Abstract

Multiphoton microscopy (MPM) allows for three-dimensional in vivo microscopy in scattering tissue with submicron resolution and high signal-to-noise ratio. MPM combined with fluorescence lifetime measurements further enables quantitative imaging of molecular concentrations, such as dissolved oxygen, with the same optical resolution as MPM, in vivo. However, biocompatible oxygen-sensitive MPM probes are not available commercially and are difficult to synthesize. Here we present a simple MPM oxygen imaging probe compatible with aqueous biological media based on a water-soluble ruthenium-complex nanomicelle. By adding a layer of silica shell to the nanomicelle assembly, oxygen sensitivity and probe stability in biological media increases dramatically. While uncoated probes are unusable in the presence of serum albumin, photophysical characterization shows that the silica coating enables quantitative oxygen measurements in biological media and increases probe stability by more than an order of magnitude.

© 2017 Optical Society of America

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    [Crossref]
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    [PubMed]
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    [PubMed]
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    [Crossref] [PubMed]

2016 (1)

Y. Zhang, A. A. Khan, G. D. Vigil, and S. S. Howard, “Investigation of signal-to-noise ratio in frequency-domain multiphoton fluorescence lifetime imaging microscopy,” Journal of the Optical Society of America A 33, B1 (2016).
[Crossref]

2015 (3)

A. A. Khan, S. K. Fullerton-Shirey, and S. S. Howard, “Easily prepared ruthenium-complex nanomicelle probes for two-photon quantitative imaging of oxygen in aqueous media,” RSC Adv. 5, 291–300 (2015).
[Crossref]

S. Kerkhofs, T. Willhammar, H. Van Den Noortgate, C. E. A. Kirschhock, E. Breynaert, G. Van Tendeloo, S. Bals, and J. A. Martens, “Self-Assembly of Pluronic F127—Silica Spherical Core–Shell Nanoparticles in Cubic Close-Packed Structures,” Chemistry of Materials 27, 5161–5169 (2015).
[Crossref]

S. P. Poland, N. Krstajić, J. Monypenny, S. Coelho, D. Tyndall, R. J. Walker, V. Devauges, J. Richardson, N. Dutton, P. Barber, D. D.-U. Li, K. Suhling, T. Ng, R. K. Henderson, and S. M. Ameer-Beg, “A high speed multifocal multiphoton fluorescence lifetime imaging microscope for live-cell FRET imaging,” Biomed. Opt. Express 6, 277–296 (2015).
[Crossref] [PubMed]

2014 (1)

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

2013 (3)

S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
[Crossref] [PubMed]

D. B. Papkovsky and R. I. Dmitriev, “Biological detection by optical oxygen sensing,” Chemical Society Reviews 42, 8700–8732 (2013).
[Crossref] [PubMed]

S. S. Howard, A. Straub, N. G. Horton, D. Kobat, and C. Xu, “Frequency-multiplexed in vivo multiphoton phosphorescence lifetime microscopy,” Nature Photonics 7, 33–37 (2013).
[Crossref]

2012 (1)

R. I. Dmitriev and D. B. Papkovsky, “Optical probes and techniques for O2 measurement in live cells and tissue,” Cellular and molecular life sciences : CMLS 69, 2025–2039 (2012).
[Crossref] [PubMed]

2011 (4)

T. V. Esipova, A. Karagodov, J. Miller, D. F. Wilson, T. M. Busch, and S. A. Vinogradov, “Two new “protected” oxyphors for biological oximetry: properties and application in tumor imaging,” Analytical Chemistry 83, 8756–8765 (2011).
[Crossref]

R. N. Ghosh, P. A. Askeland, S. Kramer, and R. Loloee, “Optical dissolved oxygen sensor utilizing molybdenum chloride cluster phosphorescence,” Applied Physics Letters 98, 221103 (2011).
[Crossref]

M. Maurin, O. Stéphan, J.-C. Vial, S. R. Marder, and B. van der Sanden, “Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles,” Journal of Biomedical Optics 16, 36001 (2011).
[Crossref]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. G. Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nature Medicine 17, 893–898 (2011).
[Crossref] [PubMed]

2010 (1)

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

2009 (3)

J. Zaias, M. Mineau, C. Cray, D. Yoon, and N. H. Altman, “Reference Values for Serum Proteins of Common Laboratory Rodent Strains,” J. Am. Assoc. Lab. Anim. Sci. 48, 387–390 (2009).
[PubMed]

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

P. P. Provenzano, K. W. Eliceiri, and P. J. Keely, “Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment,” Clin. Exp. Metastasis 26, 357–370 (2009).
[Crossref]

