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Multiplexed electrical detection of cancer markers with nanowire sensor arrays

Abstract

We describe highly sensitive, label-free, multiplexed electrical detection of cancer markers using silicon-nanowire field-effect devices in which distinct nanowires and surface receptors are incorporated into arrays. Protein markers were routinely detected at femtomolar concentrations with high selectivity, and simultaneous incorporation of control nanowires enabled discrimination against false positives. Nanowire arrays allowed highly selective and sensitive multiplexed detection of prostate specific antigen (PSA), PSA-α1-antichymotrypsin, carcinoembryonic antigen and mucin-1, including detection to at least 0.9 pg/ml in undiluted serum samples. In addition, nucleic acid receptors enabled real-time assays of the binding, activity and small-molecule inhibition of telomerase using unamplified extracts from as few as ten tumor cells. The capability for multiplexed real-time monitoring of protein markers and telomerase activity with high sensitivity and selectivity in clinically relevant samples opens up substantial possibilities for diagnosis and treatment of cancer and other complex diseases.

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Figure 1: Nanowire sensor arrays and detector properties.
Figure 2: Multiplexed detection with nanowire arrays.
Figure 3: Multiplexed detection of cancer marker proteins.
Figure 4: Schematic of the telomerase binding and activity assay.
Figure 5: Detection of telomerase.

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Acknowledgements

We thank M. Shuman (UCSF) for helpful discussion. C.M.L. acknowledges support of this work by the Defense Advanced Research Projects Agency and the National Cancer Institute.

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Correspondence to Charles M Lieber.

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Supplementary information

Supplementary Fig. 1

Nanowire device array and elements. (PDF 112 kb)

Supplementary Fig. 2

Concentration dependent detection of CEA and mucin-1 marker proteins. (PDF 127 kb)

Supplementary Fig. 3

Multiplexed detection of f-PSA and PSA-ACT. (PDF 108 kb)

Supplementary Fig. 4

Concentration-dependent binding and activity of telomerase. (PDF 123 kb)

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Zheng, G., Patolsky, F., Cui, Y. et al. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol 23, 1294–1301 (2005). https://doi.org/10.1038/nbt1138

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