Skip to main content
SpringerLink
Log in

Multiparametric Time-Correlated Single Photon Counting Luminescence Microscopy

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Classic time-correlated single photon counting (TCSPC) technique involves detection of single photons of a periodic optical signal, registration of the photon arrival time in respect to the reference pulse, and construction of photon distribution with regard to the detection times. This technique achieves extremely high time resolution and near-ideal detection efficiency. Modern TCSPC is multi-dimensional, i.e., in addition to the photon arrival time relative to the excitation pulse, spatial coordinates within the image area, wavelength, time from the start of the experiment, and many other parameters are determined for each photon. Hence, the multi-dimensional TCSPC allows generation of photon distributions over these parameters. This review describes both classic and multi-dimensional types of TCSPC microscopy and their application for fluorescence lifetime imaging in different areas of biological studies.

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

Access this article

Log in via an institution

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

Abbreviations

FLIM:

fluorescence lifetime imaging microscopy

FRET:

Förster resonance energy transfer

PLIM:

phosphorescence lifetime imaging microscopy

STED:

stimulated emission depletion

TCSPC:

time-correlated single-photon counting

References

  1. Lakowicz, J. R. (2006) Principles of Fluorescence Spectroscopy, 3rd Edn., Springer, Singapore, pp. 5–10.

    Google Scholar 

  2. Okabe, K., Inada, N., Gota, C., Harada, Y., Funatsu, T., and Uchiyama, S. (2012) Intracellular temperature map–ping with a fluorescent polymeric thermometer and fluo–rescence lifetime imaging microscopy, Nat. Commun., 3, 705.

    Article  CAS  PubMed  Google Scholar 

  3. Suhling, K. Siegel, J., Philips, D., French, P. M. W., Leveque–Fort, S., Webb, S. E. D., and Davis, D. M. (2002) Imaging the environment of green fluorescent protein, Biophys. J., 83, 3589–3595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Haidekker, M. A., and Theodorakis, E. A. (2007) Molecular rotors–fluorescence biosensors for viscosity and flow, Org. Biomol. Chem., 5, 1669–1678.

    Article  CAS  PubMed  Google Scholar 

  5. Nakabayashi, T., Wang, H. P., Kinjo, M., and Ohta, N. (2008) Application of fluorescence lifetime imaging of enhanced green fluorescent protein to intracellular pH measurements, Photochem. Photobiol. Sci., 7, 668–670.

    Article  CAS  PubMed  Google Scholar 

  6. Lakowicz, J. R., Szmacinski, H., Nowaczyk, K., and Johnson, M. (1992) Fluorescence lifetime imaging of calci–um using Quin–2, Cell Calcium, 13, 131–147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Becker, W., Shcheslavskiy, V., and Studier, H. (2015) TCSPC FLIM with different optical scanning techniques, in Advanced Time–Correlated Single Photon Counting Applications, Springer, Switzerland, pp. 65–117.

    Google Scholar 

  8. Dowling, K., Hyde, S. C. W., Dainty J. C., French, P. M. W., and Hares, J. D. (1997) 2–D fluorescence lifetime imaging using a time–gated intensifier, Opt. Comm., 135, 27–31.

    CAS  Google Scholar 

  9. Mitchell, A. C., Wall, J. E., Murray, J. G., and Morgan, C. G. (2002) Measurement of nanosecond time–resolved fluo–rescence with a directly gated interline CCD camera, J. Microsc., 206, 233–238.

    Article  CAS  PubMed  Google Scholar 

  10. Becker, W., Hirvonen, L. M., Milnes, J., Conneely, T., Jagutzki, O., Netz, H., Smietana, S., and Suhling, K. (2016) A wide–field TCSPC FLIM system based on an MCP PMT with a delay line anode, Rev. Sci. Instr., 87, 093710.

    Article  CAS  Google Scholar 

  11. Becker, W. (2005) Advanced Time–Correlated Single Photon Counting Techniques, Springer, Berlin–Heidelberg, pp. 11–26.

    Google Scholar 

  12. Alfano, A. J., Fong, F. K., and Lytle, F. E. (1983) High rep–etition rate subnanosecond gated photon counting, Rev. Sci. Instr., 54, 967–972.

    Article  CAS  Google Scholar 

  13. Gerritsen, H. C., Asselbergs, M. A. H., Agronskaia, A. V., and Van Sark, W. G. J. H. M. (2002) Fluorescence lifetime imaging in scanning microscopes: acquisition, speed, pho–ton economy and lifetime resolution, J. Microsc., 206, 218–224.

    Article  CAS  PubMed  Google Scholar 

  14. Becker, W. (2012) Fluorescence lifetime imaging–tech–niques and applications, J. Microsc., 247, 119–136.

    Article  CAS  PubMed  Google Scholar 

  15. Gratton, E., Breusegem, S., Sutin, J., Ruan, Q., and Barry, N. (2003) Fluorescence lifetime imaging for the two–pho–ton microscope: time–domain and frequency–domain methods, J. Biomed. Opt., 8, 381–390.

    Article  PubMed  Google Scholar 

  16. O’Connor, D. V., and Philips, D. (1984) Time–Correlated Single Photon Counting, Academic Press, London, pp. 36–54.

    Google Scholar 

  17. Bollinger, L. M., and Thomas, G. E. (1961) Measurement of the time dependence of scintillation intensity by a delayed coincidence method, Rev. Sci. Instr., 32, 1044–1050.

    Article  CAS  Google Scholar 

  18. Vogel, S. S., Nguen, T. A., Blank, P. S., and Wieb van der Meer, B. (2015) An introduction to interpreting time–resolved fluorescence anisotropy curves, in Advanced Time–Correlated Single Photon Counting, Springer, Switzerland, pp. 385–406.

