Skip to main content
Log in

Enzymes as versatile labels and signal amplifiers for monitoring immunochemical reactions

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Summary

Enzymes have proven to be sensitive and versatile labels for immunochemical assays. The sensitivity of an enzyme label stems from its extraordinary catalytic power which in turn provides a great amplification of signals. Its versatility, however, stems from the fact that enzyme activity can be modulated by a number of substances.

Enzyme labeled immunoassays can be divided into two categories: (a) heterogeneous and (b) homogeneous (non-separation). In the heterogeneous systems, the quantitation of the antibody bound and unbound fractions requires a physical separation of these two fractions, whereas the homogeneous or non-separation systems do not require such a separation. In the homogeneous systems, the unbound and antibody bound fractions can be distinguished functionally.

A total of 11 unique principles used in the development of enzyme labeled immunoassays are described. The advantages, disadvantages and limitations of them are considered, as well as the future paths for research and developments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yalow, R. S. & Berson, S. A., 1959. Nature 184: 1648–1649.

    Google Scholar 

  2. Yallow, R. S. & Berson, S. A., 1960. J. Clin. Invest. 30: 1157–1175.

    Google Scholar 

  3. Yalow, R. S., 1978. Science 200: 1236–1245.

    Google Scholar 

  4. Yalow, R. S., 1980. Ann. Rev. Biophys. Bioeng. 9: 327–345.

    Google Scholar 

  5. Parker, C. W., 1976. Radioimmunoassay of Biological Active Compounds, Prentice-Hall, Inc., Englewood Cliffs, New Jersey.

    Google Scholar 

  6. Abraham, G. E. (ed.), 1977. Handbook of Radioimmunoassay, Marcel Dekker, Inc., New York, and Basel.

    Google Scholar 

  7. Haimovich, J. & Sela, M., 1969. Science 164: 1279–1280.

    Google Scholar 

  8. Leute, R. K., Ullman, E. F., Goldstein, A. & Herzenberg, L. A., 1972. Nature 236: 93–94.

    Google Scholar 

  9. Soini, E. & Hemmila, I., 1979. Clin. Chem. 25: 353–361.

    Google Scholar 

  10. Simpson, J. S. A., Campbell, A. K., Ryall, M. E. T. & Woodhead, J. S., 1979. Nature 279: 646–647.

    Google Scholar 

  11. Rembaum, A. & Dreyer, W. J., 1980. Science 208: 364–368.

    Google Scholar 

  12. Adler, F. & Liu, C. T., 1971. J. Immunol. 106: 1684–1685.

    Google Scholar 

  13. Singer, S. J. & Schick, A. F., 1961. J. Biophys. Biochem. Cytol. 9: 519–537.

    Google Scholar 

  14. Cais, M., Dani, S., Eden, Y., Gandolfi, O., Horn, M., Isaacs, E. E., Josephy, Y., Saar, Y., Slovin, E. & Snarsky, L., 1977. Nature 270: 534–535.

    Google Scholar 

  15. Morris, D. L., Carrico, R. J., Ellis, P. B., Hornby, W., Schroeder, H. R., Ngo, T. T. & Boguslaski, R. C., 1980. Colorimetric immunoassays with flavin adenine dinucleotide as the label. In: Innovative Approaches to Clinical Analytical Chemistry. Cassette Album, Lab Professional Series of American Chemical Society.

  16. Ngo, T. T. et al. 1981. Manuscript submitted for publication.

  17. Nakane, P., 1980. Future trends and application of immunoassays, inDiagnostic Immunology: Current and Future Trends. (Keitges, P. W. & Nakamura, R. M., eds.), College of American Pathologists, Skokie, Illinois, pp. 73–77.

    Google Scholar 

  18. Scharpe, S. L., Cooreman, W. M., Blomme, W. J. & Laekman, G. M., 1976. Clin. Chem. 22: 733–738.

    Google Scholar 

  19. Wisdom, G. B., 1976. Clin. Chem. 22: 1243–1255.

    Google Scholar 

  20. Schuurs, A. H. A. M. & Van Weemen, B. K., 1977. Clin. Chem. Acta 21: 1–40.

    Google Scholar 

  21. Felman, G., Druet, P., Bignon, J. & Avrameas, S. (eds.), 1976. In: Immunoenzymatic Techniques, American Elsevier, New York.

