Abstract

Combined two-photon fluorescence microscopy and femtosecond laser microsurgery has many potential biomedical applications as a powerful “seek-and-treat” tool. Towards developing such a tool, we demonstrate a miniaturized probe which combines these techniques in a compact housing. The device is 10×15×40 mm3 in size and uses an air-core photonic crystal fiber to deliver femtosecond laser pulses at 80 MHz repetition rate for imaging and 1 kHz for microsurgery. A fast two-axis microelectromechanical system scanning mirror is driven at resonance to produce Lissajous beam scanning at 10 frames per second. Field of view is 310 µm in diameter and the lateral and axial resolutions are 1.64 µm and 16.4 µm, respectively. Combined imaging and microsurgery is demonstrated using live cancer cells.

© 2008 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. U. K. Tirlapur and K. König, "Targeted transfection by femtosecond laser," Nature 418, 290-291 (2002).
    [CrossRef] [PubMed]
  2. M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
    [CrossRef] [PubMed]
  3. A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, "Mechanisms of femtosecond laser nanosurgery of cells and tissues," Appl. Phys. B 81, 1015-1047 (2005).
    [CrossRef]
  4. N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).
  5. A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
    [CrossRef]
  6. I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
    [PubMed]
  7. W. Denk, J. H. Strickler, and W. W. Webb, "2-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
    [CrossRef] [PubMed]
  8. P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Annu. Rev. Biomed. Eng. 2, 399-429 (2000).
    [CrossRef]
  9. W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: Multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1368-1376 (2003).
    [CrossRef]
  10. P. Theer and W. Denk, "On the fundamental imaging-depth limit in two-photon microscopy," J. Opt. Soc. Am. A 23, 3139-3149 (2006).
    [CrossRef]
  11. P. Theer, M. Hasan, and W. Denk, "Two-photon imaging to a depth of 1000?m in living brains by use of a Ti:Al2O3 regenerative amplifier," Opt. Lett. 28, 1022-1024 (2003).
    [CrossRef] [PubMed]
  12. N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
    [CrossRef] [PubMed]
  13. K. König, O. Krauss, and I. Riemann, "Intratissue surgery with 80 MHz nanojoule femtosecond laser pulses in the near infrared," Opt. Express 10, 171-176 (2002).
  14. E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
    [CrossRef] [PubMed]
  15. L. Sacconi, I. M. Tolic´-Nørrelykke, R. Antolini, and F. S. Pavone, "Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope," J. Biomed. Opt. 10, 014002-014001 - 014002-014005 (2005).
    [CrossRef]
  16. K. König, I. Riemann, F. Stracke, and R. Le Harzic, "Nanoprocessing with nanojoule near-infrared femtosecond laser pulses," Med. Las. Appl. 20, 169-184 (2005).
    [CrossRef]
  17. F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31, 903-912 (2001).
    [CrossRef] [PubMed]
  18. J. C. Jung and M. J. Schnitzer, "Multiphoton endoscopy," Opt. Lett. 28, 902-904 (2003).
    [CrossRef] [PubMed]
  19. W. Göbel, J. N. D. Kerr, A. Nimmerjahn, and F. Helmchen, "Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective," Opt. Lett. 29, 2521-2523 (2004).
    [CrossRef] [PubMed]