    Google Scholar 

  19. Boemer, M., Wahl, M., Rahn, H.–J., Erdmann, R., and Enderlein, J. (2002) Time–resolved fluorescence correla–tion spectroscopy, Chem. Phys. Lett., 353, 439–445.

    Article  Google Scholar 

  20. Thomson, R. M., Stevenson, R. M., Shields, A. J., Farrer, I., Lobo, C. J., Ritchie, D. A., Leadbeater, M. L., and Pepper, M. (2001) Single–photon emission from exciton complexes in individual quantum dots, Phys. Rev. B, 64, 1–4.

    Google Scholar 

  21. Becker, W., Bergmann, A., Biskup, C., Zimmer, T., Kloecker, N., and Benndorf, K. (2002) Multiwavelength TCSPC lifetime imaging, Proc. SPIE, 4620, 79–84.

    Article  Google Scholar 

  22. Becker, W., Bergmann, A., and Biskup, C. (2007) Multi–spectral fluorescence lifetime imaging by TCSPC, Microsc. Res. Tech., 70, 403–409.

    Article  CAS  PubMed  Google Scholar 

  23. Digman, M. A., Caiolfa, V. R., Zamai, M., and Gratton, E. (2008) The phasor approach to fluorescence lifetime imag–ing analysis, Biophys. J., 94, L14–L16.

    Google Scholar 

  24. Stringari, C., Cinquin, A., Cinquin, O., Digman, M. A., Donovan, J. P., and Gratton, E. (2011) Phasor approach for fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue, Proc. Natl. Acad. Sci. USA, 108, 13582–13587.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Becker, W. (2017) The BH Handbook, 7th Edn., Becker&Hickl GmbH, Berlin.

    Google Scholar 

  26. Becker, W., Bergmann, A., Biscotti, G., Koenig, K., Riemann, I., Kelbauskas, L., and Biskup, C. (2004) High speed FLIM data acquisition by time–correlated single photon counting, Proc. SPIE, 5323, 2735.

    Google Scholar 

  27. Becker, W., Su, B., and Bergmann, A. (2009) Fast acquisi–tion multispectral FLIM by parallel TCSPC, Proc. SPIE, 7183, 718305.

    Article  Google Scholar 

  28. Ruck, A., Hulshoff, C., Kinzler, I., Becker, W., and Steiner, R. (2007) SLIM: a new method for molecular imaging, Micr. Res. Tech., 70, 485–492.

    Article  CAS  Google Scholar 

  29. Chorvat, D., and Chorvatova, A. (2009) Multi–wavelength fluorescence lifetime spectroscopy: a new approach to the study of endogenous fluorescence in living cells and tissues, Las. Phys. Lett., 6, 175–193.

    Article  CAS  Google Scholar 

  30. Ruck, A., Hauser, C., Mosch, S., and Kalinina, S. (2014) Spectrally resolved fluorescence lifetime imaging to investi–gate cell metabolism in malignant and nonmalignant oral mucosa cells, J. Biomed. Opt., 19, 96005.

    Article  CAS  PubMed  Google Scholar 

  31. Singhal, G. S., and Rabinovitch, E. (1969) Measurement of the fluorescence lifetime of chlorophyll in vivo, Biophys. J., 9, 586–591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Becker, W. (2015) DCS–120 confocal scanning FLIM sys–tems, in Handbook, 6th Edn., Becker&Hickl GmbH, Berlin, pp. 108–109.

    Google Scholar 

  33. Becker, W., Shcheslavskiy, V., Frere, S., and Slutsky, I. (2014) Spatially resolved recording of transient fluores–cence–lifetime effects by line–scanning TCSPC, Micr. Res. Tech., 77, 216–224.

    Article  CAS  Google Scholar 

  34. Shcheslavskiy, V. I., Neubauer, A., Bukowiecki, R., Dinter, F., and Becker, W. (2016) Combined fluorescence and phosphorescence lifetime imaging, Appl. Phys. Lett., 108, 091111.

    Article  CAS  Google Scholar 

  35. Nakabayashi, T., and Ohta, N. (2015) Sensing of intracel–lular environments by fluorescence lifetime imaging, Anal. Sci., 31, 275–285.

    Article  CAS  PubMed  Google Scholar 

  36. Suhling, K., Hirvonen, L. M., Levitt, J. A., Chung, P. H., Tregido, C., Le Marois, A., Rusakov, D., Zhengb, K., Ameer–Beg, S., Poland, S., Coelho, S., Henderson, R., and Krstaji, N. (2015) Fluorescence lifetime imaging (FLIM): basic concepts and some recent developments, Med. Phot., 27, 3–40.

    Article  Google Scholar 

  37. Biskup, C., and Gensch, T. (2014) Fluorescence lifetime imaging of ions in biological tissues, in Fluorescence Lifetime Spectroscopy and Imaging. Principles and Applications in Biomedical Diagnostics (Elson, D., French, P. W. M., and Marcu, L., eds.) Taylor&Francis, Boca Raton, pp. 497–535.

    Google Scholar 

  38. Kaneko, H., Putzier, I., Frings, S., Kaupp, U. B., and Gensch, T. (2004) Chloride accumulation in mammalian olfactory sensory neurons, J. Neurosci., 24, 7931–7938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Funk, K., Woitecki, A., Franjic–Wurtz, C., Gensch, T., Mochrlein, F., and Frings, S. (2008) Modulation of chlo–ride homeostasis by inflammatory mediators in dorsal gan–glion neurons, Mol. Pain, 4, 32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gensch, T., Untiet, V., Franzen, A., Kovermann, P., and Fahlke, C. (2015) Determination of intracellular chloride concentrations by fluorescence lifetime imaging, in Advanced Time–Correlated Single Photon Counting Applications (Becker, W., ed.) Springer, Switzerland, pp. 189–211.