    Google Scholar 

  22. Pal, S. B. (ed.), 1978. Enzyme Labeled Immunoassay of Hormones and Drugs, de Grueyter, Berlin.

    Google Scholar 

  23. Engvall, E. & Pesce, A. J., 1978. Scand. J. Immunol. 8, Suppl. 7.

    Google Scholar 

  24. Borrebaech, C. & Mattiasson, B., 1979. J. Solid Phase Biochem. 4: 57–67.

    Google Scholar 

  25. Rubenstein, K. E., Schneider, R. S. & Ullman, E. F., 1972. Biochem. Biophys. Res. Comm. 47: 846–851.

    Google Scholar 

  26. Ngo, T. T. & Lenhoff, H. M., 1981. App. Biochem. Biotech. 6: 53–64.

    Google Scholar 

  27. Burd, J. F., Wong, R. C., Feeney, J. E., Carrico, R. J. & Bogulaski, R. C., 1977. Clin. Chem. 23: 1402–1408.

    Google Scholar 

  28. Wong, R. C., Burd, J. F., Carrico, R. J., Buckler, R. T., Thoma, J. & Boguslaski, R. C., 1979. Clin Chem. 25: 686–691.

    Google Scholar 

  29. Wong, R. C., George, R., Yeung, R. & Burd, J. F., 1980. Clin. Chem. Acta 100: 65–69.

    Google Scholar 

  30. Ngo, T. T., Carrico, R. J. & Boguslaski, R. C., 1979. Homogeneous Fluorescent Immunoassay for Protein Using Beta-Galactosyl-Umbeliiferone Label. Second International Conference on Diagnostic Immunology, New England College, Henniker, New Hampshire.

