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Protein microarrays and their applications

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Abstract

In recent years, the importance of proteomic works, such as protein expression, detection and identification, has grown in the fields of proteomic and diagnostic research. This is because complete genome sequences of humans, and other organisms, progress as cellular processing and controlling are performed by proteins as well as DNA or RNA. However, conventional protein analyses are time-consuming; therefore, high throughput protein analysis methods, which allow fast, direct and quantitative detection, are needed. These are so-called protein microarrays or protein chips, which have been developed to fulfill the need for high-throughput protein analyses. Although protein arrays are still in their infancy, technical development in immobilizing proteins in their native conformation on arrays, and the development of more sensitive detection methods, will facilitate the rapid deployment of protein arrays as high-throughput protein assay tools in proteomics and diagnostics. This review summarizes the basic technologies that are needed in the fabrication of protein arrays and their recent applications.

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References

  1. Schena, M., D. Shalon, R. W. Davis, and P. O. Brown (1995) Quantitative monitoring of gene-expression patterns with a complementary-DNA microarray.Science 270: 467–470.

    Article  CAS  Google Scholar 

  2. Chee, M., R. Yang, E. Hubbell, A. Berno, X. C. Huang, D. Stern, J. Winkler, D. J. Lockhart, M. S. Morris, and S. P. A. Fodor (1996) Accessing genetic information with highdensity DNA arrays.Science 274: 610–614.

    Article  CAS  Google Scholar 

  3. Stillman, B. A. and J. L. Tonkinson (2000) FASTTM slides: A novel surface for microarrays.Biotechniques 29: 630–633.

    CAS  Google Scholar 

  4. Kukar, T., S. Eckenrode, Y. R. Gu, W. Lian, M. Megginson, J. X. She, and D. H. Wu (2002) Protein microarrays to detect protein-protein interactions using red and green fluorescent proteinsAnal. Biochem. 306: 50–54.

    Article  CAS  Google Scholar 

  5. MacBeath, G. and S. L. Schreiber (2000) Printing Proteins as microarrays for high-throughput function determination.Science 289: 1760–1763.

    CAS  Google Scholar 

  6. Blaws, A. S. and W. M. Reichert (1998) Protein patterning.Biomaterials 19: 595–609.

    Article  Google Scholar 

  7. Nakanishi, K., H. Muguruma, and I. Karube (1996) A novel method of immobilizing antibodies on a quartz crystal microbalance using plasma-ploymerized films for immunosensors.Anal. Chem. 68: 1695–1700.

    Article  CAS  Google Scholar 

  8. Shriver-Lake, L. C., B. Donner, R. Edelstein, K. Breslin, S. K. Bhatia, and F. S. Ligler (1997) Antibody immobilization using heterobifunctional crosslinkers.Biosens. Bioelectron. 12: 1101–1106.

    Article  CAS  Google Scholar 

  9. Dontha, N., W. B. Nowall, and W. G. Kuhr (1997) Generationj of biotin/avidin/enzyme nanostructures with maskles photolithography.Anal. Chem. 69: 2619–2625.

    Article  CAS  Google Scholar 

  10. Pritchard, D. J., H. Morgan, and J. M. Cooper (1995) Patterning and regeneration of surfaces with antibodies.Anal. Chem. 67: 3605–3607.

    Article  CAS  Google Scholar 

  11. Gaber, B. P., B. D. Martin, and D. C. Turner (1999) Create a protein microarray using a hydrogel “stamper”.Chemtech. 29: 20–24.

    CAS  Google Scholar 

  12. Zhu, H., M. Bilgin, R. Bangham, D. Hall, A. Casamayor, P. Bertone, N. Lan, R. Jansen, S. Bidlingmaier, T. Houfek, T. Mitchell, P. Miller, R. A. Dean, M. Gerstein, and M. Snyder (2001) Global analysis of protein activities using proteome chips.Science 293: 2101–2105.

    Article  CAS  Google Scholar 

  13. Neubert, H., E. S. Jacoby, S. S. Bansal, R. K. Lies, D. A. Cowan, and A. T. Kicman (2002) Enhanced affinity capture MALDI-TOF MS: Orientation of an immunoglobulin G using recombinant protein G.Anal. Chem. 74: 3677–3683.

    Article  CAS  Google Scholar 

  14. Peluso, P., D. S. Wilson, D. Do, H. Tran, M. Venkatasubbajah, D. Quincy, B. Heidecker, K. Poindexter, N. Tolani, M. Phelan, K. Witte, L. S. Jung, P. Wagner, and S. Nock (2003) Optimizing antibody immobilization strategies for the construction of protein arrays.Anal. Biochem. 312: 113–124.

