Abstract

We present depth-resolved spatial-domain low-coherence quantitative phase microscopy, a simple approach that utilizes coherence gating to construct a depth-resolved structural feature vector quantifying sub-resolution axial structural changes at different optical depths within the sample. We show that this feature vector is independent of sample thickness variation, and identifies nanoscale structural changes in clinically prepared samples. We present numerical simulations and experimental validation to demonstrate the feasibility of the approach. We also perform experiments using unstained cells to investigate the nanoscale structural changes in regulated cell proliferation through cell cycle and chromatin decondensation induced by histone acetylation.

© 2013 OSA

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Corrections

Shikhar Uttam, Rajan K. Bista, Kevin Staton, Sergey Alexandrov, Serah Choi, Christopher J. Bakkenist, Douglas J. Hartman, Randall E. Brand, and Yang Liu, "Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation: erratum," Biomed. Opt. Express 4, 2491-2491 (2013)
https://www.osapublishing.org/boe/abstract.cfm?uri=boe-4-11-2491

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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]

2012 (3)

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

L. Cherkezyan, H. Subramanian, V. Stoyneva, J. D. Rogers, S. Yang, D. Damania, A. Taflove, and V. Backman, “Targeted alteration of real and imaginary refractive index of biological cells by histological staining,” Opt. Lett.37(10), 1601–1603 (2012).
[CrossRef] [PubMed]

2011 (4)

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
[CrossRef] [PubMed]

H. Knecht and S. Mai, “3D imaging of telomeres and nuclear architecture: an emerging tool of 3D nano-morphology-based diagnosis,” J. Cell. Physiol.226(4), 859–867 (2011).
[CrossRef] [PubMed]

Z. Wang, K. Tangella, A. Balla, and G. Popescu, “Tissue refractive index as marker of disease,” J. Biomed. Opt.16(11), 116017 (2011).
[CrossRef] [PubMed]

2010 (5)

N. N. Boustany, S. A. Boppart, and V. Backman, “Microscopic imaging and spectroscopy with scattered light,” Annu. Rev. Biomed. Eng.12(1), 285–314 (2010).
[CrossRef] [PubMed]

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

C. Joo, C. L. Evans, T. Stepinac, T. Hasan, and J. F. de Boer, “Diffusive and directional intracellular dynamics measured by field-based dynamic light scattering,” Opt. Express18(3), 2858–2871 (2010).
[CrossRef] [PubMed]

P. Wang, R. Bista, R. Bhargava, R. E. Brand, and Y. Liu, “Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis,” Opt. Lett.35(17), 2840–2842 (2010).
[CrossRef] [PubMed]

2009 (4)

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

S. Iyer, R. M. Gaikwad, V. Subba-Rao, C. D. Woodworth, and I. Sokolov, “Atomic force microscopy detects differences in the surface brush of normal and cancerous cells,” Nat. Nanotechnol.4(6), 389–393 (2009).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

2008 (1)

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

2007 (6)

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuators A Phys.133(2), 349–354 (2007).
[CrossRef]

T. Akkin, C. Joo, and J. F. de Boer, “Depth-resolved measurement of transient structural changes during action potential propagation,” Biophys. J.93(4), 1347–1353 (2007).
[CrossRef] [PubMed]

D. Marchion and P. Münster, “Development of histone deacetylase inhibitors for cancer treatment,” Expert Rev. Anticancer Ther.7(4), 583–598 (2007).
[CrossRef] [PubMed]

A. K. Ellerbee, T. L. Creazzo, and J. A. Izatt, “Investigating nanoscale cellular dynamics with cross-sectional spectral domain phase microscopy,” Opt. Express15(13), 8115–8124 (2007).
[CrossRef] [PubMed]

C. Joo and J. F. de Boer, “Spectral-domain optical coherence reflectometric sensor for highly sensitive molecular detection,” Opt. Lett.32(16), 2426–2428 (2007).
[CrossRef] [PubMed]

2005 (3)

2004 (1)

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

1995 (1)

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

1949 (1)

G. C. Crossmon, “Mounting media for phase microscope specimens,” Stain Technol.24(4), 241–247 (1949).
[PubMed]

Akkin, T.

T. Akkin, C. Joo, and J. F. de Boer, “Depth-resolved measurement of transient structural changes during action potential propagation,” Biophys. J.93(4), 1347–1353 (2007).
[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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Ayi, T. C.