  20. B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, "In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope," Opt. Lett. 30, 2272-2274 (2005).
    [CrossRef] [PubMed]
  21. M. T. Myaing, D. J. MacDonald, and X. Li, "Fiber-optic scanning two-photon fluorescence endoscope," Opt. Lett. 31, 1076-1078 (2006).
    [CrossRef] [PubMed]
  22. L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).
  23. K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
    [CrossRef] [PubMed]
  24. D. Lee and O. Solgaard, "Two-axis gimbaled microscanner in double SOI layers actuated by self-aligned vertical electrostatic combdrive" in Proceedings of the Solid-State Sensors, Actuators and Microsystems Workshop, Hilton Head Island, Hilton Head Island, South Carolina, June 6-10, 2004, 352-355.
  25. H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
    [CrossRef]
  26. W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, "Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two-dimensional scanning mirror," Opt. Lett. 31, 2018-2020 (2006).
    [CrossRef] [PubMed]
  27. K. C. Maitland, H. J. Shin, H. Ra, D. Lee, O. Solgaard, and R. Richards-Kortum, "Single fiber confocal microscope with a two-axis gimbaled MEMS scanner for cellular imaging," Opt. Express 14, 8604-8612 (2006).
    [CrossRef] [PubMed]
  28. J. B. Guild, C. Xu, and W. W. Webb, "Measurement of group delay dispersion of high numerical aperture objective lenses using two-photon excited fluorescence," Appl. Opt. 36, 397-401 (1997).
    [CrossRef] [PubMed]
  29. D. L. Dickensheets and G. S. Kino, "Micromachined scanning confocal optical microscope," Opt. Lett. 21, 764-766 (1996).
    [CrossRef] [PubMed]
  30. M. M. Dickens, M. P. Houlne, S. Mitra, and D. J. Bornhop, "Method for depixelating micro-endoscopic images," Opt. Eng. 38, 1836-1842 (1999).
    [CrossRef]
  31. J. W. Goodman, Introduction to Fourier Optics, 3rd Edition (Roberts & Co., Englewood, 2005).
  32. B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, "Fiber-optic fluorescence imaging," Nature Methods 2, 941-950 (2005).
    [CrossRef] [PubMed]
  33. F. Bourgeois and A. Ben-Yakar, "Femtosecond laser nanoaxotomy properties and their effect on axonal recovery in C. Elegans," Opt. Express 15, 8521-8531 (2007).
    [CrossRef] [PubMed]
  34. Urey, H. , "Spot size, depth-of-focus, and diffraction ring intensity formulas for truncated Gaussian beams," Appl. Opt.,  43620-625 (2004)
    [CrossRef] [PubMed]
  35. K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, "Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes " Opt. Lett. 22, 135-136 (1997).
    [CrossRef] [PubMed]
  36. K. König, T. W. Becker, P. Fischer, I. Riemann, and K. J. Halbhuber, "Pulse-length dependence of cellular response to intense near-infrared laser pulses in multiphoton microscopes," Opt. Lett. 24, 113-115 (1999).
    [CrossRef]
  37. H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: Signal and photodamage," Biophys. J. 77, 2226-2236 (1999).
    [CrossRef] [PubMed]
  38. A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
    [CrossRef] [PubMed]
  39. H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
    [CrossRef] [PubMed]
  40. N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
    [CrossRef] [PubMed]
  41. M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

