Antibody Colocalization Microarray for Cross-Reactivity-Free Multiplexed Protein Analysis

  • Véronique Laforte
  • Pik-Shan Lo
  • Huiyan Li
  • David Juncker
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1619)

Abstract

Measuring many proteins at once is of great importance to the idea of personalized medicine, in order to get a snapshot of a person’s health status. We describe the antibody colocalization microarray (ACM), a variant of antibody microarrays which avoids reagent-induced cross-reactivity by printing individual detection antibodies atop their corresponding capture antibodies. We discuss experimental parameters that are critical for the success of ACM experiments, namely, the printing positional accuracy needed for the two printing rounds and the need for protecting dried spots during the second printing round. Using small sample volumes (less than 30 μL) and small quantities of reagents, up to 108 different targets can be measured in hundreds of samples with great specificity and sensitivity.

Key words

Microarray Antibody Sandwich immunoassay Multiplexed Fluorescence 

References

  1. 1.
    Pla-Roca M, Leulmi RF, Tourekhanova S, Bergeron S, Laforte V, Moreau E, Gosline SJ, Bertos N, Hallett M, Park M, Juncker D (2012) Antibody colocalization microarray: a scalable technology for multiplex protein analysis in complex samples. Mol Cell Proteomics 11(4):M111 011460. doi:10.1074/mcp.M111.011460 CrossRefPubMedGoogle Scholar
  2. 2.
    Juncker D, Bergeron S, Laforte V, Li H (2014) Cross-reactivity in antibody microarrays and multiplexed sandwich assays: shedding light on the dark side of multiplexing. Curr Opin Chem Biol 18:29–37. doi:10.1016/j.cbpa.2013.11.012 CrossRefPubMedGoogle Scholar
  3. 3.
    Laforte V, Olanrewaju A, Juncker D (2013) Low-cost, high liquid volume silicon quill pins for robust and reproducible printing of antibody microarrays. In: MicroTAS: miniaturized systems for chemistry and life sciences, Freiburg, Germany, 27–31 October 2013. Chemical and Biological Microsystems Society (CBMS), pp. 485–487Google Scholar
  4. 4.
    Bergeron S, Laforte V, Lo PS, Li H, Juncker D (2015) Evaluating mixtures of 14 hygroscopic additives to improve antibody microarray performance. Anal Bioanal Chem 407(28):8451–8462. doi:10.1007/s00216-015-8992-8 CrossRefPubMedGoogle Scholar
  5. 5.
    Frampton JP, White JB, Simon AB, Tsuei M, Paczesny S, Takayama S (2014) Aqueous two-phase system patterning of detection antibody solutions for cross-reaction-free multiplex ELISA. Sci Rep 4:4878. doi:10.1038/srep04878 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Assarsson E, Lundberg M, Holmquist G, Bjorkesten J, Thorsen SB, Ekman D, Eriksson A, Rennel Dickens E, Ohlsson S, Edfeldt G, Andersson AC, Lindstedt P, Stenvang J, Gullberg M, Fredriksson S (2014) Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One 9(4):e95192. doi:10.1371/journal.pone.0095192 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Fredriksson S, Dixon W, Ji H, Koong AC, Mindrinos M, Davis RW (2007) Multiplexed protein detection by proximity ligation for cancer biomarker validation. Nat Methods 4(4):327–329. doi:10.1038/nmeth1020 PubMedGoogle Scholar
  8. 8.
    Fredriksson S, Gullberg M, Jarvius J, Olsson C, Pietras K, Gústafsdóttir SM, Östman A, Landegren U (2002) Protein detection using proximity-dependent DNA ligation assays. Nat Biotechnol 20:473–477CrossRefPubMedGoogle Scholar
  9. 9.
    Aldo P, Marusov G, Svancara D, David J, Mor G (2016) Simple plex(TM): a novel multi-analyte, automated microfluidic immunoassay platform for the detection of human and mouse cytokines and chemokines. Am J Reprod Immunol 75(6):678–693. doi:10.1111/aji.12512 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Blank K, Lankenau A, Mai T, Schiffmann S, Gilbert I, Hirler S, Albrecht C, Benoit M, Gaub HE, Clausen-Schaumann H (2004) Double-chip protein arrays: force-based multiplex sandwich immunoassays with increased specificity. Anal Bioanal Chem 379(7–8):974–981. doi:10.1007/s00216-004-2607-0 PubMedGoogle Scholar
  11. 11.
