Analytical and Bioanalytical Chemistry

, Volume 407, Issue 28, pp 8451–8462

Evaluating mixtures of 14 hygroscopic additives to improve antibody microarray performance

  • Sébastien Bergeron
  • Veronique Laforte
  • Pik-Shan Lo
  • Huiyan Li
  • David Juncker
Research Paper

Abstract

Microarrays allow the miniaturization and multiplexing of biological assays while only requiring minute amounts of samples. As a consequence of the small volumes used for spotting and the assays, evaporation often deteriorates the quality, reproducibility of spots, and the overall assay performance. Glycerol is commonly added to antibody microarray printing buffers to decrease evaporation; however, it often decreases the binding of antibodies to the surface, thereby negatively affecting assay sensitivity. Here, combinations of 14 hygroscopic chemicals were used as additives to printing buffers for contact-printed antibody microarrays on four different surface chemistries. The ability of the additives to suppress evaporation was quantified by measuring the residual buffer volume in open quill pins over time. The seven best additives were then printed either individually or as a 1:1 mixture of two additives, and the homogeneity, intensity, and reproducibility of both the spotted protein and of a fluorescently labeled analyte in an assay were quantified. Among the 28 combinations on the four slides, many were found to outperform glycerol, and the best additive mixtures were further evaluated by changing the ratio of the two additives. We observed that the optimal additive mixture was dependent on the slide chemistry, and that it was possible to increase the binding of antibodies to the surface threefold compared to 50 % glycerol, while decreasing whole-slide coefficient of variation to 5.9 %. For the two best slides, improvements were made for both the limit of detection (1.6× and 5.9×, respectively) and the quantification range (1.2× and 2.1×, respectively). The additive mixtures identified here thus help improve assay reproducibility and performance, and might be beneficial to all types of microarrays that suffer from evaporation of the printing buffers.

Keywords

Antibody Protein Microarray Low evaporation Contact printing Hygroscopic Reproducibility 

Abbreviations

1,3-But

1,3-Butanediol

2,3-But

2,3-Butanediol

Ab

Antibody

ACM

Antibody colocalization microarray

AF

AlexaFluor

APTES

(3-Aminopropyl)triethoxysilane

cAb

Capture antibody

dAb

Detection antibody

DMSO

Dimethyl sulfoxide

DNA

Deoxyribonucleic acid

ELISA

Enzyme-linked immunosorbent assay

EtGly

Ethylene glycol

IgG

Immunoglobulin G

LOD

Limit of detection

OM

Orders of magnitude

PBS

Phosphate buffer saline

PBST

Phosphate buffer saline with 0.1 % Tween-20

PEG

Polyethylene glycol

PVA

Polyvinyl alcohol

Supplementary material

216_2015_8992_MOESM1_ESM.pdf (3.3 mb)
ESM 1(PDF 3366 kb)

