Abstract

Two-photon endoscopy based on a gradient-index lens has been widely utilized for studying cellular behaviors in deep-lying tissues with minimal invasiveness in vivo. Although the efficient collection of emitted light is critical to attain high-contrast spatiotemporal information, the intrinsic low numerical aperture of the endoscopic probe poses a physical limitation. We report a simple solution to overcome this limit by incorporating a reflective waveguide ensheathing the endoscopic probe, which improves the collection efficiency by approximately two-fold. We describe its principle, fabrication procedure, optical characterization, and utilities in biological tissues.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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  1. W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
    [Crossref] [PubMed]
  2. M. Choi, S. J. J. Kwok, and S. H. Yun, “In vivo fluorescence microscopy: lessons from observing cell behavior in their native environment,” Physiology (Bethesda) 30(1), 40–49 (2015).
    [Crossref] [PubMed]
  3. J. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003).
    [Crossref] [PubMed]
  4. J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
    [Crossref] [PubMed]
  5. F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A Miniature Head-Mounted Neurotechnique Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
    [Crossref] [PubMed]
  6. M. Choi and S. H. Yun, “In vivo femtosecond endosurgery: an intestinal epithelial regeneration-after-injury model,” Opt. Express 21(25), 30842–30848 (2013).
    [Crossref] [PubMed]
  7. J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
    [Crossref] [PubMed]
  8. A. Attardo, J. E. Fitzgerald, and M. J. Schnitzer, “Impermanence of dendritic spines in live adult CA1 hippocampus,” Nature 523(7562), 592–596 (2015).
    [Crossref] [PubMed]
  9. M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
    [Crossref] [PubMed]
  10. C. J. Engelbrecht, W. Göbel, and F. Helmchen, “Enhanced fluorescence signal in nonlinear microscopy through supplementary fiber-optic light collection,” Opt. Express 17(8), 6421–6435 (2009).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  14. J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
    [Crossref] [PubMed]
  15. W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
    [Crossref] [PubMed]
  16. V. Jayaraman, Y. S. Lin, M. Pakala, and R. Y. Lin, “Fabrication of ultrathin metallic membranes on ceramic supports by sputter deposition,” J. Membr. Sci. 99(1), 89–100 (1995).
    [Crossref]
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    [Crossref] [PubMed]
  18. C. Odin, T. Guilbert, A. Alkilani, O. P. Boryskina, V. Fleury, and Y. Le Grand, “Collagen and myosin characterization by orientation field second harmonic microscopy,” Opt. Express 16(20), 16151–16165 (2008).
    [Crossref] [PubMed]
  19. C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
    [Crossref] [PubMed]
  20. D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
    [Crossref] [PubMed]

2016 (1)

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

2015 (2)

M. Choi, S. J. J. Kwok, and S. H. Yun, “In vivo fluorescence microscopy: lessons from observing cell behavior in their native environment,” Physiology (Bethesda) 30(1), 40–49 (2015).
[Crossref] [PubMed]

A. Attardo, J. E. Fitzgerald, and M. J. Schnitzer, “Impermanence of dendritic spines in live adult CA1 hippocampus,” Nature 523(7562), 592–596 (2015).
[Crossref] [PubMed]

2014 (1)

J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
[Crossref] [PubMed]

2013 (1)

2012 (2)

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

2011 (2)

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

J. P. Zinter and M. J. Levene, “Maximizing fluorescence collection efficiency in multiphoton microscopy,” Opt. Express 19(16), 15348–15362 (2011).
[Crossref] [PubMed]

2010 (1)

2009 (1)

2008 (2)

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[Crossref] [PubMed]

C. Odin, T. Guilbert, A. Alkilani, O. P. Boryskina, V. Fleury, and Y. Le Grand, “Collagen and myosin characterization by orientation field second harmonic microscopy,” Opt. Express 16(20), 16151–16165 (2008).
[Crossref] [PubMed]

2007 (1)

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

2004 (1)

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

2003 (2)

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

J. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003).
[Crossref] [PubMed]

2001 (1)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A Miniature Head-Mounted Neurotechnique Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

1998 (1)

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[Crossref] [PubMed]

1995 (1)

V. Jayaraman, Y. S. Lin, M. Pakala, and R. Y. Lin, “Fabrication of ultrathin metallic membranes on ceramic supports by sputter deposition,” J. Membr. Sci. 99(1), 89–100 (1995).
[Crossref]

Aksay, E.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Alkilani, A.