    Christendat D, Yee A, Dharamsi A, Kluger Y, Savchenko A, Cort JR, Booth V, Mackereth CD, Saridakis V, Ekiel I, Kozlov G, Maxwell KL, Wu N, McIntosh LP, Gehring K, Kennedy MA, Davidson AR, Pai EF, Gerstein M, Edwards AM, Arrowsmith CH (2000) Structural proteomics of an archeon. Nat Struct Biol 7(10):903–909CrossRefPubMedGoogle Scholar
  12. 12.
    Kusnezow W, Jacob A, Walijew A, Diehl F, Hoheisel JD (2003) Antibody microarrays: an evaluation of production parameters. Proteomics 3:254–264CrossRefPubMedGoogle Scholar
  13. 13.
    Berlier JE, Rothe A, Buller G, Bradford J, Gray DR, Filanoski BJ, Telford WG, Yue S, Liu J, Cheung C-Y, Chang W, Hirsch JD, Beechem JM, Haugland RP, Haugland RP (2003) Quantitative comparison of long-wavelength alexa fluor dyes to Cy dyes: fluorescence of the dyes and their bioconjugates. J Histochem Cytochem 51(12):1699–1712CrossRefPubMedGoogle Scholar
  14. 14.
    Byerly S, Sundin K, Raja R, Stanchfield J, Bejjani BA, Shaffer LG (2009) Effects of ozone exposure during microarray posthybridization washes and scanning. J Mol Diagn 11(6):590–597. doi:10.2353/jmoldx.2009.090009 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cox WG, Beaudet MP, Agnew JY, Ruth JL (2004) Possible sources of dye-related signal correlation bias in two-color DNA microarray assays. Anal Biochem 331(2):243–254. doi:10.1016/j.ab.2004.05.010 CrossRefPubMedGoogle Scholar
  16. 16.
    Anderson GP, Nerurkar NL (2002) Improved fluoroimmunoassays using the dye alexa fluor 647 with the RAPTOR, a fiber optic biosensor. J Immunol Methods 271:17–24CrossRefPubMedGoogle Scholar
  17. 17.
    Becker W (2012) Fluorescence lifetime imaging–techniques and applications. J Microsc 247(2):119–136. doi:10.1111/j.1365-2818.2012.03618.x CrossRefPubMedGoogle Scholar
  18. 18.
    Li H, Bergeron S, Juncker D (2012) Microarray-to-microarray transfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassays. Anal Chem 84(11):4776–4783. doi:10.1021/ac3003177 CrossRefPubMedGoogle Scholar
  19. 19.
    Li H, Munzar JD, Ng A, Juncker D (2015) A versatile snap chip for high-density sub-nanoliter chip-to-chip reagent transfer. Sci Rep 5:11688. doi:10.1038/srep11688 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Sittampalam GS, Coussens NP, Nelson H, Arkin M, Auld D, Bejcek B, Glicksman M, Inglese J, Iversen PW, Li Z, McGee J, McManus O, Minor L, Napper A, Peltier JM, Riss T, Trask OJ, Weidner J (2016) Assay guidance manual. Eli Lilly & Company and the National Center for Advancing Translational Sciences, Bethesda, MDGoogle Scholar
  21. 21.
    Wilson JJ, Burgess R, Mao YQ, Luo S, Tang H, Jones VS, Weisheng B, Huang RY, Chen X, Huang RP (2015) Antibody arrays in biomarker discovery. Adv Clin Chem 69:255–324. doi:10.1016/bs.acc.2015.01.002 CrossRefPubMedGoogle Scholar
  22. 22.
    Li H, Bergeron S, Annis MG, Siegel PM, Juncker D (2015) Serial analysis of 38 proteins during the progression of human breast cancer tumor in mice using an antibody colocalization microarray. Mol Cell Proteomics 14(4):1024–1037. 10.1074/CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Wingren C, Borrebaeck CA (2009) Antibody-based microarrays. Methods Mol Biol 509:57–84. doi:10.1007/978-1-59745-372-1_5 CrossRefPubMedGoogle Scholar
  24. 24.
    Gonzalez RM, Seurynck-Servoss SL, Crowley SA, Brown M, Ommen GS, Hayes DF, Zangar RC (2008) Development and validation of sandwhich ELISA microarrays with minimal assay interference. J Proteome Res 7:2406–2414CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Véronique Laforte
    • 1
    • 2
    • 3
  • Pik-Shan Lo
    • 2
    • 3
  • Huiyan Li
    • 2
    • 3
  • David Juncker
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Neurology and Neurosurgery, Montreal Neurological InstituteMcGill UniversityMontrealCanada
  2. 2.Department of Biomedical EngineeringMcGill UniversityMontrealCanada
  3. 3.McGill University and Genome Quebec Innovation CenterMcGill UniversityMontrealCanada
  4. 4.Micro and Nanobioengineering Laboratory, Department of Biomedical EngineeringMcGill UniversityMontrealCanada

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