X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuators A Phys.133(2), 349–354 (2007).
[CrossRef]

Bacher, C. P.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

Backman, V.

L. Cherkezyan, H. Subramanian, V. Stoyneva, J. D. Rogers, S. Yang, D. Damania, A. Taflove, and V. Backman, “Targeted alteration of real and imaginary refractive index of biological cells by histological staining,” Opt. Lett.37(10), 1601–1603 (2012).
[CrossRef] [PubMed]

N. N. Boustany, S. A. Boppart, and V. Backman, “Microscopic imaging and spectroscopy with scattered light,” Annu. Rev. Biomed. Eng.12(1), 285–314 (2010).
[CrossRef] [PubMed]

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron.11(4), 759–765 (2005).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, “Elastic backscattering spectroscopic microscopy,” Opt. Lett.30(18), 2445–2447 (2005).
[CrossRef] [PubMed]

Bakkenist, C.

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

Bakkenist, C. J.

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

Balla, A.

Z. Wang, K. Tangella, A. Balla, and G. Popescu, “Tissue refractive index as marker of disease,” J. Biomed. Opt.16(11), 116017 (2011).
[CrossRef] [PubMed]

Bhargava, R.

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

P. Wang, R. Bista, R. Bhargava, R. E. Brand, and Y. Liu, “Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis,” Opt. Lett.35(17), 2840–2842 (2010).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Bista, R.

Bista, R. K.

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

Bogojevic, A.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Boppart, S. A.

N. N. Boustany, S. A. Boppart, and V. Backman, “Microscopic imaging and spectroscopy with scattered light,” Annu. Rev. Biomed. Eng.12(1), 285–314 (2010).
[CrossRef] [PubMed]

Boustany, N. N.

N. N. Boustany, S. A. Boppart, and V. Backman, “Microscopic imaging and spectroscopy with scattered light,” Annu. Rev. Biomed. Eng.12(1), 285–314 (2010).
[CrossRef] [PubMed]

Brand, R. E.

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
[CrossRef] [PubMed]

P. Wang, R. Bista, R. Bhargava, R. E. Brand, and Y. Liu, “Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis,” Opt. Lett.35(17), 2840–2842 (2010).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Brentnall, T. A.

R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

Bronner, M. P.

R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
[CrossRef] [PubMed]

Capoglu, I. R.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Chalut, K. J.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Chang, J. S.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Cherkezyan, L.

Choi, S.

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

Choma, M. A.

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Creazzo, T. L.

Crossmon, G. C.

G. C. Crossmon, “Mounting media for phase microscope specimens,” Stain Technol.24(4), 241–247 (1949).
[PubMed]

Damania, D.

L. Cherkezyan, H. Subramanian, V. Stoyneva, J. D. Rogers, S. Yang, D. Damania, A. Taflove, and V. Backman, “Targeted alteration of real and imaginary refractive index of biological cells by histological staining,” Opt. Lett.37(10), 1601–1603 (2012).
[CrossRef] [PubMed]

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

de Boer, J. F.

Ellerbee, A. K.

Elzaiat, S. Y.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

Evans, C. L.

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Fercher, A. F.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

Frank-Stöhr, M.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Gaikwad, R. M.

S. Iyer, R. M. Gaikwad, V. Subba-Rao, C. D. Woodworth, and I. Sokolov, “Atomic force microscopy detects differences in the surface brush of normal and cancerous cells,” Nat. Nanotechnol.4(6), 389–393 (2009).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Giacomelli, M. G.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Goldberg, M. J.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Hartman, D. J.

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

Hasan, T.

Heifetz, A.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Hensing, T.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Hensing, T. A.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

Hitzenberger, C. K.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Iyer, S.

S. Iyer, R. M. Gaikwad, V. Subba-Rao, C. D. Woodworth, and I. Sokolov, “Atomic force microscopy detects differences in the surface brush of normal and cancerous cells,” Nat. Nanotechnol.4(6), 389–393 (2009).
[CrossRef] [PubMed]

Izatt, J. A.

Joo, C.

Kamp, G.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

Khalbuss, W. E.

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

Kim, Y. L.

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Knecht, H.

H. Knecht and S. Mai, “3D imaging of telomeres and nuclear architecture: an emerging tool of 3D nano-morphology-based diagnosis,” J. Cell. Physiol.226(4), 859–867 (2011).
[CrossRef] [PubMed]

Knoch, T. A.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

Kunte, D.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Kuzniar, T.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

Langmead, C. J.

R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
[CrossRef] [PubMed]

Li, X.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron.11(4), 759–765 (2005).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, “Elastic backscattering spectroscopic microscopy,” Opt. Lett.30(18), 2445–2447 (2005).
[CrossRef] [PubMed]

Liang, X. J.

X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuators A Phys.133(2), 349–354 (2007).
[CrossRef]

Lim, C. S.

X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuators A Phys.133(2), 349–354 (2007).
[CrossRef]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Liu, A. Q.

X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuators A Phys.133(2), 349–354 (2007).
[CrossRef]

Liu, Y.

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
[CrossRef] [PubMed]

P. Wang, R. Bista, R. Bhargava, R. E. Brand, and Y. Liu, “Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis,” Opt. Lett.35(17), 2840–2842 (2010).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, “Elastic backscattering spectroscopic microscopy,” Opt. Lett.30(18), 2445–2447 (2005).
[CrossRef] [PubMed]

Mai, S.

H. Knecht and S. Mai, “3D imaging of telomeres and nuclear architecture: an emerging tool of 3D nano-morphology-based diagnosis,” J. Cell. Physiol.226(4), 859–867 (2011).
[CrossRef] [PubMed]

Marchion, D.

D. Marchion and P. Münster, “Development of histone deacetylase inhibitors for cancer treatment,” Expert Rev. Anticancer Ther.7(4), 583–598 (2007).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Mohammed, J.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Momcilovic, O.

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

Muldoon, J.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Müller, G.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

Münster, P.

D. Marchion and P. Münster, “Development of histone deacetylase inhibitors for cancer treatment,” Expert Rev. Anticancer Ther.7(4), 583–598 (2007).
[CrossRef] [PubMed]

Navara, C.

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

Ostrander, J. H.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Pass, H. I.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Popescu, G.

Z. Wang, K. Tangella, A. Balla, and G. Popescu, “Tissue refractive index as marker of disease,” J. Biomed. Opt.16(11), 116017 (2011).
[CrossRef] [PubMed]

Pradhan, P.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Qiu, W.

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

Ray, D.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Rippe, K.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

Rogers, J. D.

L. Cherkezyan, H. Subramanian, V. Stoyneva, J. D. Rogers, S. Yang, D. Damania, A. Taflove, and V. Backman, “Targeted alteration of real and imaginary refractive index of biological cells by histological staining,” Opt. Lett.37(10), 1601–1603 (2012).
[CrossRef] [PubMed]

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Rom, W. N.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

Roy, H. K.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

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(44), 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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Schatten, G.

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

Shah, M.

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

Sokolov, I.

S. Iyer, R. M. Gaikwad, V. Subba-Rao, C. D. Woodworth, and I. Sokolov, “Atomic force microscopy detects differences in the surface brush of normal and cancerous cells,” Nat. Nanotechnol.4(6), 389–393 (2009).
[CrossRef] [PubMed]

Staton, K.

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

Stepinac, T.

Stöhr, M.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

Stoyneva, V.

Sturgis, C.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

Subba-Rao, V.

S. Iyer, R. M. Gaikwad, V. Subba-Rao, C. D. Woodworth, and I. Sokolov, “Atomic force microscopy detects differences in the surface brush of normal and cancerous cells,” Nat. Nanotechnol.4(6), 389–393 (2009).
[CrossRef] [PubMed]

Subramanian, H.

L. Cherkezyan, H. Subramanian, V. Stoyneva, J. D. Rogers, S. Yang, D. Damania, A. Taflove, and V. Backman, “Targeted alteration of real and imaginary refractive index of biological cells by histological staining,” Opt. Lett.37(10), 1601–1603 (2012).
[CrossRef] [PubMed]

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Taflove, A.

L. Cherkezyan, H. Subramanian, V. Stoyneva, J. D. Rogers, S. Yang, D. Damania, A. Taflove, and V. Backman, “Targeted alteration of real and imaginary refractive index of biological cells by histological staining,” Opt. Lett.37(10), 1601–1603 (2012).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron.11(4), 759–765 (2005).
[CrossRef]

Tangella, K.