    Article  CAS  Google Scholar 

  15. Konig, B. and M. Gratzel (1994) A novel immunosensor for herpes virus.Anal. Chem. 66: 341–344.

    Article  CAS  Google Scholar 

  16. Turkova, J. (1999) Oriented immobilization of biologically active proteins as a tool for revealing protein interactions and function.J. Chromatogr. B 722: 11–31.

    Article  CAS  Google Scholar 

  17. Anderson, G. P., M. A. Jacoby, F. S. Ligler, and K. D. King (1997) Effectiveness of protein A for antibody immobilization for a fiber optic biosensor.Biosens. Bioelectron. 12: 329–336.

    Article  CAS  Google Scholar 

  18. Babacan, S. P. Pivarnik, S. Letcher, and A. G. Rand (2000) Evaluation of antibody immobilization methods for piezoelectric biosensor applicationBiosens. Bioelectron. 15: 615–621.

    Article  CAS  Google Scholar 

  19. Lu, B., M. R. Smyth, and R. O’Kennedy (1996) Oriented immobilization of antibodies and its applications in immunoassays and immunosensors.Analyst 121: 29R-32R.

    Article  CAS  Google Scholar 

  20. Turkova, J., L. Petkov, J. Sajdok, J. KaM, and J. Bene (1990) Carbohydrates as a tool for oriented immobilization of antigens and antibodies.J. Chromatogr. A 500: 585–593.

    Article  CAS  Google Scholar 

  21. Turkova, J., S. Vohnik, M. Helusova, J. Bene, and M. Ticha (1992) Galactosylation as a tool for the stabilization and immobilization of proteins.J. Chromatogr. A 597: 19–27.

    Article  CAS  Google Scholar 

  22. Heller, M. J. (2002) DNA microtechnology: Devices, systems, and applications.Annu. Rev. Biomed. Eng. 4: 129–153, 2002.

    Article  CAS  Google Scholar 

  23. Gracey, A. Y. and A. R. Cossins (2003) Application of microarray technology in environmental and comparative physiology.Annu. Rev. Physiol. 65: 231–259.

    Article  CAS  Google Scholar 

  24. Dhiman, N., R. Bonilla, D. O’Kane, and G. A. Poland (2001) Gene expression microarray: a 21st century tool for directed vaccine design.Vaccine 20: 22–30.

    Article  CAS  Google Scholar 

  25. Mooney, J. F., A. J. Hunt, J. R. McIntosh, C. A. Liberko, D. M. Walba, and C. T. Rogers (1996) Patterning of functional antibodies and other proteins by photolithography of silane monolayers.Proc. Natl. Acad. Sci. USA 93: 12287–12291.

    Article  CAS  Google Scholar 

  26. Mooney, J. F., C. T. Rogers, A. J. Hunter, and J. R. McIntosh (1996) A general technique for patterning of functional proteins with photolithography of silane monolayers.Biophys. J. 70: TU216-TU216.

    Google Scholar 

  27. Luo, Y. Q., J. G. Cai, I. Ginis, Y. Y. Sun, S. L. Lee, S. X. Yu, A. Hoke, and M. Rao (2003) Designing, testing, and validating a focused stem cell microarray for characterization of neutral stem cells and progenitor cells.Stem Cells 21: 575–587.

    Article  CAS  Google Scholar 

  28. Bernard, A., E. Delamarche, H. Schmid, B. Michel, H. R. Bosshard, and H. Biebuyck (1998) Printing patterns of proteins.Langmuir 14: 2225–2229.

    Article  CAS  Google Scholar 

  29. Delamarche, E., M. Geissler M., A. Bernard, H. Wolf, B. Michel, J. Hilborn, and C. Donzel (2001) Hydrophilic poly (dimethylsiloxane) stamps for microcontact printing.Adv. mater. 13: 1164.

    Article  Google Scholar 

  30. Urbanowska, T., S. Mangialaio, C. Hartmann, and E. Legay (2003) Development of protein microarray technology to monitor biomarkers of rheumatoid arthritis diseaseCell Biol. Toxicol. 19: 189–202.

    Article  CAS  Google Scholar 

  31. Newman, J. D., A. F. P. Turner, and G. Marrazza (1992) Ink-jet printing for the fabrication of amerometric glucose biosensors.Anal. Chim. Acta 262: 13–17.

    Article  CAS  Google Scholar 

  32. Roda, A., M. Gardigli, C Russo, P. Pasini, and M. Baraldini (2000) Protein microdeposition using a conventional ink-jet printer.Biotechniques 28: 492–496.

