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Label-free immunodetection with CMOS-compatible semiconducting nanowires

Nature volume 445, pages 519–522 (2007)Cite this article

Abstract

Semiconducting nanowires have the potential to function as highly sensitive and selective sensors for the label-free detection of low concentrations of pathogenic microorganisms1,2,3,4,5,6,7,8,9,10. Successful solution-phase nanowire sensing has been demonstrated for ions3, small molecules4, proteins5,6, DNA7 and viruses8; however, ‘bottom-up’ nanowires (or similarly configured carbon nanotubes11) used for these demonstrations require hybrid fabrication schemes12,13, which result in severe integration issues that have hindered widespread application. Alternative ‘top-down’ fabrication methods of nanowire-like devices9,10,14,15,16,17 produce disappointing performance because of process-induced material and device degradation. Here we report an approach that uses complementary metal oxide semiconductor (CMOS) field effect transistor compatible technology and hence demonstrate the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. This approach eliminates the need for hybrid methods and enables system-scale integration of these sensors with signal processing and information systems. Additionally, the ability to monitor antibody binding and sense the cellular immune response in real time with readily available technology should facilitate widespread diagnostic applications.

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Figure 1: Device fabrication and electrical performance.
Figure 2: Unfunctionalized device sensing.
Figure 3: Protein detection and sensitivity.
Figure 4: Demonstration of immunodetection.

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Acknowledgements

We thank R. Ilic, D. Westly, M. Metzler and V. Genova (Cornell Nanofabrication Facility) for device processing assistance; T. Ma, R. Sleight, J. Hyland, M. Young and C. Tillinghast for device processing discussions; F. Sigworth and D. Stern for functionalization and sensing discussions and for assistance in manuscript preparation; M. Saltzman, K. Klemic, A. Flyer, J. Bertram and S. Jay for functionalization and sensing discussions; Z. Jiang for scanning electron micrograph imaging assistance; S. R. Lee for Silvaco simulations; and R. Munden for device measurement assistance. This work was partially supported by DARPA through ONR and AFOSR (M.A.R.), NASA (M.A.R.), the NIH (A.D.H.), the Coulter Foundation (T.M.F.), by a Department of Homeland Security graduate fellowship (E.S.), and by a N.S.F. graduate fellowship (E.S., D.A.R.). This work was performed in part at the Cornell Nanoscale Science and Technology Facility, a member of the National Nanotechnology Infrastructure Network that is supported by the NSF.

Author Contributions E.S. performed device fabrication and measurements. J.F.K. assisted in fabrication design, D.A.R. performed device mobility experiments and analysis, and P.N.W. and A.D.H. provided molecules used for device functionalization. D.T-E. assisted in device characterization. E.S. and T.M.F. performed T-cell isolation and T-cell measurements. D.A.L., T.M.F. and M.A.R. contributed to experimental design, characterization and interpretation. E.S., J.F.K., T.M.F. and M.A.R. analysed the data and wrote the manuscript with contributions from all authors.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Yale University, P O Box 208284, New Haven, Connecticut, 06511, USA

    Eric Stern & Tarek M. Fahmy

  2. Department of Electrical Engineering, Yale University, P O Box 208284, New Haven, Connecticut, 06511, USA

    James F. Klemic, David A. Routenberg, Daniel B. Turner-Evans & Mark A. Reed

  3. Department of Mechanical Engineering, Yale University, P O Box 208284, New Haven, Connecticut, 06511, USA

    David A. LaVan

  4. Department of Applied Physics, Yale University, P O Box 208284, New Haven, Connecticut, 06511, USA

    Mark A. Reed

  5. Department of Chemistry, Yale University, P O Box 208107, New Haven, Connecticut, 06511, USA

    Pauline N. Wyrembak & Andrew D. Hamilton

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Correspondence to Tarek M. Fahmy or Mark A. Reed.

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Supplementary information

Supplementary Notes

This file contains Supplementary Notes describing the device fabrication, functionalization, and sensing as well as accumulation-mode DNA sensing and inversion-mode functionalized and unfunctionalized sensing. The document contains Supplementary Figures 1-8, Supplementary Tables 1-2 and additional references. (PDF 677 kb)

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Stern, E., Klemic, J., Routenberg, D. et al. Label-free immunodetection with CMOS-compatible semiconducting nanowires. Nature 445, 519–522 (2007). https://doi.org/10.1038/nature05498

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