2008 (2)

O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” ChemPhysChem 9, 1673–1679 (2008).
[Crossref] [PubMed]

A. Y. Lebedev, T. Troxler, and S. A. Vinogradov, “Design of metalloporphyrin-based dendritic nanoprobes for two-photon microscopy of oxygen,” Journal of Porphyrins and Phthalocyanines 12, 1261–1269 (2008).
[Crossref]

2007 (2)

K. J. Morris, M. S. Roach, W. Xu, J. N. Demas, and B. A. DeGraff, “Luminescence lifetime standards for the nanosecond to microsecond range and oxygen quenching of ruthenium(II) complexes,” Analytical Chemistry 79, 9310–9314 (2007).
[Crossref] [PubMed]

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

2005 (2)

2004 (1)

Y. E. L. Koo, Y. Cao, R. Kopelman, S. M. Koo, M. Brasuel, and M. A. Philbert, “Real-Time Measurements of Dissolved Oxygen Inside Live Cells by Organically Modified Silicate Fluorescent Nanosensors,” Analytical Chemistry 76, 2498–2505 (2004).
[Crossref] [PubMed]

2003 (2)

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nature Biotechnology 21, 1369–1377 (2003).
[Crossref] [PubMed]

K. Koenig and I. Riemann, “High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution,” Journal of Biomedical Optics 8, 432 (2003).
[Crossref]

2002 (2)

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, “Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution,” Journal of Microscopy 206, 218–224 (2002).
[Crossref] [PubMed]

I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: Phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Analytical Biochemistry 310, 191–198 (2002).
[Crossref] [PubMed]

2001 (1)

H. Xu, J. W. Aylott, R. Kopelman, T. J. Miller, and M. A. Philbert, “A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma,” Analytical Chemistry 73, 4124–4133 (2001).
[Crossref] [PubMed]

1996 (1)

A. Periasamy, P. Wodnicki, X. F. Wang, S. Kwon, G. W. Gordon, and B. Herman, “Time-resolved fluorescence lifetime imaging microscopy using a picosecond pulsed tunable dye laser system,” Review of Scientific Instruments 67, 3722–3731 (1996).
[Crossref]

1994 (1)

P. Alexandridis, J. F. Holzwarth, and T. A. Hatton, “Micellization of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymers in Aqueous Solutions: Thermodynamics of Copolymer Association,” Macromolecules 27, 2414–2425 (1994).
[Crossref]

1990 (1)

W. Denk, J. Strickler, and W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73–76 (1990).
[Crossref] [PubMed]

1987 (1)

J. M. Vanderkooi, G. Maniara, T. J. Green, and D. F. Wilson, “An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence,” J. Biol. Chem. 262, 5476–5482 (1987).
[PubMed]

Agronskaia, A. V.

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, “Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution,” Journal of Microscopy 206, 218–224 (2002).
[Crossref] [PubMed]

Alexandridis, P.

P. Alexandridis, J. F. Holzwarth, and T. A. Hatton, “Micellization of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymers in Aqueous Solutions: Thermodynamics of Copolymer Association,” Macromolecules 27, 2414–2425 (1994).
[Crossref]

Alt, C.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Altman, N. H.

J. Zaias, M. Mineau, C. Cray, D. Yoon, and N. H. Altman, “Reference Values for Serum Proteins of Common Laboratory Rodent Strains,” J. Am. Assoc. Lab. Anim. Sci. 48, 387–390 (2009).
[PubMed]

Alvarez-Pez, J. M.

A. Orte, J. M. Alvarez-Pez, and M. J. Ruedas-Rama, “Fluorescence Lifetime Imaging Microscopy for the Detection of Intracellular pH with Quantum Dot Nanosensors,” ACS Nano pp. 6387–6395 (2013).
[Crossref] [PubMed]

Ameer-Beg, S. M.

Aprelev, A.

O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” ChemPhysChem 9, 1673–1679 (2008).
[Crossref] [PubMed]

Arai, K.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

Askeland, P. A.

R. N. Ghosh, P. A. Askeland, S. Kramer, and R. Loloee, “Optical dissolved oxygen sensor utilizing molybdenum chloride cluster phosphorescence,” Applied Physics Letters 98, 221103 (2011).
[Crossref]

Asselbergs, M. A. H.

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, “Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution,” Journal of Microscopy 206, 218–224 (2002).
[Crossref] [PubMed]

Ayata, C.

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

Aylott, J. W.

H. Xu, J. W. Aylott, R. Kopelman, T. J. Miller, and M. A. Philbert, “A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma,” Analytical Chemistry 73, 4124–4133 (2001).
[Crossref] [PubMed]

Bals, S.

