Abstract

We discuss the design and performance of a miniature objective lens optimized for coherent Raman scattering microscopy. The packaged lens assembly has a numerical aperture of 0.51 in water and an outer diameter of 8 mm. The lens system exhibits minimum chromatic aberrations, and produces coherent Raman scattering images with sub-micrometer lateral resolution (0.648 μm) using near-infrared excitation pulses. We demonstrate that despite the small dimensions of the miniature objective, the performance of this lens system is comparable to standard microscope objective lenses, offering opportunities for miniaturizing coherent Raman scattering imaging probes without sacrificing the image quality.

© 2013 OSA

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  26. M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
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    [CrossRef]
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    [CrossRef]
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    [CrossRef] [PubMed]

2012

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

2011

2010

C. S. Rim, “The optical design of miniaturized microscope objective for CARS imaging catheter with fiber bundle,” J. Opt. Soc. Korea14424–430 (2010).
[CrossRef]

S. Murugkar, B. Smith, P. Srivastava, A. Moica, M. Naji, C. Brideau, P. K. Stys, and H. Anis, “Miniaturized multimodal CARS microscope based on MEMS scanning and a single laser source,” Opt. Express1823796–23804 (2010).
[CrossRef] [PubMed]

T. T. Le, H. M. Duren, M. N. Slipchenko, C. D. Hu, and J. X. Cheng, “Label-free quantitative analysis of lipid metabolism in living caenorhabditis elegans,” J. Lipid Res.51, 672–677 (2010).
[CrossRef]

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[CrossRef] [PubMed]

2009

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Meth.6, 511–512 (2009).
[CrossRef]

Y. Wu, J. Xi, M. J. Cobb, and X. Li, “Scanning fiber-optic nonlinear endomicroscopy with miniature aspherical compound lens and multimode fiber collector,” Opt. Lett.34, 953–955 (2009).
[CrossRef] [PubMed]

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

J. Zhu, B. Lee, K. K. Buhman, and J. X. Cheng, “A dynamic, cytoplasmic triacylglycerol pool in enterocytes revealed by ex vivo and in vivo coherent anti-Stokes Raman scattering imaging,” J. Lipid Res.50, 1080–1089 (2009).
[CrossRef] [PubMed]

Y. Fu, W. Sun, Y. Shi, R. Shi, and J. X. Cheng, “Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction,” PLoS one4, e6705 (2009).
[CrossRef] [PubMed]

Y. Jung, L. Tong, A. Tanaudommongkon, J. X. Cheng, and C. Yang, “In vitro and in vivo nonlinear optical imaging of silicon nanowires,” Nano Lett.9, 2440–2444 (2009).
[CrossRef] [PubMed]

2008

2007

2006

2005

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

2004

A. R. Rouse, A. Kano, J. A. Udovich, S. M. Kroto, and A. F. Gmitro, “Design and demonstration of a miniature catheter for a confocal microendoscope,” Appl. Opt.43, 5763–5771 (2004).
[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. Neurophys.92, 3121–3133 (2004).
[CrossRef]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
[CrossRef]

2002

2001

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun.188, 267–73 (2001).
[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. Neurophys.92, 3121–3133 (2004).
[CrossRef]

Allen, J.

Anis, H.

Baggett, B. K.

Bao, H.

Barretto, R. P. J.

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Meth.6, 511–512 (2009).
[CrossRef]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

Bélanger, E.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

Breunig, H. G.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Brideau, C.

Brown, C. M.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

Bückle, R.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Buess, G.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun.188, 267–73 (2001).
[CrossRef]

Buhman, K. K.

J. Zhu, B. Lee, K. K. Buhman, and J. X. Cheng, “A dynamic, cytoplasmic triacylglycerol pool in enterocytes revealed by ex vivo and in vivo coherent anti-Stokes Raman scattering imaging,” J. Lipid Res.50, 1080–1089 (2009).
[CrossRef] [PubMed]

Burns, L. D.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

Carlson, K. D.

