Nano Research

, Volume 6, Issue 2, pp 113–120 | Cite as

Multiplexed cytokine detection on plasmonic gold substrates with enhanced near-infrared fluorescence

  • Bo Zhang
  • Jordan Price
  • Guosong Hong
  • Scott M. Tabakman
  • Hailiang Wang
  • Justin A. Jarrell
  • Ju Feng
  • Paul J. Utz
  • Hongjie Dai
Research Article

Abstract

Protein microarrays based on fluorescence detection have been widely utilized for high-throughput functional proteomic analysis. However, a drawback of such assays has been low sensitivity and narrow dynamic range, limiting their capabilities, especially for detecting low abundance biological molecules such as cytokines in human samples. Here, we present fluorescence-enhancing microarrays on plasmonic gold films for multiplexed cytokine detection with up to three orders of magnitude higher sensitivity than on conventional nitrocellulose and glass substrates. Cytokine detection on the gold plasmonic substrate is about one to two orders of magnitude more sensitive than enzyme-linked immunosorbent assay (ELISA) and can be multiplexed. A panel of six cytokines (Vascular endothelial growth factor (VEGF), Interleukin 1β (IL-1β), Interleukin 4 (IL-4), Interleukin 6 (IL-6), Interferon γ (IFN-γ), and Tumor necrosis factor (TNF)) were detected in the culture media of cancer cells. This work establishes a new method of high throughput multiplexed cytokine detection with higher sensitivity and dynamic range than ELISA.

Graphical abstract

Keywords

microarray cytokine plasmonic multiplex near infrared fluorescence 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12274_2012_286_MOESM1_ESM.pdf (1.4 mb)
Supplementary material, approximately 1.40 MB.

