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Detection and identification of proteins using nanoparticle–fluorescent polymer ‘chemical nose’ sensors

Nature Nanotechnology volume 2, pages 318–323 (2007)Cite this article

Abstract

A sensor array containing six non-covalent gold nanoparticle–fluorescent polymer conjugates has been created to detect, identify and quantify protein targets. The polymer fluorescence is quenched by gold nanoparticles; the presence of proteins disrupts the nanoparticle–polymer interaction, producing distinct fluorescence response patterns. These patterns are highly repeatable and are characteristic for individual proteins at nanomolar concentrations, and can be quantitatively differentiated by linear discriminant analysis (LDA). Based on a training matrix generated at protein concentrations of an identical ultraviolet absorbance at 280 nm (A280 = 0.005), LDA, combined with ultraviolet measurements, has been successfully used to identify 52 unknown protein samples (seven different proteins) with an accuracy of 94.2%. This work demonstrates the construction of novel nanomaterial-based protein detector arrays with potential applications in medical diagnostics.

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Figure 1: Fluorophore displacement protein sensor array.
Figure 2: Structural features of nanoparticles, polymer transducer and target analytes.
Figure 3: Fluorescence intensity changes for PPE-CO2 (100 nM) at 465 nm on addition of cationic NP3
Figure 4: Array-based sensing of protein analytes at 5 µM.
Figure 5: Array-based sensing of protein analytes with identical absorbance at 280 nm.

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References

  1. Daniels, M. J., Wang, Y., Lee, M.-Y. & Venkitaraman, A. R. Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science 306, 876–879 (2004).

    Article  CAS  Google Scholar 

  2. Ross, J. S. & Fletcher, J. A. The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells 16, 413–428 (1998).

    Article  CAS  Google Scholar 

  3. Haab, B. B. Applications of antibody array platforms. Curr. Opin. Biotechnol. 17, 415–421 (2006).

    Article  CAS  Google Scholar 

  4. Albert, K. J. et al. Cross-reactive chemical sensor arrays. Chem. Rev. 100, 2595–2626 (2000).

    Article  CAS  Google Scholar 

  5. Lee, J. W., Lee, J. S., Kang, M., Su, A. I. & Chang, Y. T. Visual artifical tongue for quantitative metal-cation analysis by an off-the-shelf dye array. Chem. Eur. J. 12, 5691–5696 (2006).

    Article  CAS  Google Scholar 

  6. Rakow, N. A. & Suslick, K. S. A colorimetric sensor array for odour visualization. Nature 406, 710–713 (2000).

    Article  CAS  Google Scholar 

  7. Greene, N. T. & Shimizu, K. D. Colorimetric molecularly imprinted polymer sensor array using dye displacement. J. Am. Chem. Soc. 127, 5695–5700 (2005).

    Article  CAS  Google Scholar 

  8. Folmer-Andersen, J. F., Kitamura M. & Anslyn E. V. Pattern-based discrimination of enantiomeric and structurally similar amino acids: an optical mimic of the mammalian taste response. J. Am. Chem. Soc. 128, 5652–5653 (2006).

    Article  CAS  Google Scholar 

  9. Buryak, A. & Severin, K. A chemosensor array for the colorimetric identification of 20 natural amino acids. J. Am. Chem. Soc. 127, 3700–3701 (2005).

    Article  CAS  Google Scholar 

  10. Wright, A. T. & Anslyn, E. V. Differential receptors arrays and assays for solution-based molecular recognition. Chem. Soc. Rev. 35, 14–28 (2006)

    Article  CAS  Google Scholar 

  11. Lee, J. W., Lee, J.-S. & Chang, Y.-T. Colorimetric identification of carbohydrates by a pH indicator/pH change inducer ensemble. Angew. Chem. Int. Edn 45, 6485–6487 (2006).

    Article  CAS  Google Scholar 

  12. Baldini, L., Wilson, A. J., Hong, J. & Hamilton, A. D. Pattern-based detection of different proteins using an array of fluorescent protein surface receptors. J. Am. Chem. Soc. 126, 5656–5657 (2004).

    Article  CAS  Google Scholar 

  13. Zhou, H., Baldini, L., Hong, J., Wilson, A. J. & Hamilton, A. D. Pattern recognition of proteins based on an array of functionalized porphyrins. J. Am. Chem. Soc. 128, 2421–2425 (2006).

    Article  CAS  Google Scholar 

  14. Wright, A. T. et al. Differential receptors create patterns that distinguish various proteins. Angew. Chem. Int. Edn 44, 6375–6378 (2005).

    Article  CAS  Google Scholar 

  15. You, C.-C., Verma, A. & Rotello, V. M. Engineering the nanoparticle–biomacromolecule interface. Soft Matter 2, 190–204 (2006).