Cheng, J. X.

T. T. Le, H. M. Duren, M. N. Slipchenko, C. D. Hu, and J. X. Cheng, “Label-free quantitative analysis of lipid metabolism in living caenorhabditis elegans,” J. Lipid Res.51, 672–677 (2010).
[CrossRef]

Y. Fu, W. Sun, Y. Shi, R. Shi, and J. X. Cheng, “Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction,” PLoS one4, e6705 (2009).
[CrossRef] [PubMed]

J. Zhu, B. Lee, K. K. Buhman, and J. X. Cheng, “A dynamic, cytoplasmic triacylglycerol pool in enterocytes revealed by ex vivo and in vivo coherent anti-Stokes Raman scattering imaging,” J. Lipid Res.50, 1080–1089 (2009).
[CrossRef] [PubMed]

Y. Jung, L. Tong, A. Tanaudommongkon, J. X. Cheng, and C. Yang, “In vitro and in vivo nonlinear optical imaging of silicon nanowires,” Nano Lett.9, 2440–2444 (2009).
[CrossRef] [PubMed]

T. B. Huff and J. X. Cheng, “In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue,” J. Microsc.225175–182 (2007).
[CrossRef] [PubMed]

H. Wang, T. B. Huff, Y. Fu, K. Y. Jia, and J. X. Cheng, “Increasing the imaging depth of coherent anti-Stokes Raman scattering microscopy with a miniature microscope objective,” Opt. Lett.32, 2212–2214 (2007).
[CrossRef] [PubMed]

Chidley, M. D.

Christenson, T.

Cobb, M. J.

Cocker, E. D.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

Côté, D.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

Crépeau, J.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

De Koninck, Y.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

Descour, M. R.

Dombeck, D. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
[CrossRef]

Duren, H. M.

T. T. Le, H. M. Duren, M. N. Slipchenko, C. D. Hu, and J. X. Cheng, “Label-free quantitative analysis of lipid metabolism in living caenorhabditis elegans,” J. Lipid Res.51, 672–677 (2010).
[CrossRef]

Engelbrecht, C. J.

Evans, C. L.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

Flusberg, B. A.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

Freudiger, C. W.

B. G. Saar, R. S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, “Coherent Raman scanning fiber endoscopy,” Opt. Lett.36, 2396–2398 (2011).
[CrossRef] [PubMed]

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[CrossRef] [PubMed]

Fu, L.

Fu, Y.

Gmitro, A. F.

Gu, M.

Helmchen, F.

Henry, F. P.

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

Holtom, G.

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[CrossRef] [PubMed]

Hu, C. D.

T. T. Le, H. M. Duren, M. N. Slipchenko, C. D. Hu, and J. X. Cheng, “Label-free quantitative analysis of lipid metabolism in living caenorhabditis elegans,” J. Lipid Res.51, 672–677 (2010).
[CrossRef]

Huff, T. B.

Jia, K. Y.

Johnston, R. S.

Jung, J. C.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

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. Neurophys.92, 3121–3133 (2004).
[CrossRef]

Jung, Y.

Y. Jung, L. Tong, A. Tanaudommongkon, J. X. Cheng, and C. Yang, “In vitro and in vivo nonlinear optical imaging of silicon nanowires,” Nano Lett.9, 2440–2444 (2009).
[CrossRef] [PubMed]

Kano, A.

Kasischke, K. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
[CrossRef]

Kellner-Höfer, M.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Kester, R. T.

Knittel, J.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun.188, 267–73 (2001).
[CrossRef]

Ko, T. H.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

Kobat, D.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

Kochevar, I. E.

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

König, K.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Kroto, S. M.

Kyrish, M.

Lademann, J.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Laffray, S.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

Le, T. T.

T. T. Le, H. M. Duren, M. N. Slipchenko, C. D. Hu, and J. X. Cheng, “Label-free quantitative analysis of lipid metabolism in living caenorhabditis elegans,” J. Lipid Res.51, 672–677 (2010).
[CrossRef]

Lee, B.