S. Kerkhofs, T. Willhammar, H. Van Den Noortgate, C. E. A. Kirschhock, E. Breynaert, G. Van Tendeloo, S. Bals, and J. A. Martens, “Self-Assembly of Pluronic F127—Silica Spherical Core–Shell Nanoparticles in Cubic Close-Packed Structures,” Chemistry of Materials 27, 5161–5169 (2015).
[Crossref]

Barber, P.

Beer, D.

D. Sud, W. Zhong, D. Beer, and M.-A. Mycek, “Measurement of intracellular oxygen levels using fluorescence lifetime imaging microscopy (FLIM),” in “European Conference on Biomedical Optics 2005,” K. Licha and R. Cubeddu, eds. (International Society for Optics and Photonics, 2005), p. 585907.
[Crossref]

Bennett, J.

Boas, D. A.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

Boerckel, J. D.

A. A. Khan, S. Zhang, G. Vigil, J. D. Boerckel, and S. S. Howard, “Two-Photon Intravital Imaging of a Mouse Brain In Vivo Using Easily Prepared Ruthenium-Poloxamer Nanoprobes,” in “Optics in the Life Sciences,” (OSA, Washington, D.C., 2015), Ii, p. BT1A.3.

Brasuel, M.

Y. E. L. Koo, Y. Cao, R. Kopelman, S. M. Koo, M. Brasuel, and M. A. Philbert, “Real-Time Measurements of Dissolved Oxygen Inside Live Cells by Organically Modified Silicate Fluorescent Nanosensors,” Analytical Chemistry 76, 2498–2505 (2004).
[Crossref] [PubMed]

Breynaert, E.

S. Kerkhofs, T. Willhammar, H. Van Den Noortgate, C. E. A. Kirschhock, E. Breynaert, G. Van Tendeloo, S. Bals, and J. A. Martens, “Self-Assembly of Pluronic F127—Silica Spherical Core–Shell Nanoparticles in Cubic Close-Packed Structures,” Chemistry of Materials 27, 5161–5169 (2015).
[Crossref]

Busch, T. M.

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S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
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S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
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P. P. Provenzano, K. W. Eliceiri, and P. J. Keely, “Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment,” Clin. Exp. Metastasis 26, 357–370 (2009).
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Y. Zhang, A. A. Khan, G. D. Vigil, and S. S. Howard, “Investigation of signal-to-noise ratio in frequency-domain multiphoton fluorescence lifetime imaging microscopy,” Journal of the Optical Society of America A 33, B1 (2016).
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A. A. Khan, S. K. Fullerton-Shirey, and S. S. Howard, “Easily prepared ruthenium-complex nanomicelle probes for two-photon quantitative imaging of oxygen in aqueous media,” RSC Adv. 5, 291–300 (2015).
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A. A. Khan, S. Zhang, G. Vigil, J. D. Boerckel, and S. S. Howard, “Two-Photon Intravital Imaging of a Mouse Brain In Vivo Using Easily Prepared Ruthenium-Poloxamer Nanoprobes,” in “Optics in the Life Sciences,” (OSA, Washington, D.C., 2015), Ii, p. BT1A.3.

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Y. E. L. Koo, Y. Cao, R. Kopelman, S. M. Koo, M. Brasuel, and M. A. Philbert, “Real-Time Measurements of Dissolved Oxygen Inside Live Cells by Organically Modified Silicate Fluorescent Nanosensors,” Analytical Chemistry 76, 2498–2505 (2004).
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Y. E. L. Koo, Y. Cao, R. Kopelman, S. M. Koo, M. Brasuel, and M. A. Philbert, “Real-Time Measurements of Dissolved Oxygen Inside Live Cells by Organically Modified Silicate Fluorescent Nanosensors,” Analytical Chemistry 76, 2498–2505 (2004).
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R. N. Ghosh, P. A. Askeland, S. Kramer, and R. Loloee, “Optical dissolved oxygen sensor utilizing molybdenum chloride cluster phosphorescence,” Applied Physics Letters 98, 221103 (2011).
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Kuroki, A.

Kwon, S.

