Journal of Fluorescence

, Volume 15, Issue 4, pp 559–568 | Cite as

Lanthanide Complex-Based Fluorescence Label for Time-Resolved Fluorescence Bioassay

Article

Abstract

Different from organic fluorescence dyes, fluorescent lanthanide complexes have the fluorescence properties of long fluorescence lifetime, large Stokes shift and sharp emission profile, which makes them favorable be used as the fluorescent labeling reagents for microsecond time-resolved fluorescence bioassay. Lanthanide complex-based fluorescence labels have been successfully used for highly sensitive time-resolved fluorescence immunoassay, DNA hybridization assay, cell activity assay, and bioimaging microscopy assay. Since the technique allows easy distinction of the specific fluorescence signal of the long-lived label from short-lived background noises associated with biological samples, scattering lights (Tyndall, Rayleigh and Raman scatterings) and the optical components (cuvettes, filters and lenses), the sensitivity of fluorescence bioassay has been remarkably improved. This paper summarized the recent developments of lanthanide complex-based fluorescence labels and their applications in time-resolved fluorescence bioassays mainly based on the authors’ researches and relative publications.

Keywords

lanthanide complex fluorescence label time-resolved fluorescence bioassay 

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References

  1. 1.
    H. G. Eckert (1976). Radioimmunoassay technique. Angew. Chem. 88, 565–574.Google Scholar
  2. 2.
    P. Tijssen (1985). Practice and Theory of Enzyme Immunoassay, Elsevier, Amsterdam.Google Scholar
  3. 3.
    B. J. Gould and V. Marks (1988). in T. T. Ngo (Ed.), Nonisotopic Immunoassay, Plenum, New York, pp. 3–26.Google Scholar
  4. 4.
    E. Koller (1989). Fluorescent labels for use in biology and biomedicine. Appl. Fluoresc. Technol. 1, 1–8.Google Scholar
  5. 5.
    L. M. Smith, J. Z. Sanders, R. J. Kaiser, P. Hughes, C. Dodd, C. R. Connell, C. Heiner, S. B. H. Kent, and L. E. Hodd (1986). Fluorescence detection in automated DNA sequence analysis. Nature 321, 674–679.CrossRefPubMedGoogle Scholar
  6. 6.
    S. Beck and H. Koster (1990). Applications of dioxetane chemiluminescent probes to molecular biology. Anal. Chem. 62, 2258–2270.CrossRefPubMedGoogle Scholar
  7. 7.
    A. Mayer and S. Neuenhofer (1994). Luminescent labels-more than just an alternative to radioisotopes. Angew. Chem. Int. Ed. Engl. 33, 1044–1072.CrossRefGoogle Scholar
  8. 8.
    J. M. Prober, G. L. Trainor, R. J. Dam, F. W. Hobbs, C. W. Robertson, R. J. Zagursky, A. J. Cocuzza, M. A. Jensen, and K. Baumeister (1987). A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides. Science 238, 336–341.PubMedGoogle Scholar
  9. 9.
    M. Schena, 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.PubMedGoogle Scholar
  10. 10.
    M. Schena, D. Shalon, R. Heller, A. Chai, P. O. Brown, and R. W. Davis (1996). Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc. Natl. Acad. Sci. USA 93, 10614–10619.CrossRefPubMedGoogle Scholar
  11. 11.
    E. Soini and I. Hemmilä (1979). Fluoroimmunoassay: present status and key problems. Clin. Chem. 25, 353–361.PubMedGoogle Scholar
  12. 12.
    A. P. Sinha (1971). Fluorescence and laser action in rare earth chelates. Spectrosc. Inorg. Chem. 2, 255–265.Google Scholar
  13. 13.
    F. Halverson, J. S. Brinen, and J. R. Leto (1964). Photoluminescence of lanthanide complexes. III. Synergic agent complexes involving extended chromophores. J. Chem. Phys. 41, 2752–2760.CrossRefGoogle Scholar
  14. 14.
    Y.-Y. Xu and I. Hemmilä (1992). Co-fluorescence enhancement system based on pivaloyltrifluoroacetone and yttrium for the simultaneous detection of europium, terbium, samarium and dysprosium. Anal. Chim. Acta 256, 9–16.CrossRefGoogle Scholar
  15. 15.
