Abstract

Currently, researchers and clinicians lack achromatized endomicroscope objectives that are as narrow as biopsy needles. We present a proof-of-concept prototype that validates the optical design of an NA0.4 objective. The objective, built with plastic lenses, has a 0.9 mm clear aperture and is achromatized from 452 nm to 623 nm. The objective’s measured Strehl ratio is 0.74 ± 0.05 across a 250 μm FOV. We perform optical sectioning via structured illumination through the objective while capturing fluorescence images of breast carcinoma cells stained with proflavine and cresyl violet. This technology has the potential to improve optical biopsies and provide the next step forward in cancer diagnostics.

© 2013 OSA

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2012 (1)

2011 (4)

M. Kyrish, U. Utzinger, M. R. Descour, B. K. Baggett, and T. S. Tkaczyk, “Ultra-slim plastic endomicroscope objective for non-linear microscopy,” Opt. Express19(8), 7603–7615 (2011).
[CrossRef] [PubMed]

T. Tot and L. Tabár, “The role of radiological-pathological correlation in diagnosing early breast cancer: the pathologist’s perspective,” Virchows Arch.458(2), 125–131 (2011).
[CrossRef] [PubMed]

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

B. McCall, M. Pierce, E. A. Graviss, R. Richards-Kortum, and T. Tkaczyk, “Toward a low-cost compact array microscopy platform for detection of tuberculosis,” Tuberculosis (Edinb.)91(Suppl 1), S54–S60 (2011).
[CrossRef] [PubMed]

2010 (6)

2009 (3)

R. T. Kester, T. Christenson, R. R. Kortum, and T. S. Tkaczyk, “Low cost, high performance, self-aligning miniature optical systems,” Appl. Opt.48(18), 3375–3384 (2009).
[CrossRef] [PubMed]

D. S. Gareau, “Feasibility of digitally stained multimodal confocal mosaics to simulate histopathology,” J. Biomed. Opt.14(3), 034050 (2009).
[CrossRef] [PubMed]

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol.102(2), 1310–1314 (2009).
[CrossRef] [PubMed]

2008 (3)

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

N. Bozinovic, C. Ventalon, T. Ford, and J. Mertz, “Fluorescence endomicroscopy with structured illumination,” Opt. Express16(11), 8016–8025 (2008).
[CrossRef] [PubMed]

2007 (3)

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express15(25), 16413–16423 (2007).
[CrossRef] [PubMed]

Y. Cui, E. A. Koop, P. J. van Diest, R. A. Kandel, and T. E. Rohan, “Nuclear morphometric features in benign breast tissue and risk of subsequent breast cancer,” Breast Cancer Res. Treat.104(1), 103–107 (2007).
[CrossRef] [PubMed]

D. Wang, B. V. Hunter, M. J. Cobb, and X. Li, “Super-achromatic rapid scanning microendoscope for ultrahigh-resolution OCT imaging,” IEEE J. Sel. Top. Quantum Electron.13(6), 1596–1601 (2007).
[CrossRef]

2006 (4)

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

M. T. Myaing, D. J. MacDonald, and X. Li, “Fiber-optic scanning two-photon fluorescence endoscope,” Opt. Lett.31(8), 1076–1078 (2006).
[CrossRef] [PubMed]

M. D. Chidley, K. D. Carlson, R. R. Richards-Kortum, and M. R. Descour, “Design, assembly, and optical bench testing of a high-numerical-aperture miniature injection-molded objective for fiber-optic confocal reflectance microscopy,” Appl. Opt.45(11), 2545–2554 (2006).
[CrossRef] [PubMed]

2005 (1)

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

2004 (2)

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

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(31), 5763–5771 (2004).
[CrossRef] [PubMed]

2003 (1)

2002 (2)

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

1983 (1)

Abrat, B.

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

Anandasabapathy, S.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

Baggett, B. K.

Bartels, H.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Bartels, P. H.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Barton, J. K.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Bini, J.

