Abstract

A light-sheet-based 2D light scattering cytometer is developed for label-free characterization of senescent cells. The light-sheet provides an illumination beam with controlled thickness for single cell excitation, and 2D light scattering patterns are obtained by using a defocused imaging method. The principle of this cytometer is validated by distinguishing microspheres with submicron resolution. Automatic classification of senescent and normal cells is achieved at single cell level by using the support vector machine (SVM) algorithm, where a sensitivity of 89.1% and a specificity of 96.4% are obtained. Our results suggest that the light-sheet-based 2D light scattering label-free cytometry has the capability to perform size differentiation of beads with submicron resolution and to classify different groups of cells without fluorescent labeling, showing the potential for clinical diagnosis of senescence-related diseases.

© 2016 Optical Society of America

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References

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2015 (7)

B. G. Childs, M. Durik, D. J. Baker, and J. M. van Deursen, “Cellular senescence in aging and age-related disease: from mechanisms to therapy,” Nat. Med. 21(12), 1424–1435 (2015).
[Crossref] [PubMed]

Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
[Crossref] [PubMed]

X. Su, S. Liu, X. Qiao, Y. Yang, K. Song, and B. Kong, “Pattern recognition cytometry for label-free cell classification by 2D light scattering measurements,” Opt. Express 23(21), 27558–27565 (2015).
[Crossref] [PubMed]

S. He, C. Ye, Q. Sun, C. K. S. Leung, and J. Y. A. Qu, “Label-free nonlinear optical imaging of mouse retina,” Biomed. Opt. Express 6(3), 1055–1066 (2015).
[Crossref] [PubMed]

L. Xie, Y. Yang, X. Sun, X. Qiao, Q. Liu, K. Song, B. Kong, and X. Su, “2D light scattering static cytometry for label-free single cell analysis with submicron resolution,” Cytometry A 87(11), 1029–1037 (2015).
[Crossref] [PubMed]

L. Gao, “Optimization of the excitation light sheet in selective plane illumination microscopy,” Biomed. Opt. Express 6(3), 881–890 (2015).
[Crossref] [PubMed]

Z. Wei, H. Guo, Z. Liu, X. Zhang, Q. Liu, Y. Qian, Y. Gong, and C. Shao, “CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop,” Free Radic. Biol. Med. 79, 1–13 (2015).
[Crossref] [PubMed]

2014 (2)

2013 (6)

F. O. Fahrbach, F. F. Voigt, B. Schmid, F. Helmchen, and J. Huisken, “Rapid 3D light-sheet microscopy with a tunable lens,” Opt. Express 21(18), 21010–21026 (2013).
[Crossref] [PubMed]

H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
[Crossref] [PubMed]

M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
[Crossref] [PubMed]

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

J. Wu, J. Li, and R. K. Y. Chan, “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis,” Opt. Express 21(12), 14474–14480 (2013).
[Crossref] [PubMed]

J. Zhang, Y. Feng, M. S. Moran, J. Q. Lu, L. V. Yang, Y. Sa, N. Zhang, L. Dong, and X. H. Hu, “Analysis of cellular objects through diffraction images acquired by flow cytometry,” Opt. Express 21(21), 24819–24828 (2013).
[Crossref] [PubMed]

2012 (2)

J. H. Spille, T. Kaminski, H. P. Königshoven, and U. Kubitscheck, “Dynamic three-dimensional tracking of single fluorescent nanoparticles deep inside living tissue,” Opt. Express 20(18), 19697–19707 (2012).
[Crossref] [PubMed]

K. Fišer, T. Sieger, A. Schumich, B. Wood, J. Irving, E. Mejstříková, and M. N. Dworzak, “Detection and monitoring of normal and leukemic cell populations with hierarchical clustering of flow cytometry data,” Cytometry A 81A(1), 25–34 (2012).
[Crossref] [PubMed]

2011 (3)

2010 (1)

H. Zhao, H. D. Halicka, F. Traganos, E. Jorgensen, and Z. Darzynkiewicz, “New biomarkers probing depth of cell senescence assessed by laser scanning cytometry,” Cytometry A 77A(11), 999–1007 (2010).
[Crossref] [PubMed]

2009 (2)