References

  1. 1.
    Barbulovic-Nad I, Lucente M, Sun Y, Zhang M, Wheeler AR, Bussmann M (2006) Bio-microarray fabrication techniques—a review. Crit Rev Biotechnol 26(4):237–259CrossRefGoogle Scholar
  2. 2.
    Ellington AA, Kullo IJ, Bailey KR, Klee GG (2010) Antibody-based protein multiplex platforms: technical and operational challenges. Clin Chem 56(2):186–193. doi:10.1373/clinchem.2009.127514 CrossRefGoogle Scholar
  3. 3.
    Dufva M, Christensen CBV (2007) Optimization of oligonucleotide DNA microarrays. In: Rampal JB (ed) Microarrays, vol 381. Methods in molecular biology, vol 1, 2nd edn. Humana Press Inc, Totowa, NJ, USA, pp 93–103Google Scholar
  4. 4.
    Kricka LJ, Master SR (2009) Quality control and protein microarrays. Clin Chem 55(6):1053–1055. doi:10.1373/clinchem.2009.126557 CrossRefGoogle Scholar
  5. 5.
    Deegan RD, Bakajin O, Dupont TF, Huber G, Nagel SR, Witten TA (1997) Capillary flow as the cause of ring stains from dried liquid drops. Nature 389(6653):827–829. doi:10.1038/39827 CrossRefGoogle Scholar
  6. 6.
    Angulo J (2008) Polar modelling and segmentation of genomic microarray spots using mathematical morphology. Image Anal Sterol 27:107–124CrossRefGoogle Scholar
  7. 7.
    Safavieh R, Pla Roca M, Qasaimeh MA, Mirzaei M, Juncker D (2010) Straight SU-8 pins. J Micromech Microeng 20(5):055001. doi:10.1088/0960-1317/20/5/055001 CrossRefGoogle Scholar
  8. 8.
    Laforte V, Olanrewaju A, Juncker D (2013) Low-cost, high liquid volume silicon quill pins for robust and reproducible printing of antibody microarrays. In: Int Conf on Miniaturized Syst Chem Life Sci, Freiburg, Germany, October 27-31 2013. pp 485-487Google Scholar
  9. 9.
    McQuain MK, Seale K, Peek J, Levy S, Haselton FR (2003) Effects of relative humidity and buffer additives on the contact printing of microarrays by quill pins. Anal Biochem 320(2):281–291CrossRefGoogle Scholar
  10. 10.
    Gutmann O, Kuehlewein R, Reinbold S, Niekrawietz R, Steinert CP, de Heij B, Zengerle R, Daub M (2005) Fast and reliable protein microarray production by a new drop-in-drop technique. Lab Chip 5(6):675–681. doi:10.1039/b418765b CrossRefGoogle Scholar
  11. 11.
    Hartmann M, Sjodahl J, Stjernstrom M, Redeby J, Joos T, Roeraade J (2009) Non-contact protein microarray fabrication using a procedure based on liquid bridge formation. Anal Bioanal Chem 393(2):591–598. doi:10.1007/s00216-008-2509-7 CrossRefGoogle Scholar
  12. 12.
    Liberski A, Zhang R, Bradley M (2009) Inkjet fabrication of polymer microarrays and grids—solving the evaporation problem. Chem Commun (Camb) 3:334–336. doi:10.1039/b816920a CrossRefGoogle Scholar
  13. 13.
    Sun Y, Zhou X, Yu Y (2014) A novel picoliter droplet array for parallel real-time polymerase chain reaction based on double-inkjet printing. Lab Chip 14(18):3603–3610. doi:10.1039/c4lc00598h CrossRefGoogle Scholar
  14. 14.
    Olle EW, Messamore J, Deogracias MP, McClintock SD, Anderson TD, Johnson KJ (2005) Comparison of antibody array substrates and the use of glycerol to normalize spot morphology. Exp Mol Pathol 79(3):206–209. doi:10.1016/j.yexmp.2005.09.003 CrossRefGoogle Scholar
  15. 15.
    Gonzalez-Gonzalez M, Bartolome R, Jara-Acevedo R, Casado-Vela J, Dasilva N, Matarraz S, Garcia J, Alcazar JA, Sayagues JM, Orfao A, Fuentes M (2014) Evaluation of homo- and hetero-functionally activated glass surfaces for optimized antibody arrays. Anal Biochem 450:37–45. doi:10.1016/j.ab.2014.01.002 CrossRefGoogle Scholar
  16. 16.
    Zuo P, Zhang Y, Liu J, Ye BC (2010) Determination of beta-adrenergic agonists by hapten microarray. Talanta 82(1):61–66. doi:10.1016/j.talanta.2010.03.058 CrossRefGoogle Scholar