    Google Scholar 

  41. Herman, B., Wodnicki, P., Kwon, S., Periasami, A., Gordon, G. W., Mahajan, N., and Xue Feng, W. (1997) Recent developments in monitoring calcium and protein interactions in cells using fluorescence lifetime microscopy, J. Fluoresc., 7, 85–92.

    Article  CAS  Google Scholar 

  42. Wilms, C. D., and Eilers, J. (2007) Photo–physical proper–ties of Ca2+–indicator dyes suitable for two–photon fluores–cence lifetime recordings, J. Microsc., 225, 209–213.

    Article  CAS  PubMed  Google Scholar 

  43. Lahn, M., Dosche, C., and Hille, C. (2011) Two–photon microscopy and fluorescence lifetime imaging reveal stim–ulus–induced intracellular Na+ and Cl–changes in cock–roach salivary acinar cells, Am. J. Physiol. Cell Physiol., 300, C1323–C1336.

    Google Scholar 

  44. Szmacinski, H., and Lakowicz, J. R. (1997) Sodium green as a potential probe for intracellular sodium imaging based on fluorescence lifetime, Anal. Biochem., 250, 131–138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gilbert, D., Franjic–Wurtz, C., Funk, K., Gensch, T., Frings, S., and Mohrlein, F. (2007) Differential maturation of chloride homeostasis in primary afferent neurons of the somatosensory system, Int. J. Dev. Neurosci., 25, 479–489.

    Article  CAS  PubMed  Google Scholar 

  46. Kuchibholta, K. V., Lattarulo, C. R., Hyman, B. T., and Bacskai, B. J. (2009) Synchronous hyperactivity and intra–cellular calcium waves in astrocytes in Alzheimer mice, Science, 323, 1211–1215.

    Article  CAS  Google Scholar 

  47. Lin, H.–J., Szmacinski, H., and Lakowicz, J. R. (1999) Lifetime–based pH sensors: indicators for acidic environ–ments, Anal. Chem., 269, 162–167.

    CAS  Google Scholar 

  48. Sanders, R., Draaijer, A., Gerritsen, H. C., Houpt, P. M., and Levine, Y. K. (1995) Quantitative pH imaging in cells using confocal fluorescence lifetime imaging microscopy, Anal. Biochem., 227, 302–308.

    Article  CAS  PubMed  Google Scholar 

  49. Lin, H.–J., Herman, P., and Lakowicz, J. R. (2003) Fluorescence lifetime–resolved pH imaging of living cells, Cytometry Part A, 52A, 77–89.

    Google Scholar 

  50. Orte, A., Alvarez–Pez, J. M., and Ruedas–Rama, M. J. (2013) Fluorescence lifetime imaging microscopy for the detection of intracellular pH with quantum dots nanosen–sors, ACS Nano, 7, 6387–6395.

    Article  CAS  PubMed  Google Scholar 

  51. Germond, A., Fujita, H., Ichimura, T., and Watanabe, T. M. (2016) Design and development of genetically encoded fluorescent sensors to monitor intracellular chemical and physical parameters, Biophys. Rev., 8, 121–138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Battisti, A., Digman, M. A., Gratton, E., Storti, B., Beltram, F., and Bizzari, R. (2012) Intracellular pH meas–urements made simple by fluorescent protein probes and the phasor approach to fluorescence lifetime imaging, Chem. Comm., 48, 5127–5129.

    Article  CAS  PubMed  Google Scholar 

  53. Poea–Guyon, S., Pasquier, H., Merola, F., Morel, N., and Erard, M. (2013) The enhanced cyan fluorescent protein: a sensitive pH sensor for fluorescence lifetime imaging, Analyt. Bioanalyt. Chem., 405, 3983–3987.

    Article  CAS  Google Scholar 

  54. Tantama, M., Hung, Y. P., and Yellen, G. (2011) Imaging intracellular pH in live cells with a genetically encoded red flu–orescent protein sensor, J. Am. Chem. Soc., 133, 10034–10037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Haidekker, M. A., Nipper, M., Mustafic, A., Lichlyter, D., Dakanali, M., and Teodarakis, E. A. (2010) Dyes with seg–mental mobility: molecular rotors, in Advanced Fluorescence Reporters in Chemistry and Biology. I. Fundamentals and Molecular Design (Demchenko, A. P., ed.) Springer, Berlin, pp. 267–308.

    Google Scholar 

  56. Kuimova, M., Yahioglu, G., Levitt, J. A., and Suhling, K. (2008) Molecular rotor measures viscosity of live cells via fluorescence lifetime imaging, J. Am. Chem. Soc., 130, 6672–6673.

    Article  CAS  PubMed  Google Scholar 

  57. Hosny, N. A., Mohamedi, G., Rademeyer, P., Owen, J., Wu, Y., Tang, M. X., Eckersley, R. J., Stride, E., and Kuimova, M. K. (2013) Mapping microbubble viscosity using fluorescence lifetime imaging of molecular rotors, Proc. Natl. Acad. Sci. USA, 110, 9225–9230.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Loison, P., Hosny, N. A., Gervais, P., Champion, D., Kuimova, M. K., and Perrier–Cornet, J. M. (2013) Direct investigation of viscosity of an atypical inner membrane of Bacillus spores: a molecular rotor/FLIM study, Biochim. Biophys. Acta, 1828, 2436–2443.

    Article  CAS  PubMed  Google Scholar 

  59. Shimolina, L. E., Izquierdo, M. A., Lopez–Duarte, I., Bull, J. A., Shirmanova, M. V., Klapshina, L. G., Zagaynova, E. V., and Kuimova, M. K. (2017) Imaging tumor microscopic viscosity in vivo using molecular rotors, Sci. Rep., 7, 41097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Shirmanova, M. V., Shimolina, L. E., Lukina, M. M., Zagaynova, E. V., and Kuimova, M. K. (2017) Live cell imaging of viscosity in 3D tumor cell models, in Multi–Parametric Live Cell Microscopy of 3D Tissue Models. Advances in Experimental Medicine and Biology, Vol. 1035, Springer, pp. 143–153.

    Google Scholar 

  61. Patel, D., and Franklin, K. A. (2009) Temperature–regula–tion of plant architecture, Plant Signal Behav., 4, 577–579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bahat, A., Tur–Kaspa, I., Gakamsky, A., Giojalas, L. C., Breibart, H., and Eisenbach, M. (2003) Thermotaxis of mammalian sperm cells: a potential navigation mechanism in the female genital tract, Nat. Med., 9, 149–150.

    Article  CAS  PubMed  Google Scholar 

  63. Lowell, B. B., and Spiegelman, B. M. (2000) Towards a molecular understanding of adaptive thermogenesis, Nature, 404, 652–660.

    Article  CAS  PubMed  Google Scholar 

  64. Suhling, K., Siegel, J., Philips, D., French, P. M. W., Leveque–Fort, S., Webb, S. E. D., and Davis, D. M. (2002) Imaging the environment of green fluorescent protein, Biophys. J., 83, 3589–3595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tregidgo, C., Levitt, J. A., and Suhling, K. (2008) Effect of refractive index on the fluorescence lifetime of green fluo–rescent protein, J. Biomed. Opt., 13, 031218.

    Article  CAS  PubMed  Google Scholar 

  66. Borst, J. W., Hink, M. A., Hoek, A., and Visser, A. J. (2005) Effects of refractive index and viscosity on fluorescence and anisotropy decays of enhanced cyan and yellow fluorescent proteins, J. Fluores., 15, 153–160.

    Article  CAS  Google Scholar 

  67. Van Manen, H. J., Verkuijlen, P., Wittendorp, P., Subramaniam, V., van den Berg, T. K., Roos, D., and Otto, C. (2008) Refractive index sensing of green fluorescent pro–teins in living cells using fluorescence lifetime imaging microscopy, Biophys. J., 94, L67–L69.

    Google Scholar 

  68. Pliss, A., Zhao, L. L., Ohulchanskyy, T. Y., Qu, J. L., and Prasad, P. N. (2012) Fluorescence lifetime of fluorescent proteins as an intracellular environment probe sensing the cell cycle progression, ACS Chem. Biol., 7, 1385–1392.

    Article  CAS  PubMed  Google Scholar 

  69. Fort, E., and Gresillon, S. (2008) Surface enhanced fluo–rescence, J. Phys. D–Appl. Phys., 41, 013001.

    Article  CAS  Google Scholar 

  70. Kawata, S., Inouye, Y., and Ichimura, T. (2004) Near–field optics and spectroscopy for molecular nanoimaging, Sci. Prog., 87, 25–49.

    Article  CAS  PubMed  Google Scholar 

  71. Cade, N. I., Fruhwirth, G., Archibald, S. J., and Richards, D. (2010) A cellular screening assay using analysis of metal–modified fluorescence lifetime, Biophys. J., 98, 2752–2757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Dmitriev, R. I., and Papkovsky, D. B. (2012) Optical probes and techniques for O2 measurement in live cells and tissue, Cell. Mol. Life Sci., 69, 2025–2039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Dunphy, I., Vinogradov, S. A., and Wilson, D. F. (2002) Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen–dependent quenching of phosphorescence, Anal. Biochem., 310, 191–198.

    Article  CAS  PubMed  Google Scholar 

  74. Zhang, S., Hosaka, M., Yoshihara, T., Negishi, K., Iida, Y., Tobita, S., and Takeuchi, T. (2010) Phosphorescent light–emitting iridium complexes serve as a hypoxia sensing probe for tumor imaging in living animals, Cancer Res., 70, OF1–OF9.

    Book  Google Scholar 

  75. Koshel, E. I., Chelushkin, P. S., Melnikov, A. S., Serdobintsev, P. Y., Stolbovaia, A. Y., Saifitdinova, A. F., Shcheslavskiy, V. I., Chernavskiy, O., Gaginskaya, E. R., Koshevoy, I. O., and Tunik, S. P. (2017) Lipophilic phos–phorescent gold (1) clusters as selective probes for visuali–zation of lipid droplets by two–photon microscopy, J. Photochem. Photobiol. A Chem., 332, 122–130.

    Article  CAS  Google Scholar 

  76. Solomatina, A. I., Chelushkin, P. S., Krupenya, D. V., Podkorytov, I. S., Artamonova, T. O., Sizov, V. V., Melnikov, A. S., Gurzhiy, V. V., Koshel, E. I., Shcheslavskiy, V. I., and Tunik, S. P. (2017) Coordination to imidazole ring switches on phosphorescence of platinum cyclometalated complexes: the route to selective labelling of peptides and proteins via histidine residues, Biocon. Chem., 28, 426–437.

    Article  CAS  Google Scholar 

  77. Forster, Th. (1946) Energiewanderung und Fluoreszenz, Naturwissenschaften, 6, 166–175.

    Article  Google Scholar 

  78. Cleg, R. M. (2006) The history of FRET: from conception through the labors of birth, in Reviews in Fluorescence (Geddes, C. D., and Lakowicz, J. R., eds.) Springer, New York, pp. 1–45.

    Google Scholar 

  79. Periasami, A., and Day, R. N. (2005) Molecular Imaging: FRET Microscopy and Spectroscopy, Oxford University Press, New York, pp. 21–56.

    Google Scholar 

  80. Periasami, A., Mazumder, N., Sun, Y., Christopher, K. G., and Day, R. N. (2015) FRET microscopy: basics, issues, and advantages of FLIM–FRET imaging, in Advanced Time–Correlated Single Photon Counting Applications, Springer, Heidelberg, pp. 189–276.

    Google Scholar 

  81. Lleres, D., Swift, S., and Lamond, A. I. (2007) Detecting protein–protein interactions in vivo with FRET using mul–tiphoton fluorescence lifetime imaging microscopy (FLIM), Cur. Protoc. Cytom., 42, 10.1–12.10.19.

    Google Scholar 

  82. Cremazy, F. G., Manders, E. M., Bastianes, P. I., Kramer, G., Hager, G. L., van Munster, E. B., Verschure, P. J., Gadella, T. J., and van Driel, R. (2005) Imaging in situ pro–tein–DNA interactions in the cell nucleus using FRET–FLIM, Exp. Cell. Res., 309, 390–396.

    Article  CAS  PubMed  Google Scholar 

  83. Abe, K., Zhao, L., Periasami, A., Intes, X., and Barroso, M. (2013) Non–invasive in vivo imaging of near infrared–labeled transferrin in breast cancer cells and tumors using fluorescence lifetime FRET, PLoS One, 8, e80269.

    Book  Google Scholar 

  84. Meshri, S. E., Dujardin, D., Godet, J., Richert, L., Boudier, C., Darlix, J. L., Didier, P., Mely, Y., and de Rocquigny, H. (2015) Role of the nucleocapsid domain in HIV–1Gag oligomerization and trafficking to the plasma membrane: a fluorescence lifetime imaging microscopy investigation, J. Mol. Biol., 427, 1480–1494.

    Article  CAS  PubMed  Google Scholar 

  85. Ghukassian, V., Hsu, Y.–Y., Kung, S.–H., and Kao, F.–J. (2007) Application of fluorescence resonance energy trans–fer resolved by fluorescence lifetime imaging microscopy for the detection of enterovirus 71 infection in cells, J. Biomed. Opt., 12, 0240161–0240168.

    Google Scholar 

  86. Calleja, V., Ameer–Beg, S. M., Vojnovic, B., Woschelski, R., Downward, J., and Larijani, B. (2003) Monitoring conformational changes of proteins in cells by fluores–cence lifetime imaging microscopy, Biochem. J., 372, 33–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Borsch, M., Diez, M., Zimmerman, B., Reuter, R., and Graber, P. (2002) Stepwise rotation of the γ–subunit of EF0F1–ATP synthase observed by intramolecular single–molecule fluorescence resonance energy transfer, FEBS Lett., 527, 147–152.

    Article  CAS  PubMed  Google Scholar 

  88. Bacskai, B. J., Skoch, J., Hickey, G. A., Allen, R., and Hyman, B. T. (2003) Fluorescence resonance energy trans–fer determinations using multiphoton fluorescence lifetime imaging microscopy to characterize amyloid–beta plaques, J. Biomed. Opt., 8, 368–375.

    Article  CAS  PubMed  Google Scholar 

  89. Savitsky, A. P., Rusanov, A. L., Zherdeva, V. V., Gorodnicheva, T. V., Khrenova, M. G., and Nemukhin, A. V. (2012) FLIM–FRET imaging of caspase–3 activity in live cells using pair of red fluorescent proteins, Theranostics, 2, 215–226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sergeeva, T. F., Shirmanova, M. V., Zlobovskaya, O. A., Gavrina, A. I., Dudenkova, V. V., Lukina, M. M., Lukyanov, K. A., and Zagaynova, E. V. (2017) Relationship between intracellular pH, metabolic co–factors and cas–pase–3 activation in cancer cells during apoptosis, Biochim. Biophys. Acta, 1864, 604–611.

    Article  CAS  Google Scholar 

  91. Zherdeva, V. V., Kazachkina, N. I., Shcheslavskiy, V. I., and Savitsky, A. P. (2018) Long–term fluorescence lifetime imaging of a genetically encoded sensor for caspase–3 activ–ity in mouse tumor xenografts, J. Biomed. Opt., 23, 1–11.

    PubMed  Google Scholar 

  92. Jyothikumar, V., Sun, Y., and Periasami, A. (2013) Investigation of tryptophan–NADH in live human cells using 3–photon fluorescence lifetime imaging, J. Biomed. Opt., 18, 060501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Mitchell, P. (1961) Coupling of phosphorylation to elec–tron and hydrogen transfer by a chemiosmotic type of mechanism, Nature, 191, 144–148.

    Article  CAS  PubMed  Google Scholar 

  94. Chance, B., Schoener, B., Oshino, R., Itshak, F., and Nakaze, Y. (1979) Oxidation–reduction ratio studies of mitochondria in freeze–trapped samples. NADH and flavoprotein fluorescence signals, J. Biol. Chem., 254, 4764–4771.

    CAS  PubMed  Google Scholar 

  95. Warburg, O. (1956) On respiratory impairment in cancer cells, Science, 124, 269–270.

    CAS  PubMed  Google Scholar 

  96. Skala, M. C., Riching, K. M., Gendron–Fitzpatrick, A., Eickhoff, J., Eliceiri, K. W., White, J. G., and Ramanujam, N. (2007) In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia, Proc. Natl. Acad. Sci. USA, 104, 19494–19499.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Walsh, A. J., Cook, R. S., Manning, H. C., Hicks, D. J., Lafontant, A., Arteaga, C. L., and Skala, M. C. (2013) Optical metabolic imaging identifies glycolytic levels, sub–types, and early–treatment response in breast cancer, Cancer Res., 73, 6164–6174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Lukina, M. M., Dudenkova, V. V., Ignatova, N. I., Druzhkova, I. N., Shimolina, L. E., Zagaynova, E. V., and Shirmanova, M. V. (2018) Metabolic cofactors NAD(P)H and FAD as potential indicators of cancer cell response to chemotherapy with paclitaxel, Biochim. Biophys. Acta, 1862, 1693–1700.