J. Zhu, B. Lee, K. K. Buhman, and J. X. Cheng, “A dynamic, cytoplasmic triacylglycerol pool in enterocytes revealed by ex vivo and in vivo coherent anti-Stokes Raman scattering imaging,” J. Lipid Res.50, 1080–1089 (2009).
[CrossRef] [PubMed]

Lee, D.

Levene, M. J.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
[CrossRef]

Li, X.

Liang, C.

Lin, C. P.

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

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. Neurophys.92, 3121–3133 (2004).
[CrossRef]

Messerschmidt, B.

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Meth.6, 511–512 (2009).
[CrossRef]

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun.188, 267–73 (2001).
[CrossRef]

Moica, A.

Molloy, R. P.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
[CrossRef]

Mukamel, E. A.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

Murugkar, S.

Naji, M.

Nimmerjahn, A.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

Ouzounov, D. G.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

Pattie, R.

Pavlova, I.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

Pierce, M. C.

Possner, T.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun.188, 267–73 (2001).
[CrossRef]

Potma, E. O.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

Puoris’haag, M.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

Ra, H.

Randolph, M. A.

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

Redmond, R. W.

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

Reichman, J.

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[CrossRef] [PubMed]

Richards-Kortum, R.

Richards-Kortum, R. R.

Rim, C. S.

Rivera, D. R.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

Rouse, A. R.

Rust, E. A. Z.

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

Saar, B. G.

B. G. Saar, R. S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, “Coherent Raman scanning fiber endoscopy,” Opt. Lett.36, 2396–2398 (2011).
[CrossRef] [PubMed]

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[CrossRef] [PubMed]

Schnieder, L.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun.188, 267–73 (2001).
[CrossRef]

Schnitzer, M. J.

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Meth.6, 511–512 (2009).
[CrossRef]

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

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. Neurophys.92, 3121–3133 (2004).
[CrossRef]

Seibel, E. J.

Shi, R.

Y. Fu, W. Sun, Y. Shi, R. Shi, and J. X. Cheng, “Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction,” PLoS one4, e6705 (2009).
[CrossRef] [PubMed]

Shi, Y.

Y. Fu, W. Sun, Y. Shi, R. Shi, and J. X. Cheng, “Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction,” PLoS one4, e6705 (2009).
[CrossRef] [PubMed]

Shin, H. J.

Slipchenko, M. N.

T. T. Le, H. M. Duren, M. N. Slipchenko, C. D. Hu, and J. X. Cheng, “Label-free quantitative analysis of lipid metabolism in living caenorhabditis elegans,” J. Lipid Res.51, 672–677 (2010).
[CrossRef]

Smith, B.

Solgaard, O.

Srivastava, P.

Stanley, M. C.

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[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. Neurophys.92, 3121–3133 (2004).
[CrossRef]

Sterry, W.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Stys, P. K.

Sun, W.

Y. Fu, W. Sun, Y. Shi, R. Shi, and J. X. Cheng, “Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction,” PLoS one4, e6705 (2009).
[CrossRef] [PubMed]

Sung, K. B.

Tanaudommongkon, A.

Y. Jung, L. Tong, A. Tanaudommongkon, J. X. Cheng, and C. Yang, “In vitro and in vivo nonlinear optical imaging of silicon nanowires,” Nano Lett.9, 2440–2444 (2009).
[CrossRef] [PubMed]

Tkaczyk, T. S.

Tong, L.

Y. Jung, L. Tong, A. Tanaudommongkon, J. X. Cheng, and C. Yang, “In vitro and in vivo nonlinear optical imaging of silicon nanowires,” Nano Lett.9, 2440–2444 (2009).
[CrossRef] [PubMed]

Udovich, J. A.

Utzinger, U.

Vallée, R.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

Vance, R.

Wang, H.

