Skip to main content
Log in

Strategies for signal amplification in nucleic acid detection

  • Review
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

Many aspects of molecular genetics necessitate the detection of nucleic acid sequences. Current approaches involving target amplification (in situ PCR, Primed in situ Labeling, Self-Sustained Sequence Replication, Strand Displacement Amplification), probe amplification (Ligase Chain Reaction, Padlock Probes, Rolling Circle Amplification) and signal amplification (Tyramide Signal Amplification, Branched DNA Amplification) are summarized in the present review, together with their advantages and limitations.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Southern, E. M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98, 503–507.

    Article  PubMed  CAS  Google Scholar 

  2. Jeffreys, A. J., Wilson, V., and Thein, S. L. (1985) Individual-specific “fingerprints” of human DNA. Nature 316, 76–79.

    Article  PubMed  CAS  Google Scholar 

  3. Wang, D. G., Fan, J.-B., Siao, C.-J., et al. (1998) Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082.

    Article  PubMed  CAS  Google Scholar 

  4. Winn-Deen, E. S. (1996) Automation of molecular genetic methods-Part 2: DNA amplification techniques. J. Clin. Ligand Assay 19, 21–26.

    Google Scholar 

  5. Haase, A. T., Retzel, E. F., and Staskus, K. A. (1990) Amplification and detection of lentiviral DNA inside cells. Proc. Natl. Acad. Sci. USA 87, 4971–4975.

    Article  PubMed  CAS  Google Scholar 

  6. Nuovo, G., MacConnell, P., Forde, A., and Delvenne, P. (1991) Detection of human papillomavirus DNA in formalin-fixed tissues by in situ hybridization after amplification by polymerase chain reaction. Am. J. Pathol. 139, 847–854.

    PubMed  CAS  Google Scholar 

  7. Ray, R., Komminoth, P., Machado, M., and Wolfe, H. J. (1991) Combined polymerase chain reaction and in situ hybridization for the detection of single copy genes and viral genomic sequences in intact cells. Mod. Pathol. 4, 124A.

    Google Scholar 

  8. Spann, W., Pachman, K., Zabinienska, H., Pielmeier, A., and Emmerich, B. (1991) In situ amplification of single copy gene segments in individual cells by the polymerase chain reaction. Infection 19, 242–244.

    Article  PubMed  CAS  Google Scholar 

  9. Komminoth, P. and Werner, M. (1997) Target and signal amplification: approaches to increase the sensitivity of in situ hybridization. Histochem. Cell Biol. 108, 325–333.

    Article  PubMed  CAS  Google Scholar 

  10. Nuovo, G. (1992) PCR in situ hybridization. Raven Press, New York.

    Google Scholar 

  11. Chen, R. H. and Fuggle, S. V. (1993) In situ cDNA polymerase chain reaction. A novel technique for detecting mRNA expression. Am. J. Pathol. 143, 1527–1534.

    PubMed  CAS  Google Scholar 

  12. Komminoth, P., Adams, V., Long, A. A., et al. (1994) Evaluation of methods for hepatitis C virus (HCV) detection in liver biopsies: comparison of histology, immunochemistry, in situ hybridization, reverse transcriptase (RT) PCR and in situ RT PCR. Pathol. Res. Pract. 190, 1017–1025.

    PubMed  CAS  Google Scholar 

  13. Isaacson, S. H., Asher, D. M., Godec, M. S., Gibbs, C. J., and Gajdusek, D. C. (1996) Widespread, restricted low-level measles virus infection of brain in a case of subacute sclerosing panencephalitis. Acta Neuropathol. 91, 135–139.

    Article  PubMed  CAS  Google Scholar 

  14. Levin, M. C., Fox, R. J., Lehky, T., et al. (1996) PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease. J. Virol. 70, 924–933.

    PubMed  CAS  Google Scholar 

  15. Bagasra, O., Seshamma, T., and Pomerantz, R. (1993) Polymerase chain reaction in situ: intracellular amplification and detection of HIV-1 proviral DNA and other specific genes. J. Immunol. Methods 158, 131–145.

    Article  PubMed  CAS  Google Scholar 

  16. Cao, Y., Kopplow, K., and Liu, G. Y. (2000) In situ immuno-PCR to detect antigens. Lancet 356, 1002, 1003.

    Article  PubMed  CAS  Google Scholar 

  17. Embretson, J., Zupancic, M., Beneke, J., et al. (1993) Analysis of human immunodeficiency virus-infected tissue by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution. Proc. Natl. Acad. Sci. USA 90, 357–361.

    Article  PubMed  CAS  Google Scholar 

  18. Long, A. A., Komminoth, P., Lee, E., and Wolfe, H. J. (1993) Comparison of indirect and direct in situ polymerase chain reaction in cell preparations and tissue sections. Detection of viral DNA, gene rearrangements and chromosomal translocations. Histochemistry 99, 151–162.

    Article  PubMed  CAS  Google Scholar 

  19. Koch, J., Hinhkjaer, J., Mogensen, J., Kolvraa, S., and Bolund, L. (1991) An improved method for chromosome-specific labeling of alpha satellite DNA in situ by using denaturated double-stranded DNA probes as primers in a primed in situ labeling (PRINS) procedure. Genet. Anal. Tech. Appl. 8, 171–178.

    PubMed  CAS  Google Scholar 

  20. Koch, J., Mongensen, J., Pedersen, S., et al. (1992) Fast one-step procedure for the detection of nucleic acids in situ by primer-induced sequence-specific labeling with fluorescein-12-dUTP. Cytogenet. Cell Genet. 60, 1–3.

    Article  PubMed  CAS  Google Scholar 

  21. Pellestor, F., Girardet, A., Coignet, L., Andreo, B., and Charlieu, J. P. (1996) Assessment of aneuploidy for chromosomes 8, 9, 13, 16 and 21 in human sperm by using in situ labeling technique. Am. J. Hum. Genet. 58, 797–802.

    PubMed  CAS  Google Scholar 

  22. Wilkens, L., Komminoth, P., Nasarek, A., von Wasielewski, R., and Werner, M. (1997) Rapid detection of karyotype changes in interphase bone marrow cells by oligonucleotide primed in situ labeling (PRINS). J. Pathol. 181, 368–373.

    Article  PubMed  CAS  Google Scholar 

  23. Hindkjaer, J., Hammoudah, S. A., Hansen, K. B., Jensen, P. D., Koch, J., and Pedersen, B. (1995) Translocation (1;16) identified by chromosome painting, and PRimed IN Situ-labeling (PRINS). Report of two cases and review of the cytogenetic literature. Cancer Genet. Cytogenet. 79, 15–20.

    Article  PubMed  CAS  Google Scholar 

  24. Therkelsen, A. J., Nielsen, A., Koch, J., Hindkjaer, J., and Kolvraa, S. (1995) Staining of human telomeres with primed in situ labeling (PRINS). Cytogenet. Cell Genet. 63, 235–237.

    Google Scholar 

  25. Kubalakova, M., Lysak, M. A., Vrana, J., Simkova, H., Cihalikova, J., and Dolezel, J. (2000) Rapid identification and determination of purity of flow-sorted plant chromosomes using c-PRINS. Cytometry 41, 102–108.

    Article  PubMed  CAS  Google Scholar 

  26. Terkelsen, C., Koch, J., Kolvraa, S., Hindkjaer, J., Pedersen, S., and Bolund, P, (1993) Repeated primed in situ labeling: formation and labeling of specific DNA sequences in chromosomes and nuclei. Cytogenet. Cell Genet. 63, 235–237.

    Article  PubMed  CAS  Google Scholar 

  27. Gosden, J. and Lawson, D. (1995) In situ cyclic amplification of oligonucleotide primed synthesis (cycling PRINS). In: PCR application manual, Boehringer Mannheim Corporation, Mannheim, pp. 115–118.

    Google Scholar 

  28. Kwoh, D. Y., Davis, G. R., Whitfield, K. M., Chappelle, H. L., DiMichele, L. J., and Gingeras, T. R. (1989) Transcription-based amplification system and detection of amplified human immunodeficiency virus type 1 with a bead-based sandwich hybridization format. Proc. Natl. Acad. Sci. USA 86, 1173–1177.

    Article  PubMed  CAS  Google Scholar 

  29. Guatelli, J. C., Whitfield, K. M., Kwoh, D. Y., Barringer, K. J., Richman, D. D., and Gingeras, T. R. (1990) Isothermal in vitro amplification of nucleic acids by a multienzyme reaction modeled after retroviral replication. Proc. Natl. Acad. Sci. USA 87, 1874–1878.

    Article  PubMed  CAS  Google Scholar 

  30. Compton, J. (1991) Nucleic acid sequence-based amplification. Nature 350, 91–92.

    Article  PubMed  CAS  Google Scholar 

  31. Gingeras, T. R., and Kwoh, D. Y. (1992) In vitro nucleic acid target amplification techniques: issues and benefits. Praxis Biotechnol. 4, 403–429.

    Google Scholar 

  32. Miller, N., Hernandez, S. G., and Cleary, T. J. (1994) Evaluation of Gen-Probe amplified Mycobacterium tuberculosis direct test and PCR for direct detection of Mycobacterium tuberculosis in clinical specimens. J. Clin. Microbiol. 32, 393–397.

    PubMed  CAS  Google Scholar 

  33. Zaaijer, H. L., Kok, W., ten-Veen, J. H., et al. (1995) Detection of HIV-1 RNA in plasma by isothermal amplification (NASBA) irrespective of the stage of HIV-1 infection. J. Virol. Methods 52, 175–181.

    Article  PubMed  CAS  Google Scholar 

  34. Vandamme, A. M., Van-Dooren, S., Kok, W., et al. (1995) Detection of HIV-1 RNA in plasma and serum samples using the NASBA amplification system compared to RNA-PCR. J. Virol. Methods 52, 121–132.

    Article  PubMed  CAS  Google Scholar 

  35. Simpkin, S. A., Chan, A. B., Hays, J., Popping, B., and Cook, N. (2000) An RNA transcription-based amplification technique (NASBA) for the detection of viable Salmonella enterica. Lett. Appl. Microbiol. 31, 186,187.

    Article  Google Scholar 

  36. Voisset, C., Mandrand, B., and Paranhos-Baccala, G. (2000) RNA amplification technique, NASBA, also amplifies homologous plasmid DNA in non-denaturing conditions. Biotechniques 29, 236.

    PubMed  CAS  Google Scholar 

  37. Walker, G. T., Little, M. C., Nadeau, J. G., and Shank, D. D. (1992) Isothermal in vitro amplification of DNA by a restriction enzyme/DNA polymerase system. Proc. Natl. Acad. Sci. USA 89, 392–396.

    Article  PubMed  CAS  Google Scholar 

  38. Walker, G. T., Fraiser, M. S., Schram, J. L., Little, M. C., Nadeau, J. G., and Malinowski, D. P. (1992) Strand displacement amplification — an isothermal, in vitro DNA amplification technique. Nucl. Acids Res. 20, 1691–1696.

    Article  PubMed  CAS  Google Scholar 

  39. Spargo, C. A., Haaland, P. D., Jurgensen, S. R., Shank, D. D., and Walker, G. T. (1993) Chemiluminiscent detection of strand displacement amplified DNA from species comprising the Mycobacterium tuberculosis complex. Mol. Cell Probes 7, 395–404.

    Article  PubMed  CAS  Google Scholar 

  40. Walker, G. T., Nadeau, J. G., Spears, P. A., Schram, J. L., Nycz, C. M., and Shank, D. D. (1994) Multiplex strand displacement amplification (SDA) and detection of DNA sequences from Mycobacterium tuberculosis and other mycobacteria. Nucl. Acids Res. 22, 2670–2677.

    Article  PubMed  CAS  Google Scholar 

  41. Walker, G. T. and Linn, C. P. (1996) Detection of Mycobacterium tuberculosis DNA with termophilic strand displacement amplification and fluorescent polarization. Clin. Chem. 42, 1604–1608.

    PubMed  CAS  Google Scholar 

  42. Nycz, C. M., Dean, C. H., Haaland, P. D., Spargo, C., and Walker, G. T. (1998) Quantitative reverse transcription strand displacement amplification: quantitation of nucleic acids using an isothermal amplification technique. Anal. Biochem. 259, 226–234.

    Article  PubMed  CAS  Google Scholar 

  43. Nadeau, J. G., Pitner, J. B., Linn, C. P., Schram, J. L., Dean, C. H., and Nycz, C. M. (1999) Real-time, sequence-specific detection of nucleic acids during strand displacement amplification. Anal. Biochem. 276, 177–187.

    Article  PubMed  CAS  Google Scholar 

  44. Wu, D. Y. and Wallace, R. B. (1989) The ligation amplification reaction (LAR) — amplification of specific DNA sequences using sequential rounds of template-dependant ligation. Genomics 4, 560–569.

    Article  PubMed  CAS  Google Scholar 

  45. Barany, F. (1991) Genetic disease detection and DNA amplification using cloned thermostable ligase. Proc. Natl. Acad. Sci. USA 88, 189–193.

    Article  PubMed  CAS  Google Scholar 

  46. Barany, F. (1991) The ligase chain reaction in a PCR world. PCR Methods Appl. 1, 5–16.

    PubMed  CAS  Google Scholar 

  47. Birkenmeyer, L. G. and Mushahwar, I. K. (1991) DNA probe amplification methods. J. Virol. Methods 35, 117–126.

    Article  PubMed  CAS  Google Scholar 

  48. Segev, D. (1992) Amplification of nucleic acid sequences by the repair chain reaction, In Nonradioactive Labeling and Detection of Biomolecules (Kessler, C., ed.), Springer Verlag, Berlin, pp. 212–218.

    Google Scholar 

  49. Abravaya, K., Carrino, J. J., Muldoon, S., and Lee, H. H. (1995) Detection of point mutations with a modified ligase chain reaction (Gap-LCR). Nucl. Acid Res. 23, 675–682.

    Article  CAS  Google Scholar 

  50. Reyes, A. A., Carrera, P., Cardilla, E., et al. (1997) Ligase chain reaction assay for human mutations: the sickle cell by LCR assay. Clin. Chem. 43, 40–44.

    PubMed  CAS  Google Scholar 

  51. Birkenmeyer, L. G. and Armstrong, A. S. (1992) Preliminary evaluation of the ligase chain reaction for specific detection of Neisseria gonorrhoeae. J. Clin. Microbiol. 30, 3089–3094.

    PubMed  CAS  Google Scholar 

  52. van Doornum, G. J. J., Buimer, M., Prins, M., et al. (1995) Detection of Chlamydia trachomatis infection in urine samples from men and women by Ligase Chain Reaction. J. Clin. Microbiol. 33, 2042–2047.

    PubMed  Google Scholar 

  53. Kapala, J., Copes, D., Sproston, A., et al. (2000) Pooling cervical swabs and testing by ligase chain reaction are accurate and cost-saving strategies for diagnosis of Chlamydia trachomastis. J. Clin. Microbiol. 38, 2480–2483.

    PubMed  CAS  Google Scholar 

  54. Rohner, P., Jahn, E. I., Ninet, B., et al. (1988) Rapid diagnosis of pulmonary tuberculosis with the LCx Mycobacterium tuberculosis assay and comparison with conventional diagnostic techniques. J. Clin. Microbiol. 36, 3046,3047.

    Google Scholar 

  55. Viinanen, A. H., Soini, H., Marjamaki, M., Liippo, K., and Viljanen, M. K. (2000) Ligase chain reaction assay is clinically useful in the discrimination of smear-positive pulmonary tuberculosis from atypical mycobacterioses. Ann. Med. 32, 279–283.

    PubMed  CAS  Google Scholar 

  56. Nilsson, M., Malmgren, H., Samiotaki, M., Kwiatkowski, M., Cowdhary, B. P., and Landegren, U. (1994) Padlock probes: circularizing oligonucleotides for localized DNA detection. Science 265, 2085–2088.

    Article  PubMed  CAS  Google Scholar 

  57. Landegren, U. and Nilsson, M. (1997) Locked on the target: strategies for future gene diagnostics. Ann. Med. 29, 585–590.

    PubMed  CAS  Google Scholar 

  58. Fire, A. and Xu, S-Q. (1995) Rolling replication of short DNA circles. Proc. Natl. Acad. Sci. USA 92, 4641–4645.

    Article  PubMed  CAS  Google Scholar 

  59. Liu, D., Daubendiek, S. L., Zillman, M. A., Ryan, K., and Kool, E. T. (1996). Rolling circle DNA synthesis: small circular oligonucleotides as efficient templates for DNA polymerases. J. Am. Chem. Soc. 118, 1587–1594.

    Article  CAS  Google Scholar 

  60. Lizardi, P. M., Huang, X., Zhu, Z., Bray-Ward, P., Thomas, D. C., and Ward, D. C. (1998) Mutation detection and single-molecule counting using isothermal rolling-circle amplification. Nature Genet. 19, 225–232.

    Article  PubMed  CAS  Google Scholar 

  61. Banér, J., Nilsson, M., Mendel-Hartvig, M., and Landegren, U. (1998) Signal amplification of padlock probes by rolling circle replication. Nucl. Acids Res. 26, 5073–5078.

    Article  PubMed  Google Scholar 

  62. Schweitzer, B., Wiltshire, S., Lambert, J., et al. (2000) Immunoassays with rolling circle DNA amplification: A versatile platform for ultrasensitive antigen detection. Proc. Natl. Acad. Sci. USA 97, 10,113–10,119.

    Article  CAS  Google Scholar 

  63. Urdea, M., Running, J., Horn, T., Clyne, J., Ku, L., and Warner, B. (1987) A novel method for the rapid detection of specific nucleotide sequences in crude biological samples without blotting or radioactivity; application to the analysis of hepatitis B virus in human serum. Gene 61, 253–264.

    Article  PubMed  CAS  Google Scholar 

  64. Horn, T. and Urdea, M. (1989) Forks and combs and DNA: The synthesis of branched oligodeoxyribonucleotides. Nucl. Acids Res. 17, 6959–6967.

    Article  PubMed  CAS  Google Scholar 

  65. Horn, T., Chang, C-A., and Urdea, M. S. (1997) Chemical synthesis and characterization of branched oligodeoxynucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays. Nucl. Acids Res. 25, 4842–4849.

    Article  PubMed  CAS  Google Scholar 

  66. Collins, M. L., Irvine, B., Tyner, D., et al. (1997) A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/mL. Nucl. Acids Res. 25, 2979–2984.

    Article  PubMed  CAS  Google Scholar 

  67. Martell, M., Esteban, J. I., Quer, J., and Genesca, J. (1992) Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J. Virol. 66, 3225–3239.

    PubMed  CAS  Google Scholar 

  68. Lau, J. Y., Davis, G. L., Kniffen, J., and Qian, K. P. (1993) Significance of serum hepatitis C virus RNA levels in chronic hepatitis. Lancet 341, 1501–1504.