    J. Yuan and K. Matsumoto (1996). Fluorescence enhancement by electron-withdrawing groups on β-diketonates in Eu(III)-β-diketonato-topo ternary complexes. Anal. Sci. 12, 31–36.Google Scholar
  16. 16.
    H. Siitari, I. Hemmilä, E. Soini, T. Lövgren, and V. Koistinen (1983). Detection of hepatitis B surface antigen using time-resolved fluoroimmunoassay. Nature 301, 258–260.CrossRefPubMedGoogle Scholar
  17. 17.
    I. Hemmilä (1985). Fluoroimmunoassays and immunofluorometric assays. Clin. Chem. 31, 359–370.PubMedGoogle Scholar
  18. 18.
    E. Soini and T. Lövgren (1987). Time-resolved fluorescence of lanthanide probes and applications in biotechnology. CRC Crit. Rev. Anal. Chem. 18, 105–154.Google Scholar
  19. 19.
    E. P. Diamandis (1988). Immunoassay with time-resolved fluorescence spectroscopy: principle and applications. Clin. Biochem. 21, 139–150.PubMedGoogle Scholar
  20. 20.
    I. Hemmilä (1988). Lanthanides as probes for time-resolved fluorometric immunoassays. Scand. J. Clin. Lab. Invest. 48, 389–400.PubMedGoogle Scholar
  21. 21.
    E. P. Diamandis and T. K. Christopoulos (1990). Europium chelate labels in time-resolved fluorescence immunoassays and DNA hybridization assays. Anal. Chem. 62, 1149A–1157A.PubMedGoogle Scholar
  22. 22.
    E. F. G. Dickson, A. Pollak, and E. P. Diamandis (1995). Ultrasensitive bioanalytical assays using time-resolved fluorescence detection. Pharmac. Ther. 66, 207–235.CrossRefGoogle Scholar
  23. 23.
    J. Yuan and K. Matsumoto (1999). Functionalization of fluorescent lanthanide complexes and their applications to biotechnology. Bunseki Kagaku 48, 1077–1083.Google Scholar
  24. 24.
    I. Hemmilä, V.-M. Mukkala (2001). Time-resolution in fluorometry: technologies, labels, and applications in bioanalytical assays. Crit. Rev. Clin. Lab. Sci. 38, 441–519.CrossRefGoogle Scholar
  25. 25.
    K. Matsumoto and J. Yuan, Metal Ions in Biological Systems, In A. Sigel and H. Sigel (Eds.), Marcel Dekker, Inc., New York and Basel, Vol. 40, 2003, pp. 191–232.Google Scholar
  26. 26.
    W. D. Horrocks and D. R. Sudnick (1979). Lanthanide ion probes of structure in biology. Laser-induced luminescence decay constants provide a direct measure of the number of metal-coordinated water molecules. J. Am. Chem. Soc. 101, 334–340.CrossRefGoogle Scholar
  27. 27.
    A. G. Goryushko and N. K. Davidenko (1980). Stability of complexes of europium(III) with new fluorinated β-diketones. Zh. Neorg. Khim. 25, 2666–2668.Google Scholar
  28. 28.
    J. Yuan and K. Matsumoto (1996). Synthesis of a new tetradentate β-diketonate-europium chelate that can be covalently bound to protein in time-resolved fluorometry. Anal. Sci. 12, 695–699.Google Scholar
  29. 29.
    J. Yuan and K. Matsumoto (1997). Synthesis of a new tetradentate β-diketonate-europium chelate and its application for time-resolved fluorimetry of albumin. J. Pharm. Biomed. Anal. 15, 1397–1403.CrossRefPubMedGoogle Scholar
  30. 30.
    J. Yuan, K. Matsumoto, and H. Kimura (1998). A new tetradentate β-diketonate-europium chelate that can be covalently bound to proteins for time-resolved fluoroimmunoassay. Anal. Chem. 70, 596–601.CrossRefPubMedGoogle Scholar
  31. 31.
    R. Connally, D. Veal, and J. Piper (2002). High resolution detection of fluorescently labeled microorganisms in environmental samples using time-resolved fluorescence microscopy. FEMS Microbiol. Ecol. 41, 239–245.CrossRefGoogle Scholar
  32. 32.
    F.-B. Wu, S.-Q. Han, C. Zhang, and Y.-F. He (2002). Synthesis of a highly fluorescent β-diketone-europium chelate and its utility in time-resolved fluoroimmunoassay of serum total thyroxine. Anal. Chem. 74, 5882–5889.CrossRefPubMedGoogle Scholar
  33. 33.