2007 (6)

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
[CrossRef]

F. Bourgeois and A. Ben-Yakar, "Femtosecond laser nanoaxotomy properties and their effect on axonal recovery in C. Elegans," Opt. Express 15, 8521-8531 (2007).
[CrossRef] [PubMed]

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[CrossRef] [PubMed]

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

2006 (5)

2005 (6)

K. König, I. Riemann, F. Stracke, and R. Le Harzic, "Nanoprocessing with nanojoule near-infrared femtosecond laser pulses," Med. Las. Appl. 20, 169-184 (2005).
[CrossRef]

A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, "Mechanisms of femtosecond laser nanosurgery of cells and tissues," Appl. Phys. B 81, 1015-1047 (2005).
[CrossRef]

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, "In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope," Opt. Lett. 30, 2272-2274 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, "Fiber-optic fluorescence imaging," Nature Methods 2, 941-950 (2005).
[CrossRef] [PubMed]

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

2004 (3)

2003 (5)

I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
[PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: Multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1368-1376 (2003).
[CrossRef]

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

J. C. Jung and M. J. Schnitzer, "Multiphoton endoscopy," Opt. Lett. 28, 902-904 (2003).
[CrossRef] [PubMed]

P. Theer, M. Hasan, and W. Denk, "Two-photon imaging to a depth of 1000?m in living brains by use of a Ti:Al2O3 regenerative amplifier," Opt. Lett. 28, 1022-1024 (2003).
[CrossRef] [PubMed]

2002 (2)

2001 (2)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31, 903-912 (2001).
[CrossRef] [PubMed]

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

2000 (1)

P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Annu. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

1999 (3)

K. König, T. W. Becker, P. Fischer, I. Riemann, and K. J. Halbhuber, "Pulse-length dependence of cellular response to intense near-infrared laser pulses in multiphoton microscopes," Opt. Lett. 24, 113-115 (1999).
[CrossRef]

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: Signal and photodamage," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

M. M. Dickens, M. P. Houlne, S. Mitra, and D. J. Bornhop, "Method for depixelating micro-endoscopic images," Opt. Eng. 38, 1836-1842 (1999).
[CrossRef]

1997 (2)

1996 (2)

D. L. Dickensheets and G. S. Kino, "Micromachined scanning confocal optical microscope," Opt. Lett. 21, 764-766 (1996).
[CrossRef] [PubMed]

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

1990 (1)

W. Denk, J. H. Strickler, and W. W. Webb, "2-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Anderson, E. P.

Antolini, R.

L. Sacconi, I. M. Tolic´-Nørrelykke, R. Antolini, and F. S. Pavone, "Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope," J. Biomed. Opt. 10, 014002-014001 - 014002-014005 (2005).
[CrossRef]

Barretto, R. P. J.

Baur, D.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: Signal and photodamage," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

Becker, T. W.

Ben-Yakar, A.

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[CrossRef] [PubMed]

F. Bourgeois and A. Ben-Yakar, "Femtosecond laser nanoaxotomy properties and their effect on axonal recovery in C. Elegans," Opt. Express 15, 8521-8531 (2007).
[CrossRef] [PubMed]

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
[CrossRef] [PubMed]

Berland, K. M.

P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Annu. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

Bornhop, D. J.

M. M. Dickens, M. P. Houlne, S. Mitra, and D. J. Bornhop, "Method for depixelating micro-endoscopic images," Opt. Eng. 38, 1836-1842 (1999).
[CrossRef]

Bourgeois, F.

Bückle, R.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

Cheng, J. X.

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Cheung, E. L. M.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, "Fiber-optic fluorescence imaging," Nature Methods 2, 941-950 (2005).
[CrossRef] [PubMed]

Chisholm, A. D.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
[CrossRef] [PubMed]

Cinar, H.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
[CrossRef] [PubMed]

Cinar, H. N.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
[CrossRef] [PubMed]

Cocker, E. D.

Contag, C. H.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

Cranfield, C.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).

Da Silva, L. B.

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

Darash-Yahana, M.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Datta, D.

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

Denk, W.

P. Theer and W. Denk, "On the fundamental imaging-depth limit in two-photon microscopy," J. Opt. Soc. Am. A 23, 3139-3149 (2006).
[CrossRef]

P. Theer, M. Hasan, and W. Denk, "Two-photon imaging to a depth of 1000?m in living brains by use of a Ti:Al2O3 regenerative amplifier," Opt. Lett. 28, 1022-1024 (2003).
[CrossRef] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31, 903-912 (2001).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, "2-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Dickens, M. M.

M. M. Dickens, M. P. Houlne, S. Mitra, and D. J. Bornhop, "Method for depixelating micro-endoscopic images," Opt. Eng. 38, 1836-1842 (1999).
[CrossRef]

Dickensheets, D. L.

Dong, C. Y.

P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Annu. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

Durr, N. J.

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[CrossRef] [PubMed]

Ehlers, A.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

Fee, M. S.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31, 903-912 (2001).
[CrossRef] [PubMed]

Feit, M. D.

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

Ferincz, I. E.

I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
[PubMed]

Fischer, P.

Flusberg, B. A.