    Article  CAS  Google Scholar 

  99. Lakowicz, J. R., Szmacinski, H., Nowaczyk, K., and Johnson, M. L. (1992) Fluorescence lifetime imaging of free and protein–bound NADH, Proc. Natl. Acad. Sci. USA, 89, 1271–1275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Paul, R. J., and Schneckenburger, H. (1996) Oxygen con–centration and the oxidation–reduction state of yeast: determination of free/bound NADH and flavins by time–resolved spectroscopy, Naturwissenschaften, 83, 32–35.

    Article  CAS  PubMed  Google Scholar 

  101. Sharik, J. T., Favreau, P. F., Gillette, A. A., Sdao, S. M., Merrins, M. J., and Skala, M. C. (2018) Protein–bound NAD(P)H lifetime is sensitive to multiple fates of glucose carbon, Sci. Rep., 8, 5456.

    Article  CAS  Google Scholar 

  102. Van den Berg, P. A. W., Feenstra, K. A., Mark, A. E., Berendsen, H. J. C., and Visser, A. J. W. G. (2002) Dynamic conformations of flavin adenine dinucleotide: simulated molecular dynamics of the flavin cofactor relat–ed to the time–resolved fluorescence characteristics, J. Phys. Chem. B, 106, 8858–8869.

    Article  CAS  Google Scholar 

  103. Chorvat, D., and Chrorvatova, A. (2006) Spectrally resolved time–correlated single photon counting: a novel approach for characterization of endogenous fluorescence in isolated cardiac myocytes, Eur. Biophys. J., 36, 73–83.

    Article  PubMed  Google Scholar 

  104. Qu, Y., and Heikal, A. A. (2009) Two–photon autofluores–cence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiolo–gy at the single–cell level, J. Photochem. Photobiol. B, 95, 46–57.

    Article  CAS  Google Scholar 

  105. Shah, A. T., Beckler, M. D., Walsh, A. J., Jones, W. P., Pohlmann, P. R., and Skala, M. C. (2014) Optical meta–bolic imaging of treatment response in human head and neck squamous cell carcinoma, PLoS One, 9, e90746.

    Google Scholar 

  106. Zagaynova, E., Shirmanova, M., Lukina, M., Dudenkova, V., Ignatova, N., Elagin, V., Shlivko, I., Shcheslavskiy, V., and Orliskay, N. (2018) Metabolic imaging of tumor for diagnosis and response for therapy, Proc. SPIE, 10498, 1049804.

    Google Scholar 

  107. Shirmanova, M. V., Druzhkova, I. N., Lukina, M. M., Dudenkova, V. V., Ignatova, N. I., Snopova, L. B., Shcheslavskiy, V. I., Beloisov, V. V., and Zagaynova, E. V. (2017) Chemotherapy with cisplatin: insights into intracel–lular pH and metabolic landscape of cancer cells in vitro and in vivo, Sci. Rep., 7, 8911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Alam, S. R., Wallrabe, H., Svindrych, Z., Chaudhary, A. K., Christopher, K. G., Chandra, D., and Periasami, A. (2017) Investigation of mitochondrial metabolic response to doxorubicin in prostate cancer cells: an NADH, FAD and tryptophan FLIM assay, Sci. Rep., 7, 10451.

    PubMed  Google Scholar 

  109. Lukina, M. M., Dudenkova, V. V., Shimolina, L. E., Snopova, L. B., Zagaynova, E. V., and Shirmanova, M. V. (2019) In vivo metabolic and SHG imaging for monitoring of tumor response to chemotherapy, Cytometry A, accepted for publication.

    Book  Google Scholar 

  110. Wang, H. W., Ghukassian, V., Chen, C. T., Wei, Y. H., Guo, H. W., Yu, J. S., and Kao, F. J. (2008) Differentiation of apoptosis from necrosis by dynamic changes of reduced nicotinamide adenine dinucleotide fluorescence lifetime in live cells, J. Biomed. Opt., 13, 054011.

    Article  CAS  PubMed  Google Scholar 

  111. Sanchez, W. Y., Prow, T. W., Sanchez, W. H., Grice, J., and Roberts, M. S. (2010) Analysis of the metabolic deteriora–tion of ex vivo skin from ischemic necrosis through the imaging of intracellular NAD(P)H by multiphoton tomog–raphy and fluorescence lifetime imaging microscopy, J. Biomed. Opt., 15, 046008.

    Article  CAS  PubMed  Google Scholar 

  112. Konig, K., Uchugonova, A., and Gorjup, E. (2011) Multiphoton fluorescence lifetime imaging of 3D–stem cell spheroids during differentiation, Micros. Res. Tech., 74, 9–17.

    Article  Google Scholar 

  113. Meleshina, A. V., Dudenkova, V. V., Bystrova, A. S., Kuznetsova, D. S., Shirmanova, M. V., and Zagaynova, E. V. (2017) Two–photon FLIM of NAD(P)H and FAD in mesenchymal stem cells undergoing either osteogenic or chromogenic differentiation, Stem Cell Res. Ther., 8, 15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Meleshina, A. V., Dudenkova, V. V., Shirmanova, V. V., Bystrova, A. S., and Zagaynova, E. V. (2016) Multiphoton fluorescence lifetime imaging of metabolic status in mes–enchymal stem cell during adipogenic differentiation, Proc. SPIE, 9712, 97121T.