    Article  CAS  Google Scholar 

  16. Rosi, N. L. & Mirkin C. A. Nanostructures in biodiagnostics. Chem. Rev. 105, 1547–1562 (2005).

    Article  CAS  Google Scholar 

  17. Katz, E. & Willner I. Integrated nanoparticle–biomolecule hybrid systems: synthesis, properties, and applications. Angew. Chem. Int. Edn 43, 6042–6108 (2004)

    Article  CAS  Google Scholar 

  18. Fischer, N. O., McIntosh, C. M., Simard, J. M. & Rotello V. M. Inhibition of chymotrypsin through surface binding using nanoparticle-based receptors. Proc. Natl Acad. Sci. USA 99, 5018–5023 (2002)

    Article  CAS  Google Scholar 

  19. You, C.-C., De, M., Han, G. & Rotello V. M. Tunable inhibition and denaturation of α-chymotrypsin with amino acid-functionalized gold nanoparticles. J. Am. Chem. Soc. 127, 12873–12881 (2005).

    Article  CAS  Google Scholar 

  20. Bayraktar, H., Ghosh, P. S., Rotello, V. M. & Knapp, M. J. Disruption of protein–protein interactions using nanoparticles: inhibition of cytochrome c peroxidase. Chem. Commun. 1390–1392 (2006).

  21. Nath, S. et al. Is gold really softer than silver? HSAB principle revisited. J. Nanoparticle Res. 8, 111–116 (2006).

    Article  CAS  Google Scholar 

  22. Fan, C. et al. Beyond superquenching: hyper-efficient energy transfer from conjugated polymers to gold nanoparticles. Proc. Natl Acad. Sci. USA 100, 6297–6301 (2003).

    Article  CAS  Google Scholar 

  23. Bunz, U. H. F. Synthesis and structure of PAEs. Adv. Polym. Sci. 177, 1–52 (2005).

    Article  CAS  Google Scholar 

  24. Zheng, J. & Swager, T. M. Poly(arylene ethynylene)s in chemosensing and biosensing. Adv. Polym. Sci. 177, 151–179 (2005).

    Article  CAS  Google Scholar 

  25. Kim, I.-B., Dunkhorst, A., Gilbert, J. & Bunz, U. H. F. Sensing of lead ions by a carboxylate-substituted PPE: multivalency effects. Macromolecules 38, 4560–4562 (2005).

    Article  CAS  Google Scholar 

  26. Aguila, A. & Murray, R. W. Monolayer-protected clusters with fluorescent dansyl ligands. Langmuir 16, 5949–5954 (2000).

    Article  CAS  Google Scholar 

  27. Sandanaraj, B. S., Demont, R., Aathimanikandan, S. V., Savariar, E. N. & Thayumanavan, S. Selective sensing of metalloproteins from nonselective binding using a fluorogenic amphiphilic polymer. J. Am. Chem. Soc. 128, 10686–10687 (2006).

    Article  CAS  Google Scholar 

  28. Jurs, P. C., Bakken, G. A. & McClelland, H. E. Computational methods for the analysis of chemical sensor array data from volatile analytes. Chem. Rev. 100, 2649–2678 (2000).

    Article  CAS  Google Scholar 

  29. Brust, M., Walker, M., Bethell, D., Schiffrin, D. J. & Whyman, R. Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid-liquid system. J. Chem. Soc., Chem. Commun. 801–802 (1994).

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Acknowledgements

This work was supported by the National Science Foundation (NSF) Center for Hierarchical Manufacturing at the University of Massachusetts (NSEC, DMI-0531171), the NSF (VR, CHE-0518487), and the NIH (GM077173). U.B. and I.B.K. thank the Department of Energy for generous financial support (DE-FG02-04ER46141).

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Authors and Affiliations

  1. Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, 01003, Massachusetts, USA

    Chang-Cheng You, Oscar R. Miranda, Basar Gider, Partha S. Ghosh, Belma Erdogan, Sai Archana Krovi & Vincent M. Rotello

  2. School of Chemistry and Biochemistry, Georgia Institute of Technology, 770 State Street, Atlanta, 30332, Georgia, USA

    Ik-Bum Kim & Uwe H. F. Bunz

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  1. Chang-Cheng You
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Correspondence to Vincent M. Rotello.

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Supplementary figures S1—S3 and supplementary tables S1—S5 (PDF 1058 kb)

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You, CC., Miranda, O., Gider, B. et al. Detection and identification of proteins using nanoparticle–fluorescent polymer ‘chemical nose’ sensors. Nature Nanotech 2, 318–323 (2007). https://doi.org/10.1038/nnano.2007.99

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