E. S. Hwang, G. Yoon, and H. T. Kang, “A comparative analysis of the cell biology of senescence and aging,” Cell. Mol. Life Sci. 66(15), 2503–2524 (2009).
[Crossref] [PubMed]

F. Debacq-Chainiaux, J. D. Erusalimsky, J. Campisi, and O. Toussaint, “Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo,” Nat. Protoc. 4(12), 1798–1806 (2009).
[Crossref] [PubMed]

2008 (2)

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, “Autofluorescence of epithelial tissue: single-photon versus two-photon excitation,” J. Biomed. Opt. 13(5), 054010 (2008).
[Crossref] [PubMed]

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[Crossref] [PubMed]

2007 (2)

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
[Crossref] [PubMed]

J. Campisi and F. d’Adda di Fagagna, “Cellular senescence: when bad things happen to good cells,” Nat. Rev. Mol. Cell Biol. 8(9), 729–740 (2007).
[Crossref] [PubMed]

2004 (1)

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. K. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
[Crossref] [PubMed]

2003 (1)

M. Narita, S. Nũnez, E. Heard, M. Narita, A. W. Lin, S. A. Hearn, D. L. Spector, G. J. Hannon, and S. W. Lowe, “Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence,” Cell 113(6), 703–716 (2003).
[Crossref] [PubMed]

2002 (1)

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

2001 (1)

J. Campisi, “Cellular senescence as a tumor-suppressor mechanism,” Trends Cell Biol. 11(11), S27–S31 (2001).
[Crossref] [PubMed]

2000 (2)

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[Crossref] [PubMed]

T. S. Furey, N. Cristianini, N. Duffy, D. W. Bednarski, M. Schummer, and D. Haussler, “Support vector machine classification and validation of cancer tissue samples using microarray expression data,” Bioinformatics 16(10), 906–914 (2000).
[Crossref] [PubMed]

1999 (1)

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

1998 (2)

1995 (1)

G. P. Dimri, X. Lee, G. Basile, M. Acosta, G. Scott, C. Roskelley, E. E. Medrano, M. Linskens, I. Rubelj, and O. Pereira-Smith, “A biomarker that identifies senescent human cells in culture and in aging skin in vivo,” Proc. Natl. Acad. Sci. U.S.A. 92(20), 9363–9367 (1995).
[Crossref] [PubMed]

Aanstad, P.

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

Acosta, M.

G. P. Dimri, X. Lee, G. Basile, M. Acosta, G. Scott, C. Roskelley, E. E. Medrano, M. Linskens, I. Rubelj, and O. Pereira-Smith, “A biomarker that identifies senescent human cells in culture and in aging skin in vivo,” Proc. Natl. Acad. Sci. U.S.A. 92(20), 9363–9367 (1995).
[Crossref] [PubMed]

Ahrens, M. B.

M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
[Crossref] [PubMed]

Arendt, J. T.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[Crossref] [PubMed]

Arendt, T.

E. Sikora, T. Arendt, M. Bennett, and M. Narita, “Impact of cellular senescence signature on ageing research,” Ageing Res. Rev. 10(1), 146–152 (2011).
[Crossref] [PubMed]

Backhouse, C.

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
[Crossref] [PubMed]

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
[Crossref] [PubMed]

Backman, V.

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

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[Crossref] [PubMed]

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

Badizadegan, K.

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

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[Crossref] [PubMed]

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

Baker, D. J.

B. G. Childs, M. Durik, D. J. Baker, and J. M. van Deursen, “Cellular senescence in aging and age-related disease: from mechanisms to therapy,” Nat. Med. 21(12), 1424–1435 (2015).
[Crossref] [PubMed]

Basile, G.

G. P. Dimri, X. Lee, G. Basile, M. Acosta, G. Scott, C. Roskelley, E. E. Medrano, M. Linskens, I. Rubelj, and O. Pereira-Smith, “A biomarker that identifies senescent human cells in culture and in aging skin in vivo,” Proc. Natl. Acad. Sci. U.S.A. 92(20), 9363–9367 (1995).
[Crossref] [PubMed]

Becker, K.

S. Saghafi, K. Becker, C. Hahn, and H. U. Dodt, “3D-ultramicroscopy utilizing aspheric optics,” J. Biophotonics 7(1-2), 117–125 (2014).
[Crossref] [PubMed]

Bednarski, D. W.

T. S. Furey, N. Cristianini, N. Duffy, D. W. Bednarski, M. Schummer, and D. Haussler, “Support vector machine classification and validation of cancer tissue samples using microarray expression data,” Bioinformatics 16(10), 906–914 (2000).
[Crossref] [PubMed]

Bennett, M.

E. Sikora, T. Arendt, M. Bennett, and M. Narita, “Impact of cellular senescence signature on ageing research,” Ageing Res. Rev. 10(1), 146–152 (2011).
[Crossref] [PubMed]

Bertrand, F. E.

Boone, C. W.

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

Brock, R. S.

Burges, C. J.

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H. Zhao, H. D. Halicka, F. Traganos, E. Jorgensen, and Z. Darzynkiewicz, “New biomarkers probing depth of cell senescence assessed by laser scanning cytometry,” Cytometry A 77A(11), 999–1007 (2010).
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Heard, E.

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

Johnson, T. M.

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H. Zhao, H. D. Halicka, F. Traganos, E. Jorgensen, and Z. Darzynkiewicz, “New biomarkers probing depth of cell senescence assessed by laser scanning cytometry,” Cytometry A 77A(11), 999–1007 (2010).
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V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
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Kubitscheck, U.

Lee, X.

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Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
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Liu, Z.

Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
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Marquez-Curtis, L.

McGilligan, J. A.

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K. Fišer, T. Sieger, A. Schumich, B. Wood, J. Irving, E. Mejstříková, and M. N. Dworzak, “Detection and monitoring of normal and leukemic cell populations with hierarchical clustering of flow cytometry data,” Cytometry A 81A(1), 25–34 (2012).
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V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
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E. Sikora, T. Arendt, M. Bennett, and M. Narita, “Impact of cellular senescence signature on ageing research,” Ageing Res. Rev. 10(1), 146–152 (2011).
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M. Narita, S. Nũnez, E. Heard, M. Narita, A. W. Lin, S. A. Hearn, D. L. Spector, G. J. Hannon, and S. W. Lowe, “Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence,” Cell 113(6), 703–716 (2003).
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M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
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V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
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V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
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X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
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Z. Wei, H. Guo, Z. Liu, X. Zhang, Q. Liu, Y. Qian, Y. Gong, and C. Shao, “CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop,” Free Radic. Biol. Med. 79, 1–13 (2015).
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L. Xie, Y. Yang, X. Sun, X. Qiao, Q. Liu, K. Song, B. Kong, and X. Su, “2D light scattering static cytometry for label-free single cell analysis with submicron resolution,” Cytometry A 87(11), 1029–1037 (2015).
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X. Su, S. Liu, X. Qiao, Y. Yang, K. Song, and B. Kong, “Pattern recognition cytometry for label-free cell classification by 2D light scattering measurements,” Opt. Express 23(21), 27558–27565 (2015).
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Qu, J. Y.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, “Autofluorescence of epithelial tissue: single-photon versus two-photon excitation,” J. Biomed. Opt. 13(5), 054010 (2008).
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Qu, J. Y. A.

Robson, D. N.

M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
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B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
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G. P. Dimri, X. Lee, G. Basile, M. Acosta, G. Scott, C. Roskelley, E. E. Medrano, M. Linskens, I. Rubelj, and O. Pereira-Smith, “A biomarker that identifies senescent human cells in culture and in aging skin in vivo,” Proc. Natl. Acad. Sci. U.S.A. 92(20), 9363–9367 (1995).
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Rubelj, I.

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B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
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V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
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B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
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Z. Wei, H. Guo, Z. Liu, X. Zhang, Q. Liu, Y. Qian, Y. Gong, and C. Shao, “CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop,” Free Radic. Biol. Med. 79, 1–13 (2015).
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Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
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H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
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V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
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Sieger, T.

K. Fišer, T. Sieger, A. Schumich, B. Wood, J. Irving, E. Mejstříková, and M. N. Dworzak, “Detection and monitoring of normal and leukemic cell populations with hierarchical clustering of flow cytometry data,” Cytometry A 81A(1), 25–34 (2012).
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Sikora, E.

E. Sikora, T. Arendt, M. Bennett, and M. Narita, “Impact of cellular senescence signature on ageing research,” Ageing Res. Rev. 10(1), 146–152 (2011).
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X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
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Song, K.