Z. Wang, K. Tangella, A. Balla, and G. Popescu, “Tissue refractive index as marker of disease,” J. Biomed. Opt.16(11), 116017 (2011).
[CrossRef] [PubMed]

Tóth, K. F.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

Uttam, S.

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

Varum, S.

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Wachsmuth, M.

K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
[CrossRef] [PubMed]

Wang, P.

R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

P. Wang, R. Bista, R. Bhargava, R. E. Brand, and Y. Liu, “Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis,” Opt. Lett.35(17), 2840–2842 (2010).
[CrossRef] [PubMed]

Wang, Z.

Z. Wang, K. Tangella, A. Balla, and G. Popescu, “Tissue refractive index as marker of disease,” J. Biomed. Opt.16(11), 116017 (2011).
[CrossRef] [PubMed]

Wax, A.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Woodworth, C. D.

S. Iyer, R. M. Gaikwad, V. Subba-Rao, C. D. Woodworth, and I. Sokolov, “Atomic force microscopy detects differences in the surface brush of normal and cancerous cells,” Nat. Nanotechnol.4(6), 389–393 (2009).
[CrossRef] [PubMed]

Yang, C.

Yang, S.

Yap, P. H.

X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuators A Phys.133(2), 349–354 (2007).
[CrossRef]

Yu, J.

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

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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(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Zhang, L.

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

Annu. Rev. Biomed. Eng. (1)

N. N. Boustany, S. A. Boppart, and V. Backman, “Microscopic imaging and spectroscopy with scattered light,” Annu. Rev. Biomed. Eng.12(1), 285–314 (2010).
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R. K. Bista, P. Wang, R. Bhargava, S. Uttam, D. J. Hartman, R. E. Brand, and Y. Liu, “Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer,” Breast Cancer Res. Treat.135(1), 115–124 (2012).
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Cancer Res. (3)

H. K. Roy, H. Subramanian, D. Damania, T. A. Hensing, W. N. Rom, H. I. Pass, D. Ray, J. D. Rogers, A. Bogojevic, M. Shah, T. Kuzniar, P. Pradhan, and V. Backman, “Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening,” Cancer Res.70(20), 7748–7754 (2010).
[CrossRef] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res.69(13), 5357–5363 (2009).
[CrossRef] [PubMed]

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
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X. Li, A. Taflove, and V. Backman, “Recent progress in exact and reduced-order modeling of light-scattering properties of complex structures,” IEEE J. Sel. Top. Quantum Electron.11(4), 759–765 (2005).
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R. K. Bista, T. A. Brentnall, M. P. Bronner, C. J. Langmead, R. E. Brand, and Y. Liu, “Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia,” Inflamm. Bowel Dis.17(12), 2427–2435 (2011).
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J. Biomed. Opt. (4)

Z. Wang, K. Tangella, A. Balla, and G. Popescu, “Tissue refractive index as marker of disease,” J. Biomed. Opt.16(11), 116017 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. E. Khalbuss, W. Qiu, S. Uttam, K. Staton, L. Zhang, T. A. Brentnall, R. E. Brand, and Y. Liu, “Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy,” J. Biomed. Opt.15(6), 066028 (2010).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, D. J. Hartman, W. Qiu, J. Yu, L. Zhang, R. E. Brand, and Y. Liu, “Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model,” J. Biomed. Opt.17(6), 066014 (2012).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
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K. F. Tóth, T. A. Knoch, M. Wachsmuth, M. Frank-Stöhr, M. Stöhr, C. P. Bacher, G. Müller, and K. Rippe, “Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin,” J. Cell Sci.117(18), 4277–4287 (2004).
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Nat. Nanotechnol. (1)

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Opt. Express (2)

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Proc. Natl. Acad. Sci. U.S.A. (2)

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

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(44), 17255–17260 (2007).
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Sens. Actuators A Phys. (1)

X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi, and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sens. Actuators A Phys.133(2), 349–354 (2007).
[CrossRef]

Stain Technol. (1)

G. C. Crossmon, “Mounting media for phase microscope specimens,” Stain Technol.24(4), 241–247 (1949).
[PubMed]

Stem Cells (1)

O. Momčilović, S. Choi, S. Varum, C. Bakkenist, G. Schatten, and C. Navara, “Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells,” Stem Cells27(8), 1822–1835 (2009).
[CrossRef] [PubMed]

Other (4)

D. J. Cook, Cellular Pathology: Introduction to Techniques and Applications, 2nd ed. (Scion, 2006), pp. xxxii, 384 p.

B. E. A. Saleh and M. C. Teich, Fundamentals of Photonics, 2nd ed., Wiley series in pure and applied optics (Wiley-Interscience, 2007), pp. xix, 1177 p.