    CAS  Google Scholar 

  33. Pardo, L., W. C. Wilson, and T. J. Boland (2003) Characterization of patterned self-assembled monolayers and protein arrays generated by the ink-jet method.Langmuir 19: 1462–1466.

    Article  CAS  Google Scholar 

  34. Watanabe, K., T. Miyazaki, and R. Matsuda (2003) Growth factor array fabrication using a color ink jet printer.Zool. Sci. 20: 429–434.

    Article  CAS  Google Scholar 

  35. Turcu, F., K. Tratsk-Nitz, S. Thanos, W. Schuhmann, and P. Hieduschka (2003) Ink-jet printing for micropattern generation of laminin for neuronal adhesion.J. Neurosci. Meth. 131: 141–148.

    Article  CAS  Google Scholar 

  36. Lee, B. H., J. W. Kim, K. Ishimoto, Y. Yamagata, A. Tanioka, and T. Nagamune (2003) Fabrication of protein microarrays for immunoassay using the electrospray deposition (ESD) method.J. Chem. Eng. Jap. 36: 1370–1375.

    Article  CAS  Google Scholar 

  37. Wiese, R. (2003) Analysis of several fluorescent detector molecules for protein microarray use.Luminescence 18: 25–30.

    Article  CAS  Google Scholar 

  38. Lundgren, J. S., A. N. Watkins, D. Racz, and F. S. Ligler (2000) A liquid crystal pixel array for signal discrimination in array biosensors.Biosens. Bioelectron. 15: 417–421.

    Article  CAS  Google Scholar 

  39. Pawlak, M., E. Grell, E. Schick, D. Anselmetti, and M. Ehrat (1998) Functional immobilization of biomemrane fragments on planar waveguides for the investigation of side-directed ligand binding by surface-confined fluorescence.Faraday Discuss. 111: 273–288.

    Article  CAS  Google Scholar 

  40. Rowe, C. A., L. M. Tender, M. J. Feldstein, J. P. Golden, S. B. Scruggs, B. D. MacCraith, J. J. Cras, and F. S. Ligler (1999) Array biosensor for simultaneous identification of bacterial, viral, and protein analyte.Anal. Chem. 71: 3846–3852.

    Article  CAS  Google Scholar 

  41. Rowe, C. A., S. B. Scruggs, M. J. Feldstein, J. P. Golden, and F. S. Ligler (1999) An array immunosensor for simultaneous detection of clinical analyte.Anal. Chem. 71: 433–439.

    Article  CAS  Google Scholar 

  42. Rowe, C. A., J. W. Hazzard, K. E. Hoffman, J. J. Cras, J. P. Golden, and F. S. Ligler (2000) Simultaneous detection of six biohazardous agents using a planar waveguide array biosensor.Biosens. Bioelectron. 15: 579–589.

    Article  Google Scholar 

  43. Duveneck, G. L., M. Pawlak, and D. Neuschaefer (1997) Novel bioaffinity sensors for trace analysis based on luminescence excitation by planar waveguides.Sens. Actuators B 38: 88–95.

    Article  Google Scholar 

  44. Weinberger, S. R., T. S. Morris, and M. Pawlak (2003) Recent trends in protein biochip technology.Pharmacogenomics 1: 395–416.

    Article  Google Scholar 

  45. Lizardi, P. M., X. H. Huang, Z. R. Zhu, P. Bray-Ward, D. C. Thomas, and D. C. Ward (1998) Mutation detection and single-molecule counting using isothermal rollingcircle amplification.Nat. Genet. 19: 225–232.

    Article  CAS  Google Scholar 

  46. Schweitzer, B., S. Wiltshire, J. Lambert, S. O’Malley, K. Kukanskis, Z. R. Zhu, S. F. Kingsmore, P. M. Lizardi, and D. C. Ward (2000) Immunoassays with rolling circle DNA amplification: A versatile platform for ultrasensitive antigen detection.Proc. Natl. Acad. Sci. USA 97: 10113–10119.

    Article  CAS  Google Scholar 

  47. Schweitzer B., S. Roberts, B. Grimwade, W. P. Shao, M. J. Wang, Q. Fu, Q. P. Shu, I. Laroche, Z. M. Zhou, V. T. Tcherney, J. Chrstiansen, M. Velleca, and S. F. Kingsmore (2002) Multiplexed protein profiling on microarrays by rolling-circle amplification.Nat. Biotechnol. 20: 359–365.