Friedman, B.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
[CrossRef] [PubMed]

Fu, L.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).

Galun, E.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Glinsky, M. E.

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

Göbel, W.

Gratton, E.

Gu, M.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).

Guild, J. B.

Halbhuber, K. J.

Hasan, M.

He, W.

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Hell, S. W.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: Signal and photodamage," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

Helmchen, F.

W. Göbel, J. N. D. Kerr, A. Nimmerjahn, and F. Helmchen, "Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective," Opt. Lett. 29, 2521-2523 (2004).
[CrossRef] [PubMed]

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31, 903-912 (2001).
[CrossRef] [PubMed]

Honigman, A.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Hopt, A.

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

Houlne, M. P.

M. M. Dickens, M. P. Houlne, S. Mitra, and D. J. Bornhop, "Method for depixelating micro-endoscopic images," Opt. Eng. 38, 1836-1842 (1999).
[CrossRef]

Hsiung, P.-L.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

Huff, T. B.

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Hüttman, G.

A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, "Mechanisms of femtosecond laser nanosurgery of cells and tissues," Appl. Phys. B 81, 1015-1047 (2005).
[CrossRef]

Hyam, E.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Ingber, D. E.

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

Jain, A.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).

Jin, Y. S.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
[CrossRef] [PubMed]

Juhasz, T.

I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
[PubMed]

Jung, J. C.

Kaatz, M.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

Kerr, J. N. D.

Khatchatouriants, A.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Kino, G. S.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

D. L. Dickensheets and G. S. Kino, "Micromachined scanning confocal optical microscope," Opt. Lett. 21, 764-766 (1996).
[CrossRef] [PubMed]

Kleinfeld, D.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
[CrossRef] [PubMed]

Ko, T. H.

Koester, H. J.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: Signal and photodamage," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

König, K.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

K. König, I. Riemann, F. Stracke, and R. Le Harzic, "Nanoprocessing with nanojoule near-infrared femtosecond laser pulses," Med. Las. Appl. 20, 169-184 (2005).
[CrossRef]

U. K. Tirlapur and K. König, "Targeted transfection by femtosecond laser," Nature 418, 290-291 (2002).
[CrossRef] [PubMed]

K. König, O. Krauss, and I. Riemann, "Intratissue surgery with 80 MHz nanojoule femtosecond laser pulses in the near infrared," Opt. Express 10, 171-176 (2002).

K. König, T. W. Becker, P. Fischer, I. Riemann, and K. J. Halbhuber, "Pulse-length dependence of cellular response to intense near-infrared laser pulses in multiphoton microscopes," Opt. Lett. 24, 113-115 (1999).
[CrossRef]

K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, "Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes " Opt. Lett. 22, 135-136 (1997).
[CrossRef] [PubMed]

Korgel, B. A.

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[CrossRef] [PubMed]

Krauss, O.

Krueger, R. R.

I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
[PubMed]

Kurtz, R. M.

I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
[PubMed]

Larson, T.

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[CrossRef] [PubMed]

Le Harzic, R.

K. König, I. Riemann, F. Stracke, and R. Le Harzic, "Nanoprocessing with nanojoule near-infrared femtosecond laser pulses," Med. Las. Appl. 20, 169-184 (2005).
[CrossRef]

LeDuc, P.

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

Lee, D.

Lewis, A.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Li, X.

Liu, J. T. C.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

Low, P. S.

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Lyden, P. D.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
[CrossRef] [PubMed]

MacDonald, D. J.

Maitland, K. C.

Mammini, B.

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

Mandella, M. J.

H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
[CrossRef]

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

Manevitch, A.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Mantulin, W. W.

Masters, B. R.

P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Annu. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

Mazur, E.

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

Mitra, S.

M. M. Dickens, M. P. Houlne, S. Mitra, and D. J. Bornhop, "Method for depixelating micro-endoscopic images," Opt. Eng. 38, 1836-1842 (1999).
[CrossRef]

Myaing, M. T.