G. Popescu, Quantitative Phase Imaging of Cells and Tissues, McGraw-Hill biophotonics (McGraw-Hill, 2011), pp. xx, 362 p.

M. Born and E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, 7th (expanded) ed. (Cambridge University Press, 1999).

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Figures (19)

Fig. 1
Fig. 1

The reflection-mode common-path interferometry setup based on clinically prepared glass slide. The setup dimensions and the axial refractive index profile have been exaggerated for clarity.

Fig. 2
Fig. 2

Illustration of depth-resolved SL-QPM via coherence gating at fixed depth locations (shown as red dots).

Fig. 3
Fig. 3

A representative sample thickness profile of a tissue sectioned using a microtome.

Fig. 4
Fig. 4

A representative axial refractive index profile of the scattering sample.

Fig. 5
Fig. 5

Variation in δp as a function of variation in sample thickness.

Fig. 6
Fig. 6

The sub-resolution in change in OPL (δp) as a function of SNR for the same refractive index profile at fixed optical-depth locations of 1.5µm, 3µm, 4.5µm and 6µm.

Fig. 7
Fig. 7

The sub-resolution in change in OPL (δp) at optical depth location of 1.5µm as a function of refractive index mismatch at the optical depth of 6.5 µm, quantified by m <Δn> .

Fig. 8
Fig. 8

The relationship between δp and changes in local mean refractive index (δn).

Fig. 9
Fig. 9

Relationship between δp and the profile correlation length, δl (nm).

Fig. 10
Fig. 10

The depth-resolved sub-resolution change in OPL (δp).

Fig. 11
Fig. 11

The depth-resolved sub-resolution change in OPL (δp) for 4µm and 5µm thick sections at fixed optical-depth locations within the tissue section of (i) 1.5µm and (ii) 3µm respectively.

Fig. 12
Fig. 12

Temporal stability of depth-resolved δp values as a function of time at four fixed optical depth locations.

Fig. 13
Fig. 13

Flow cytometry of HeLa cells arrested at (i) G1/S-phase (ii) G2/M-phase.

Fig. 14
Fig. 14

Spectral signal from a cell nucleus and its Fourier transform.

Fig. 15
Fig. 15

The depth-resolved sub-resolution change in OPL (δp) at four fixed optical-depth locations within the nuclei for cells at G1/S and G2/M phase. The two-sided p-value is shown on each figure, calculated from the student t-test.

Fig. 16
Fig. 16

The depth-resolved distribution of altered nuclear density in cells at G2/M phase compared to those at G1/S phase. The gray scale bar shows the change in δp for G2/M with respect to that of G1/S phase.

Fig. 17
Fig. 17

Immunoblot of acetyl-Histone H4 in asynchronous and synchronized G1-phase HeLa cells treated with vehicle or TSA for 6 hours. Increased acetyl-Histone H4 associated with chromatin decondensation is seen in cells treated with TSA.

Fig. 18
Fig. 18

The depth-resolved sub-resolution change in OPL (δp) at four fixed optical-depth locations within the nuclei for control cells and TSA-treated cells.

Fig. 19
Fig. 19

The depth-resolved changes in nuclear structural feature vector distribution for the TSA-treated cells when compared to control cells.

Equations (7)

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P( k )=S( k )[ r r 2 + 0 Z r s 2 ( z )d z +2 0 Z r s ( z ) r r cos( 2kn( z ) z )d z ],
P( K )=S( K 2 )[ R r + R s +2 0 Z r s ( z ) r r cos( 4π K 2 n( z ) z )d z ],
p( z opl )=2Γ[ ( R r + R s )δ(0)+2 r r 1 ( 0 Z r s ( z )cos( 4π K 2 n( z ) z )d z ) ]( 2 z opl ),
δp( z opl )= λ 0 22π arctan( Im( p( z opl ) ) Re(p( z opl )) ) ,
N noise = η P ref τ hν 2 N ,
N Signal = 2η P sig P ref τ hν 2 N .
SNR=10 log 10 4η P sig τ hν 2 N   dB.

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