  17. 17.
    Rodriguez-Segui SA, Pons Ximenez JI, Sevilla L, Ruiz A, Colpo P, Rossi F, Martinez E, Samitier J (2011) Quantification of protein immobilization on substrates for cellular microarray applications. J Biomed Mater Res A 98(2):245–256. doi:10.1002/jbm.a.33089 CrossRefGoogle Scholar
  18. 18.
    Liu YS, Li CM, Yu L, Chen P (2007) Optimization of printing buffer for protein microarrays based on aldehyde-modified glass slides. Front Biosci 12:3768–3773. doi:10.2741/2350 CrossRefGoogle Scholar
  19. 19.
    Ruwona TB, McBride R, Chappel R, Head SR, Ordoukhanian P, Burton DR, Law M (2014) Optimization of peptide arrays for studying antibodies to hepatitis C virus continuous epitopes. J Immunol Methods 402(1-2):35–42. doi:10.1016/j.jim.2013.11.005 CrossRefGoogle Scholar
  20. 20.
    Monroe MR, Reddington AP, Collins AD, LaBoda C, Cretich M, Chiari M, Little FF, Ünlü MS (2011) Multiplexed method to calibrate and quantitate fluorescence signal for allergen-specific IgE. Anal Chem 83(24):9485–9491. doi:10.1021/ac202212k CrossRefGoogle Scholar
  21. 21.
    Hegde P, Qi R, Abernathy K, Gay C, Dharap S, Gaspard R, Hugues JE, Snesrud E, Lee N, Quackenbush J (2000) A concise guide to cDNA microarray analysis. BioTechniques 29(3):548–562Google Scholar
  22. 22.
    Diehl F, Grahlmann S, Beier M, Hoheisel JD (2001) Manufacturing DNA microarrays of high spot homogeneity and reduced background signal. Nucleic Acids Res 29(7):E38CrossRefGoogle Scholar
  23. 23.
    Csonka LN, Ikeda TP, Fletcher SA, Kustu S (1994) The accumulation of glutamate is necessary for optimal growth of Salmonella typhimurium in media of high osmolality but not induction of the proU operon. J Bacteriol 176(20):6324–6333Google Scholar
  24. 24.
    Preininger C, Sauer U, Dayteg J, Pichler R (2005) Optimizing processing parameters for signal enhancement of oligonucleotide and protein arrays on ARChip Epoxy. Bioelectrochemistry 67(2):155–162. doi:10.1016/j.bioelechem.2004.06.010 CrossRefGoogle Scholar
  25. 25.
    Lee C-S, Kim B-G (2002) Improvement of protein stability in protein microarrays. Biotechnol Lett 24:839–844CrossRefGoogle Scholar
  26. 26.
    Rickman DS, Herbert CJ, Aggerbeck LP (2003) Optimizing spotting solutions for increased reproducibility of cDNA microarrays. Nucleic Acids Res 31(18):e109CrossRefGoogle Scholar
  27. 27.
    Wu P, Grainger DW (2006) Comparison of hydroxylated print additives on antibody microarray performance. J Proteome Res 5(11):2956–2965. doi:10.1021/pr060217d CrossRefGoogle Scholar
  28. 28.
    Glycerine: an overview (1990) New YorkGoogle Scholar
  29. 29.
    Tamaru S-I, Yamaguchi S, Hamachi I (2005) Simple and practical semi-wet protein/peptide array utilizing a micelle-mixed agarose hydrogel. Chem Lett 34(3):294–295. doi:10.1246/cl.2005.294 CrossRefGoogle Scholar
  30. 30.
    Finch CA (1973) Polyvinyl alcohol properties and applications. Wiley, New York, NYGoogle Scholar
  31. 31.
    Xu B-J, Jin Q-H, Zhao J-L (2007) A novel method of producing protein microarray for immunoassay. Chinese J Anal Chem 35(1):153–158CrossRefGoogle Scholar
  32. 32.
    The Merck Index (2014)Google Scholar
  33. 33.
    Avseenko NV, Morozova TY, Ataullakhanov FI, Morozov VN (2001) Immobilization of proteins in immunochemical microarrays fabricated by electrospray deposition. Anal Chem 73:6047–6052CrossRefGoogle Scholar
  34. 34.
    Moerman R, Frank J, Marijnissen JCM, Schalkhammer TGM, van Dedem GWK (2001) Miniaturized electrospraying as a technique for the production of microarrays of reproducible micrometer-sized proteins spots. Anal Chem 73:2183–2189CrossRefGoogle Scholar