    Article  PubMed  CAS  Google Scholar 

  69. Hendricks, D. A., Stowe, B. J., Hoo, B. S., et al. (1995) Quantitation of HBV DNA in human serum using a branched DNA (bDNA) signal amplification assay. Am. J. Clin. Pathol. 104, 537–546.

    PubMed  CAS  Google Scholar 

  70. Cao, Y., Ho, D. D., Todd, J., et al. (1995) Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma. AIDS Res. Hum. Retrovir. 11, 353–361.

    Article  PubMed  CAS  Google Scholar 

  71. Urdea, M. (1993) Synthesis and characterization of branched DNA (bDNA) for the direct quantitative detection of CMV, HBV, HCV and HIV. Clin. Chem. 39, 725,726.

    Google Scholar 

  72. Iqbal, S. S., Chambers, J. P., Brubaker, R. R., Goode, M. T., and Valdes, J. J. (1999) Detection of Yersinia pestis using branched DNA. Mol. Cell Probes 13, 315–320.

    Article  PubMed  CAS  Google Scholar 

  73. Bobrow, M. N., Harris, T. D., Shaughnessy, K. J., and Litt, G. J. (1989) Catalysed reporter deposition, a novel method of signal amplification. Application to immunoassays. J. Immunol. Methods 125, 279–285.

    Article  PubMed  CAS  Google Scholar 

  74. Adams, J. C. (1992) Biotin amplification of biotin and horseradish peroxidase signals in histochemical stains. J. Histochem. Cytochem. 40, 1457–1463.

    PubMed  CAS  Google Scholar 

  75. Raap, A. K., van de Corput, M. P. C., Vervenne, R. A. W., van Gijlswijk, R. P. M., Tanke, H. J., and Wiegant, J. 1995 Ultra-sensitive FISH using peroxidase-mediated deposition of biotin or fluorochrome tyramides. Hum. Mol. Gen. 4, 529–534.

    Article  PubMed  CAS  Google Scholar 

  76. van Gijlswijk, R. P. M., Zijlmans, H. J. M. A. A., Wiegant, J., et al. (1997) Fluorochrome-labeled tyramides: use in immuno-cytochemistry and fluorescent in situ. J. Histochem. Cytochem. 45, 375–382.

    PubMed  Google Scholar 

  77. NEN Life Science Products web site: http://www.nen.com/

  78. Merz, H., Malisius, R., Mannweiler, S., et al. (1995) ImmunoMax. A maximized immunohistochemical method for the retrieval and enhancement of hidden antigens. Lab. Invest. 73, 149–156.

    PubMed  CAS  Google Scholar 

  79. Werner, M., von Wasielewski, R., and Komminoth, P. (1996) Antigen retrieval, signal amplification and intensification in immunohistochemistry. Histochem. Cell. Biol. 105, 253–260.

    Article  PubMed  CAS  Google Scholar 

  80. Adler, K., Erickson, T., and Bobrow, M. (1997) High sensitivity detection of HPV- 16 in SiHa and CaSki cells using FISH enhanced by TSA. Histochem. Cell Biol. 108, 321–324.

    Article  PubMed  CAS  Google Scholar 

  81. Wiedorn, K. H., Kuhl, H., Galle, J., Caselitz, J., and Vollmer, E. (1999) Comparison of in situ hybridization, direct and indirect in situ PCR as well as tyramide signal amplification for detection of HPV. Histochem. Cell Biol. 111, 89–95.

    Article  PubMed  CAS  Google Scholar 

  82. Yang, H., Wanner, I. B., Roper, S. D., and Chaudhari, N. (1999) An optimized method for in situ hybridization with signal amplification that allows the detection of rare mRNAs. J. Histochem. Cytochem. 47, 431–445.