Attardo, A.

A. Attardo, J. E. Fitzgerald, and M. J. Schnitzer, “Impermanence of dendritic spines in live adult CA1 hippocampus,” Nature 523(7562), 592–596 (2015).
[Crossref] [PubMed]

Balaban, R. S.

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

Barretto, R. P. J.

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[Crossref] [PubMed]

Blanquet, V.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Boryskina, O. P.

Brown, C. M.

Choi, J. W.

J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
[Crossref] [PubMed]

Choi, M.

M. Choi, S. J. J. Kwok, and S. H. Yun, “In vivo fluorescence microscopy: lessons from observing cell behavior in their native environment,” Physiology (Bethesda) 30(1), 40–49 (2015).
[Crossref] [PubMed]

J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
[Crossref] [PubMed]

M. Choi and S. H. Yun, “In vivo femtosecond endosurgery: an intestinal epithelial regeneration-after-injury model,” Opt. Express 21(25), 30842–30848 (2013).
[Crossref] [PubMed]

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Combs, C. A.

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

Couderc, V.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Delp, S. L.

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[Crossref] [PubMed]

Denk, W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A Miniature Head-Mounted Neurotechnique Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[Crossref] [PubMed]

Engelbrecht, C. J.

Fee, M. S.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A Miniature Head-Mounted Neurotechnique Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

Fitzgerald, J. E.

A. Attardo, J. E. Fitzgerald, and M. J. Schnitzer, “Impermanence of dendritic spines in live adult CA1 hippocampus,” Nature 523(7562), 592–596 (2015).
[Crossref] [PubMed]

Fleury, V.

Gandjbakhche, A. H.

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

Göbel, W.

Guilbert, T.

Helmchen, F.

C. J. Engelbrecht, W. Göbel, and F. Helmchen, “Enhanced fluorescence signal in nonlinear microscopy through supplementary fiber-optic light collection,” Opt. Express 17(8), 6421–6435 (2009).
[Crossref] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A Miniature Head-Mounted Neurotechnique Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[Crossref] [PubMed]

Howard, S. S.

Huland, D. M.

Jayaraman, V.

V. Jayaraman, Y. S. Lin, M. Pakala, and R. Y. Lin, “Fabrication of ultrathin metallic membranes on ceramic supports by sputter deposition,” J. Membr. Sci. 99(1), 89–100 (1995).
[Crossref]

Jiang, Y.

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

Jung, J. C.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

J. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003).
[Crossref] [PubMed]

Jung, K.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kano, H.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Kim, J. K.

J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
[Crossref] [PubMed]

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kim, P.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kim, S.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Kim, Y. R.

J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
[Crossref] [PubMed]

Kleinfeld, D.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[Crossref] [PubMed]

Knutson, J. R.

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

Kwok, S. J. J.

M. Choi, S. J. J. Kwok, and S. H. Yun, “In vivo fluorescence microscopy: lessons from observing cell behavior in their native environment,” Physiology (Bethesda) 30(1), 40–49 (2015).
[Crossref] [PubMed]

Le Grand, Y.

Lee, W. M.

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Lefort, C.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Leproux, P.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Levene, M. J.

Lévêque, P.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Liao, Y.

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

Lin, R. Y.

V. Jayaraman, Y. S. Lin, M. Pakala, and R. Y. Lin, “Fabrication of ultrathin metallic membranes on ceramic supports by sputter deposition,” J. Membr. Sci. 99(1), 89–100 (1995).
[Crossref]

Lin, Y. S.

V. Jayaraman, Y. S. Lin, M. Pakala, and R. Y. Lin, “Fabrication of ultrathin metallic membranes on ceramic supports by sputter deposition,” J. Membr. Sci. 99(1), 89–100 (1995).
[Crossref]

Llewellyn, M. E.

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[Crossref] [PubMed]

Magnol, L.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

McMullen, J. D.

Mehta, A. D.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Mitra, P. P.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[Crossref] [PubMed]

O’Connor, R. P.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Odin, C.

Ouzounov, D. G.

Pakala, M.

V. Jayaraman, Y. S. Lin, M. Pakala, and R. Y. Lin, “Fabrication of ultrathin metallic membranes on ceramic supports by sputter deposition,” J. Membr. Sci. 99(1), 89–100 (1995).
[Crossref]

Pavlova, I.

Riley, J. D.

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

Rivera, D. R.

Schnitzer, M. J.

A. Attardo, J. E. Fitzgerald, and M. J. Schnitzer, “Impermanence of dendritic spines in live adult CA1 hippocampus,” Nature 523(7562), 592–596 (2015).
[Crossref] [PubMed]

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[Crossref] [PubMed]

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

J. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003).
[Crossref] [PubMed]

Smirnov, A. V.

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

Stepnoski, R.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A Miniature Head-Mounted Neurotechnique Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

Tian, M.

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

Tombelaine, V.

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

Wang, K.

Wang, W.

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

Webb, W. W.

Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Xu, C.

Yun, S. H.

M. Choi, S. J. J. Kwok, and S. H. Yun, “In vivo fluorescence microscopy: lessons from observing cell behavior in their native environment,” Physiology (Bethesda) 30(1), 40–49 (2015).
[Crossref] [PubMed]

J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
[Crossref] [PubMed]

M. Choi and S. H. Yun, “In vivo femtosecond endosurgery: an intestinal epithelial regeneration-after-injury model,” Opt. Express 21(25), 30842–30848 (2013).
[Crossref] [PubMed]

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Zhang, L.

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

Zinter, J. P.

Zipfel, W. R.

J. D. McMullen and W. R. Zipfel, “A multiphoton objective design with incorporated beam splitter for enhanced fluorescence collection,” Opt. Express 18(6), 5390–5398 (2010).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Zou, H.

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

Endoscopy (1)

J. W. Choi, J. K. Kim, M. Choi, Y. R. Kim, and S. H. Yun, “In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis,” Endoscopy 46(12), 1110–1116 (2014).
[Crossref] [PubMed]

J. Biophotonics (1)

C. Lefort, R. P. O’Connor, V. Blanquet, L. Magnol, H. Kano, V. Tombelaine, P. Lévêque, V. Couderc, and P. Leproux, “Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source,” J. Biophotonics 9(7), 709–714 (2016).
[Crossref] [PubMed]

J. Colloid Interface Sci. (1)

W. Wang, Y. Jiang, Y. Liao, M. Tian, H. Zou, and L. Zhang, “Fabrication of silver-coated silica microspheres through mussel-inspired surface functionalization,” J. Colloid Interface Sci. 358(2), 567–574 (2011).
[Crossref] [PubMed]

J. Membr. Sci. (1)

V. Jayaraman, Y. S. Lin, M. Pakala, and R. Y. Lin, “Fabrication of ultrathin metallic membranes on ceramic supports by sputter deposition,” J. Membr. Sci. 99(1), 89–100 (1995).
[Crossref]

J. Microsc. (1)

C. A. Combs, A. V. Smirnov, J. D. Riley, A. H. Gandjbakhche, J. R. Knutson, and R. S. Balaban, “Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector,” J. Microsc. 228(3), 330–337 (2007).
[Crossref] [PubMed]

J. Neurophysiol. (1)

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Nat. Biotechnol. (1)

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Nat. Protoc. (1)

J. K. Kim, W. M. Lee, P. Kim, M. Choi, K. Jung, S. Kim, and S. H. Yun, “Fabrication and operation of GRIN probes for in vivo fluorescence cellular imaging of internal organs in small animals,” Nat. Protoc. 7(8), 1456–1469 (2012).
[Crossref] [PubMed]

Nature (2)