    Google Scholar 

  31. Ngo, T. T., Carrico, R. J., Boguslaski, R. C. & Burd, J. F., 1981. J. Immunol. Methods, 42: 93–103.

    Google Scholar 

  32. Ngo, T. T. & Lenhoff, H. M., 1980. FEBS Letters 116: 285–288.

    Google Scholar 

  33. Jodal, U., Ahlstedt, S., Carlsson, B., Hanson, L. A., Lindberg, U. & Sohl, A., 1974. Int. Arch. Allergy 47: 537–546.

    Google Scholar 

  34. Voller, A., Bidwell, D. E. & Bartlett, A., 1976. Bull. WHO 53: 55–65.

    Google Scholar 

  35. Holmgren, J. & Svennerholm, A. M., 1973. Infect. Immunol. 7: 759–763.

    Google Scholar 

  36. Halle, S., Dasch, G. A. & Weiss, E., 1977. L. Clin. Microbiol. 6: 101–110.

    Google Scholar 

  37. Saunders, G. C., 1977. Am. J. Vet. Res. 38: 21–25.

    Google Scholar 

  38. Gilman, S. C. & Docherty, J. J., 1977. J. Inf. Dis. 136S: S 286–294.

    Google Scholar 

  39. Gravell, M., Dorsett, P. H., Gutenson, O. & Ley, A. C., 1977. J. Inf. Dis., 136S: S 300–303.

    Google Scholar 

  40. Ngo, T. T. & Lenhoff, H. M., 1981. Biochem. Biophys. Res. Comm. 99: 496–503.

    Google Scholar 

  41. Tateishi, K., Yamamoto, H., Ogihara, T. & Hayashi, C., 1977. Steroids 30: 25–32.

    Google Scholar 

  42. Joyce, B. G., Read, G. F. & Fahmy, D. R., 1977. Steroids, 29: 761–770.

    Google Scholar 

  43. Ogihara, T., Miyai, K., Nishi, K., Ishibashi, U. & Kumahara, Y., 1977. J. Clin. Endocrinol. Metab. 44: 91–95.

    Google Scholar 

  44. Kominami, G., Fujisaka, I., Yamauchi, A. & Kono,M., 1980. Clin. Chim. Acta 103: 381–391.

    Google Scholar 

  45. Van Weemen, B. K. & Schuurs, A. H. W. M., 1971. FEBS Letters, 15: 232–235.

    Google Scholar 

  46. Kikutani, M., Ishiguro, M., Kitagawa, T., Imamura, S. & Miura, S., 1978.. Clin. Endocrinol. Metab., 47: 980–984.

    Google Scholar 

  47. Van Hell, H., Brands, J. A. M. & Schuurs, A. H. W. M., 1979. Clin. Chim. Acta, 91:L 309–316.

    Google Scholar 

  48. Engvall, E. & Pearlman, P., 1971. Immunochem. 8:871–874.

    Google Scholar 

  49. Wang, H. P. & Chu, C. Y. T., 1979. Clin. Chem. 25: 546–549.

    Google Scholar 

  50. Bosh, A. M. G., van Hell, H., Brands J. & Schuurs, A. H. W. M., 1978. InEnzyme Labelled Immunoassays of Hormones and Drugs (S.P. Pal, ed.): 175–187, Walter de Gruyter, Berlin.

    Google Scholar 

  51. Kato, K., Hamaguchi, Y., Fukui, H. & Ishikawa, E., 1976. Eur. J. Biochem. 62: 285–292.

    Google Scholar 

  52. Maiolini, R., Ferrua, B., Quaranta, J. F., Pinoteau, A., Fuller, L., Ziegler, G. & Masseyeff, R., 1978. J. Immunol. Methods 20: 25–34.

    Google Scholar 

  53. Kato, K., Umeda, Y., Suzuki, F., Hayashi, D. & Kosaka, A., 1979. Clin. Chem. 25: 1306–1308.

    Google Scholar 

  54. Ishikawa, E., Yoshitake, S., Endo, Y. & Ohtaki, S., 1980. FEBS Letters 111: 353–355.

    Google Scholar 

  55. Shinkai, H., Sohma, M., Takahashi, Y., Kojima, R., Hashimoto, M. & Ogawa, N., 1980. Mol. Immunol. 17: 377–381.

    Google Scholar 

  56. Walters, G., Kuijpers, L., Kacaki, J. & Schuurs, A. H. W. M., 1976. J. Clin. Path. 29: 873–879.

    Google Scholar 

  57. Gemmi, E., O'Sullivan, M. J., Chieregatti, G., Simmons, M., Simmods, A., Bridges, J. W. & Marks, V., 1978. In: Enzyme Labelled Immunoassays of Hormones and Drugs (S.P. Pal, ed.), Walter de Gruyter, Berlin, pp. 29–41.

    Google Scholar 

  58. Halliday, M. I. & G. B. Wisdom, 1978. FEBS Letters 96: 298–300.

    Google Scholar 

  59. Rowley, G. L., Rubenstein, K. E., Huisjen, J. & Ullman, E. F., 1975. J. Biol. Chem. 250: 3759–3766.

    Google Scholar 

  60. Ullman, E. F., Yoshida, R. A., Blakemore, J. E., Maggio, E. & Leute, R., 1979. Biochim. Biophys. Acta 567: 66–74.

    Google Scholar 

  61. Curtis, E. G. & Patel, J. A., 1978. CRC Critic. Reve. Clin. Lab. Sci. 9: 303–320.

    Google Scholar 

  62. Ullman, E. F., 1979. J. Histochem. Cytol. 27: 717.

    Google Scholar 

  63. Litman, D. J., Hanlon, T. M. & Ullman, E. F., 1980. Anal. Biochem. 106: 223–229.

    Google Scholar 

  64. Goldman, R. & Katchalski, E., 1971. J. Theor. Biol. 32: 243–258.

    Google Scholar 

  65. Mosbach, K. & Mattiasson, B., 1978. In: Current Topics in Cellular Regulation (Horecker, B. L. & Stadtman, E. R., eds.), Academic Press, New York, pp. 197–241.

    Google Scholar 

  66. Finley, P. R., Williams, R. J. & Lichti, D. A., 1980. Clin. Chem. 26: 1723–1726.

    Google Scholar 

  67. Landon, J., 1977. Nature 269: 483–484.

    Google Scholar 

  68. Gibbons, I., Skold, C., Rowley, G. L. & Ullman, E. F., 1980. Anal. Biochem. 102: 167–170.

    Google Scholar 

  69. Curme, H. G., Columbus, R. L., Dappen, G. M., et al., 1978. Clin. Chem. 24: 1335–1342.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ngo, T.T., Lenhoff, H.M. Enzymes as versatile labels and signal amplifiers for monitoring immunochemical reactions. Mol Cell Biochem 44, 3–12 (1982). https://doi.org/10.1007/BF00573840

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00573840

Keywords

Navigation