Neher, E.

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

Nimmerjahn, A.

Nishimura, N.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
[CrossRef] [PubMed]

Noack, J.

A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, "Mechanisms of femtosecond laser nanosurgery of cells and tissues," Appl. Phys. B 81, 1015-1047 (2005).
[CrossRef]

Oraevsky, A. A.

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

Paltauf, G.

A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, "Mechanisms of femtosecond laser nanosurgery of cells and tissues," Appl. Phys. B 81, 1015-1047 (2005).
[CrossRef]

Pappo, O.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Pavone, F. S.

L. Sacconi, I. M. Tolic´-Nørrelykke, R. Antolini, and F. S. Pavone, "Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope," J. Biomed. Opt. 10, 014002-014001 - 014002-014005 (2005).
[CrossRef]

Perry, M. D.

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

Piyawattanametha, W.

H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
[CrossRef]

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, "Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two-dimensional scanning mirror," Opt. Lett. 31, 2018-2020 (2006).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, "Fiber-optic fluorescence imaging," Nature Methods 2, 941-950 (2005).
[CrossRef] [PubMed]

Ra, H.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
[CrossRef]

W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, "Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two-dimensional scanning mirror," Opt. Lett. 31, 2018-2020 (2006).
[CrossRef] [PubMed]

K. C. Maitland, H. J. Shin, H. Ra, D. Lee, O. Solgaard, and R. Richards-Kortum, "Single fiber confocal microscope with a two-axis gimbaled MEMS scanner for cellular imaging," Opt. Express 14, 8604-8612 (2006).
[CrossRef] [PubMed]

Ratkay-Traub, I.

I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
[PubMed]

Richards-Kortum, R.

Riemann, I.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

K. König, I. Riemann, F. Stracke, and R. Le Harzic, "Nanoprocessing with nanojoule near-infrared femtosecond laser pulses," Med. Las. Appl. 20, 169-184 (2005).
[CrossRef]

K. König, O. Krauss, and I. Riemann, "Intratissue surgery with 80 MHz nanojoule femtosecond laser pulses in the near infrared," Opt. Express 10, 171-176 (2002).

K. König, T. W. Becker, P. Fischer, I. Riemann, and K. J. Halbhuber, "Pulse-length dependence of cellular response to intense near-infrared laser pulses in multiphoton microscopes," Opt. Lett. 24, 113-115 (1999).
[CrossRef]

Rubenchik, A. M.

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

Sacconi, L.

L. Sacconi, I. M. Tolic´-Nørrelykke, R. Antolini, and F. S. Pavone, "Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope," J. Biomed. Opt. 10, 014002-014001 - 014002-014005 (2005).
[CrossRef]

Schaffer, C. B.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
[CrossRef] [PubMed]

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

Schenkl, S.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

Schnitzer, M. J.

Shen, N.

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

Shin, H. J.

Smith, D. K.

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[CrossRef] [PubMed]

So, P. T. C.

P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Annu. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, "Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes " Opt. Lett. 22, 135-136 (1997).
[CrossRef] [PubMed]

Sokolov, K.

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[CrossRef] [PubMed]

Solgaard, O.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
[CrossRef]

W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, "Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two-dimensional scanning mirror," Opt. Lett. 31, 2018-2020 (2006).
[CrossRef] [PubMed]

K. C. Maitland, H. J. Shin, H. Ra, D. Lee, O. Solgaard, and R. Richards-Kortum, "Single fiber confocal microscope with a two-axis gimbaled MEMS scanner for cellular imaging," Opt. Express 14, 8604-8612 (2006).
[CrossRef] [PubMed]

Stracke, F.

K. König, I. Riemann, F. Stracke, and R. Le Harzic, "Nanoprocessing with nanojoule near-infrared femtosecond laser pulses," Med. Las. Appl. 20, 169-184 (2005).
[CrossRef]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, "2-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Taguchi, Y.

H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
[CrossRef]

Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31, 903-912 (2001).
[CrossRef] [PubMed]

Tavor, E.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Theer, P.

Tirlapur, U. K.

U. K. Tirlapur and K. König, "Targeted transfection by femtosecond laser," Nature 418, 290-291 (2002).
[CrossRef] [PubMed]

Tolic´-Nørrelykke, I. M.

L. Sacconi, I. M. Tolic´-Nørrelykke, R. Antolini, and F. S. Pavone, "Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope," J. Biomed. Opt. 10, 014002-014001 - 014002-014005 (2005).
[CrossRef]

Tsai, P. S.

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
[CrossRef] [PubMed]

Uhl, R.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: Signal and photodamage," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

Urey,

Vogel, A.

A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, "Mechanisms of femtosecond laser nanosurgery of cells and tissues," Appl. Phys. B 81, 1015-1047 (2005).
[CrossRef]

Wang, H. F.

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Wang, T. D.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

Webb, W. W.

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: Multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1368-1376 (2003).
[CrossRef]

J. B. Guild, C. Xu, and W. W. Webb, "Measurement of group delay dispersion of high numerical aperture objective lenses using two-photon excited fluorescence," Appl. Opt. 36, 397-401 (1997).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, "2-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Wei, A.

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: Multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1368-1376 (2003).
[CrossRef]

Wong, L. K.

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

Xie, H.

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).

Xu, C.

Yanik, M. F.

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
[CrossRef] [PubMed]

Zeira, E.

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Zipfel, W. R.

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: Multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1368-1376 (2003).
[CrossRef]

Zweifel, D. A.

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Annu. Rev. Biomed. Eng. (1)

P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Annu. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

Appl. Opt. (2)

Appl. Phys. B (1)

A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, "Mechanisms of femtosecond laser nanosurgery of cells and tissues," Appl. Phys. B 81, 1015-1047 (2005).
[CrossRef]

Biophys. J. (2)

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: Signal and photodamage," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

A. A. Oraevsky, L. B. Da Silva, A. M. Rubenchik, M. D. Feit, M. E. Glinsky, M. D. Perry, B. Mammini, M. W. Small, IV, and B. C. Stuart, "Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: Relative role of linear and nonlinear absorption," IEEE J. Sel. Top. Quantum Electron. 2, 801-809 (1996).
[CrossRef]

J. Microelectromech. Syst. (1)

H. Ra, W. Piyawattanametha, Y. Taguchi, D. Lee, M. J. Mandella, and O. Solgaard, "Two-dimensional MEMS scanner for dual-axes confocal microscopy," J. Microelectromech. Syst. 16, 969-976 (2007).
[CrossRef]

J. Opt. Soc. Am. A (1)

J. Refract. Surg. (1)

I. Ratkay-Traub, I. E. Ferincz, T. Juhasz, R. M. Kurtz, and R. R. Krueger, "First clinical results with the femtosecond neodynium-glass laser in refractive surgery," J. Refract. Surg. 19, 94-103 (2003).
[PubMed]

JBO Lett. (1)

L. Fu, A. Jain, C. Cranfield, H. Xie, and M. Gu, "Three-dimensional nonlinear optical endoscopy," JBO Lett. 12, 0405011-04050113 (2007).

Mech. Chem. Biosyst. (1)

N. Shen, D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur, "Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor," Mech. Chem. Biosyst. 2, 17-25 (2005).

Med. Las. Appl. (1)

K. König, I. Riemann, F. Stracke, and R. Le Harzic, "Nanoprocessing with nanojoule near-infrared femtosecond laser pulses," Med. Las. Appl. 20, 169-184 (2005).
[CrossRef]

Microsc. Res. Tech. (1)

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, "Clinical two-photon microendoscopy," Microsc. Res. Tech. 70, 398-402 (2007).
[CrossRef] [PubMed]

Mol. Ther. (1)

E. Zeira, A. Manevitch, A. Khatchatouriants, O. Pappo, E. Hyam, M. Darash-Yahana, E. Tavor, A. Honigman, A. Lewis, and E. Galun, "Femtosecond infrared laser—an efficient and safe in vivo gene delivery system for prolonged expression," Mol. Ther. 8, 342-350 (2003).
[CrossRef] [PubMed]

Nano Lett. (1)

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, "Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods," Nano Lett. 7, 941-945 (2007).
[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, 1368-1376 (2003).
[CrossRef]

Nature (2)

U. K. Tirlapur and K. König, "Targeted transfection by femtosecond laser," Nature 418, 290-291 (2002).
[CrossRef] [PubMed]

M. F. Yanik, H. Cinar, H. N. Cinar, A. D. Chisholm, Y. S. Jin, and A. Ben-Yakar, "Functional regeneration after laser axotomy," Nature 432, 822-822 (2004).
[CrossRef] [PubMed]

Nature Methods (2)

N. Nishimura, C. B. Schaffer, B. Friedman, P. S. Tsai, P. D. Lyden, and D. Kleinfeld, "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke," Nature Methods 3, 99-108 (2006).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, and M. J. Schnitzer, "Fiber-optic fluorescence imaging," Nature Methods 2, 941-950 (2005).
[CrossRef] [PubMed]

Neuron (1)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, "A miniature head-mounted two-photon microscope: High-resolution brain imaging in freely moving animals," Neuron 31, 903-912 (2001).
[CrossRef] [PubMed]

Opt. Eng. (1)

M. M. Dickens, M. P. Houlne, S. Mitra, and D. J. Bornhop, "Method for depixelating micro-endoscopic images," Opt. Eng. 38, 1836-1842 (1999).
[CrossRef]

Opt. Express (3)

Opt. Lett. (9)

P. Theer, M. Hasan, and W. Denk, "Two-photon imaging to a depth of 1000?m in living brains by use of a Ti:Al2O3 regenerative amplifier," Opt. Lett. 28, 1022-1024 (2003).
[CrossRef] [PubMed]

J. C. Jung and M. J. Schnitzer, "Multiphoton endoscopy," Opt. Lett. 28, 902-904 (2003).
[CrossRef] [PubMed]

W. Göbel, J. N. D. Kerr, A. Nimmerjahn, and F. Helmchen, "Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective," Opt. Lett. 29, 2521-2523 (2004).
[CrossRef] [PubMed]

B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, "In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope," Opt. Lett. 30, 2272-2274 (2005).
[CrossRef] [PubMed]

M. T. Myaing, D. J. MacDonald, and X. Li, "Fiber-optic scanning two-photon fluorescence endoscope," Opt. Lett. 31, 1076-1078 (2006).
[CrossRef] [PubMed]

K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, "Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes " Opt. Lett. 22, 135-136 (1997).
[CrossRef] [PubMed]

K. König, T. W. Becker, P. Fischer, I. Riemann, and K. J. Halbhuber, "Pulse-length dependence of cellular response to intense near-infrared laser pulses in multiphoton microscopes," Opt. Lett. 24, 113-115 (1999).
[CrossRef]

W. Piyawattanametha, R. P. J. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, "Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two-dimensional scanning mirror," Opt. Lett. 31, 2018-2020 (2006).
[CrossRef] [PubMed]

D. L. Dickensheets and G. S. Kino, "Micromachined scanning confocal optical microscope," Opt. Lett. 21, 764-766 (1996).
[CrossRef] [PubMed]

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

H. F. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, and J. X. Cheng, "In vitro and in vivo two-photon luminescence imaging of single gold nanorods," Proc. Natl. Acad. Sci. U. S. A. 102, 15752-15756 (2005).
[CrossRef] [PubMed]

Proc. SPIE (1)

M. J. Mandella, J. T. C. Liu, W. Piyawattanametha, H. Ra, P.-L. Hsiung, L. K. Wong, O. Solgaard, T. D. Wang, C. H. Contag, and G. S. Kino, "Compact optical design for dual-axes confocal endoscopic microscopes," Proc. SPIE 6443, E1-E9 (2007).