A. Attardo, J. E. Fitzgerald, and M. J. Schnitzer, “Impermanence of dendritic spines in live adult CA1 hippocampus,” Nature 523(7562), 592–596 (2015).
[Crossref] [PubMed]

M. E. Llewellyn, R. P. J. Barretto, S. L. Delp, and M. J. Schnitzer, “Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans,” Nature 454(7205), 784–788 (2008).
[Crossref] [PubMed]

Neuron (1)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A Miniature Head-Mounted Neurotechnique Two-Photon Microscope. High-Resolution Brain Imaging in Freely Moving Animals,” Neuron 31(6), 903–912 (2001).
[Crossref] [PubMed]

Opt. Express (5)

Opt. Lett. (1)

Physiology (Bethesda) (1)

M. Choi, S. J. J. Kwok, and S. H. Yun, “In vivo fluorescence microscopy: lessons from observing cell behavior in their native environment,” Physiology (Bethesda) 30(1), 40–49 (2015).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[Crossref] [PubMed]

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Figures (5)

Fig. 1
Fig. 1 Principle of a reflective waveguiding endoscopy. (a,b) Schematic representations for excitation and emission rays in bare and reflection-coated singlet GRIN probes. Note that the reflective waveguiding in the coated probe selectively improves the emission NA (NAem). (c) Integration of the probe to two-photon system. Note that the excitation NA (NAex) is determined by the NA of the GRIN probe (NA ≈0.5) but the emission NA is determined by an objective lens (NA = 1.1). (d) Simulated beam profiles for collected light at the non-descanned detector. Area-integrated intensity represents collected signal at the detector. Pseudocolor indicates normalized intensity. (e) Quantification of collection efficiency with different external media in (d).
Fig. 2
Fig. 2 Fabrication of reflective waveguiding probes. (a) A step-by-step fabrication protocol for silver coating. Scale bars, 1 mm. (b) Scanning electron micrograph of the coated probe. Scalebars, 100 nm for the upper image and 250 μm for the lower image. (c) Measured reflectance spectrum of the silver film on a planar glass substrate formed by the sputter-based deposition method. Dashed line represents reflectance spectrum of the commercial silver mirror (Thorlabs, PF10-03-P01).
Fig. 3
Fig. 3 Characterization of collection efficiency. (a,b) Measurement of lateral and axial resolutions (n = 3 fluorescent beads for each traces). Excitation wavelength was tuned to 920 nm and emission was collected in a red channel (605 ± 35 nm). (c) Representative fluorescent images of a Rhodamine B solution (0.1 mM). (d) Quantification of fluorescent intensity (n = 3 samples; p < 0.0001 by unpaired t-test). (e) Representative SHG images of barium titanite (BaTiO3) microparticles. (f) Quantification of SHG intensity (n = 5 particles; p = 0.0017 by unpaired t-test).
Fig. 4
Fig. 4 Applications on biological tissues ex vivo. (a) Representative two-photon fluorescence images of the brain slice of a Thy1-YFP-H mouse taken on the same field-of-view. (b) Quantification of fluorescence intensity in soma denoted by arrowheads in (a). n = 13 neurons, p < 0.0001 by paired t-test. (c) Representative SHG images of the striated muscle. We maintained the orientation of the muscle fibers to avoid the influence of input polarization on SHG intensity. Excitation wavelength was tuned to 920 nm and emission was collected in a blue channel (460 ± 25 nm). (d) Representative line profiles of periodic sarcomere structures. (e) Quantification of the sarcomeric SHG amplitude in bare and coated probes. p = 0.009 by unpared t-test.
Fig. 5
Fig. 5 Applications on biological tissues in vivo. (a) Representative two-photon fluorescent images of cortical vasculature in vivo taken on the same field-of-view by bare or coated probes. A mouse was in anesthesia and blood plasma was labeled with rhodamine-dextran. (b) Quantification of arterial blood flow using a line-scanning method [20]. The measured vascular segment is indicated by black dashed lines in (a). The dark streaks indicate flowing RBCs. Scalebar: x, 40 μm. t, 20 ms.

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