    F.-B. Wu and C. Zhang (2002). A new europium b-diketone chelate for ultrasensitive time-resolved fluorescence immunoassays. Anal. Biochem. 311, 57–67.CrossRefPubMedGoogle Scholar
  34. 34.
    J. Yuan, S. Sueda, R. Somazawa, K. Matsumoto, and K. Matsumoto (2003). Structure and luminescence properties of the tetradentate b-diketonate-europium(III) complexes. Chem. Lett. 32, 492–493.CrossRefGoogle Scholar
  35. 35.
    R. A. Evangelista, A. pollak, B. Allore, E. F. Templeton, R. C. Morton, and E. P. Diamandis (1988). A new europium chelate for protein labelling and time-resolved fluorometric applications. Clin. Biochem. 21, 173–177.CrossRefPubMedGoogle Scholar
  36. 36.
    G. Mathis (1993). Rare earth cryptates and homogeneous fluoroimmunoassays with human sera. Clin. Chem. 39, 1953–1959.PubMedGoogle Scholar
  37. 37.
    A. K. Saha, K. Kross, E. D. Kloszewski, D. A. Upson, J. L. Toner, R. A. Snow, C. D. V. Black, and V. C. Desai (1993). Time-resolved fluorescence of a new europium-chelate complex: demonstration of highly sensitive detection of protein and DNA samples. J. Am. Chem. Soc. 115, 11032–11033.CrossRefGoogle Scholar
  38. 38.
    V.-M. Mukkala, M. Helenius, I. Hemmilä, J. Kankare, and H. Takalo (1993). Development of luminescent europium(III) and terbium(III) chelates of 2, 2′:6′,2″-terpyridine derivatives for protein labeling. Helv. Chim. Acta 76, 1361–1378.CrossRefGoogle Scholar
  39. 39.
    D. Horiguchi, K. Sasamoto, H. Terasawa, H. Mochizuki, and Y. Ohkura (1994). A novel time-resolved fluoroimmunoassay using a macrocyclic europium ligand as a label. Chem. Pharm. Bull. 42, 972–975.Google Scholar
  40. 40.
    H. Takalo, V.-M. Mukkala, H. Mikola, P. Liitti, and I. Hemmilä (1994). Synthesis of europium(III) chelates suitable for labeling of bioactive molecules. Bioconjugate Chem. 5, 278–282.CrossRefGoogle Scholar
  41. 41.
    M. Latva, H. Takalo, V.-M. Mukkala, C. Matachescu, J. C. Rodríguez-Ubis, and J. Kankare (1997). Correlation between the lowest triplet state energy level of the ligand and lanthanide(III) luminescence quantum yield. J. Lumin. 75, 149–169.CrossRefGoogle Scholar
  42. 42.
    H. Takalo, V.-M. Mukkala, L. Meriö, J. C. Rodríguez-Ubis, R. Sedano, O. Juanes, and E. Brunet (1997). Development of luminescent terbium(III) chelates for protein labeling: effect of triplet-state energy level. Helv. Chim. Acta 80, 372–387.CrossRefGoogle Scholar
  43. 43.
    H. Karsilayan, I. Hemmilä, H. Takalo, A. Toivonen, K. Pettersson, T. Lövgren, and V.-M. Mukkala (1997). Influence of coupling method on the luminescence properties, coupling efficiency, and binding affinity of antibodies labeled with europium(III) chelates. Bioconjugate Chem. 8, 71–75.CrossRefGoogle Scholar
  44. 44.
    J. Yuan, M. Tan, and G. Wang (2004). Synthesis and luminescence properties of lanthanide(III) chelates with polyacid derivatives of thienyl-substituted terpyridine analogues. J. Lumin. 106, 91–101.CrossRefGoogle Scholar
  45. 45.
    N. Weibel, L. J. Charbonniere, M. Guardigli, A. Roda, and R. Ziessel (2004). Engineering of highly luminescent lanthanide tags suitable for protein labeling and time-resolved luminescence imaging. J. Am. Chem. Soc. 126, 4888–4896.CrossRefPubMedGoogle Scholar
  46. 46.
    M. Li and P. R. Selvin (1995). Luminescent polyaminocarboxylate chelates of terbium and europium: the effect of chelate structure. J. Am. Chem. Soc. 117, 8132–8138.CrossRefGoogle Scholar
  47. 47.
