Abstract

We report a method of assessing the contribution of whole cell body and its nucleus to the clinically most relevant backward light scattering. We first construct an experimental system that can measure forward scattering and use the system to precisely extract the optical properties of a specimen such as the refractive index contrast, size distribution, and their density. A system that can simultaneously detect the backscattered light is installed to collect the backscattering for the same specimen. By comparing the measured backscattering spectrum with that estimated from the parameters determined by the forward scattering experiment, the contribution of cell body and nucleus to the backward light scattering is quantitatively assessed. For the HeLa cells in suspension, we found that the cell body contributes less than 10% and cell nucleus on the order of 0.1% to the total backscattering signal. Quantitative determination of the origin of backscattered light may help design a system that aims for detecting particular structure of biological tissues.

© 2012 OSA

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    [CrossRef] [PubMed]

2009 (1)

2008 (2)

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt. 13(2), 024015 (2008).
[CrossRef] [PubMed]

2007 (2)

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]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

2006 (2)

C. C. Yu, C. Lau, J. W. Tunnell, M. Hunter, M. Kalashnikov, C. Fang-Yen, S. F. Fulghum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy,” Opt. Lett. 31(21), 3119–3121 (2006).
[CrossRef] [PubMed]

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

2005 (1)

2003 (2)

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

2002 (4)

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

J. R. Masters, “HeLa cells 50 years on: the good, the bad and the ugly,” Nat. Rev. Cancer 2(4), 315–319 (2002).
[CrossRef] [PubMed]

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. Richards-Kortum, and K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance,” J. Biomed. Opt. 7(3), 388–397 (2002).
[CrossRef] [PubMed]

2001 (2)

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

2000 (1)

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

1999 (3)

1998 (1)

1974 (1)

A. Brunsting and P. F. Mullaney, “Differential Light Scattering from Spherical Mammalian Cells,” Biophys. J. 14(6), 439–453 (1974).
[CrossRef] [PubMed]

1957 (1)

Aida, T.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

Arendt, J. T.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Backman, V.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

Badizadegan, K.

M. Kalashnikov, W. Choi, C.-C. Yu, Y. Sung, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Assessing light scattering of intracellular organelles in single intact living cells,” Opt. Express 17(22), 19674–19681 (2009).
[CrossRef] [PubMed]

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]

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

C. C. Yu, C. Lau, J. W. Tunnell, M. Hunter, M. Kalashnikov, C. Fang-Yen, S. F. Fulghum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy,” Opt. Lett. 31(21), 3119–3121 (2006).
[CrossRef] [PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

Baldwin, A.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Barer, R.

Bigio, I. J.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Bocklage, T. J.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Boone, C. W.

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

Brunsting, A.

A. Brunsting and P. F. Mullaney, “Differential Light Scattering from Spherical Mammalian Cells,” Biophys. J. 14(6), 439–453 (1974).
[CrossRef] [PubMed]

Bullock, K. L.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Carpenter, S.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

Choi, W.

Cipolloni, P. B.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Crawford, J. M.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Dasari, R. R.

M. Kalashnikov, W. Choi, C.-C. Yu, Y. Sung, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Assessing light scattering of intracellular organelles in single intact living cells,” Opt. Express 17(22), 19674–19681 (2009).
[CrossRef] [PubMed]

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]

C. C. Yu, C. Lau, J. W. Tunnell, M. Hunter, M. Kalashnikov, C. Fang-Yen, S. F. Fulghum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy,” Opt. Lett. 31(21), 3119–3121 (2006).
[CrossRef] [PubMed]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

Dorin, M. H.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Drezek, R.

Dunn, A.

Eick, A. A.

Fang, H.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Fang-Yen, C.

Feld, M.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Feld, M. S.

M. Kalashnikov, W. Choi, C.-C. Yu, Y. Sung, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Assessing light scattering of intracellular organelles in single intact living cells,” Opt. Express 17(22), 19674–19681 (2009).
[CrossRef] [PubMed]

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]

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

C. C. Yu, C. Lau, J. W. Tunnell, M. Hunter, M. Kalashnikov, C. Fang-Yen, S. F. Fulghum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy,” Opt. Lett. 31(21), 3119–3121 (2006).
[CrossRef] [PubMed]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

Fitzmaurice, M.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Foster, T. H.

Freedman, S. D.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Freyer, J. P.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37(16), 3586–3593 (1998).
[CrossRef] [PubMed]

Fulghum, S. F.

Georgakoudi, I.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

Gopal, V.

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

Gossage, K.

Greene, H. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Greiner, C.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Guerra, A.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

Gurjar, R.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

Gurjar, R. S.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

Hanlon, E. B.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Hielscher, A. H.

Hunter, M.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

C. C. Yu, C. Lau, J. W. Tunnell, M. Hunter, M. Kalashnikov, C. Fang-Yen, S. F. Fulghum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy,” Opt. Lett. 31(21), 3119–3121 (2006).
[CrossRef] [PubMed]

Itzkan, I.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Itzkan, L.

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

Johnson, T. M.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37(16), 3586–3593 (1998).
[CrossRef] [PubMed]

Kabani, S.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Kalashnikov, M.

M. Kalashnikov, W. Choi, C.-C. Yu, Y. Sung, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Assessing light scattering of intracellular organelles in single intact living cells,” Opt. Express 17(22), 19674–19681 (2009).
[CrossRef] [PubMed]

C. C. Yu, C. Lau, J. W. Tunnell, M. Hunter, M. Kalashnikov, C. Fang-Yen, S. F. Fulghum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy,” Opt. Lett. 31(21), 3119–3121 (2006).
[CrossRef] [PubMed]

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

Kim, Y. L.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Kimerer, L. M.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Kline, E.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Lau, C.

Levin, H. S.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Levitt, J. M.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Lue, N.

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]

Marr-Lyon, L. R.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Masters, J. R.

J. R. Masters, “HeLa cells 50 years on: the good, the bad and the ugly,” Nat. Rev. Cancer 2(4), 315–319 (2002).
[CrossRef] [PubMed]

McGilligan, J. A.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Mourant, J. R.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37(16), 3586–3593 (1998).
[CrossRef] [PubMed]

Mueller, M.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

Mujat, C.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Mullaney, P. F.

A. Brunsting and P. F. Mullaney, “Differential Light Scattering from Spherical Mammalian Cells,” Biophys. J. 14(6), 439–453 (1974).
[CrossRef] [PubMed]

Müller, M. G.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Münger, K.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Myakov, A.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. Richards-Kortum, and K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance,” J. Biomed. Opt. 7(3), 388–397 (2002).
[CrossRef] [PubMed]

Nieman, L.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. Richards-Kortum, and K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance,” J. Biomed. Opt. 7(3), 388–397 (2002).
[CrossRef] [PubMed]

Nines, R.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Oh, S.

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]

Ollero, M.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Perelman, L. T.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

Popescu, G.

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

Powers, T. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Qu, J. Y.

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt. 13(2), 024015 (2008).
[CrossRef] [PubMed]

Richards-Kortum, R.

Seiler, M.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Shapshay, S.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Shen, D.

Smith, H. O.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Sokolov, K.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. Richards-Kortum, and K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance,” J. Biomed. Opt. 7(3), 388–397 (2002).
[CrossRef] [PubMed]

K. Sokolov, R. Drezek, K. Gossage, and R. Richards-Kortum, “Reflectance spectroscopy with polarized light: is it sensitive to cellular and nuclear morphology,” Opt. Express 5(13), 302–317 (1999).
[CrossRef] [PubMed]

Steele, V. E.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Stoner, G. D.

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Stucenski, L. A.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Sung, Y.

Tian, F.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

Tunnell, J. W.

Utzinger, U.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. Richards-Kortum, and K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance,” J. Biomed. Opt. 7(3), 388–397 (2002).
[CrossRef] [PubMed]

Valdez, T.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Van Dam, J.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Vitkin, E.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Wallace, M. B.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Wax, A.

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

Waxman, A. G.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Wicky, L.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. Richards-Kortum, and K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance,” J. Biomed. Opt. 7(3), 388–397 (2002).
[CrossRef] [PubMed]

Wilson, J. D.

Wu, T. T.

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt. 13(2), 024015 (2008).
[CrossRef] [PubMed]

Xu, M.

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt. 13(2), 024015 (2008).
[CrossRef] [PubMed]

Yang, C.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

Yu, C. C.

Yu, C.-C.

Zaman, M. M.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

Zhang, Q.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Zonios, G.

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Zsemlye, M. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

Appl. Opt. (2)

Biophys. J. (2)

A. Brunsting and P. F. Mullaney, “Differential Light Scattering from Spherical Mammalian Cells,” Biophys. J. 14(6), 439–453 (1974).
[CrossRef] [PubMed]

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
[CrossRef] [PubMed]

Cancer Res. (1)

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Gynecol. Oncol. (1)

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105(2), 439–445 (2007).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (3)

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
[CrossRef]

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 9(2), 267–276 (2003).
[CrossRef]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7(6), 887–893 (2001).
[CrossRef]

Int. J. Cancer (1)

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122(2), 363–371 (2008).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt. 13(2), 024015 (2008).
[CrossRef] [PubMed]

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, and J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7(3), 378–387 (2002).
[CrossRef] [PubMed]

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. Richards-Kortum, and K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: Design and performance,” J. Biomed. Opt. 7(3), 388–397 (2002).
[CrossRef] [PubMed]

J. Opt. Soc. Am. (1)

Nat. Med. (1)

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med. 7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

Nat. Methods (1)

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]

Nat. Rev. Cancer (1)

J. R. Masters, “HeLa cells 50 years on: the good, the bad and the ugly,” Nat. Rev. Cancer 2(4), 315–319 (2002).
[CrossRef] [PubMed]

Nature (1)

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, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[CrossRef] [PubMed]

Opt. Express (2)

Opt. Lett. (2)

Phys. Rev. Lett. (1)

M. Hunter, V. Backman, G. Popescu, M. Kalashnikov, C. W. Boone, A. Wax, V. Gopal, K. Badizadegan, G. D. Stoner, and M. S. Feld, “Tissue self-affinity and polarized light scattering in the born approximation: A new model for precancer detection,” Phys. Rev. Lett. 97(13), 138102 (2006).
[CrossRef] [PubMed]

Other (2)

H. Hulst, Light Scattering by Small Particles (Dover Publications, New York, 1981).

J. Goodman, Introduction to Fourier Optics (Roberts and Company Publishers, 2005).

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Figures (6)

Fig. 1
Fig. 1

Polar plots of differential scattering cross-section σ as a function of scattering angles θ and φ (Mie simulation). Color bar is the magnitude of the differential cross-section in μm2/sr. Origin of the maps is either 0° (forward scattering) or 180° (backscattering). Top row for 5 μm-size particle. Bottom row for 50 nm-size particle. (a,b) Backscattering parallel cross-section. (c,d) Backscattering perpendicular cross-section. (e,f) Forward scattering cross-section.

Fig. 2
Fig. 2

Light scattering instrument. System components: P1, P2 incident beam polarizers, BS-beam splitter, A – analyzer, FP – Fourier plane, F-focal distance of Fourier Lens, IL1 and IL2 – imaging lenses with focal distances of a and b. Traces of the incident light are shown in green. Brown and light brown traces belong to scattered light at 0°, 180° and at θ degrees away from them.

Fig. 3
Fig. 3

(a) Phase contrast image of HeLa cells at 40x magnification. (b) Light scattering measurements normalized in wavelength λ and angle θ. Color bar is in 1/R99 units.

Fig. 4
Fig. 4

Results of fitting experimental data to Mie theory. Scattering measurements and Mie theory are mean-centered. (a) Wavelength spectrum measurements (blue) at fixed scattering angles with fits to Mie theory (red). (b) Angular spectrum measurements (blue) at fixed wavelengths with fits to Mie theory (red).

Fig. 5
Fig. 5

Phase contrast image of HeLa cells in regular culture media (a) and in the media containing BSA (b). Measured forward light scattering distribution in culture media (c) and in BSA solution (d). Angular light scattering distribution for BSA and no-BSA samples from the measurement (e) and Mie theory (f).

Fig. 6
Fig. 6

(a) Measured backscattering cross-section of the HeLa cells in suspension. (b) Calculated backscattering cross-section for the whole cell body. Both intensities are in 1/R99 units. (c) Comparison of the cross-sections at θ = 178°.

Tables (1)

Tables Icon

Table 1 Comparing Observed Backscattering Intensity and Predicted Whole Cell and Nucleus Signala

Metrics