    PubMed  CAS  Google Scholar 

  83. Acar, H., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., and Largaespada, D. A. (2000) Detection of integrated murine leukemia viruses in a mouse model of acute myeloid leukemia by fluorescence in situ hybridization combined with tyramide signal amplification. Cancer Genet. Cytogenet. 121, 44–51.

    Article  PubMed  CAS  Google Scholar 

  84. Klockars, T., Isosomppi, J., Laan, M., Kakko, N., Palotie, A., and Peltonen, L. (1997) The visual assignment of genes by Fiber-FISH: BTF3 protein homologue gene (BTF3) and a novel pseudogene of human RNA helicase A (DDX9P) on 13q22. Genomics 44, 355–357.

    Article  PubMed  CAS  Google Scholar 

  85. Horelli-Kuitunen, N., Aaltonen, J., Yaspo, M-L., et al. (1999) Mapping ESTs by FIBER-FISH. Genome Methods 9, 62–71.

    CAS  Google Scholar 

  86. Mayer, G. and Bendayan, M. (1997) Biotinyl-tyramide: A novel approach for electron microscopic immunocytochemistry. J. Histochem. Cytochem. 45, 1449–1454.

    PubMed  CAS  Google Scholar 

  87. Stanarius, A., Faber-Zuschratter, H., Topel, I., Schulz, S., and Wolf, G. (1999) Tyramide signal amplification in brain immunocytochemistry: adaptation to electron microscopy. J. Neurosci. Methods 88, 55–61.

    Article  PubMed  CAS  Google Scholar 

  88. Kohler, A., Lauritzen, B., and Van Noorden, C. J. F. (2000) Signal amplification in immunochemistry at the light microscopic level using biotinylated tyramide and nanogold-silver staining. J. Histochem. Cytochem. 48, 933–941.

    PubMed  CAS  Google Scholar 

  89. Prichard, C. G. and Stefano, J. E. (1991) Detection of viral nucleic acids by Qb replicase amplification. Med. Virol. 10, 67–80.

    Google Scholar 

  90. Cahil, P., Foster, K., and Mahan, D. E. (1991) Polymerase chain reaction and Qb replicase amplification. Clin. Chem. 37, 1482–1485.

    Google Scholar 

  91. Isaksson, A. and Landegren, U. (1999) Accessing genomic information: alternatives to PCR. Curr. Opin. Biotechnol. 10, 11–15.

    Article  PubMed  CAS  Google Scholar 

  92. Ray, R. A. and Shaikh, H. (2000) The progress and promise of intracellular nucleic acid amplification in histopathology. Microscopy Anal. 78, 7–9.

    Google Scholar 

  93. Raap, A. K., Marijnen, J. G. J., Vrolijk, J., and van der Ploeg, M. (1986) Denaturation, renaturation and loss of DNA during in situ hybridisation procedures. Cytometry 7, 235–242.

    Article  PubMed  CAS  Google Scholar 

  94. Andras, S. C., Hartman, T. P. V., Marshall, J. A., et al. (1999) A drop-spreading technique to produce cytoplasm-free mitotic preparations from plants with small chromosomes. Chromosome Res. 7, 641–647.

    Article  PubMed  CAS  Google Scholar 

  95. Andras, S. C., Hartman, T. P. V., Alexander, J., et al. (2000) Combined PI-DAPI staining (CPD) reveals NOR asymmetry and facilitates karyotyping of plant chromosomes. Chromosome Res. 8, 387–391.

    Article  PubMed  CAS  Google Scholar 

  96. Pastinen, T., Perola, M., Niini, P., et al. (1988) Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population. Hum. Mol. Genet. 7, 1453–1462.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael R. Davey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andras, S.C., Power, J.B., Cocking, E.C. et al. Strategies for signal amplification in nucleic acid detection. Mol Biotechnol 19, 29–44 (2001). https://doi.org/10.1385/MB:19:1:029

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/MB:19:1:029

Index Entries

Navigation