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

Birch, G. C.

Bozinovic, N.

Brucker, D.

Carlson, K. D.

Chia, T. H.

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol.102(2), 1310–1314 (2009).
[CrossRef] [PubMed]

Chidley, M. D.

Christenson, T.

Christenson, T. C.

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

Cobb, M. J.

D. Wang, B. V. Hunter, M. J. Cobb, and X. Li, “Super-achromatic rapid scanning microendoscope for ultrahigh-resolution OCT imaging,” IEEE J. Sel. Top. Quantum Electron.13(6), 1596–1601 (2007).
[CrossRef]

Collier, T.

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

Côté, D.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Cui, Y.

Y. Cui, E. A. Koop, P. J. van Diest, R. A. Kandel, and T. E. Rohan, “Nuclear morphometric features in benign breast tissue and risk of subsequent breast cancer,” Breast Cancer Res. Treat.104(1), 103–107 (2007).
[CrossRef] [PubMed]

Davis, J.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Dereniak, E. L.

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

Descour, M.

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

Descour, M. R.

DiMarzio, C.

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

Drexler, W.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Ehrhardt, A.

Eigenbrod, S.

Ezhov, E. G.

Fischer, S.

Follen, M.

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

Ford, T.

Frank, D.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Gaalema, S.

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

Gareau, D. S.

D. S. Gareau, “Feasibility of digitally stained multimodal confocal mosaics to simulate histopathology,” J. Biomed. Opt.14(3), 034050 (2009).
[CrossRef] [PubMed]

Genet, M.

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

Gillenwater, A.

Gmitro, A. F.

Göbel, W.

Goetz, M.

Gordon, R. J.

Granchelli, G.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Graviss, E. A.

B. McCall, M. Pierce, E. A. Graviss, R. Richards-Kortum, and T. Tkaczyk, “Toward a low-cost compact array microscopy platform for detection of tuberculosis,” Tuberculosis (Edinb.)91(Suppl 1), S54–S60 (2011).
[CrossRef] [PubMed]

Greisukh, G. I.

Hariri, L. P.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Harpaz, N.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

Hazelwood, V.

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

Hermann, B.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Herms, J.

Hunter, B. V.

D. Wang, B. V. Hunter, M. J. Cobb, and X. Li, “Super-achromatic rapid scanning microendoscope for ultrahigh-resolution OCT imaging,” IEEE J. Sel. Top. Quantum Electron.13(6), 1596–1601 (2007).
[CrossRef]

Irion, K.-M.

Johansson, A.

Jung, J. C.

Kandel, R. A.

Y. Cui, E. A. Koop, P. J. van Diest, R. A. Kandel, and T. E. Rohan, “Nuclear morphometric features in benign breast tissue and risk of subsequent breast cancer,” Breast Cancer Res. Treat.104(1), 103–107 (2007).
[CrossRef] [PubMed]

Kano, A.

Kester, R. T.

Kienast, Y.

Kim, P.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Kniebühler, G.

Koop, E. A.

Y. Cui, E. A. Koop, P. J. van Diest, R. A. Kandel, and T. E. Rohan, “Nuclear morphometric features in benign breast tissue and risk of subsequent breast cancer,” Breast Cancer Res. Treat.104(1), 103–107 (2007).
[CrossRef] [PubMed]

Kortum, R. R.

Kreth, F.-W.

Kroto, S. M.

Kyrish, M.

Lacombe, F.

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

Laemmel, E.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

Landau, S. M.

Le Gargasson, J.-F.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

Le Goualher, G.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

Leiner, D. C.

Levene, M. J.

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol.102(2), 1310–1314 (2009).
[CrossRef] [PubMed]

Levin, I. A.

Li, X.

Liang, C.

S. M. Landau, C. Liang, R. T. Kester, T. S. Tkaczyk, and M. R. Descour, “Design and evaluation of an ultra-slim objective for in-vivo deep optical biopsy,” Opt. Express18(5), 4758–4775 (2010).
[CrossRef] [PubMed]

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

Lin, C. P.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Loiseau, S.

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

MacDonald, D. J.

Mariuzzi, G. M.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Mariuzzi, L.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Maru, D.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

McCall, B.

B. McCall, M. Pierce, E. A. Graviss, R. Richards-Kortum, and T. Tkaczyk, “Toward a low-cost compact array microscopy platform for detection of tuberculosis,” Tuberculosis (Edinb.)91(Suppl 1), S54–S60 (2011).
[CrossRef] [PubMed]

McNally, J.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Mertz, J.

Mombello, A.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Muldoon, T. J.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express15(25), 16413–16423 (2007).
[CrossRef] [PubMed]

Myaing, M. T.

Nakamura, H.

Nehal, K.

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

Nida, D. L.

Osdoit, A.

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

Perchant, A.

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

Pierce, M.

B. McCall, M. Pierce, E. A. Graviss, R. Richards-Kortum, and T. Tkaczyk, “Toward a low-cost compact array microscopy platform for detection of tuberculosis,” Tuberculosis (Edinb.)91(Suppl 1), S54–S60 (2011).
[CrossRef] [PubMed]

Pierce, M. C.

Potack, J.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

Povazay, B.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Prescott, R.

Puoris’haag, M.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Rahman, M.

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

Rajadhyaksha, M.

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

Richards-Kortum, R.

B. McCall, M. Pierce, E. A. Graviss, R. Richards-Kortum, and T. Tkaczyk, “Toward a low-cost compact array microscopy platform for detection of tuberculosis,” Tuberculosis (Edinb.)91(Suppl 1), S54–S60 (2011).
[CrossRef] [PubMed]

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express15(25), 16413–16423 (2007).
[CrossRef] [PubMed]

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

Richards-Kortum, R. R.

Roblyer, D.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

Rogers, J. D.

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

Rohan, T. E.

Y. Cui, E. A. Koop, P. J. van Diest, R. A. Kandel, and T. E. Rohan, “Nuclear morphometric features in benign breast tissue and risk of subsequent breast cancer,” Breast Cancer Res. Treat.104(1), 103–107 (2007).
[CrossRef] [PubMed]

Rouse, A. R.

Rucco, V.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Rühm, A.

Sattmann, H.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Schnitzer, M. J.

Spain, J.

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

Stepanov, S. A.

Stepp, H.

Sung, K.-B.

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

Tabár, L.

T. Tot and L. Tabár, “The role of radiological-pathological correlation in diagnosing early breast cancer: the pathologist’s perspective,” Virchows Arch.458(2), 125–131 (2011).
[CrossRef] [PubMed]

Tarocco, E.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Thekkek, N.

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

Thompson, D.

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Tkaczyk, T.

B. McCall, M. Pierce, E. A. Graviss, R. Richards-Kortum, and T. Tkaczyk, “Toward a low-cost compact array microscopy platform for detection of tuberculosis,” Tuberculosis (Edinb.)91(Suppl 1), S54–S60 (2011).
[CrossRef] [PubMed]

Tkaczyk, T. S.

Tot, T.

T. Tot and L. Tabár, “The role of radiological-pathological correlation in diagnosing early breast cancer: the pathologist’s perspective,” Virchows Arch.458(2), 125–131 (2011).
[CrossRef] [PubMed]

Tumlinson, A. R.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Udovich, J. A.

Unterhuber, A.

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

Utzinger, U.

van Diest, P. J.

Y. Cui, E. A. Koop, P. J. van Diest, R. A. Kandel, and T. E. Rohan, “Nuclear morphometric features in benign breast tissue and risk of subsequent breast cancer,” Breast Cancer Res. Treat.104(1), 103–107 (2007).
[CrossRef] [PubMed]

Ventalon, C.

Vicaut, E.

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

Wang, D.