A. Periasamy, P. Wodnicki, X. F. Wang, S. Kwon, G. W. Gordon, and B. Herman, “Time-resolved fluorescence lifetime imaging microscopy using a picosecond pulsed tunable dye laser system,” Review of Scientific Instruments 67, 3722–3731 (1996).
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J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. G. Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nature Medicine 17, 893–898 (2011).
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Lin, C. P.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
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S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
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R. N. Ghosh, P. A. Askeland, S. Kramer, and R. Loloee, “Optical dissolved oxygen sensor utilizing molybdenum chloride cluster phosphorescence,” Applied Physics Letters 98, 221103 (2011).
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H. Xu, J. W. Aylott, R. Kopelman, T. J. Miller, and M. A. Philbert, “A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma,” Analytical Chemistry 73, 4124–4133 (2001).
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J. Zaias, M. Mineau, C. Cray, D. Yoon, and N. H. Altman, “Reference Values for Serum Proteins of Common Laboratory Rodent Strains,” J. Am. Assoc. Lab. Anim. Sci. 48, 387–390 (2009).
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Morris, K. J.

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J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
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O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” ChemPhysChem 9, 1673–1679 (2008).
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D. B. Papkovsky and R. I. Dmitriev, “Biological detection by optical oxygen sensing,” Chemical Society Reviews 42, 8700–8732 (2013).
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Parpaleix, A.

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. G. Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nature Medicine 17, 893–898 (2011).
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A. Periasamy, P. Wodnicki, X. F. Wang, S. Kwon, G. W. Gordon, and B. Herman, “Time-resolved fluorescence lifetime imaging microscopy using a picosecond pulsed tunable dye laser system,” Review of Scientific Instruments 67, 3722–3731 (1996).
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Philbert, M. A.

Y. E. L. Koo, Y. Cao, R. Kopelman, S. M. Koo, M. Brasuel, and M. A. Philbert, “Real-Time Measurements of Dissolved Oxygen Inside Live Cells by Organically Modified Silicate Fluorescent Nanosensors,” Analytical Chemistry 76, 2498–2505 (2004).
[Crossref] [PubMed]

H. Xu, J. W. Aylott, R. Kopelman, T. J. Miller, and M. A. Philbert, “A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma,” Analytical Chemistry 73, 4124–4133 (2001).
[Crossref] [PubMed]

Poland, S. P.

Provenzano, P. P.

P. P. Provenzano, K. W. Eliceiri, and P. J. Keely, “Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment,” Clin. Exp. Metastasis 26, 357–370 (2009).
[Crossref]

Ramanujam, N.

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

Richardson, J.

Riching, K. M.

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

Riemann, I.

K. Koenig and I. Riemann, “High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution,” Journal of Biomedical Optics 8, 432 (2003).
[Crossref]

Roach, M. S.

K. J. Morris, M. S. Roach, W. Xu, J. N. Demas, and B. A. DeGraff, “Luminescence lifetime standards for the nanosecond to microsecond range and oxygen quenching of ruthenium(II) complexes,” Analytical Chemistry 79, 9310–9314 (2007).
[Crossref] [PubMed]

Roussakis, E.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
[Crossref] [PubMed]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. G. Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nature Medicine 17, 893–898 (2011).
[Crossref] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

Ruedas-Rama, M. J.

A. Orte, J. M. Alvarez-Pez, and M. J. Ruedas-Rama, “Fluorescence Lifetime Imaging Microscopy for the Detection of Intracellular pH with Quantum Dot Nanosensors,” ACS Nano pp. 6387–6395 (2013).
[Crossref] [PubMed]

Runnels, J. M.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Ruvinskaya, S.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

Sakadžic, S.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

Salvaggio, A. J.

S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
[Crossref] [PubMed]

Scadden, D. T.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Shaydyuk, N. K.

S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
[Crossref] [PubMed]

Skala, M. C.

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

Spencer, J. A.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Srinivasan, V. J.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

Stéphan, O.

M. Maurin, O. Stéphan, J.-C. Vial, S. R. Marder, and B. van der Sanden, “Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles,” Journal of Biomedical Optics 16, 36001 (2011).
[Crossref]

Straub, A.

S. S. Howard, A. Straub, N. G. Horton, D. Kobat, and C. Xu, “Frequency-multiplexed in vivo multiphoton phosphorescence lifetime microscopy,” Nature Photonics 7, 33–37 (2013).
[Crossref]

Strickler, J.

W. Denk, J. Strickler, and W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73–76 (1990).
[Crossref] [PubMed]

Sud, D.

D. Sud, W. Zhong, D. Beer, and M.-A. Mycek, “Measurement of intracellular oxygen levels using fluorescence lifetime imaging microscopy (FLIM),” in “European Conference on Biomedical Optics 2005,” K. Licha and R. Cubeddu, eds. (International Society for Optics and Photonics, 2005), p. 585907.
[Crossref]

Suhling, K.

Troxler, T.

O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” ChemPhysChem 9, 1673–1679 (2008).
[Crossref] [PubMed]

A. Y. Lebedev, T. Troxler, and S. A. Vinogradov, “Design of metalloporphyrin-based dendritic nanoprobes for two-photon microscopy of oxygen,” Journal of Porphyrins and Phthalocyanines 12, 1261–1269 (2008).
[Crossref]

Turcotte, R.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Tyndall, D.

Vaccarezza, M. N.

Van Den Noortgate, H.

S. Kerkhofs, T. Willhammar, H. Van Den Noortgate, C. E. A. Kirschhock, E. Breynaert, G. Van Tendeloo, S. Bals, and J. A. Martens, “Self-Assembly of Pluronic F127—Silica Spherical Core–Shell Nanoparticles in Cubic Close-Packed Structures,” Chemistry of Materials 27, 5161–5169 (2015).
[Crossref]

van der Sanden, B.

M. Maurin, O. Stéphan, J.-C. Vial, S. R. Marder, and B. van der Sanden, “Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles,” Journal of Biomedical Optics 16, 36001 (2011).
[Crossref]

Van Sark, W. G. J. H. M.

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, “Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution,” Journal of Microscopy 206, 218–224 (2002).
[Crossref] [PubMed]

Van Tendeloo, G.

S. Kerkhofs, T. Willhammar, H. Van Den Noortgate, C. E. A. Kirschhock, E. Breynaert, G. Van Tendeloo, S. Bals, and J. A. Martens, “Self-Assembly of Pluronic F127—Silica Spherical Core–Shell Nanoparticles in Cubic Close-Packed Structures,” Chemistry of Materials 27, 5161–5169 (2015).
[Crossref]

Vanderkooi, J. M.

J. M. Vanderkooi, G. Maniara, T. J. Green, and D. F. Wilson, “An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence,” J. Biol. Chem. 262, 5476–5482 (1987).
[PubMed]

Vial, J.-C.

M. Maurin, O. Stéphan, J.-C. Vial, S. R. Marder, and B. van der Sanden, “Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles,” Journal of Biomedical Optics 16, 36001 (2011).
[Crossref]

Vigil, G.

A. A. Khan, S. Zhang, G. Vigil, J. D. Boerckel, and S. S. Howard, “Two-Photon Intravital Imaging of a Mouse Brain In Vivo Using Easily Prepared Ruthenium-Poloxamer Nanoprobes,” in “Optics in the Life Sciences,” (OSA, Washington, D.C., 2015), Ii, p. BT1A.3.

Vigil, G. D.

Y. Zhang, A. A. Khan, G. D. Vigil, and S. S. Howard, “Investigation of signal-to-noise ratio in frequency-domain multiphoton fluorescence lifetime imaging microscopy,” Journal of the Optical Society of America A 33, B1 (2016).
[Crossref]

Vinogradov, S. A.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
[Crossref] [PubMed]

T. V. Esipova, A. Karagodov, J. Miller, D. F. Wilson, T. M. Busch, and S. A. Vinogradov, “Two new “protected” oxyphors for biological oximetry: properties and application in tumor imaging,” Analytical Chemistry 83, 8756–8765 (2011).
[Crossref]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. G. Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nature Medicine 17, 893–898 (2011).
[Crossref] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” ChemPhysChem 9, 1673–1679 (2008).
[Crossref] [PubMed]

A. Y. Lebedev, T. Troxler, and S. A. Vinogradov, “Design of metalloporphyrin-based dendritic nanoprobes for two-photon microscopy of oxygen,” Journal of Porphyrins and Phthalocyanines 12, 1261–1269 (2008).
[Crossref]

D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44, 5239 (2005).
[Crossref] [PubMed]

I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: Phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Analytical Biochemistry 310, 191–198 (2002).
[Crossref] [PubMed]

Walker, R. J.

Wang, X. F.

A. Periasamy, P. Wodnicki, X. F. Wang, S. Kwon, G. W. Gordon, and B. Herman, “Time-resolved fluorescence lifetime imaging microscopy using a picosecond pulsed tunable dye laser system,” Review of Scientific Instruments 67, 3722–3731 (1996).
[Crossref]

Webb, W.

W. Denk, J. Strickler, and W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248, 73–76 (1990).
[Crossref] [PubMed]

Webb, W. W.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nature Biotechnology 21, 1369–1377 (2003).
[Crossref] [PubMed]

White, J. G.

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

Willhammar, T.