Science (1)

W. Denk, J. H. Strickler, and W. W. Webb, "2-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Other (3)

J. W. Goodman, Introduction to Fourier Optics, 3rd Edition (Roberts & Co., Englewood, 2005).

L. Sacconi, I. M. Tolic´-Nørrelykke, R. Antolini, and F. S. Pavone, "Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope," J. Biomed. Opt. 10, 014002-014001 - 014002-014005 (2005).
[CrossRef]

D. Lee and O. Solgaard, "Two-axis gimbaled microscanner in double SOI layers actuated by self-aligned vertical electrostatic combdrive" in Proceedings of the Solid-State Sensors, Actuators and Microsystems Workshop, Hilton Head Island, Hilton Head Island, South Carolina, June 6-10, 2004, 352-355.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (4)

Fig. 1.
Fig. 1.

The 10×15×40 mm3 miniaturized two-photon microscope and femtosecond laser microsurgery probe. (a) The model includes 1) air-core PCF and GRIN collimating lens, 2) two-axis MEMS scanner, 3) miniature aspheric relay lenses, 4) mirror, 5) dichroic mirror, 6) 0.46-NA GRIN objective lens, and 7) 2mm-core plastic optical fiber. (b) The photograph shows the miniature probe as built without the delivery fiber and the lid that was used to seal the probe. The PCF and its collimating GRIN lens were mounted separately and aligned to the probe during experiments. (c) SEM micrographs of the PCF core and cladding structure, and MEMS scanning mirror design (d). The scale bars are 15 µm in (c) (3 µm in inset), and 600 µm in (d) (120 µm in inset).

Fig. 2.
Fig. 2.

Two-photon fluorescence imaging characterization of the miniature TPM/FLMS probe. (a) 1 µm fluorescent beads on glass, demonstrating 310 µm maximum FOV. Laser power at the sample was measured to be 8.2 mW. (b) A representative lateral point spread function from 100 nm fluorescent beads in agar (shown in inset). Black dots represent measured intensity values while the red line is the Gaussian curve fit. (c) Pollen grains imaged using 9.0 mW average power at the sample. Image (a) is averaged over 0.6 seconds, while images (b) and (c) are averaged over 5 seconds, all at 10 fps. Images (a) and (c) were spatially filtered. Scale bars are 50 µm in (a), 5 µm in (b), and 25 µm in (c).

Fig. 3.
Fig. 3.

Combined two-photon microscopy and femtosecond laser microsurgery of a single layer of breast carcinoma cells. (a) Two photon image of a single layer of live breast carcinoma cells after uptake of calcein AM taken prior to irradiation with high intensity pulses. (b) The same FOV as (a), immediately after irradiation with a single pulse at 280 nJ pulse energy. Average laser power used for imaging in both images was 10 mW. Both images were averaged over 5 seconds at 10 fps and spatially filtered. Note that the targeted cell has lost fluorescence while the cell touching the targeted cell is left intact. Scale bars are 20 µm.

Figure 4.
Figure 4.

Combined two-photon microscopy and femtosecond laser microsurgery of breast carcinoma cells in a collagen tissue phantom. (a) Lateral slices with FOV of 116×160 µm2 depicting a cell targeted for ablation as well as cells above it. The distance between the center of the targeted cell and those of the two cells above it is ~35 µm. (b) The same cells shown in (a) after irradiation of the targeted cell with 5000 pulses at 213 nJ pulse energy. (c, d) Vertical slice reconstruction through the same targeted cell and the cells above it before and after laser irradiation, respectively. Total imaging depth was 210 µm and the axial spacing between lateral slices was 6.6 µm. Scale bars are 20 µm.

Tables (1)

Tables Icon

Table 1. Comparison of imaging conditions proven not to affect cell viability to imaging conditions used in this study.

Metrics