D. Wang, B. V. Hunter, M. J. Cobb, and X. Li, “Super-achromatic rapid scanning microendoscope for ultrahigh-resolution OCT imaging,” IEEE J. Sel. Top. Quantum Electron.13(6), 1596–1601 (2007).
[CrossRef]

Williams, M. D.

Wu, Y.

Yun, S. H.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Zhao, Y.

Appl. Opt. (6)

Biomed. Opt. Express (2)

Breast Cancer Res. Treat. (1)

Y. Cui, E. A. Koop, P. J. van Diest, R. A. Kandel, and T. E. Rohan, “Nuclear morphometric features in benign breast tissue and risk of subsequent breast cancer,” Breast Cancer Res. Treat.104(1), 103–107 (2007).
[CrossRef] [PubMed]

Gastrointest. Endosc. (1)

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc.68(4), 737–744 (2008).
[CrossRef] [PubMed]

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

D. Wang, B. V. Hunter, M. J. Cobb, and X. Li, “Super-achromatic rapid scanning microendoscope for ultrahigh-resolution OCT imaging,” IEEE J. Sel. Top. Quantum Electron.13(6), 1596–1601 (2007).
[CrossRef]

IEEE Trans. Biomed. Eng. (1)

K.-B. Sung, C. Liang, M. Descour, T. Collier, M. Follen, and R. Richards-Kortum, “Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues,” IEEE Trans. Biomed. Eng.49(10), 1168–1172 (2002).
[CrossRef] [PubMed]

J. Biomed. Opt. (5)

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

T. J. Muldoon, N. Thekkek, D. Roblyer, D. Maru, N. Harpaz, J. Potack, S. Anandasabapathy, and R. Richards-Kortum, “Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett’s esophagus,” J. Biomed. Opt.15(2), 026027 (2010).
[CrossRef] [PubMed]

J. Bini, J. Spain, K. Nehal, V. Hazelwood, C. DiMarzio, and M. Rajadhyaksha, “Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance,” J. Biomed. Opt.16(7), 076008 (2011).
[CrossRef] [PubMed]

D. S. Gareau, “Feasibility of digitally stained multimodal confocal mosaics to simulate histopathology,” J. Biomed. Opt.14(3), 034050 (2009).
[CrossRef] [PubMed]

A. R. Tumlinson, B. Povazay, L. P. Hariri, J. McNally, A. Unterhuber, B. Hermann, H. Sattmann, W. Drexler, and J. K. Barton, “In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope,” J. Biomed. Opt.11(6), 064003 (2006).
[CrossRef] [PubMed]

J. Neurophysiol. (1)

T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol.102(2), 1310–1314 (2009).
[CrossRef] [PubMed]

J. Vasc. Res. (1)

E. Laemmel, M. Genet, G. Le Goualher, A. Perchant, J.-F. Le Gargasson, and E. Vicaut, “Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy,” J. Vasc. Res.41(5), 400–411 (2004).
[CrossRef] [PubMed]

Mod. Pathol. (1)

L. Mariuzzi, A. Mombello, G. Granchelli, V. Rucco, E. Tarocco, D. Frank, J. Davis, D. Thompson, H. Bartels, G. M. Mariuzzi, and P. H. Bartels, “Quantitative study of breast cancer progression: different pathways for various in situ cancers,” Mod. Pathol.15(1), 18–25 (2002).
[CrossRef] [PubMed]

Opt. Express (5)

Opt. Lett. (2)

Proc. SPIE (2)

A. Osdoit, M. Genet, A. Perchant, S. Loiseau, B. Abrat, and F. Lacombe, “In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist,” Proc. SPIE6082, 608208, 608208-10 (2006).
[CrossRef]

T. S. Tkaczyk, J. D. Rogers, M. Rahman, T. C. Christenson, S. Gaalema, E. L. Dereniak, R. Richards-Kortum, and M. R. Descour, “Multi-modal miniature microscope: 4M Device for bio-imaging applications - an overview of the system,” Proc. SPIE5959, 59590N, 59590N-9 (2005).
[CrossRef]

