OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 4, Iss. 2 — Feb. 1, 2013
  • pp: 287–297

Achromatized endomicroscope objective for optical biopsy

Matthew Kyrish and Tomasz S. Tkaczyk  »View Author Affiliations

Biomedical Optics Express, Vol. 4, Issue 2, pp. 287-297 (2013)

View Full Text Article

Enhanced HTML    Acrobat PDF (1405 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



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

OCIS Codes
(080.3620) Geometric optics : Lens system design
(170.2520) Medical optics and biotechnology : Fluorescence microscopy
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(220.0220) Optical design and fabrication : Optical design and fabrication
(220.1920) Optical design and fabrication : Diamond machining

ToC Category:
Endoscopes, Catheters and Micro-Optics

Original Manuscript: November 13, 2012
Revised Manuscript: January 9, 2013
Manuscript Accepted: January 18, 2013
Published: January 18, 2013

Matthew Kyrish and Tomasz S. Tkaczyk, "Achromatized endomicroscope objective for optical biopsy," Biomed. Opt. Express 4, 287-297 (2013)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. National Cancer Institute, “Breast Cancer Risk in American Women,” http://www.cancer.gov/cancertopics/factsheet/detection/probability-breast-cancer .
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. J. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett.28(11), 902–904 (2003). [CrossRef] [PubMed]
  10. 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]
  11. Y. Zhao, H. Nakamura, and R. J. Gordon, “Development of a versatile two-photon endoscope for biological imaging,” Biomed. Opt. Express1(4), 1159–1172 (2010). [CrossRef] [PubMed]
  12. Y. Wu and X. Li, “Combined influences of chromatic aberration and scattering in depth-resolved two-photon fluorescence endospectroscopy,” Biomed. Opt. Express1(4), 1234–1243 (2010). [CrossRef] [PubMed]
  13. GRINTECH GmbH, “GRIN lens systems for medical applications,” http://www.grintech.de/grin-lens-systems-for-medical-applications.html .
  14. D. C. Leiner and R. Prescott, “Correction of chromatic aberrations in GRIN endoscopes,” Appl. Opt.22(3), 383–386 (1983). [CrossRef] [PubMed]
  15. 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]
  16. T. H. Chia and M. J. Levene, “Microprisms for in vivo multilayer cortical imaging,” J. Neurophysiol.102(2), 1310–1314 (2009). [CrossRef] [PubMed]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. 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]
  25. G. C. Birch, M. R. Descour, and T. S. Tkaczyk, “Hyperspectral Shack-Hartmann test,” Appl. Opt.49(28), 5399–5406 (2010). [CrossRef] [PubMed]
  26. G. I. Greisukh, E. G. Ezhov, I. A. Levin, and S. A. Stepanov, “Design of achromatic and apochromatic plastic micro-objectives,” Appl. Opt.49(23), 4379–4384 (2010). [CrossRef] [PubMed]
  27. N. Bozinovic, C. Ventalon, T. Ford, and J. Mertz, “Fluorescence endomicroscopy with structured illumination,” Opt. Express16(11), 8016–8025 (2008). [CrossRef] [PubMed]
  28. 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]
  29. D. S. Gareau, “Feasibility of digitally stained multimodal confocal mosaics to simulate histopathology,” J. Biomed. Opt.14(3), 034050 (2009). [CrossRef] [PubMed]
  30. W. Göbel, D. Brucker, Y. Kienast, A. Johansson, G. Kniebühler, A. Rühm, S. Eigenbrod, S. Fischer, M. Goetz, F.-W. Kreth, A. Ehrhardt, H. Stepp, K.-M. Irion, and J. Herms, “Optical needle endoscope for safe and precise stereotactically guided biopsy sampling in neurosurgery,” Opt. Express20(24), 26117–26126 (2012). [CrossRef] [PubMed]
  31. 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]
  32. 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]
  33. 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]
  34. S. Bäumer, Handbook of Plastic Optics (Wiley, 2011).
  35. 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 .

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited