OSA's Digital Library

Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics


  • Editors: Andrew Dunn and Anthony Durkin
  • Vol. 6, Iss. 1 — Jan. 3, 2011

Full-field optical coherence microscopy for identifying live cancer cells by quantitative measurement of refractive index distribution

Woo June Choi, Do In Jeon, Sang-Gun Ahn, Jung-Hoon Yoon, Sungho Kim, and Byeong Ha Lee  »View Author Affiliations

Optics Express, Vol. 18, Issue 22, pp. 23285-23295 (2010)

View Full Text Article

Enhanced HTML    Acrobat PDF (1266 KB) Open Access

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



The feasibility of identifying cancer cells by measuring the refractive index (RI) distribution across a single live cell with ultrahigh resolution full-field optical coherence microscopy (FF-OCM) is presented. The FF-OCM is utilized to quantify integral RI distributions of unmodified cells without any cell treatments and used as a biophysical indicator for diagnosing cell malignancy. Firstly, the physical thickness distribution of the cell adherent to a culture dish is measured by taking a series of 0.6 µm resolved en-face tomograms. Subsequently, from the en-face image of the bottom surface of the cell or the top surface of the dish, the phase gain image of the cell is extracted. Then, from these two measurements the axially averaged RI map of the cell is extracted. The implemented FF-OCM system had a 0.8 µm axial resolution and the phase measurement sensitivity of the system was around 124 mrad. With the system, RI maps of several living cell lines of normal and cancer cells were constructed and quantitatively analyzed. The experiments showed that cancer cells had higher RI than normal ones. This approach using the FF-OCM has significant potential for cancer diagnosis and dynamic cell analysis as in situ label-free biophysical assay.

© 2010 OSA

OCIS Codes
(170.1530) Medical optics and biotechnology : Cell analysis
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: August 2, 2010
Revised Manuscript: October 7, 2010
Manuscript Accepted: October 9, 2010
Published: October 20, 2010