  35. 35.
    Moerman R, Van Den Doel LR, Picioreanu S, Frank J, Marijnissen JCM, Van Dedem G, Hjelt KT, Vellekoop MJ, Sarro PM, Young IT (1999) Micro-injection of beta-D-glucose standards and amplex Red reagent on micro-arrays. SPIE Conference on Micro- and Nanofabricated Structures and Devices for Biomedical Environmental Applications II, San Jose, CA, USA, pp 119–128Google Scholar
  36. 36.
    CRC handbook of physics and chemistry (2014–2015) 95th Edition ednGoogle Scholar
  37. 37.
    MacBeath G, Schreiber SL (2000) Printing proteins as microarrays for high-throughput function determination. Science 289:1760–1763Google Scholar
  38. 38.
    Ressine A, Marko-Varga G, Laurell T (2007) Porous silicon protein microarray technology and ultra-/superhydrophobic states for improved bioanalytical readout. Biotechnol Annu Rev 13:149–200CrossRefGoogle Scholar
  39. 39.
    Mueller M, Loh MQ, Tee DH, Yang Y, Jungbauer A (2013) Liquid formulations for long-term storage of monoclonal IgGs. Appl Biochem Biotechnol 169(4):1431–1448. doi:10.1007/s12010-012-0084-z CrossRefGoogle Scholar
  40. 40.
    Zhou G, Bergeron S, Juncker D (2015) High-performance Low-cost antibody microarrays using enzyme-mediated silver amplification. J Proteome Res. doi:10.1021/pr501259e Google Scholar
  41. 41.
    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 CrossRefGoogle Scholar
  42. 42.
    Wingren C, Ingvarsson J, Dexlin L, Szul D, Borrebaeck CA (2007) Design of recombinant antibody microarrays for complex proteome analysis: choice of sample labeling-tag and solid support. Proteomics 7(17):3055–3065. doi:10.1002/pmic.200700025 CrossRefGoogle Scholar
  43. 43.
    Guilleaume B, Buness A, Schmidt C, Klimek F, Moldenhauer G, Huber W, Arlt D, Korf U, Wiemann S, Poustka A (2005) Systematic comparison of surface coatings for protein microarrays. Proteomics 5(18):4705–4712. doi:10.1002/pmic.200401324 CrossRefGoogle Scholar
  44. 44.
    Zhao X, Pan F, Cowsill B, Lu JR, Garcia-Gancedo L, Flewitt AJ, Ashley GM, Luo J (2011) Interfacial immobilization of monoclonal antibody and detection of human prostate-specific antigen. Langmuir 27(12):7654–7662. doi:10.1021/la201245q CrossRefGoogle Scholar
  45. 45.
    Wolter A, Niessner R, Seidel M (2007) Preparation and characterization of functional poly(ethylene glycol) surfaces for the use of antibody microarrays. Anal Chem 79(12):4529–4537. doi:10.1021/ac070243a CrossRefGoogle Scholar
  46. 46.
    Delehanty JB, Ligler FS (2002) A microarray immunoassay for simultaneous detection of proteins and bacteria. Anal Chem 74(21):5681–5687CrossRefGoogle Scholar
  47. 47.
    Luo W, Pla-Roca M, Juncker D (2011) Taguchi design-based optimization of sandwich immunoassay microarrays for detecting breast cancer biomarkers. Anal Chem 83(14):5767–5774. doi:10.1021/ac103239f CrossRefGoogle Scholar
  48. 48.
    Kuster SK, Pabst M, Zenobi R, Dittrich PS (2015) Screening for protein phosphorylation using nanoscale reactions on microdroplet arrays. Angew Chem 54(5):1671–1675. doi:10.1002/anie.201409440 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Sébastien Bergeron
    • 1
    • 2
  • Veronique Laforte
    • 1
    • 2
    • 3
  • Pik-Shan Lo
    • 1
    • 2
  • Huiyan Li
    • 1
    • 2
  • David Juncker
    • 1
    • 2
    • 3
  1. 1.McGill University & Genome Quebec Innovation CentreMcGill UniversityMontrealCanada
  2. 2.Biomedical Engineering DepartmentMcGill UniversityMontrealCanada
  3. 3.Neurology and Neurosurgery DepartmentMcGill UniversityMontrealCanada

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