    Google Scholar 

  115. Meleshina, A. V., Dudenkova, V. V., Shirmanova, M. V., Shcheslavskiy, V. I., Becker, W., Bystrova, A. S., Cherkasova, E. I., and Zagaynova, E. V. (2016) Probing metabolic states of differentiating stem cells using two–photon FLIM, Sci. Rep., 6, 21853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Meleshina, A. V., Rogovaya, O. S., Dudenkova, V. V., Sirotkina, M. A., Lukina, M. M., Bystrova A. S., Krut, V. G., Kuznetsova, D. S., Kalabusheva, E. P., Vasiliev, A. V., Vorotelyak, E. A., and Zagaynova, E. V. (2018) Multimodal label–free imaging of living dermal equivalents including dermal papilla cells, Stem Cell Res. Ther., 9, 84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kuznetsova, D. S., Dudenkova, V. V., Rodimova, S. A., Bobrov, N. V., Zagainov, V. E., and Zagaynova, E. V. (2018) In vivo multiphoton and fluorescence lifetime imaging microscopy of the healthy and cholestatic liver, Proc. SPIE, 10498, 1049827.

    Google Scholar 

  118. Koehler, M. J., Konig, K., Elsner, P., Buckle, R., and Kaatz, M. (2006) In vivo assessment of human skin aging by multiphoton laser scanning tomography, Opt. Lett., 31, 2879–2881.

    Article  PubMed  Google Scholar 

  119. Becker, W., Shcheslavskiy, V., and Ruck, A. (2017) Simultaneous phosphorescence and fluorescence lifetime imaging by multi–dimensional TCSPC and multi–pulse excitation, Adv. Exp. Med. Biol., 1035, 19–30.

    Article  CAS  PubMed  Google Scholar 

  120. Kalinina, S., Breymayer, J., Schafer, P., Calzia, E., Shcheslavskiy, V., Becker, W., and Ruck, A. (2016) Correlative NAD(P)H−FLIM and oxygen sensing–PLIM for metabolic mapping, J. Biophot., 9, 800–811.

    Article  CAS  Google Scholar 

  121. Solomatina, A. I., Su, S. H., Lukina, M. M., Dudenkova, V. V., Shcheslavskiy, V. I., Wu, C. H., Chelushkin, P. S., Chou, P. T., Koshevoi, I. O., and Tunik, S. P. (2018) Water–soluble cyclometalated platinum(II) and iridium(III) complexes: synthesis, tuning of the photo–physical properties, and in vitro and in vivo phosphores–cence lifetime imaging, RCS Adv., 8, 17224–17236.

    CAS  Google Scholar 

  122. Kalinina, S., Breymayer, J., Reeβ, K., Lilge, L., Mandel, A., and Ruck, A. (2018) Correlation of intracellular oxy–gen and cell metabolism by simultaneous PLIM of phos–phorescent TLD1433 and FLIM of NAD(P)H, J. Biophotonics, 11, e201800085.

    Google Scholar 

  123. Lukina, M., Orlova, A., Shirmanova, M., Shirokov, D., Pavlikov, A., Neubauer, A., Studier, H., Becker, W., Zagaynova, E., Yoshihara, T., Tobita, S., and Shcheslavskiy, V. (2017) Interrogation of metabolic and oxygen states of tumors with fiber–based luminescence lifetime spectroscopy, Opt. Lett., 42, 731–734.

    Article  CAS  PubMed  Google Scholar 

  124. Shcheslavskiy, V. I., Shirmanova, M. V., Dudenkova, V. V., Lukyanov, K. A., Gavrina, A. I., Shumilova, A. V., Zagaynova, E. V., and Becker, W. (2018) Fluorescence time–resolved macroimaging, Opt. Lett., 43, 3152–3155.

    Article  CAS  PubMed  Google Scholar 

  125. Hell, S. W. (2010) Far–Field Optical Nanoscopy, in Single Molecule Spectroscopy in Chemistry, Physics and Biology, Springer Series in Chemical Physics, Vol. 96, pp. 365–398.

    Google Scholar 

  126. Auksorius, E., Boruah, B. R., Dunsby, C., Lanigan, P. M. P., Kennedy, G., Neil, M. A. A., and French, P. M. W. (2008) Stimulated emission depletion microscopy with a supercontinuum source and fluorescence lifetime imaging, Opt. Lett., 33, 113–115.

    Article  PubMed  Google Scholar 

  127. Cadby, A., Dean, R., Fox, A. M., Jones, R. A. L., and Lidzey, D. G. (2005) Imaging the fluorescence decay time of a conjugated polymer in a phase–separated blend using a scanning near–field optical microscope, Nano Lett., 5, 2232–2237.

    Article  CAS  PubMed  Google Scholar 

  128. Micic, M., Hu, D., Suh, Y. D., Newton, G., Romine, M., and Lu, H. P. (2004) Correlated atomic force microscopy and fluorescence lifetime imaging of live bacterial cells, Colloids Surf. B Biointerfaces, 34, 205–212.

    Article  CAS  PubMed  Google Scholar 

  129. Hirvonen, L. M., Becker, W., Milnes, J., Conneely, T., Smietana, S., Le Marois, A., Jagutzki, O., and Suhling, K. (2016) Picosecond wide–field time–correlated single pho–ton counting fluorescence microscopy with a delay line anode detector, Appl. Phys. Lett., 109, 071101.

    Article  CAS  Google Scholar 

  130. Becker, W., and Shcheslavskiy, V. (2015) Fluorescence life–time imaging with near–infrared dyes, Photon. Las. Med., 4, 73–83.