    Article  CAS  Google Scholar 

  48. Huang, R. P., R. C. Huang, Y. Fan, and Y. Lin (2001) Simultaneous detection of multiple cytokines from conditioned media a patient’s sera by an antibody-based protein array system.Anal. Biochem. 294: 55–62.

    Article  CAS  Google Scholar 

  49. Tu, C. Y., T. Kitamori, and T. Sawada (1993) Ultrasensitive heterogeneous immunoassay using photothermal deflection spectroscopy.Anal. Chem. 65: 3631–3635.

    Article  CAS  Google Scholar 

  50. Sato, K., M. Tokeshi, T. Odake, H. Kimura, T. Oosi, M. Nakao, and T. Kitamori (2000) Integration of an immunoabsorbent assay system: analysis of secretory human immunoglobulin A on polystyrene beads in a microchip.Anal. Chem. 72: 1144–1147.

    Article  CAS  Google Scholar 

  51. Sato, K., M. Tokeshi, H. Kimura, and T. Kitamori (2001) Determination of carcinoembryonic antigen in human sera by intergrated bead-bed immunoassay in a microchip for cancer diagnosis.Anal. Chem. 73: 1213–1218.

    Article  CAS  Google Scholar 

  52. Kimura, H., K. Sekiguchi, T. Kitamori, T. Sawada, and M. Mukaida (2001) Assay of spherical cell surface molecules by thermal lens microscopy and its application to blood cell substances.Anal. Chem. 73: 4333–4337.

    Article  CAS  Google Scholar 

  53. Silzel, J. W., B. Cercek, C. Dodson, T. Tsay, and R. J. Obremski (1998) Mass-sensing, multianalyte microarray immunoassay with imaging detection.Clin. Chem. 44: 2036–2043.

    CAS  Google Scholar 

  54. Joos, T. O., M. Schrenk, P. Hopfl, K. Kroger, U. Chowdhury, D. Stoll, D. Schorner, M. Durr, K. Herick, S. Rupp, K. Sohn, and H. Hammerle (2000) A microarray enzymelinked immunosorbent assay for autoimmune diagnostics.Eletrophoresis 21 2641–2650.

    Article  CAS  Google Scholar 

  55. Harwanegg, C., S. Laffer, R. Hiller, M. W. Mueller, D. Kraft, S. Spitzauer, and R. Valenta (2003) Microarrayed recombinant allergens for diagnosis of allergy.Clin. Exp. Allergy 33: 7–13.

    Article  CAS  Google Scholar 

  56. Barbara, I., B. Eberlein-Konig, H. Behrendt, R. Niessner, J. Ring, and M. G. Weller (2003) Microarrays for the screening of allergen-specific IgE in human serum.Anal. Chem. 75: 556–562.

    Article  Google Scholar 

  57. Huang, R. P. (2001) Simultaneous detection of multiple proteins with an array-based enzyme-linked immunosorbent assay (ELISA) and enhanced chemiluminescence (ECL).Clin. Chem. Lab. Med. 39: 209–214.

    Article  CAS  Google Scholar 

  58. Wang, C. C., R. P. Huang, M. Sommer, H. Lioukov, R. C. Huang, Y. Lin, T. Miller, and J. Burke (2002) Array-based multiplexed screening and quantitation of human cytokines and chemokines.J. Proteome Res. 1: 337–343.

    Article  CAS  Google Scholar 

  59. Belov, L., O. de la Vega, C. G. dos Remedios, S. P. Mulligan, and R. I. Christopherson (2001) Immunophenotype of leukemias using a cluster of differentiation antibody microarray.Cancer Res. 61: 4483–4489.

    CAS  Google Scholar 

  60. Belov, L., P. Huang, N. Barber, S. P. Mulligan, and R. I. Christopherson (2003) Identification of repertoires of surface antigens on leukemias using an antibody microarray.Proteomics 3: 2147–2154.

    Article  CAS  Google Scholar 

  61. Miller, J. C., H. P. Zhou, J. Kwekel, R. Cavallo, J. Burke, E. B. Butler, B. S. The, and B. B. Haab (2003) Antibody microarray profiling of human prostate cancer sera: Antibody screening and identification of potential biomarkers.Proteomics 3: 56–63.

    Article  CAS  Google Scholar 

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  1. Digital Bio Technology, 440-301, Kyonggi, Korea

    Bum Hwan Lee

  2. Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 113-8656, Tokyo, Japan

    Teruyuki Nagamune

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Lee, B.H., Nagamune, T. Protein microarrays and their applications. Biotechnol Bioproc E 9, 69–75 (2004). https://doi.org/10.1007/BF02932987

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