    M. Li and P. R. Selvin (1997). Amine-reactive forms of a luminescent diethylenetriaminepentaacetic acid chelate of terbium and europium: attachment to DNA and energy transfer measurements. Bioconjugate Chem. 8, 127–132.CrossRefGoogle Scholar
  48. 48.
    J. Chen and P. R. Selvin (1999). Thiol-reactive luminescent chelates of terbium and europium. Bioconjugate Chem. 10, 311–315.CrossRefGoogle Scholar
  49. 49.
    A. Scorilas and E. P. Diamandis (2000). Polyvinylamine-streptavidin complexes labeled with a europium chelator: a universal detection reagent for solid-phase time resolved fluorometric applications. Clin. Biochem. 33, 345–350.CrossRefPubMedGoogle Scholar
  50. 50.
    A. Scorilas, A. Bjartell, H. Lilja, C. Moller, and E. P. Diamandis (2000). Streptavidin-polyvinylamine conjugates labeled with a europium chelate: applications in immunoassay, immunohistochemistry, and microarrays. Clin. Chem. 46, 1450–1455.PubMedGoogle Scholar
  51. 51.
    L.-Y. Luo and E. P. Diamandis (2000). Preliminary examination of time-resolved fluorometry for protein array applications. Luminescence 15, 409–413.CrossRefPubMedGoogle Scholar
  52. 52.
    Q.-P. Qin, T. Lövgren, and K. Pettersson (2001). Development of highly fluorescent detection reagents for the construction of ultrasensitive immunoassays. Anal. Chem. 73, 1521–1529.CrossRefPubMedGoogle Scholar
  53. 53.
    H. Härmä, T. Soukka, and T. Lövgren (2001). Europium nanoparticles and time-resolved fluorescence for ultrasensitive detection of prostate-specific antigen. Clin. Chem. 47, 561–568.PubMedGoogle Scholar
  54. 54.
    T. Soukka, H. Härmä, J. Paukkunen, and T. Lövgren (2001). Utilization of kinetically enhanced monovalent binding affinity by immunoassays based on multivalent nanoparticle-antibody bioconjugates. Anal. Chem. 73, 2254–2260.CrossRefPubMedGoogle Scholar
  55. 55.
    T. Soukka, J. Paukkunen, H. Härmä, S. Lönnberg, H. Lindroos, and T. Lövgren (2001). Supersensitive time-resolved immunofluorometric assay of free prostate-specific antigen with nanoparticle label technology. Clin. Chem. 47, 1269–1278.PubMedGoogle Scholar
  56. 56.
    T. Soukka, K. Antonen, H. Härmä, A.-M. Pelkkikangas, P. Huhtinen, and T. Lövgren (2003). Highly sensitive immunoassay of free prostate-specific antigen in serum using europium(III) nanoparticle label technology. Clin. Chim. Acta 328, 45–58.Google Scholar
  57. 57.
    T. Matsuya, S. Tashiro, N. Hoshino, N. Shibata, Y. Nagasaki, and K. Kataoka (2003). A core-shell-type fluorescent nanosphere possessing reactive poly(ethylene glycol) tethered chains on the surface for zeptomole detection of protein in time-resolved fluorometric immunoassay. Anal. Chem. 75, 6124–6132.CrossRefPubMedGoogle Scholar
  58. 58.
    Z. Ye, M. Tan, G. Wang, and J. Yuan (2004). Preapration, characterization, and time-resolved fluorometric application of silica-coated terbium(III) fluorescent nanoparticles. Anal. Chem. 76, 513–518.CrossRefPubMedGoogle Scholar
  59. 59.
    Z. Ye, M. Tan, G. Wang, and J. Yuan (2004). Novel fluorescent europium chelate-doped silica nanoparticles: preparation, characterization and time-resolved fluorometric application. J. Mater. Chem. 14, 851–856.CrossRefGoogle Scholar
  60. 60.
    M. Tan, Z. Ye, G. Wang, and J. Yuan (2004). Preparation and time-resolved fluorometric application of luminescent europium nanoparticles. Chem. Mater. 16, 2494–2498.CrossRefGoogle Scholar
  61. 61.