S. Kerkhofs, T. Willhammar, H. Van Den Noortgate, C. E. A. Kirschhock, E. Breynaert, G. Van Tendeloo, S. Bals, and J. A. Martens, “Self-Assembly of Pluronic F127—Silica Spherical Core–Shell Nanoparticles in Cubic Close-Packed Structures,” Chemistry of Materials 27, 5161–5169 (2015).
[Crossref]

Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nature Biotechnology 21, 1369–1377 (2003).
[Crossref] [PubMed]

Wilson, D. F.

T. V. Esipova, A. Karagodov, J. Miller, D. F. Wilson, T. M. Busch, and S. A. Vinogradov, “Two new “protected” oxyphors for biological oximetry: properties and application in tumor imaging,” Analytical Chemistry 83, 8756–8765 (2011).
[Crossref]

D. F. Wilson, S. A. Vinogradov, P. Grosul, M. N. Vaccarezza, A. Kuroki, and J. Bennett, “Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging,” Appl. Opt. 44, 5239 (2005).
[Crossref] [PubMed]

I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: Phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Analytical Biochemistry 310, 191–198 (2002).
[Crossref] [PubMed]

J. M. Vanderkooi, G. Maniara, T. J. Green, and D. F. Wilson, “An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence,” J. Biol. Chem. 262, 5476–5482 (1987).
[PubMed]

Wodnicki, P.

A. Periasamy, P. Wodnicki, X. F. Wang, S. Kwon, G. W. Gordon, and B. Herman, “Time-resolved fluorescence lifetime imaging microscopy using a picosecond pulsed tunable dye laser system,” Review of Scientific Instruments 67, 3722–3731 (1996).
[Crossref]

Wu, J.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Xu, C.

S. S. Howard, A. Straub, N. G. Horton, D. Kobat, and C. Xu, “Frequency-multiplexed in vivo multiphoton phosphorescence lifetime microscopy,” Nature Photonics 7, 33–37 (2013).
[Crossref]

Xu, H.

H. Xu, J. W. Aylott, R. Kopelman, T. J. Miller, and M. A. Philbert, “A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma,” Analytical Chemistry 73, 4124–4133 (2001).
[Crossref] [PubMed]

Xu, W.

K. J. Morris, M. S. Roach, W. Xu, J. N. Demas, and B. A. DeGraff, “Luminescence lifetime standards for the nanosecond to microsecond range and oxygen quenching of ruthenium(II) complexes,” Analytical Chemistry 79, 9310–9314 (2007).
[Crossref] [PubMed]

Yaseen, M. A.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
[Crossref]

Yoon, D.

J. Zaias, M. Mineau, C. Cray, D. Yoon, and N. H. Altman, “Reference Values for Serum Proteins of Common Laboratory Rodent Strains,” J. Am. Assoc. Lab. Anim. Sci. 48, 387–390 (2009).
[PubMed]

Yuan, S.

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

Yusuf, R.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Zaher, W.

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
[Crossref] [PubMed]

Zaias, J.

J. Zaias, M. Mineau, C. Cray, D. Yoon, and N. H. Altman, “Reference Values for Serum Proteins of Common Laboratory Rodent Strains,” J. Am. Assoc. Lab. Anim. Sci. 48, 387–390 (2009).
[PubMed]

Zhang, S.

A. A. Khan, S. Zhang, G. Vigil, J. D. Boerckel, and S. S. Howard, “Two-Photon Intravital Imaging of a Mouse Brain In Vivo Using Easily Prepared Ruthenium-Poloxamer Nanoprobes,” in “Optics in the Life Sciences,” (OSA, Washington, D.C., 2015), Ii, p. BT1A.3.

Zhang, Y.

Y. Zhang, A. A. Khan, G. D. Vigil, and S. S. Howard, “Investigation of signal-to-noise ratio in frequency-domain multiphoton fluorescence lifetime imaging microscopy,” Journal of the Optical Society of America A 33, B1 (2016).
[Crossref]

Zhong, W.

D. Sud, W. Zhong, D. Beer, and M.-A. Mycek, “Measurement of intracellular oxygen levels using fluorescence lifetime imaging microscopy (FLIM),” in “European Conference on Biomedical Optics 2005,” K. Licha and R. Cubeddu, eds. (International Society for Optics and Photonics, 2005), p. 585907.
[Crossref]

Zipfel, W. R.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nature Biotechnology 21, 1369–1377 (2003).
[Crossref] [PubMed]

Analytical Biochemistry (1)

I. Dunphy, S. A. Vinogradov, and D. F. Wilson, “Oxyphor R2 and G2: Phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence,” Analytical Biochemistry 310, 191–198 (2002).
[Crossref] [PubMed]

Analytical Chemistry (4)