Webb, W. W.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
[CrossRef]

Weinigel, M.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Winograd, J. M.

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

Wu, Y.

Xi, J.

Xie, X. S.

B. G. Saar, R. S. Johnston, C. W. Freudiger, X. S. Xie, and E. J. Seibel, “Coherent Raman scanning fiber endoscopy,” Opt. Lett.36, 2396–2398 (2011).
[CrossRef] [PubMed]

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

Xu, C.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

Yang, C.

Y. Jung, L. Tong, A. Tanaudommongkon, J. X. Cheng, and C. Yang, “In vitro and in vivo nonlinear optical imaging of silicon nanowires,” Nano Lett.9, 2440–2444 (2009).
[CrossRef] [PubMed]

Zhu, J.

J. Zhu, B. Lee, K. K. Buhman, and J. X. Cheng, “A dynamic, cytoplasmic triacylglycerol pool in enterocytes revealed by ex vivo and in vivo coherent anti-Stokes Raman scattering imaging,” J. Lipid Res.50, 1080–1089 (2009).
[CrossRef] [PubMed]

Appl. Opt.

J. Biomed. Opt.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

J. Lipid Res.

T. T. Le, H. M. Duren, M. N. Slipchenko, C. D. Hu, and J. X. Cheng, “Label-free quantitative analysis of lipid metabolism in living caenorhabditis elegans,” J. Lipid Res.51, 672–677 (2010).
[CrossRef]

J. Zhu, B. Lee, K. K. Buhman, and J. X. Cheng, “A dynamic, cytoplasmic triacylglycerol pool in enterocytes revealed by ex vivo and in vivo coherent anti-Stokes Raman scattering imaging,” J. Lipid Res.50, 1080–1089 (2009).
[CrossRef] [PubMed]

J. Microsc.

T. B. Huff and J. X. Cheng, “In vivo coherent anti-Stokes Raman scattering imaging of sciatic nerve tissue,” J. Microsc.225175–182 (2007).
[CrossRef] [PubMed]

J. Neurophys.

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. Neurophys.92, 3121–3133 (2004).
[CrossRef]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophys.91, 1908–1912 (2004).
[CrossRef]

J. Opt. Soc. Korea

Microsc. Res. Techn.

H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, J. Lademann, W. Sterry, and K. König, “Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin,” Microsc. Res. Techn.75, 492–498 (2012).
[CrossRef]

Nano Lett.

Y. Jung, L. Tong, A. Tanaudommongkon, J. X. Cheng, and C. Yang, “In vitro and in vivo nonlinear optical imaging of silicon nanowires,” Nano Lett.9, 2440–2444 (2009).
[CrossRef] [PubMed]

Nat. Meth.

B. A. Flusberg, A. Nimmerjahn, E. D. Cocker, E. A. Mukamel, R. P. J. Barretto, T. H. Ko, L. D. Burns, J. C. Jung, and M. J. Schnitzer, “High-speed, miniaturized fluorescence microscopy in freely moving mice,” Nat. Meth.5, 935–938 (2008).
[CrossRef]

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Meth.6, 511–512 (2009).
[CrossRef]

Opt. Commun.

J. Knittel, L. Schnieder, G. Buess, B. Messerschmidt, and T. Possner, “Endoscope-compatible confocal microscope using a gradient index-lens system,” Opt. Commun.188, 267–73 (2001).
[CrossRef]

Opt. Express

Opt. Lett.

