Abstract

The origins of side scattering from a fibroblast and cervical cell line were determined by comparing side-scatter images with images stained for lysosomes, nuclei, and mitochondria on a cell by cell basis. Lysosomes or nuclei are the most efficient type of scatterer depending on the cell type and incident light polarization. The relative scattering efficiencies of lysosomes and mitochondria were the same for both cell lines, while the scattering efficiencies of the nuclei differed. The percent of 90° scattering from the nucleus, mitochondria, and lysosomes as well as the group of other internal cellular objects was estimated. The nucleus was the largest contributor to side scatter in the cervical carcinoma cells. The contributions of lysosomes, mitochondria, the nucleus, and particles unstained by either Hoechst, LysoSensor or MitoTracker ranges from ∼20% to ∼30% in fibroblast cells. The contribution of lysosomes to side scatter was much stronger when the incident light was polarized perpendicular to the scattering plane than when the polarization of the side scatter laser was parallel to the scattering plane. This dependence on side scatter polarization indicates that lysosomes contain scattering structures that are much smaller than the wavelength of light used in the measurements (785 nm). In conclusion, mitochondria were not found to be either the most efficient scatterer or to have the largest contribution to scattering in either cell line, in contrast to previous reports. Rather lysosomes, nuclei and unknown particles all have significant contributions to 90° scattering and the contributions of some of these particles can be modulated by changing the polarization of the incident light.

© 2012 OSA

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2011 (1)

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

2010 (3)

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
[CrossRef] [PubMed]

R. M. Pasternack, J.-Y. Zheng, and N. N. Boustany, “Optical scatter changes at the onset of apoptosis are spatially associated with mitochondria,” J.Biomed.Opt.15, 040504 (2010).
[CrossRef] [PubMed]

2009 (2)

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[CrossRef] [PubMed]

2008 (2)

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

R. A. Schwarz, W. Gao, D. Daye, M. D. Williams, R. Richards-Kortum, and A. M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,” Appl. Opt.47, 825–834 (2008).
[CrossRef] [PubMed]

2007 (3)

J. D. Wilson, W. J. Cottrell, and T. H. Foster, “Index-of-refraction-dependent subcellular light scattering observed with organelle-specific dyes,” J. Biomed. Opt.12, 014010 (2007).
[CrossRef] [PubMed]

I. Itzkan, L. Qui, 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]

J.D. Wilson and T.H. Foster, “Characterization of lysosomal contribution to whole-cell light scattering by organelle ablation,” J. Biomed. Opt.12, 030503 (2007).
[CrossRef] [PubMed]

2006 (2)

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

A. E. Frazier, C. Kiu, D. Stojanovski, N. J. Hoogenraad, and M. T. Ryan, “Mitochondrial morphology and distribution in mammalian cells,” Biol. Chem.387, 1551–1558 (2006).
[CrossRef] [PubMed]

2005 (1)

2004 (2)

P. K. Kennady, M. G. Ormerod, S. Singh, and G. Pande, “Variation of mitochondrial size during the cell cycle: a multiparameter flow cytometric and microscopic study,” Cytometry Part A62A, 97–108 (2004).
[CrossRef]

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J.87, 1298–1306 (2004).
[CrossRef] [PubMed]

2003 (1)

D. Arifler, M. G. A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8, 484–494 (2003).
[CrossRef] [PubMed]

2002 (2)

N. Demaurex, “pH homeostasis of cellular organelle,” News Physiol. Sci.17, 1–5 (2002).
[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]

2000 (1)

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[CrossRef] [PubMed]

1999 (2)

1998 (1)

1996 (1)

A. M. James, Y.-H. Wei, C.-Y. Pang, and M. P. Murphy, “Altered mitochondrial function in fibroblasts containing Melas or Merrf mitochondrial DNA mutations,” Biochem J.318, 401–407 (1996).
[PubMed]

1994 (1)

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J.67, 2501–2510 (1994).
[CrossRef] [PubMed]

1989 (1)

J. Heuser, “Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH,” J. Cell. Biol.108, 855–864 (1989).
[CrossRef] [PubMed]

1977 (1)

A. Blouin, R. P. Bolender, and E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol.72, 441–455 (1977).
[CrossRef] [PubMed]

1975 (1)

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

1973 (1)

L. S. Cram and A. Brunsting, “Fluorescence and light-scattering measurements on hog cholera-infected PK-15 cells,” Exp. Cell Res.78, 209–213 (1973).
[CrossRef] [PubMed]

Aerts, J. G.

S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
[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]

Amelink, A.

S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
[CrossRef] [PubMed]

Andersson, C.

I. Itzkan, L. Qui, 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]

Arifler, D.

D. Arifler, M. G. A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8, 484–494 (2003).
[CrossRef] [PubMed]

Atkinson, E. N.

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

Barry, W. T.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

Basiji, D. A.

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

Beauvoit, B.

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J.67, 2501–2510 (1994).
[CrossRef] [PubMed]

Bigio, I.

I. Itzkan, L. Qui, 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]

Bigio, I. J.

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[CrossRef] [PubMed]

Blouin, A.

A. Blouin, R. P. Bolender, and E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol.72, 441–455 (1977).
[CrossRef] [PubMed]

Bocklage, T. J.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

Bolender, R. P.

A. Blouin, R. P. Bolender, and E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol.72, 441–455 (1977).
[CrossRef] [PubMed]

Boustany, N. N.

R. M. Pasternack, J.-Y. Zheng, and N. N. Boustany, “Optical scatter changes at the onset of apoptosis are spatially associated with mitochondria,” J.Biomed.Opt.15, 040504 (2010).
[CrossRef] [PubMed]

Bown, S. G.

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[CrossRef] [PubMed]

Brocker, C.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[CrossRef] [PubMed]

Brown, J. Q.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

Brunsting, A.

L. S. Cram and A. Brunsting, “Fluorescence and light-scattering measurements on hog cholera-infected PK-15 cells,” Exp. Cell Res.78, 209–213 (1973).
[CrossRef] [PubMed]

Bydlon, T. M.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

Canpolat, M.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[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, 378–387 (2002).
[CrossRef] [PubMed]

Carraro, M. G. A.

D. Arifler, M. G. A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8, 484–494 (2003).
[CrossRef] [PubMed]

Chachisvilis, M.

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J.87, 1298–1306 (2004).
[CrossRef] [PubMed]

Chance, B.

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J.67, 2501–2510 (1994).
[CrossRef] [PubMed]

Cipolloni, P. B.

I. Itzkan, L. Qui, 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]

Clark, B.

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[CrossRef] [PubMed]

Coder, D.

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

Cottrell, W. J.

J. D. Wilson, W. J. Cottrell, and T. H. Foster, “Index-of-refraction-dependent subcellular light scattering observed with organelle-specific dyes,” J. Biomed. Opt.12, 014010 (2007).
[CrossRef] [PubMed]

Cox, D. D.

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

Cram, L. S.

L. S. Cram and A. Brunsting, “Fluorescence and light-scattering measurements on hog cholera-infected PK-15 cells,” Exp. Cell Res.78, 209–213 (1973).
[CrossRef] [PubMed]

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Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
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I. Itzkan, L. Qui, 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).
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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).
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J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
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W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
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V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
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W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
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J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
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I. Itzkan, L. Qui, 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).
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Gillenwater, A. M.

Greene, H. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
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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).
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D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J.87, 1298–1306 (2004).
[CrossRef] [PubMed]

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W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
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I. Itzkan, L. Qui, 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).
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S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
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Imarisio, S.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
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Itzkan, I.

I. Itzkan, L. Qui, 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).
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Jahreiss, L.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
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A. M. James, Y.-H. Wei, C.-Y. Pang, and M. P. Murphy, “Altered mitochondrial function in fibroblasts containing Melas or Merrf mitochondrial DNA mutations,” Biochem J.318, 401–407 (1996).
[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]

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[CrossRef] [PubMed]

T. M. Johnson and J. R. Mourant, “Polarized wavelength-dependent measurements of turbid media,” Opt. Express4, 200–216 (1999).
[CrossRef] [PubMed]

Junker, M. K.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

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S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
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S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
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P. K. Kennady, M. G. Ormerod, S. Singh, and G. Pande, “Variation of mitochondrial size during the cell cycle: a multiparameter flow cytometric and microscopic study,” Cytometry Part A62A, 97–108 (2004).
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J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

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I. Itzkan, L. Qui, 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).
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A. E. Frazier, C. Kiu, D. Stojanovski, N. J. Hoogenraad, and M. T. Ryan, “Mitochondrial morphology and distribution in mammalian cells,” Biol. Chem.387, 1551–1558 (2006).
[CrossRef] [PubMed]

Korolchuk, V. I.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Kumar, G.

LaBauve, P. M.

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

Lichtenberg, M.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Lim, K.-H.

I. Itzkan, L. Qui, 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]

Lovat, L. B.

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[CrossRef] [PubMed]

MacAulay, C.

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

Mackenzie, G.

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[CrossRef] [PubMed]

Malpica, A.

D. Arifler, M. G. A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8, 484–494 (2003).
[CrossRef] [PubMed]

Marchand, P.

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J.87, 1298–1306 (2004).
[CrossRef] [PubMed]

Martin, J. C.

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

Matanock, A.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[CrossRef] [PubMed]

Menzies, F. M.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Modell, M.

I. Itzkan, L. Qui, 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]

Morrissey, P. J.

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

Mourant, J. R.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

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]

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[CrossRef] [PubMed]

T. M. Johnson and J. R. Mourant, “Polarized wavelength-dependent measurements of turbid media,” Opt. Express4, 200–216 (1999).
[CrossRef] [PubMed]

Mullaney, P. F.

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

Murphy, M. P.

A. M. James, Y.-H. Wei, C.-Y. Pang, and M. P. Murphy, “Altered mitochondrial function in fibroblasts containing Melas or Merrf mitochondrial DNA mutations,” Biochem J.318, 401–407 (1996).
[PubMed]

O’Kane, C. J.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Ormerod, M. G.

P. K. Kennady, M. G. Ormerod, S. Singh, and G. Pande, “Variation of mitochondrial size during the cell cycle: a multiparameter flow cytometric and microscopic study,” Cytometry Part A62A, 97–108 (2004).
[CrossRef]

Ortyn, W. E.

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

Pande, G.

P. K. Kennady, M. G. Ormerod, S. Singh, and G. Pande, “Variation of mitochondrial size during the cell cycle: a multiparameter flow cytometric and microscopic study,” Cytometry Part A62A, 97–108 (2004).
[CrossRef]

Pang, C.-Y.

A. M. James, Y.-H. Wei, C.-Y. Pang, and M. P. Murphy, “Altered mitochondrial function in fibroblasts containing Melas or Merrf mitochondrial DNA mutations,” Biochem J.318, 401–407 (1996).
[PubMed]

Pasternack, R. M.

R. M. Pasternack, J.-Y. Zheng, and N. N. Boustany, “Optical scatter changes at the onset of apoptosis are spatially associated with mitochondria,” J.Biomed.Opt.15, 040504 (2010).
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Perelman, L. T.

I. Itzkan, L. Qui, 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]

Perry, D. J.

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

Powers, T. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

Qui, L.

I. Itzkan, L. Qui, 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]

Ramanujam, N.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

Richards, L. M.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

Richards-Kortum, R.

R. A. Schwarz, W. Gao, D. Daye, M. D. Williams, R. Richards-Kortum, and A. M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,” Appl. Opt.47, 825–834 (2008).
[CrossRef] [PubMed]

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

D. Arifler, M. G. A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8, 484–494 (2003).
[CrossRef] [PubMed]

Roberts, E. A.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Romero, A.

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

Rubinsztein, D. C.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Ryan, M. T.

A. E. Frazier, C. Kiu, D. Stojanovski, N. J. Hoogenraad, and M. T. Ryan, “Mitochondrial morphology and distribution in mammalian cells,” Biol. Chem.387, 1551–1558 (2006).
[CrossRef] [PubMed]

Sachs, B. P.

I. Itzkan, L. Qui, 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]

Saftig, P.

P. Saftig, Lysosomes (Springer-Verlag, 2005).

Saiki, S.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Salahuddin, S.

I. Itzkan, L. Qui, 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]

Salzman, G. C.

G. C. Salzman, “Light scatter: detection and usage,” Curr. Protoc. Cytom.9, 1.13.1 (1999).

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

Sarkar, S.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Schmitt, J. M.

Schwarz, R. A.

R. A. Schwarz, W. Gao, D. Daye, M. D. Williams, R. Richards-Kortum, and A. M. Gillenwater, “Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe,” Appl. Opt.47, 825–834 (2008).
[CrossRef] [PubMed]

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

Siddiqi, F. H.

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

Singh, S.

P. K. Kennady, M. G. Ormerod, S. Singh, and G. Pande, “Variation of mitochondrial size during the cell cycle: a multiparameter flow cytometric and microscopic study,” Cytometry Part A62A, 97–108 (2004).
[CrossRef]

Smith, H. O.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

Sterenborg, H. J.

S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
[CrossRef] [PubMed]

Stetter, K.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[CrossRef] [PubMed]

Stojanovski, D.

A. E. Frazier, C. Kiu, D. Stojanovski, N. J. Hoogenraad, and M. T. Ryan, “Mitochondrial morphology and distribution in mammalian cells,” Biol. Chem.387, 1551–1558 (2006).
[CrossRef] [PubMed]

Trujillo, T. T.

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

van der Leest, C.

S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
[CrossRef] [PubMed]

Vitkin, E.

I. Itzkan, L. Qui, 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]

Watson, D.

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J.87, 1298–1306 (2004).
[CrossRef] [PubMed]

Waxman, A. G.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

Weber, C. R.

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

Wei, Y.-H.

A. M. James, Y.-H. Wei, C.-Y. Pang, and M. P. Murphy, “Altered mitochondrial function in fibroblasts containing Melas or Merrf mitochondrial DNA mutations,” Biochem J.318, 401–407 (1996).
[PubMed]

Weibel, E. R.

A. Blouin, R. P. Bolender, and E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol.72, 441–455 (1977).
[CrossRef] [PubMed]

Wilke, L. G.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

Williams, M. D.

Wilson, J. D.

J. D. Wilson, W. J. Cottrell, and T. H. Foster, “Index-of-refraction-dependent subcellular light scattering observed with organelle-specific dyes,” J. Biomed. Opt.12, 014010 (2007).
[CrossRef] [PubMed]

J. D. Wilson and T. M. Foster, “Mie theory interpretations of light scattering from intact cells,” Opt. Lett.30, 2442–2444 (2005).
[CrossRef] [PubMed]

Wilson, J.D.

J.D. Wilson and T.H. Foster, “Characterization of lysosomal contribution to whole-cell light scattering by organelle ablation,” J. Biomed. Opt.12, 030503 (2007).
[CrossRef] [PubMed]

Yu, B.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

Zaman, M. M.

I. Itzkan, L. Qui, 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]

Zheng, J.-Y.

R. M. Pasternack, J.-Y. Zheng, and N. N. Boustany, “Optical scatter changes at the onset of apoptosis are spatially associated with mitochondria,” J.Biomed.Opt.15, 040504 (2010).
[CrossRef] [PubMed]

Zhu, Y.

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[CrossRef] [PubMed]

Zimmerman, C. A.

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

Zsemlye, M. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

Acta Cytol. (1)

G. C. Salzman, J. M. Crowell, J. C. Martin, T. T. Trujillo, A. Romero, P. F. Mullaney, and P. M. LaBauve, “Cell classification by laser light scattering: identification and separation of unstained leukocytes,” Acta Cytol.19, 374–377 (1975).
[PubMed]

Appl. Opt. (2)

Biochem J. (1)

A. M. James, Y.-H. Wei, C.-Y. Pang, and M. P. Murphy, “Altered mitochondrial function in fibroblasts containing Melas or Merrf mitochondrial DNA mutations,” Biochem J.318, 401–407 (1996).
[PubMed]

Biol. Chem. (1)

A. E. Frazier, C. Kiu, D. Stojanovski, N. J. Hoogenraad, and M. T. Ryan, “Mitochondrial morphology and distribution in mammalian cells,” Biol. Chem.387, 1551–1558 (2006).
[CrossRef] [PubMed]

Biophys. J. (2)

D. Watson, N. Hagen, J. Diver, P. Marchand, and M. Chachisvilis, “Elastic light scattering from single cells: orientational dynamics in optical trap,” Biophys. J.87, 1298–1306 (2004).
[CrossRef] [PubMed]

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J.67, 2501–2510 (1994).
[CrossRef] [PubMed]

Curr. Protoc. Cytom. (1)

G. C. Salzman, “Light scatter: detection and usage,” Curr. Protoc. Cytom.9, 1.13.1 (1999).

Cytometry A (1)

W. E. Ortyn, B. E. Hall, T. C. George, K. Frost, D. A. Basiji, D. J. Perry, C. A. Zimmerman, D. Coder, and P. J. Morrissey, “Sensitivity measurement and compensation in spectral imaging,” Cytometry A69, 852–862 (2006).
[PubMed]

Cytometry Part A (1)

P. K. Kennady, M. G. Ormerod, S. Singh, and G. Pande, “Variation of mitochondrial size during the cell cycle: a multiparameter flow cytometric and microscopic study,” Cytometry Part A62A, 97–108 (2004).
[CrossRef]

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L. S. Cram and A. Brunsting, “Fluorescence and light-scattering measurements on hog cholera-infected PK-15 cells,” Exp. Cell Res.78, 209–213 (1973).
[CrossRef] [PubMed]

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

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. K. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16, 530–544 (2010).
[CrossRef] [PubMed]

J. Biomed. Opt. (8)

S. C. Kanick, C. van der Leest, J. G. Aerts, H. C. Hoogsteden, S. Kascakova, H. J. Sterenborg, and A. Amelink, “Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes,” J. Biomed. Opt.15, 017004 (2010).
[CrossRef] [PubMed]

Y. Zhu, T. Fearn, G. Mackenzie, B. Clark, J. M. Dunn, I. J. Bigio, S. G. Bown, and L. B. Lovat, “Elastic scattering spectroscopy for detection of cancer risk in Barrett’s esophagus: experimental and clinical validation of error removal by orthogonal subtraction for increasing accuracy,” J. Biomed. Opt.14, 044022 (2009).
[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]

C. R. Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. MacAulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt.13, 064016 (2008).
[CrossRef]

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt.5, 131–137 (2000).
[CrossRef] [PubMed]

J. D. Wilson, W. J. Cottrell, and T. H. Foster, “Index-of-refraction-dependent subcellular light scattering observed with organelle-specific dyes,” J. Biomed. Opt.12, 014010 (2007).
[CrossRef] [PubMed]

D. Arifler, M. G. A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8, 484–494 (2003).
[CrossRef] [PubMed]

J.D. Wilson and T.H. Foster, “Characterization of lysosomal contribution to whole-cell light scattering by organelle ablation,” J. Biomed. Opt.12, 030503 (2007).
[CrossRef] [PubMed]

J. Cell Biol. (1)

A. Blouin, R. P. Bolender, and E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol.72, 441–455 (1977).
[CrossRef] [PubMed]

J. Cell. Biol. (1)

J. Heuser, “Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH,” J. Cell. Biol.108, 855–864 (1989).
[CrossRef] [PubMed]

J. Low Genit. Tract. Dis. (1)

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering,” J. Low Genit. Tract. Dis.13, 216–223 (2009).
[CrossRef]

J.Biomed.Opt. (1)

R. M. Pasternack, J.-Y. Zheng, and N. N. Boustany, “Optical scatter changes at the onset of apoptosis are spatially associated with mitochondria,” J.Biomed.Opt.15, 040504 (2010).
[CrossRef] [PubMed]

Nature Cell Biol. (1)

V. I. Korolchuk, S. Saiki, M. Lichtenberg, F. H. Siddiqi, E. A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F. M. Menzies, C. J. O’Kane, V. Deretic, and D. C. Rubinsztein, “Lysosomal positioning coordinates cellular nutrient responses,” Nature Cell Biol.13, 453–460 (2011).
[CrossRef] [PubMed]

News Physiol. Sci. (1)

N. Demaurex, “pH homeostasis of cellular organelle,” News Physiol. Sci.17, 1–5 (2002).
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Opt. Express (1)

Opt. Lett. (1)

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

I. Itzkan, L. Qui, 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)

P. Saftig, Lysosomes (Springer-Verlag, 2005).

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Figures (10)

Fig. 1
Fig. 1

Schematic of the parts of the optical train in the Amnis flow cytometer that we used. The λ/2 waveplate and the linear polarizer were only inserted into the instrument when measurements were made with the polarization of the 785 nm light scattering laser perpendicular to the scattering plane. Camera 1 was used for the brightfield, lysosomal and mitochondrial images while camera 2 collected the nuclear images.

Fig. 2
Fig. 2

Example raw images: a) Brightfield b) Lysosomes c) Mitochondria d) Nuclei e) Side scatter (SSC). The yellow lines are the outline of the mask used for the cell. Other colored lines are the outlines of masks covering areas where the dye fluorescence is considered significant. Black lines are the outlines of regions where only the dye in that image fluoresces. The mask for the non-fluorescent regions is shown on the SSC image. The thick white line on the Hoechst image has a length of 10μm.

Fig. 3
Fig. 3

Effects of cell staining on light scattering for 4 types of experiments.

Fig. 4
Fig. 4

Correlation of fluorescence intensities in the images from one experiment with MR1 cells. a) The similarity of mitochondrial and nuclear fluorescence demonstrates that mitochondrial fluorescence is weak where nuclear fluorescence is strong and vice versa. b) Similarity of lysosomal and nuclear fluorescence demonstrates that for most cells lysosomal fluorescence is weak where nuclear fluorescence is strong and vice versa. c) The similarity of mitochondrial and lysosomal fluorescence shows that for many cells the location of mitochondrial and lysosomal fluorescence overlaps significantly.

Fig. 5
Fig. 5

Mean and standard deviation of the average similarity between the fluorescence of two dyes. a) Similarity of Hoechst and MitoTracker Orange fluorescence. b) Similarity of LysoSensor Green and MitoTracker Orange fluorescence. c) Similarity of Hoechst and MitoTracker Orange fluorescence. Results are for 3 each of the SiHa experiments and for 3 experiments with MR1 cells using parallel polarization and 4 experiments with perpendicular polarization.

Fig. 6
Fig. 6

Scattering efficiencies of cell regions stained only with specific dyes or in one case (d) with no fluorescence compared to the total cell scattering efficiency on a cell by cell basis. Results are for SiHa cells with the 785 nm light scattering laser polarized parallel to the scattering plane. a) LysoSensor. b) MitoTracker. c) Hoechst. d) Nonfluorescent. e) MitoTracker, LysoSensor or both.

Fig. 7
Fig. 7

Medians of distributions of scattering efficiencies divided on a cell by cell bases by the scattering efficiency of the cell. The data points and error bars are the averages and standard deviations of the medians from three separate experiments each with more than 1500 cells.

Fig. 8
Fig. 8

Average and standard deviation of the mean and median of the distributions of scattering efficiencies normalized to the scattering efficiency of mitochondria. The plotted data are the averages of three or more experiments each with at least 3000 cells. a) and b) Average and standard deviation of the mean and median, respectively, for MR1 and SiHa cells with parallel polarization. c) and d) Average and standard deviation of the mean and median, respectively, for MR1 and SiHa cells with perpendicular polarization. The open symbols show the maximum and minimum nuclear scattering efficiency due to the uncertainty in the calculated increase in nuclear scattering due to Hoechst staining.

Fig. 9
Fig. 9

Average and standard deviation (from 3 separate experiments) of the median of the distribution of scattering efficiency of lysosomes relative to that of mitochondria. The scattering efficiency of lysosomes was divided by the scattering efficiency of mitochondria on a cell by cell basis.

Fig. 10
Fig. 10

Estimates of the percent of side scattering originating from each type of structure. The results are offset slightly for MR1 and SiHa cells for clarity.

Tables (1)

Tables Icon

Table 1 Scattering of unstained samples relative to Hoechst stained samples

Equations (5)

Equations on this page are rendered with MathJax. Learn more.

nuclear scattering efficiency = I scat ( nuclear region ) Area ( nuclear region )
cell scattering efficiency = I scat ( Cell ) Area ( Cell )
nuclear scattering efficiency cell scattering efficiency × nuclear volume cell volume × 100
I scat ( nuclear region ) ( f I scat ( Cell ) I scat ( Cytoplasm ) ) I scat ( nucleus )
similarity = ln ( 1 + r 1 r )

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