Tuberculosis (Edinb.) (1)

B. McCall, M. Pierce, E. A. Graviss, R. Richards-Kortum, and T. Tkaczyk, “Toward a low-cost compact array microscopy platform for detection of tuberculosis,” Tuberculosis (Edinb.)91(Suppl 1), S54–S60 (2011).
[CrossRef] [PubMed]

Virchows Arch. (1)

T. Tot and L. Tabár, “The role of radiological-pathological correlation in diagnosing early breast cancer: the pathologist’s perspective,” Virchows Arch.458(2), 125–131 (2011).
[CrossRef] [PubMed]

Other (4)

GRINTECH GmbH, “GRIN lens systems for medical applications,” http://www.grintech.de/grin-lens-systems-for-medical-applications.html .

S. Bäumer, Handbook of Plastic Optics (Wiley, 2011).

ISO, “Photography—electronic still-picture cameras—resolution measurements,” ISO 12233:2000, http://www.iso.org/iso/home/store/catalogue_tc/catalogue_detail.htm?csnumber=33715 .

National Cancer Institute, “Breast Cancer Risk in American Women,” http://www.cancer.gov/cancertopics/factsheet/detection/probability-breast-cancer .

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Figures (9)

Fig. 1
Fig. 1

Schematic representation of the achromatic objective. The diameter of the lenses is 0.9 mm.

Fig. 2
Fig. 2

Nominal performance of the achromatic objective. (a) Diffraction limited polychromatic MTF. (b) Diffraction limited image space chromatic focal shift.

Fig. 3
Fig. 3

(a) SolidWorks cutaway of the assembled achromatic objective with built-in alignment features used to validate the optical design. The insets show optical surfaces (left) and alignment features (right). (b) Example of two singlet lenses next to a US quarter with the clear apertures of the lenses circled. (c) Fully assembled prototype achromatic objective.

Fig. 4
Fig. 4

(a) Measuring tilt with a white light interferometer. The doublet’s average tilt was 0.093° with a standard deviation of 0.055°. (b) Measuring decenter with an integrated gage amplifier. The doublet’s average decenter was 6.1 μm with a standard deviation of 0.7 μm.

Fig. 5
Fig. 5

Custom achromatic objective and commercial Zeiss objectives (a) relaying images in reverse and (b) relaying images as designed.

Fig. 6
Fig. 6

(a) The center of a hi-resolution 1951 USAF target illuminated with white light in transmission. The achromatic objective is operating in reverse, which means the resolution is limited by the image space NA = 0.14. (b) The region of interest outlined in (a). The smallest resolvable feature is group 8, element 5, which has a spatial frequency of 406 lp/mm. The theoretical diffraction limit is 417 lp/mm. (c) Set of four edges measured with the slanted edge method to determine the achromatic objective’s MTF and Strehl ratio.

Fig. 7
Fig. 7

(a) Polychromatic MTF of the achromatic objective. (b) Chromatic focal shifts of the achromatic objective and the monochromatic objective.

Fig. 8
Fig. 8

Images of cells from the 435S breast carcinoma cell line stained with proflavine and cresyl violet. The commercial Zeiss objective and the prototype achromatic objective provide high resolution images for proflavine and cresyl violet simultaneously. In contrast, cresyl violet is out of focus with the monochromatic objective.

Fig. 9
Fig. 9

Structured illumination images of cells from the 435S breast carcinoma cell line stained with proflavine and cresyl violet. Structured illumination was created with the Zeiss ApoTome and the cells were imaged with (a) the NA0.45 Zeiss commercial objective, (b) the monochromatic objective, and (c) the achromatic objective.

Tables (3)

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Table 1 Achromatic ultra-slim objective design specifications

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Table 2 Lens prescription of the achromatic objective

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Table 3 Tolerancing of the achromatic objective

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