Virtual Issues
Vol. 6, Iss. 1 Virtual Journal for Biomedical Optics

Woo June Choi, Do In Jeon, Sang-Gun Ahn, Jung-Hoon Yoon, Sungho Kim, and Byeong Ha Lee, "Full-field optical coherence microscopy for identifying live cancer cells by quantitative measurement of refractive index distribution," Opt. Express 18, 23285-23295 (2010)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, “Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28(4), 312–316 (1999). [CrossRef] [PubMed]
  2. G. Zhang, M. Long, Z.-Z. Wu, and W.-Q. Yu, “Mechanical properties of hepatocellular carcinoma cells,” World J. Gastroenterol. 8(2), 243–246 (2002). [PubMed]
  3. J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88(5), 3689–3698 (2005). [CrossRef] [PubMed]
  4. S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, “Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria,” Acta Biomater. 1(1), 15–30 (2005). [CrossRef]
  5. M. J. Rosenbluth, W. A. Lam, and D. A. Fletcher, “Force Microscopy of Nonadherent Cells: A Comparison of Leukemia Cell Deformability,” Biophys. J. 90(8), 2994–3003 (2006). [CrossRef] [PubMed]
  6. S. Park, D. Koch, R. Cardenas, J. Käs, and C. K. Shih, “Cell motility and local viscoelasticity of fibroblasts,” Biophys. J. 89(6), 4330–4342 (2005). [CrossRef] [PubMed]
  7. S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3(4), 413–438 (2007). [CrossRef] [PubMed]
  8. V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, M. S. Feld, and T. McGillican, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000). [CrossRef] [PubMed]
  9. D. Bourgaize, T. R. Jewell, and R. G. Buiser, Biotechnology: Demystifying the Concepts (Addison Westly Longman, San Francisco, 1999).
  10. X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuator A 133(2), 349–354 (2007). [CrossRef]
  11. R. Barer, “Refractometry and interferometry of living cells,” J. Opt. Soc. Am. 47(6), 545–556 (1957). [CrossRef] [PubMed]
  12. W. Z. Song, X. M. Zhang, A. Q. Liu, C. S. Lim, P. H. Yap, and H. M. M. Hosseini, “Refractive index measurement of single living cells using on-chip Fabry-Perot cavity,” Appl. Phys. Lett. 89(20), 203901 (2006). [CrossRef]
  13. L. K. Chin, A. Q. Liu, C. S. Lim, X. M. Zhang, J. H. Ng, J. Z. Hao, and S. Takahashi, “Differential single living cell refractometry using grating resonant cavity with optical trap,” Appl. Phys. Lett. 91(24), 243901 (2007). [CrossRef]
  14. N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett. 31(18), 2759–2761 (2006). [CrossRef] [PubMed]
  15. C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65A(1), 88–92 (2005). [CrossRef]
  16. N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy,” J. Phys. Chem. A 113(47), 13327–13330 (2009). [CrossRef] [PubMed]
  17. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991). [CrossRef] [PubMed]
  18. A. Dubois, K. Grieve, G. Moneron, R. Lecaque, L. Vabre, and C. Boccara, “Ultrahigh-resolution full-field optical coherence tomography,” Appl. Opt. 43(14), 2874–2883 (2004). [CrossRef] [PubMed]
  19. M. Akiba, N. Maeda, K. Yumikake, T. Soma, K. Nishida, Y. Tano, and K. P. Chan, “Ultrahigh-resolution imaging of human donor cornea using full-field optical coherence tomography,” J. Biomed. Opt. 12(4), 041202 (2007). [CrossRef] [PubMed]
  20. A. Dubois, “Phase-map measurements by interferometry with sinusoidal phase modulation and four integrating buckets,” J. Opt. Soc. Am. A 18(8), 1972–1979 (2001). [CrossRef]
  21. W. J. Choi, J. Na, S. Y. Ryu, B. H. Lee, and D.-S. Ko, “Realization of 3-D Topographic and Tomographic Images with Ultrahigh-resolution Full-field Optical Coherence Tomography,” J. Opt. Soc. Korea 11(1), 18–25 (2007). [CrossRef]
  22. J. Na, W. J. Choi, H. Y. Choi, S. Y. Ryu, E. S. Choi, and B. H. Lee, “Thickness and Refractive Index Measurements by Full-Field Optical Coherence Microscopy,” IEEE Sens. J. 9(12), 1996–1997 (2009). [CrossRef]
  23. T. Yamauchi, H. Iwai, M. Miwa, and Y. Yamashita, “Low-coherent quantitative phase microscope for nanometer-scale measurement of living cells morphology,” Opt. Express 16(16), 12227–12238 (2008). [CrossRef] [PubMed]
  24. W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007). [CrossRef] [PubMed]
  25. S.-A. Kim, H.-W. Kim, D.-K. Kim, S.-G. Kim, J.-C. Park, D.-W. Kang, S.-W. Kim, S.-G. Ahn, and J.-H. Yoon, “Rapid induction of malignant tumor in Sprague-Dawley rats by injection of RK3E-ras cells,” Cancer Lett. 235(1), 53–59 (2006). [CrossRef]
  26. S.-A. Kim, S.-M. Kwon, J.-H. Yoon, and S.-G. Ahn, “The antitumor effect of PLK1 and HSF1 double knockdown on human oral carcinoma cells,” Int. J. Oncol. 36(4), 867–872 (2010). [PubMed]
  27. Y.-H. Moon, J.-H. Park, S.-A. Kim, J.-B. Lee, S.-G. Ahn, and J.-H. Yoon, “Anticancer effect of photodynamic therapy with hexenyl ester of 5-aminolevulinic acid in oral squamous cell carcinoma,” Head Neck 32(9), 1136–1142 (2010). [CrossRef]
  28. T. Yasokawa, I. Ishimaru, M. Kondo, S. Kuriyama, T. Masaki, K. Takegawa, and N. Tanaka, “A Method for Measuring the Three-Dimensional Refractive-Index Distribution of Single Cells Using Proximal Two-Beam Optical Tweezers and a Phase-Shifting Mach-Zehnder Interferometer,” Opt. Rev. 14(4), 161–164 (2007). [CrossRef]
  29. J.-Y. Lee, C.-W. Lee, E.-H. Lin, and P.-K. Wei, “Single live cell refractometer using nanoparticle coated fiber tip,” Appl. Phys. Lett. 93(17), 173110 (2008). [CrossRef]
  30. F. Lanni, A. S. Waggoner, and D. L. Taylor, “Structural organization of interphase 3T3 fibroblasts studied by total internal reflection fluorescence microscopy,” J. Cell Biol. 100(4), 1091–1102 (1985). [CrossRef] [PubMed]
  31. R. Barer, K. F. A. Ross, and S. Tkaczyk, “Refractometry of living cells,” Nature 171(4356), 720–724 (1953). [CrossRef] [PubMed]
  32. H. Iwai, C. Fang-Yen, G. Popescu, A. Wax, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Quantitative phase imaging using actively stabilized phase-shifting low-coherence interferometry,” Opt. Lett. 29(20), 2399–2401 (2004). [CrossRef] [PubMed]

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.


Fig. 1 Fig. 2 Fig. 3
Fig. 4 Fig. 5

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited