. Electrical detection of single viruses. Proc. Natl. Acad. Sci. USA 101, 14017–14022 (2004).

    Article  CAS  Google Scholar 

  14. Zheng, G.F., Patolsky, F., Cui, Y., Wang, W.U. & Lieber, C.M. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat. Biotechnol. 23, 1294–1301 (2005).

    Article  CAS  Google Scholar 

  15. Hu, J.T., Odom, T.W. & Lieber, C.M. Chemistry and physics in one dimension: Synthesis and properties of nanowires and nanotubes. Acc. Chem. Res. 32, 435–445 (1999).

    Article  CAS  Google Scholar 

  16. Cui, Y., Lauhon, L.J., Gudiksen, M.S., Wang, J. & Lieber, C.M. Diameter-controlled synthesis of single-crystal silicon nanowires. Appl. Phys. Lett. 78, 2214–2216 (2001).

    Article  CAS  Google Scholar 

  17. Wu, Y. Controlled growth and structures of molecular-scale silicon nanowires. Nano Lett. 4, 433–436 (2004).

    Article  CAS  Google Scholar 

  18. Zheng, G.F., Lu, W., Jin, S. & Lieber, C.M. Synthesis and fabrication of high-performance n-type silicon nanowire transistors. Adv. Mater. 16, 1890–1893 (2004).

    Article  CAS  Google Scholar 

  19. Iler, R.K. The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties and Biochemistry of Silica (John Wiley & Sons, New York, 1979).

  20. Ward, A.M., Catto, J.W.F. & Hamdy, F.C. Prostate specific antigen: biology, biochemistry and available commercial assays. Ann. Clin. Biochem. 38, 633–651 (2001).

    Article  CAS  Google Scholar 

  21. Mirkin, C.A. et al. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609 (1996).

    Article  CAS  Google Scholar 

  22. Campagnolo, C. et al. Real-Time, label-free monitoring of tumor antigen and serum antibody interactions. J. Biochem. Biophys. Methods 61, 283–298 (2004).

    Article  CAS  Google Scholar 

  23. Wu, G.H. et al. Bioassay of prostate-specific antigen (PSA) using microcantilevers. Nat. Biotechnol. 19, 856–860 (2001).

    Article  CAS  Google Scholar 

  24. Chen, R.J. et al. Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors. Proc. Natl. Acad. Sci. USA 100, 4984–4989 (2003).

    Article  CAS  Google Scholar 

  25. Patolsky, F., Zheng, G.F. & Lieber, C.M. Nanowire sensors for medicine and the life sciences. Nanomedicine 1, 51–65 (2006).

    Article  CAS  Google Scholar 

  26. Patolsky, F., Zheng, G.F. & Lieber, C.M. Nanowire-based biosensors. Anal. Chem. 78, 4261–4269 (2006).

    Article  Google Scholar 

  27. Becker, J. Signal transduction inhibitors – a work in progress. Nat. Biotechnol. 22, 15–18 (2004).

    Article  CAS  Google Scholar 

  28. Patolsky, F. et al. Detection, stimulation and inhibition of neuronal signals with high-density nanowire transistor arrays. Science 313, 1100–1104 (2006).

    Article  CAS  Google Scholar 

  29. MacBeath, G. & Schreiber, S.L. Printing proteins as microarrays for high-throughput function determination. Science 289, 1760–1763 (2000).

    CAS  Google Scholar 

  30. Whitesides, G.M., Ostuni, E., Takayama, S., Jiang, X. & Ingber, D.E. Soft lithography in biology and biochemistry. Annu. Rev. Biomed. Eng. 3, 335 (2001).

    Article  CAS  Google Scholar 

  31. Huang, Y., Duan, X.F., Wei, Q.Q. & Lieber, C.M. Directed assembly of one-dimensional nanostructures into functional networks. Science 291, 630–633 (2001).

    Article  CAS  Google Scholar 

  32. Whang, D., Jin, S. & Lieber, C.M. Large-scale hierarchical organization of nanowires for functional nanosystems. Japan. J. Appl. Phys. 43, 4465–4470 (2004).

    Article  CAS  Google Scholar 

  33. Wu, Y., Xiang, J., Yang, C., Lu, W. & Lieber, C.M. Single-crystal metallic nanowires and metal/semiconductor nanowire heterostructures. Nature 430, 61–65 (2004).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, 02138, MA, USA

    Fernando Patolsky, Gengfeng Zheng & Charles M Lieber

Authors
  1. Fernando Patolsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gengfeng Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Charles M Lieber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles M Lieber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patolsky, F., Zheng, G. & Lieber, C. Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species. Nat Protoc 1, 1711–1724 (2006). https://doi.org/10.1038/nprot.2006.227

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2006.227

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing