Abstract

We report on the design and construction of a confocal light scattering spectroscopic imaging system aimed ultimately to conduct depth-resolved characterization of biological tissues. The confocal sectioning ability of the system is demonstrated using a two-layer sample consisting of a 200μm thick cancer cell layer on top of a scattering layer doped with a green absorber. The measurement results demonstrate that distinct light scattering signals can be isolated from each layer with an axial and a lateral resolution of 30 and 27μm, respectively. Such a system is expected to have significant applications in the areas of tissue engineering and disease diagnostics and monitoring.

© 2009 Optical Society of America

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  1. C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1983).
  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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
    [CrossRef]
  3. 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, 887-893 (2001).
    [CrossRef]
  4. G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
    [CrossRef] [PubMed]
  5. 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, 3119-3121 (2006).
    [CrossRef] [PubMed]
  6. 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, 378-387(2002).
    [CrossRef] [PubMed]
  7. V. Ost, J. Neukammer, and H. Rinneberg, “Flow cytometric differentiation of erythrocytes and leukocytes in dilute whole blood by light scattering,” Cytometry 32, 191-197(1998).
    [CrossRef] [PubMed]
  8. M. T. Valentine, A. K. Popp, D. A. Weitz, and P. D. Kaplan, “Microscope-based static light-scattering instrument,” Opt. Lett. 26, 890-892 (2001).
    [CrossRef]
  9. W. J. Cottrell, J. D. Wilson, and T. H. Foster, “Microscope enabling multimodality imaging, angle-resolved scattering, and scattering spectroscopy,” Opt. Lett. 32, 2348-2350 (2007).
    [CrossRef] [PubMed]
  10. Y. Liu, X. Li, Y. L. Kim, and V. Backman, “Elastic backscattering spectroscopic microscopy,” Opt. Lett. 30, 2445-2447(2005).
    [CrossRef] [PubMed]
  11. I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
    [CrossRef] [PubMed]
  12. Y. L. Kim, Y. Liu, V. M. Turzhitsky, R. K. Wali, H. K. Roy, and V. Backman, “Depth-resolved low-coherence enhanced backscattering,” Opt. Lett. 30, 741-743 (2005).
    [CrossRef] [PubMed]
  13. J. M. Schmitt, “Optical coherence tomography (OCT): a review,” IEEE J. Sel. Top. Quantum Electron. 5, 1205-1215(1999).
    [CrossRef]
  14. K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
    [CrossRef] [PubMed]

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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[CrossRef] [PubMed]

2007 (2)

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

W. J. Cottrell, J. D. Wilson, and T. H. Foster, “Microscope enabling multimodality imaging, angle-resolved scattering, and scattering spectroscopy,” Opt. Lett. 32, 2348-2350 (2007).
[CrossRef] [PubMed]

2006 (1)

2005 (3)

2002 (1)

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, 378-387(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, 887-893 (2001).
[CrossRef]

M. T. Valentine, A. K. Popp, D. A. Weitz, and P. D. Kaplan, “Microscope-based static light-scattering instrument,” Opt. Lett. 26, 890-892 (2001).
[CrossRef]

1999 (1)

J. M. Schmitt, “Optical coherence tomography (OCT): a review,” IEEE J. Sel. Top. Quantum Electron. 5, 1205-1215(1999).
[CrossRef]

1998 (1)

V. Ost, J. Neukammer, and H. Rinneberg, “Flow cytometric differentiation of erythrocytes and leukocytes in dilute whole blood by light scattering,” Cytometry 32, 191-197(1998).
[CrossRef] [PubMed]

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, 378-387(2002).
[CrossRef] [PubMed]

Andersson, C.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, “Elastic backscattering spectroscopic microscopy,” Opt. Lett. 30, 2445-2447(2005).
[CrossRef] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, R. K. Wali, H. K. Roy, and V. Backman, “Depth-resolved low-coherence enhanced backscattering,” Opt. Lett. 30, 741-743 (2005).
[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, 887-893 (2001).
[CrossRef]

Badizadegan, K.

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, 3119-3121 (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, 887-893 (2001).
[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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Bigio, I.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Bohren, C. F.

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1983).

Boone, C. W.

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, 887-893 (2001).
[CrossRef]

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, 378-387(2002).
[CrossRef] [PubMed]

Chalut, K. J.

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[CrossRef] [PubMed]

Chen, S.

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[CrossRef] [PubMed]

Cipolloni, P. B.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Cottrell, W. J.

Dasari, R. R.

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, 3119-3121 (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, 887-893 (2001).
[CrossRef]

Fang, H.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Feld, M. S.

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, 3119-3121 (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, 887-893 (2001).
[CrossRef]

Finan, J. D.

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[CrossRef] [PubMed]

Foster, T. H.

Freedman, S. D.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

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, 378-387(2002).
[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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[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, 887-893 (2001).
[CrossRef]

Ghiran, I. C.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Giacomelli, M. G.

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[CrossRef] [PubMed]

Gopal, V.

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, 887-893 (2001).
[CrossRef]

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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

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, 378-387(2002).
[CrossRef] [PubMed]

Guilak, F.

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[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, 887-893 (2001).
[CrossRef]

Hanlon, E. B.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Huffman, D. R.

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1983).

Huie, P.

G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
[CrossRef] [PubMed]

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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

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, 3119-3121 (2006).
[CrossRef] [PubMed]

Itzkan, I.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

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, 378-387(2002).
[CrossRef] [PubMed]

Kalashnikov, M.

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, 3119-3121 (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, 887-893 (2001).
[CrossRef]

Kaplan, P. D.

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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, “Elastic backscattering spectroscopic microscopy,” Opt. Lett. 30, 2445-2447(2005).
[CrossRef] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, R. K. Wali, H. K. Roy, and V. Backman, “Depth-resolved low-coherence enhanced backscattering,” Opt. Lett. 30, 741-743 (2005).
[CrossRef] [PubMed]

Kimerer, L. M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Lau, C.

Leong, K. W.

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Li, X.

Lim, K.-H.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Liu, Y.

Modell, M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Mourant, J. R.

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, 378-387(2002).
[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, 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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Munger, 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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Neukammer, J.

V. Ost, J. Neukammer, and H. Rinneberg, “Flow cytometric differentiation of erythrocytes and leukocytes in dilute whole blood by light scattering,” Cytometry 32, 191-197(1998).
[CrossRef] [PubMed]

O'Connell-Rodwell, C.

G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
[CrossRef] [PubMed]

Ost, V.

V. Ost, J. Neukammer, and H. Rinneberg, “Flow cytometric differentiation of erythrocytes and leukocytes in dilute whole blood by light scattering,” Cytometry 32, 191-197(1998).
[CrossRef] [PubMed]

Palanker, D.

G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
[CrossRef] [PubMed]

Perelman, L. T.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
[CrossRef] [PubMed]

Popp, A. K.

Qiu, L.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Rinneberg, H.

V. Ost, J. Neukammer, and H. Rinneberg, “Flow cytometric differentiation of erythrocytes and leukocytes in dilute whole blood by light scattering,” Cytometry 32, 191-197(1998).
[CrossRef] [PubMed]

Roy, H. K.

Sachs, B. P.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Salahuddin, S.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Schmitt, J. M.

J. M. Schmitt, “Optical coherence tomography (OCT): a review,” IEEE J. Sel. Top. Quantum Electron. 5, 1205-1215(1999).
[CrossRef]

Schuele, G.

G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
[CrossRef] [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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Tunnell, J. W.

Turzhitsky, V. M.

Valentine, M. T.

Vitkin, E.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
[CrossRef] [PubMed]

Wali, R. K.

Wax, A.

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[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, 887-893 (2001).
[CrossRef]

Weitz, D. A.

Wilson, J. D.

Yu, C.-C.

Zaman, M. M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Biophys. J. (1)

K. J. Chalut, S. Chen, J. D. Finan, M. G. Giacomelli, F. Guilak, K. W. Leong, and A. Wax, “Label-free, high-throughput measurements of dynamic changes in cell nuclei using angle-resolved low coherence interferometry,” Biophys. J. 94, 4948-4956 (2008).
[CrossRef] [PubMed]

Cytometry (1)

V. Ost, J. Neukammer, and H. Rinneberg, “Flow cytometric differentiation of erythrocytes and leukocytes in dilute whole blood by light scattering,” Cytometry 32, 191-197(1998).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (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, 887-893 (2001).
[CrossRef]

J. M. Schmitt, “Optical coherence tomography (OCT): a review,” IEEE J. Sel. Top. Quantum Electron. 5, 1205-1215(1999).
[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. Munger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

J. Biomed. Opt. (2)

G. Schuele, E. Vitkin, P. Huie, C. O'Connell-Rodwell, D. Palanker, and L. T. Perelman, “Optical spectroscopy noninvasively monitors response of organelles to cellular stress,” J. Biomed. Opt. 10, 051404 (2005).
[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, 378-387(2002).
[CrossRef] [PubMed]

Opt. Lett. (5)

Proc. Natl. Acad. Sci. U.S.A. (1)

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K.-H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A. 104, 17255-17260 (2007).
[CrossRef] [PubMed]

Other (1)

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1983).

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Figures (3)

Fig. 1
Fig. 1

(a) Schematic of the CLSSM. (b) Confocal axial resolution measurement of the CLSSM system. The circular markers are experimental measurements, while the solid line is a fit to the data. (c) Lateral resolution measurement of the CLSSM system. The circular markers are experimental measurements while the solid line is a fit to the data. (d) Light scattering spectral characteristics of 5 μm beads at polar angles of 4 ° and 5 ° , measured under collimated illumination and compared with Mie theory predictions.

Fig. 2
Fig. 2

Schematic of the layering of leukemia cancer cells (NALM-6) on top of a green scattering solution.

Fig. 3
Fig. 3

(a) Scattering polar angle versus wavelength map of the NALM-6 cells on the top half of the aggregate sample shown in Fig. 2. (b) Scattering polar angle versus wavelength map of the green scattering layer on the bottom half of the aggregate sample shown in Fig. 2. (c) Spectral dependence of the integrated backscattering intensities for stand-alone control group samples and the stacked experimental group samples: NALM-6 cells alone (black solid line; control group), green scattering solution alone (black dashed line; control group), and the stacked NALM-6 (gray solid line; experimental group) and green scattering solution (gray dashed line; experimental).

Equations (1)

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I norm = I raw I BG I 99 % ,

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