Plastic and reconstructive surgery

F. P. Henry, D. Côté, M. A. Randolph, E. A. Z. Rust, R. W. Redmond, I. E. Kochevar, C. P. Lin, and J. M. Winograd, “Real-time in vivo assessment of the nerve microenvironment with coherent antiStokes Raman scattering microscopy,” Plastic and reconstructive surgery123, 123S–130S (2009).
[CrossRef]

PLoS one

Y. Fu, W. Sun, Y. Shi, R. Shi, and J. X. Cheng, “Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction,” PLoS one4, e6705 (2009).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, C. P. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy,” Proc. Natl. Acad. Sci. USA102, 16807–16812 (2005).
[CrossRef] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. USA108, 17598–17603 (2011).
[CrossRef] [PubMed]

Science

B. G. Saar, C. W. Freudiger, J. Reichman, M. C. Stanley, G. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science3301368–1370 (2010).
[CrossRef] [PubMed]

Other

J. X. Cheng and X. S. Xie, Eds., Coherent Raman Scattering Microscopy (CRC Press, 2013).

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Figures (7)

Fig. 1:
Fig. 1:

Aberration corrected miniature objective. (a) Optical ray diagram of multiple lens elements combined to form a 5mm diameter, 0.51 NA miniature objective lens. (b) Rendering of the lenses and brass holder components (8 mm total outer diameter) with rings supporting lenses on both sides. (c) Photograph of the fabricated and assembled miniature objective next to a commercial objective.

Fig. 2:
Fig. 2:

ZEMAX predicted performance of the objective design. (a) Geometric spot size diagram for two radial distances from the optical axis (blue: 817 nm, red: 1064 nm wavelength). (b) Modulation transfer function (MTF) plot.

Fig. 3:
Fig. 3:

Transmission images taken at the fundamental excitation wavelengths. (a) High-resolution USAF 1951 target visualized at 817 nm. (b) Cross section taken at the red line in (a). Scale bar is 5 μm. (c) USAF 1951 target visualized at 1064 nm. (d) Cross section taken at the red line in (c). Scale bar is 5 μm. (e) Ronchi ruling with 5 μm per line pair visualized at 817 nm. (e) Lateral deviation across the field of view for both excitation wavelengths.

Fig. 4:
Fig. 4:

Resolution measurement of the miniature objective lens. (a) Lateral and (b) axial CARS intensity profile measurement for a 0.51 NA miniature objective. FWHM values (0.648 ± 0.073 μm lateral; 4.9 ± 0.16 μm axial) were determined by averaging the results from n = 11 particles. The pump and stokes laser wavelength was 817 nm and 1064 nm, respectively, corresponding to a Raman shift of 2845 cm−1. The pump and Stokes laser power at the sample are 10 mW and 20 mW respectively.

Fig. 5:
Fig. 5:

CARS images of 16 μm polystyrene beads over an extended field of view. (a) Image of beads acquired with the 0.51 NA miniature objective. (b) Image obtained with the 0.6 NA aspheric lens. (c) Image acquired using the Zeiss, 20X, 0.5NA objective lens. A fs pump source was used. All images are 512 × 512 pixels. Scale bar is 20 μm

Fig. 6:
Fig. 6:

CARS imaging of mouse ear tissue using the miniature objective lens at 2845 cm−1. (a, b) Adipocytes of the subcutaneous layer at ∼80 μm from the skin surface. (c) Lipid contrast from the stratum corneum (d) Hair structures near the surface of the tissue. The pump and Stokes laser power at the sample are 20 mW and 28 mW respectively. Images were acquired in the forward detection geometry. All images are 512 × 512 pixels and acquired in 2 s. A fs pump source was used. Scale bar is 20 μm.

Fig. 7:
Fig. 7:

Multimodal imaging of tissue samples ex vivo at 2845 cm−1 using the miniature objective (a) Epi-detection SHG (green) and CARS (red) image of thick rabbit skin tissue. A fs pump source was used. (b) Forward-detected SRS images of adipocytes in the mouse ear sample. A ps pump source was used. All images are 512 × 512 pixels. Scale bar is 20 μm.

Tables (2)

Tables Icon

Table 1 Specifications and experimental lateral resolution of the packaged miniature objective, the aspheric lens, and the commercial objective lens. Lateral resolution is given for the CARS imaging mode.

Tables Icon

Table 2 Axial and lateral focal widths of the miniature objective in the CARS imaging mode.

Metrics