T. V. Esipova, A. Karagodov, J. Miller, D. F. Wilson, T. M. Busch, and S. A. Vinogradov, “Two new “protected” oxyphors for biological oximetry: properties and application in tumor imaging,” Analytical Chemistry 83, 8756–8765 (2011).
[Crossref]

H. Xu, J. W. Aylott, R. Kopelman, T. J. Miller, and M. A. Philbert, “A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma,” Analytical Chemistry 73, 4124–4133 (2001).
[Crossref] [PubMed]

Y. E. L. Koo, Y. Cao, R. Kopelman, S. M. Koo, M. Brasuel, and M. A. Philbert, “Real-Time Measurements of Dissolved Oxygen Inside Live Cells by Organically Modified Silicate Fluorescent Nanosensors,” Analytical Chemistry 76, 2498–2505 (2004).
[Crossref] [PubMed]

K. J. Morris, M. S. Roach, W. Xu, J. N. Demas, and B. A. DeGraff, “Luminescence lifetime standards for the nanosecond to microsecond range and oxygen quenching of ruthenium(II) complexes,” Analytical Chemistry 79, 9310–9314 (2007).
[Crossref] [PubMed]

Appl. Opt. (1)

Applied optics (1)

S. Sakadžić, S. Yuan, E. Dilekoz, S. Ruvinskaya, S. A. Vinogradov, C. Ayata, and D. A. Boas, “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied optics 48, D169–D177 (2009).
[Crossref]

Applied Physics Letters (1)

R. N. Ghosh, P. A. Askeland, S. Kramer, and R. Loloee, “Optical dissolved oxygen sensor utilizing molybdenum chloride cluster phosphorescence,” Applied Physics Letters 98, 221103 (2011).
[Crossref]

Biomed. Opt. Express (1)

Biomedical Optics Express (1)

S. M. S. Kazmi, A. J. Salvaggio, A. D. Estrada, M. A. Hemati, N. K. Shaydyuk, E. Roussakis, T. A. Jones, S. A. Vinogradov, and A. K. Dunn, “Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion,” Biomedical Optics Express 4, 1061–1073 (2013).
[Crossref] [PubMed]

Cellular and molecular life sciences : CMLS (1)

R. I. Dmitriev and D. B. Papkovsky, “Optical probes and techniques for O2 measurement in live cells and tissue,” Cellular and molecular life sciences : CMLS 69, 2025–2039 (2012).
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Chemical Society Reviews (1)

D. B. Papkovsky and R. I. Dmitriev, “Biological detection by optical oxygen sensing,” Chemical Society Reviews 42, 8700–8732 (2013).
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Chemistry of Materials (1)

S. Kerkhofs, T. Willhammar, H. Van Den Noortgate, C. E. A. Kirschhock, E. Breynaert, G. Van Tendeloo, S. Bals, and J. A. Martens, “Self-Assembly of Pluronic F127—Silica Spherical Core–Shell Nanoparticles in Cubic Close-Packed Structures,” Chemistry of Materials 27, 5161–5169 (2015).
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ChemPhysChem (1)

O. S. Finikova, A. Y. Lebedev, A. Aprelev, T. Troxler, F. Gao, C. Garnacho, S. Muro, R. M. Hochstrasser, and S. A. Vinogradov, “Oxygen microscopy by two-photon-excited phosphorescence,” ChemPhysChem 9, 1673–1679 (2008).
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Clin. Exp. Metastasis (1)

P. P. Provenzano, K. W. Eliceiri, and P. J. Keely, “Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment,” Clin. Exp. Metastasis 26, 357–370 (2009).
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J. Am. Assoc. Lab. Anim. Sci. (1)

J. Zaias, M. Mineau, C. Cray, D. Yoon, and N. H. Altman, “Reference Values for Serum Proteins of Common Laboratory Rodent Strains,” J. Am. Assoc. Lab. Anim. Sci. 48, 387–390 (2009).
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J. Biol. Chem. (1)

J. M. Vanderkooi, G. Maniara, T. J. Green, and D. F. Wilson, “An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence,” J. Biol. Chem. 262, 5476–5482 (1987).
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Journal of Biomedical Optics (2)

M. Maurin, O. Stéphan, J.-C. Vial, S. R. Marder, and B. van der Sanden, “Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles,” Journal of Biomedical Optics 16, 36001 (2011).
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K. Koenig and I. Riemann, “High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution,” Journal of Biomedical Optics 8, 432 (2003).
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Journal of Microscopy (1)

H. C. Gerritsen, M. A. H. Asselbergs, A. V. Agronskaia, and W. G. J. H. M. Van Sark, “Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution,” Journal of Microscopy 206, 218–224 (2002).
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Journal of Porphyrins and Phthalocyanines (1)