References

  1. [1]
    Oppenheim, J. J.; Rossio, J. L.; Gearing, A. J. H. Clinical Applications of Cytokines: Role in Pathogenesis, Diagnosis, and Therapy; Oxford University Press: New York, 1993.Google Scholar
  2. [2]
    Lequin, R. M. Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin. Chem. 2005, 51, 2415–2418.CrossRefGoogle Scholar
  3. [3]
    Diaz-Mitoma, F.; Kumar, A.; Karimi, S.; Kryworuchko, M.; Daftarian, M. P.; Creery, W. D.; Filion, L. G.; Cameron, W. Expression of IL-10, IL-4 and interferon-gamma in unstimulated and mitogen-stimulated peripheral blood lymphocytes from HIV-seropositive patients. Clin. Exp. Immunol. 1995, 102, 31–39.CrossRefGoogle Scholar
  4. [4]
    de Jager, W.; te Velthuis, H.; Prakken, B. J.; Kuis, W.; Rijkers, G. T. Simultaneous detection of 15 human cytokines in a single sample of stimulated peripheral blood mononuclear cells. Clin. Vaccine Immunol. 2003, 10, 133–139.CrossRefGoogle Scholar
  5. [5]
    Khan, S. S.; Smith, M. S.; Reda, D.; Suffredini, A. F.; McCoy, J. P. Jr. Multiplex bead array assays for detection of soluble cytokines: Comparisons of sensitivity and quantitative values among kits from multiple manufacturers. Cytom. Part B: Clin. Cytom. 2004, 61B, 35–39.CrossRefGoogle Scholar
  6. [6]
    Dossus, L.; Becker, S.; Achaintre, D.; Kaaks, R.; Rinaldi, S. Validity of multiplex-based assays for cytokine measurements in serum and plasma from “non-diseased” subjects: Comparison with ELISA. J. Immunol. Methods. 2009, 350, 125–132.CrossRefGoogle Scholar
  7. [7]
    Utz, P. J. Multiplexed assays for identification of biomarkers and surrogate markers in systemic lupus erythematosus. Lupus 2004, 13, 304–311.CrossRefGoogle Scholar
  8. [8]
    Robinson, W. H.; Utz, P. J.; Steinman, L. Genomic and proteomic analysis of multiple sclerosis: Opinion. Curr. Opin. Immunol. 2003, 15, 660–667.CrossRefGoogle Scholar
  9. [9]
    Hueber, W.; Kidd, B. A.; Tomooka, B. H.; Lee, B. J.; Bruce, B.; Fries, J. F.; Sønderstrup, G.; Monach, P.; Drijfhout, J. W.; van Venrooij, W. J. et al. Antigen microarray profiling of autoantibodies in rheumatoid arthritis. Arthritis Rheum. 2005, 52, 2645–2655.CrossRefGoogle Scholar
  10. [10]
    Garren, H.; Robinson, W. H.; Krasulová, E.; Havrdová, E.; Nadj, C.; Selmaj, K.; Losy, J.; Nadj, I.; Radue, E. W.; Kidd, B. A. et al. Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Ann. Neurol. 2008, 63, 611–620.CrossRefGoogle Scholar
  11. [11]
    Bar-Or, A.; Vollmer, T.; Antel, J.; Arnold, D. L.; Bodner, C. A.; Campagnolo, D.; Gianettoni, J.; Jalili, F.; Kachuck, N.; Lapierre, Y. et al. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Arch. Neurol. 2007, 64, 1407–1415.CrossRefGoogle Scholar
  12. [12]
    MacBeath, G. Protein microarrays and proteomics. Nat. Genet. 2002, 32, 526–532.CrossRefGoogle Scholar
  13. [13]
    Madoz-Gúrpide, J.; Wang, H.; Misek, D. E.; Brichory, F.; Hanash, S. M. Protein based microarrays: A tool for probing the proteome of cancer cells and tissues. Proteomics 2001, 1, 1279–1287.CrossRefGoogle Scholar
  14. [14]
    MacBeath, G.; Schreiber, S. L. Printing proteins as microarrays for high-throughput function determination. Science 2000, 289, 1760–1763.Google Scholar
  15. [15]
    Graf, R.; Friedl, P. Detection of immobilized proteins on nitrocellulose membranes using a biotinylation-dependent system. Anal. Biochem. 1999, 273, 291–297.CrossRefGoogle Scholar
  16. [16]
    Li, Y. W.; Reichert, W. M. Adapting cDNA microarray format to cytokine detection protein arrays. Langmuir 2003, 19, 1557–1566.CrossRefGoogle Scholar
  17. [17]
    Zhu, H.; Snyder, M. Protein arrays and microarrays. Curr. Opin. Chem. Biol. 2001, 5, 40–45.CrossRefGoogle Scholar
  18. [18]
    Lesaicherre, M. L.; Uttamchandani, M.; Chen, G. Y. J.; Yao, S. Q. Developing site-specific immobilization strategies of peptides in a microarray. Bioorg. Med. Chem. Lett. 2002, 12, 2079–2083.CrossRefGoogle Scholar
  19. [19]
    Schweitzer, B.; Roberts, S.; Grimwade, B.; Shao, W. P.; Wang, M. J.; Fu, Q.; Shu, Q. P.; Laroche, I.; Zhou, Z. M.; Tchernev, V. T. et al. Multiplexed protein profiling on microarrays by rolling-circle amplification. Nat. Biotechnol. 2002, 20, 359–365.CrossRefGoogle Scholar
  20. [20]
    Tabakman, S. M.; Chen, Z.; Casalongue, H. S.; Wang, H. L.; Dai, H. J. A new approach to solution-phase gold seeding for SERS substrates. Small 2011, 7, 499–505.CrossRefGoogle Scholar
  21. [21]
    Hong, G. S.; Tabakman, S. M.; Welsher, K.; Wang, H. L.; Wang, X. R.; Dai, H. J. Metal-enhanced fluorescence of carbon nanotubes. J. Am. Chem. Soc. 2010, 132, 15920–15923.CrossRefGoogle Scholar
  22. [22]
    Hong, G. S.; Tabakman, S. M.; Welsher, K.; Chen, Z.; Robinson, J. T.; Wang, H. L.; Zhang, B.; Dai, H. J. Nearinfrared-fluorescence-enhanced molecular imaging of live cells on gold substrates. Angew. Chem. Int. Edit. 2011, 50, 4644–4648.CrossRefGoogle Scholar
  23. [23]
    Tabakman, S. M.; Lau, L.; Robinson, J. T.; Price, J.; Sherlock, S. P.; Wang, H. L.; Zhang, B.; Chen, Z.; Tangsombatvisit, S.; Jarrell, J. A. et al. Plasmonic substrates for multiplexed protein microarrays with femtomolar sensitivity and broad dynamic range. Nat. Commun. 2011, 2, 466.CrossRefGoogle Scholar
  24. [24]
    Hong, G. S.; Wu, J. Z.; Robinson, J. T.; Wang, H. L.; Zhang, B.; Dai, H. J. Three-dimensional imaging of single nanotube molecule endocytosis on plasmonic substrates. Nat. Commun. 2012, 3, 700.CrossRefGoogle Scholar
  25. [25]
    Canney, P. A.; Moore, M.; Wilkinson, P. M.; James, R. D. Ovarian cancer antigen CA125: A prospective clinical assessment of its role as a tumour marker. Br. J. Cancer 1984, 50, 765–769.CrossRefGoogle Scholar
  26. [26]
    Moertel, C. G.; Fleming, T. R.; Macdonald, J. S.; Haller, D. G.; Laurie, J. A.; Tangen, C. An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. JAMA. 1993, 270, 943–947.CrossRefGoogle Scholar
  27. [27]
    Gorelik, E.; Landsittel, D. P.; Marrangoni, A. M.; Modugno, F.; Velikokhatnaya, L.; Winans, M. T.; Bigbee, W. L.; Herberman, R. B.; Lokshin, A. E. Multiplexed immunobeadbased cytokine profiling for early detection of ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 981–987.CrossRefGoogle Scholar
  28. [28]
    Foti, E.; Ferrandina, G.; Martucci, R.; Romanini, M. E.; Benedetti Panici, P.; Testa, U.; Mancuso, S.; Scambia, G. IL-6, M-CSF and IAP cytokines in ovarian cancer: Simultaneous assessment of serum levels. Oncology 1999, 57, 211–215.CrossRefGoogle Scholar
  29. [29]
    Gadducci, A.; Ferdeghini, M.; Castellani, C.; Annicchiarico, C.; Gagetti, O.; Prontera, C.; Bianchi, R.; Facchini, V. Serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55- and 75-kDa sTNFr), and soluble CD14 (sCD14) in epithelial ovarian cancer. Gynecol. Oncol. 1995, 58, 184–188.CrossRefGoogle Scholar
  30. [30]
    Gadducci, A.; Ferdeghini, M.; Fanucchi, A.; Annicchiarico, C.; Ciampi, B.; Prontera, C.; Genazzani, A. R. Serum preoperative vascular endothelial growth factor (VEGF) in epithelial ovarian cancer: Relationship with prognostic variables and clinical outcome. Anticancer Res. 1999, 19, 1401–1405.Google Scholar
  31. [31]
    Penson, R. T.; Kronish, K.; Duan, Z.; Feller, A. J.; Stark, P.; Cook, S. E.; Duska, L. R.; Fuller, A. F.; Goodman, A. K.; Nikrui, N. et al. Cytokines IL-1β, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFα in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel. Int. J. Gynecol. Cancer 2000, 10, 33–41.CrossRefGoogle Scholar
  32. [32]
    Nilsson, M. B.; Langley, R. R.; Fidler, I. J. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res. 2005, 65, 10794–10800.CrossRefGoogle Scholar
  33. [33]
    Bast, R. C. Jr. Status of tumor markers in ovarian cancer screening. J. Clin. Oncol. 2003, 21, 200s–205s.CrossRefGoogle Scholar
  34. [34]
    Gorelik, E.; Landsittel, D. P.; Marrangoni, A. M.; Modugno, F.; Velikokhatnaya, L.; Winans, M. T.; Bigbee, W. L.; Herberman, R. B.; Lokshin, A. E. Multiplexed immunobeadbased cytokine profiling for early detection of ovarian cancer. Cancer Epidemiol. Biomarkers prev. 2005, 14, 981–987.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Bo Zhang
    • 1
  • Jordan Price
    • 2
  • Guosong Hong
    • 1
  • Scott M. Tabakman
    • 1
  • Hailiang Wang
    • 1
  • Justin A. Jarrell
    • 2
  • Ju Feng
    • 1
  • Paul J. Utz
    • 2
    • 3
  • Hongjie Dai
    • 1
  1. 1.Department of ChemistryStanford UniversityStanfordUSA
  2. 2.Department of Medicine, Division of Immunology and RheumatologyStanford University School of MedicineStanfordUSA
  3. 3.Institute for Immunity, Transplantation and InfectionStanford University School of MedicineStanfordUSA

Personalised recommendations