    Z. Ye, M. Tan, G. Wang, and J. Yuan (2005). Development of functionalized terbium fluorescent nanoparticles for antibody labeling and time-resolved fluoroimmunoassay application. Talanta 65, 206–210.Google Scholar
  62. 62.
    M. Tan, Z. Ye, G. Wang, and J. Yuan (2004). Development of functionalized fluorescent europium nanoparticles for biolabeling and time-resolved fluorometric applications. J. Mater. Chem. 14, 2896–2901.CrossRefGoogle Scholar
  63. 63.
    J. Yuan, G. Wang, H. Kimura, and K. Matsumoto (1997). Highly sensitive time-resolved fluoroimmunoassay of human immunoglobulin E by using a new europium fluorescent chelate as a label. Anal. Biochem. 254, 283–287.CrossRefPubMedGoogle Scholar
  64. 64.
    J. Yuan, G. Wang, H. Kimura, and K. Matsumoto (1998). Sensitive time-resolved fluoroimmunoassay of human thyroid-stimulating hormone by using a new europium fluorescent chelate as a label. Anal. Sci. 14, 421–423.CrossRefGoogle Scholar
  65. 65.
    M. Ikegawa, J. Yuan, K. Matsumoto, S. Herrmann, A. Iwamoto, T. Nakamura, S. Matsushita, T. Kimura, T. Honjo, and K. Tashiro (2001). Elevated plasma stromal cell-derived factor 1 protein level in the progression of HIV type 1 infection/AIDS. AIDS Res. Hum. Retrov. 17, 587–595.CrossRefGoogle Scholar
  66. 66.
    H. Kimura, M. Suzui, F. Nagao, and K. Matsumoto (2001). Highly sensitive determination of plasma cytokines by time-resolved fluoroimmunoassay: effect of bicycle exercise on plasma level of interleukin-1a (IL-1α), tumor necrosis factor α (TNFα), and interferon λ (IFNλ). Anal. Sci. 17, 593–597.CrossRefPubMedGoogle Scholar
  67. 67.
    M. Kobayashi, H. Kimura, J. Liao, M. Abe, S. Hirose, and Y. Tomino (2003). Measurement of mouse urinary type IV collagen using time-resolved fluoroimmunoassay. Anal. Sci. 19, 205–210.CrossRefPubMedGoogle Scholar
  68. 68.
    H. Kimura, J. Yuan, G. Wang, K. Matsumoto, and M. Mukaida (1999). Highly sensitive quantitation of methamphetamine by time-resolved fluoroimmunoassay using a new europium chelate as a label. J. Anal. Toxicol. 23, 11–16.PubMedGoogle Scholar
  69. 69.
    G. Wang, J. Yuan, K. Matsumoto, and H. Kimura (2001). Quantitative measurement of p21 protein in human serum by time-resolved fluoroimmunoassay. Anal. Sci. 17, 881–883.CrossRefPubMedGoogle Scholar
  70. 70.
    J. Yuan, G. Wang, H. Kimura, and K. Matsumoto (1999). Highly sensitive detection of bensulfuron-methyl by time-resolved fluoroimmunoassay using a tetradentate β-diketonate europium chelate as a label. Anal. Sci. 15, 125–128.CrossRefGoogle Scholar
  71. 71.
    K. Majima, T. Fukui, J. Yuan, G. Wang, and K. Matsumoto (2002). Quantitative measurement of 17β-estradiol and estriol in river water by time-resolved fluoroimmunoassay. Anal. Sci. 18, 869–874.CrossRefPubMedGoogle Scholar
  72. 72.
    K. Matsumoto, J. Yuan, G. Wang, and H. Kimura (1999). Simultaneous determination of α-fetoprotein and carcinoembryonic antigen in human serum by time-resolved fluoroimmunoassay. Anal. Biochem. 276, 81–87.CrossRefPubMedGoogle Scholar
  73. 73.
    H. Kimura, M. Mukaida, G. Wang, J. Yuan, and K. Matsumoto (2000). Dual-label time-resolved fluoroimmunoassay of psychopharmaceuticals and stimulants in serum. Forensic Sci. Int. 113, 345–351.CrossRefPubMedGoogle Scholar
  74. 74.
    J. Yuan, G. Wang, K. Majima, and K. Matsumoto (2001). Synthesis of a terbium fluorescent chelate and its application to time-resolved fluoroimmunoassay. Anal. Chem. 73, 1869–1876.CrossRefPubMedGoogle Scholar
  75. 75.
