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 aircore 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

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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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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

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).

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

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).

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).

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

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).

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).

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).

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

1997 (2)

1996 (2)

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

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).

1990 (1)

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

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

Hopt, A.

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

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

Mandella, M. J.

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).

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).

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).

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).

Myaing, M. T.

Neher, E.

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

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).

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).

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).

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).

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).

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).

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).

Piyawattanametha, W.

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).

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).

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).

Ra, H.

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

Solgaard, O.

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).

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).

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).

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).

Strickler, J. H.

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

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).

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).

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).

Theer, P.

Tirlapur, U. K.

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

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).

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).

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).

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).

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).

Wang, T. D.

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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).

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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).

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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).

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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).

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Nature (2)

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