    CAS  Google Scholar 

  131. Becker, W. (2015) Introduction to multi–dimensional TCSPC, in Advanced Time–Correlated Single Photon Counting Application, Springer, Heidelberg, pp. 1–63.

    Google Scholar 

  132. Shcheslavskiy, V. I., Morozov, P., Divochiy, A., Vakhtomin, Yu., Smirnov, K., and Becker, W. (2016) Ultrafast time measurements by time–correlated single photon counting coupled with superconducting single photon detector, Rev. Sci. Instr., 87, 053117.

    Article  CAS  Google Scholar 

  133. Becker, W. (2018) Fast acquisition TCSPC FLIM system with sub–25ps IRF width, Application Note, www.becker–hickl.de.

    Google Scholar 

  134. Jentsch, S., Schweitzer, D., Schmidtke, K. U., Peters, S., Dawczynski, J., Bar, K. J., and Hammer, M. (2014) Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer’s disease, Acta Ophthalmol., 93, e241–e247.

    Google Scholar 

  135. Dysli, C., Wolf, S., Berezin, M. Y., Sauer, L., Hammer, M., and Zinkernagel, M. S. (2017) Fluorescence lifetime imaging ophthalmoscopy, Prog. Retin. Eye Res., 60, 120–143.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Leite–Silva, V. R., Le Lamer, M., Sanchez, W. Y., Liu, D. C., Sanchez, W. H., Morrow, I., Martin, D., Silva, H. D. T., Prow, T. W., Grice, J. E., and Roberts, M. S. (2013) The effect on formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epider–mis of human skin in vivo, Eur. J. Pharm. Biopharm., 84, 297–308.

    Article  CAS  PubMed  Google Scholar 

  137. Roberts, M. S., Roberts, M. J., Robertson, T. A., Sanchez, W., Thorling, C., Zou, W., Zhao, X., Becker, W., and Zvyagin, A. V. (2008) In vitro and in vivo imaging of xeno–biotic transport in human skin and in the rat liver, J. Biophoton., 1, 478–493.

    Article  CAS  Google Scholar 

  138. Prow, T. W., Grice, J. E., Lin, L. L., Faye, R., Butler, M., Becker, W., Wurm, E. M. T., Yoong, C., Robertson, T. A., Soyer, H. P., and Roberts, M. (2011) Nanoparticles and microparticles for skin drug delivery, Adv. Drug Deliv. Rev., 63, 470–491.

    Article  CAS  PubMed  Google Scholar 

  139. Seidenari, S., Arginelli, F., Bassoli, S., Cautela, J., French, P. M. W., Konig, K., Magnoni, C., Talbot, C., and Ponti, G. (2013) Multiphoton laser tomography and fluo–rescence lifetime imaging of melanoma: morphologic fea–tures and quantitative data for sensitive and specific non–invasive diagnostics, PLoS One, 8, e70682.

    Google Scholar 

  140. Huck, V., Gorzelanni, C., Thomas, K., Getova, V., Niemeyer, V., Zens, K., Unnerstall, T. R., Feger, J. S., Fallah, M. A., Metze, D., Stander, S., Luger, T. A., Konig, K., Mess, C., and Schneider, S. W. (2016) From morphol–ogy to biochemical state–intravital multiphoton fluores–cence lifetime imaging of inflamed human skin, Sci. Rep., 6, 22789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Balu, M., Zachary, C. B., Harris, R. M., Krasieva, T. B., Konig, K., Tromberg, B. J., and Kelly, K. M. (2015) In vivo multiphoton microscopy of basal cell carcinoma, JAMA Dermatol., 151, 1068–1074.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Gora, M. J., Suter, M. J., Tearney, G. J., and Li, X. (2017) Endoscopic optical coherence tomography: technologies and clinical applications, Biomed. Opt. Express, 8, 2405–2444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Lombardini, A., Mutskaniuk, V., Sivankutty, S., Andresen, E. R., Chen, X., Wenger, J., Fabert, M., Joly, N., Louradour, F., Kudlinski, A., and Rigneault, H. (2018) High–resolution multimodal flexible coherent Raman endoscope, Light Sci. Appl., 7, 10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Yakovlev, V. V., Shcheslavskiy, V., and Ivanov, A. (2002) High–energy femtosecond Cr4+:forsterite oscillators and their applications in biomedical and material sciences, Appl. Phys. B Lasers Optics, 74, s145–s152.

    Google Scholar 

  145. Shcheslavskiy, V. I., Saltiel, S. M., Faustov, A., Petrov, G. I., and Yakovlev, V. V. (2005) Third–harmonic Rayleigh scattering: theory and experiment, J. Opt. Soc. Am. B Opt. Physics, 22, 2402–2408.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Becker&Hickl GmbH, 12277, Berlin, Germany

    V. I. Shcheslavskiy, A. Jelzow & W. Becker

  2. Privolzhskiy Medical Research University, 603005, Nizhny Novgorod, Russia

    V. I. Shcheslavskiy & M. V. Shirmanova

Authors
  1. V. I. Shcheslavskiy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Shirmanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Jelzow
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. I. Shcheslavskiy.

Additional information

Russian Text © V. I. Shcheslavskiy, M. V. Shirmanova, A. Jelzow, W. Becker, 2019, published in Uspekhi Biologicheskoi Khimii, 2019, Vol. 59, pp. 103–138.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shcheslavskiy, V.I., Shirmanova, M.V., Jelzow, A. et al. Multiparametric Time-Correlated Single Photon Counting Luminescence Microscopy. Biochemistry Moscow 84 (Suppl 1), 51–68 (2019). https://doi.org/10.1134/S0006297919140049

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297919140049

Keywords

Search

Navigation