    S. Inoue and R. Honda (1990). Microplate hybridization of amplified viral DNA segment. J. Clin. Microbiol. 28, 1469–1472.PubMedGoogle Scholar
  76. 76.
    T. Sekiya, M. Fushimi, H. Hori, S. Hirohashi, S. Nishimura, and T. Sugimura (1984). Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient. Proc. Natl. Acad. Sci. USA 81, 4771–4775.PubMedGoogle Scholar
  77. 77.
    I. C. Hsu, R. A. Metcalf, T. Sun, J. A. Welsh, N. J. Wang, and C. C. Harris (1991). Mutational hot spot in the p53 gene in human hepatocellular carcinomas. Nature 350, 427–429.CrossRefPubMedGoogle Scholar
  78. 78.
    R. A. Cardullo, S. Agrawal, C. Flores, P. C. Zamecnik, and D. E. Wolf (1988). Detection of nucleic acid hybridization by nonradiative fluorescence resonance energy transfer. Proc. Natl. Acad. Sci. USA 85, 8790–8794.PubMedGoogle Scholar
  79. 79.
    J.-L. Mergny, A. S. Boutorine, T. Garestier, F. Belloc, M. Rougèe, N. V. Bulychev, A. A. Koshikin, J. Bourson, A. V. Lebedev, B. Valeur, N. T. Thuong, and C. Hèlène (1994). Fluorescence energy transfer as a probe for nucleic acid structures and sequences. Nucleic Acids Res. 22, 920–928.PubMedGoogle Scholar
  80. 80.
    S. Sueda, J. Yuan, and K. Matsumoto (2000). Homogeneous DNA hybridization assay by using europium luminescence energy transfer. Bioconjugate Chem. 11, 827–831.CrossRefGoogle Scholar
  81. 81.
    S. Sueda, J. Yuan, and K. Matsumoto (2002). A homogeneous DNA hybridization system by using a new luminescence terbium chelate. Bioconjugate Chem. 13, 200–205.CrossRefGoogle Scholar
  82. 82.
    G. Wang, J. Yuan, K. Matsumoto, and Z. Hu (2001). Homogeneous time-resolved fluorescence DNA hybridization assay by DNA-mediated formation of an EDTA-Eu(III)-β-diketonate ternary complex. Anal. Biochem. 299, 169–172.CrossRefPubMedGoogle Scholar
  83. 83.
    L. Seveus, M. Väisälä, S. Syrjänen, M. Sandberg, A. Kuusisto, R. Harju, J. Salo, I. Hemmilä, H. Kojola, and E. Soini (1992). Time-resolved fluorescence imaging of europium chelate label in immunohistochemistry and in situ hybridization. Cytometry 13, 329–338.CrossRefPubMedGoogle Scholar
  84. 84.
    G. Marriott, M. Heidecker, E. P. Diamandis, and Y. Yan-Marriott (1994). Time-resolved delayed luminescence image microscopy using an europium ion chelate complex. Biophys. J. 67, 957–965.PubMedGoogle Scholar
  85. 85.
    R. Connally, D. Veal, and J. A. Piper, Proceedings of SPIE, In J.-A. Conchello, C. J. Cogswell, T. Wilson (Eds.), The International Society for Optical Engineering, Vol. 4964, 2003, pp. 14–23.Google Scholar
  86. 86.
    R. Connally, D. Veal, and J. A. Piper in Proceedings of SPIE, In A. P. Savitsky, D. J. Bornhop, R. Raghavachari, and S. I. Achilefu (Eds.), The International Society for Optical Engineering, Vol. 4967, 2003, pp. 146–155.Google Scholar
  87. 87.
    R. Connally, D. Veal, and J. A. Piper (2004). Flash lamp-excited time-resolved fluorescence microscope suppresses autofluorescence in water concentrates to deliver an 11-fold increase in signal-to-noise ratio. J. Biomed. Opt. 9, 725–734.CrossRefPubMedGoogle Scholar
  88. 88.
    X. Gao, Y. Cui, R. M. Levenson, L. W. K. Chung, and S. Nie (2004). In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotech. 22, 969–976.CrossRefGoogle Scholar
  89. 89.
    E. B. Voura, J. K. Jaiswal, H. Mattoussi, and S. Simon (2004). Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat. Med. 10, 993–998.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Analytical Chemistry, Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalianP. R. China

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