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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 conventional0020nitrocellulose 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.
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 conventional0020nitrocellulose 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.
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.
Lequin, R. M. Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin. Chem. 2005, 51, 2415-2418.
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.
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.
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.
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.
Utz, P. J. Multiplexed assays for identification of biomarkers and surrogate markers in systemic lupus erythematosus. Lupus 2004, 13, 304-311.
Robinson, W. H.; Utz, P. J.; Steinman, L. Genomic and proteomic analysis of multiple sclerosis: Opinion. Curr. Opin. Immunol. 2003, 15, 660-667.
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.
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.
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.
MacBeath, G. Protein microarrays and proteomics. Nat. Genet. 2002, 32, 526-532.
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.
MacBeath, G.; Schreiber, S. L. Printing proteins as microarrays for high-throughput function determination. Science 2000, 289, 1760-1763.
Graf, R.; Friedl, P. Detection of immobilized proteins on nitrocellulose membranes using a biotinylation-dependent system. Anal. Biochem. 1999, 273, 291-297.
Li, Y. W.; Reichert, W. M. Adapting cDNA microarray format to cytokine detection protein arrays. Langmuir 2003, 19, 1557-1566.
Zhu, H.; Snyder, M. Protein arrays and microarrays. Curr. Opin. Chem. Biol. 2001, 5, 40-45.
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.
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.
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.
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.
Hong, G. S.; Tabakman, S. M.; Welsher, K.; Chen, Z.; Robinson, J. T.; Wang, H. L.; Zhang, B.; Dai, H. J. Near-infrared-fluorescence-enhanced molecular imaging of live cells on gold substrates. Angew. Chem. Int. Edit. 2011, 50, 4644-4648.
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.
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.
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.
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.
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 immunobead-based cytokine profiling for early detection of ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 981-987.
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.
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.
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.
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.
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.
Bast, R. C. Jr. Status of tumor markers in ovarian cancer screening. J. Clin. Oncol. 2003, 21, 200s-205s.
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 immunobead-based cytokine profiling for early detection of ovarian cancer. Cancer Epidemiol. Biomarkers prev. 2005, 14, 981-987.
This work was supported by National Institutes of Health-National Cancer Institute (NIH-NCI) No. 5R01CA135109-02.