A. Y. Lebedev, T. Troxler, and S. A. Vinogradov, “Design of metalloporphyrin-based dendritic nanoprobes for two-photon microscopy of oxygen,” Journal of Porphyrins and Phthalocyanines 12, 1261–1269 (2008).
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Journal of the Optical Society of America A (1)

Y. Zhang, A. A. Khan, G. D. Vigil, and S. S. Howard, “Investigation of signal-to-noise ratio in frequency-domain multiphoton fluorescence lifetime imaging microscopy,” Journal of the Optical Society of America A 33, B1 (2016).
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Macromolecules (1)

P. Alexandridis, J. F. Holzwarth, and T. A. Hatton, “Micellization of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymers in Aqueous Solutions: Thermodynamics of Copolymer Association,” Macromolecules 27, 2414–2425 (1994).
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Nature (1)

J. A. Spencer, F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, R. Turcotte, R. Yusuf, D. Côté, S. A. Vinogradov, D. T. Scadden, and C. P. Lin, “Direct measurement of local oxygen concentration in the bone marrow of live animals,” Nature 508, 269–273 (2014).
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Nature Biotechnology (1)

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nature Biotechnology 21, 1369–1377 (2003).
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Nature Medicine (1)

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. G. Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nature Medicine 17, 893–898 (2011).
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Nature Methods (2)

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nature Methods 7, 755–759 (2010).
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Nature Photonics (1)

S. S. Howard, A. Straub, N. G. Horton, D. Kobat, and C. Xu, “Frequency-multiplexed in vivo multiphoton phosphorescence lifetime microscopy,” Nature Photonics 7, 33–37 (2013).
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Proc. Natl. Acad. Sci. U. S. A. (1)

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U. S. A. 104, 19494–19499 (2007).
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Review of Scientific Instruments (1)

A. Periasamy, P. Wodnicki, X. F. Wang, S. Kwon, G. W. Gordon, and B. Herman, “Time-resolved fluorescence lifetime imaging microscopy using a picosecond pulsed tunable dye laser system,” Review of Scientific Instruments 67, 3722–3731 (1996).
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RSC Adv. (1)

A. A. Khan, S. K. Fullerton-Shirey, and S. S. Howard, “Easily prepared ruthenium-complex nanomicelle probes for two-photon quantitative imaging of oxygen in aqueous media,” RSC Adv. 5, 291–300 (2015).
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A. Orte, J. M. Alvarez-Pez, and M. J. Ruedas-Rama, “Fluorescence Lifetime Imaging Microscopy for the Detection of Intracellular pH with Quantum Dot Nanosensors,” ACS Nano pp. 6387–6395 (2013).
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D. Sud, W. Zhong, D. Beer, and M.-A. Mycek, “Measurement of intracellular oxygen levels using fluorescence lifetime imaging microscopy (FLIM),” in “European Conference on Biomedical Optics 2005,” K. Licha and R. Cubeddu, eds. (International Society for Optics and Photonics, 2005), p. 585907.
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Figures (7)

Fig. 1
Fig. 1

Illustration of [Ru(dpp)3]2+–nanomicelle with deposited silica shell.

Fig. 2
Fig. 2

Preparation procedure for silica-coated [Ru(dpp)3]2+–nanomicelles, modified from [29].

Fig. 3
Fig. 3

Experimental setup for frequency-domain lifetime measurement with two-photon excitation. (EOM: electro-optic modulator. DAQ: data acquisition card. PMT: photomultiplier tube.)

Fig. 4
Fig. 4

Stern-Volmer plots for probes with different levels of silica coating at 37 °C. Inset: Variation of oxygen sensitivity with silica coating. Error bars represent standard deviation over 3 prepared batches. (1 hPa = 10−2 Pa = 1 millibar)

Fig. 5
Fig. 5

Stability data for probes with different levels of silica coating.

Fig. 6
Fig. 6

Two-decay micelle failure model. Decay profile of (a) 10%- and (b) 50%-coated probes and their biexponential fits. (c) Relative contributions and half-lives of the slow and fast decay process versus silica coating level.

Fig. 7
Fig. 7

Oxygen-sensitivity (Ksv) and stable half-life of the probe versus silica coating level.

Tables (2)

Tables Icon

Table 1 List of precursors

Tables Icon

Table 2 Stern-Volmer parameters for various levels of silica coating at 37 °C.

Equations (2)

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τ 0 τ = 1 + K sv × p O 2
P ( t ) = A 2 t / h A + B 2 t / h B

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