X. Su, S. Liu, X. Qiao, Y. Yang, K. Song, and B. Kong, “Pattern recognition cytometry for label-free cell classification by 2D light scattering measurements,” Opt. Express 23(21), 27558–27565 (2015).
[Crossref] [PubMed]

L. Xie, Y. Yang, X. Sun, X. Qiao, Q. Liu, K. Song, B. Kong, and X. Su, “2D light scattering static cytometry for label-free single cell analysis with submicron resolution,” Cytometry A 87(11), 1029–1037 (2015).
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M. Narita, S. Nũnez, E. Heard, M. Narita, A. W. Lin, S. A. Hearn, D. L. Spector, G. J. Hannon, and S. W. Lowe, “Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence,” Cell 113(6), 703–716 (2003).
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Stelzer, E. H. K.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. K. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
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Su, X. T.

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
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X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
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Sun, Q.

Sun, X.

L. Xie, Y. Yang, X. Sun, X. Qiao, Q. Liu, K. Song, B. Kong, and X. Su, “2D light scattering static cytometry for label-free single cell analysis with submicron resolution,” Cytometry A 87(11), 1029–1037 (2015).
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Swoger, J.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. K. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
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Thierbach, K.

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
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H. Zhao, H. D. Halicka, F. Traganos, E. Jorgensen, and Z. Darzynkiewicz, “New biomarkers probing depth of cell senescence assessed by laser scanning cytometry,” Cytometry A 77A(11), 999–1007 (2010).
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Valdez, T.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
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Van Dam, J.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
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B. G. Childs, M. Durik, D. J. Baker, and J. M. van Deursen, “Cellular senescence in aging and age-related disease: from mechanisms to therapy,” Nat. Med. 21(12), 1424–1435 (2015).
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Wallace, M. B.

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[Crossref] [PubMed]

Wang, Y.

H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
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Wax, A.

D. Ho, S. Kim, T. K. Drake, W. J. Eldridge, and A. Wax, “Wavelet transform fast inverse light scattering analysis for size determination of spherical scatterers,” Biomed. Opt. Express 5(10), 3292–3304 (2014).
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A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
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Weber, M.

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
[Crossref] [PubMed]

Wei, Z.

Z. Wei, H. Guo, Z. Liu, X. Zhang, Q. Liu, Y. Qian, Y. Gong, and C. Shao, “CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop,” Free Radic. Biol. Med. 79, 1–13 (2015).
[Crossref] [PubMed]

Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
[Crossref] [PubMed]

H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
[Crossref] [PubMed]

Wittbrodt, J.

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. K. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
[Crossref] [PubMed]

Wood, B.

K. Fišer, T. Sieger, A. Schumich, B. Wood, J. Irving, E. Mejstříková, and M. N. Dworzak, “Detection and monitoring of normal and leukemic cell populations with hierarchical clustering of flow cytometry data,” Cytometry A 81A(1), 25–34 (2012).
[Crossref] [PubMed]

Wu, J.

Wu, Y.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, “Autofluorescence of epithelial tissue: single-photon versus two-photon excitation,” J. Biomed. Opt. 13(5), 054010 (2008).
[Crossref] [PubMed]

Xie, L.

L. Xie, Y. Yang, X. Sun, X. Qiao, Q. Liu, K. Song, B. Kong, and X. Su, “2D light scattering static cytometry for label-free single cell analysis with submicron resolution,” Cytometry A 87(11), 1029–1037 (2015).
[Crossref] [PubMed]

Xu, B.

H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
[Crossref] [PubMed]

Xu, X.

Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
[Crossref] [PubMed]

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

Yang, L. V.

Yang, Y.

L. Xie, Y. Yang, X. Sun, X. Qiao, Q. Liu, K. Song, B. Kong, and X. Su, “2D light scattering static cytometry for label-free single cell analysis with submicron resolution,” Cytometry A 87(11), 1029–1037 (2015).
[Crossref] [PubMed]

X. Su, S. Liu, X. Qiao, Y. Yang, K. Song, and B. Kong, “Pattern recognition cytometry for label-free cell classification by 2D light scattering measurements,” Opt. Express 23(21), 27558–27565 (2015).
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Yoon, G.

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Zhang, J.

Zhang, N.

Zhang, Q.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[Crossref] [PubMed]

Zhang, X.

Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
[Crossref] [PubMed]

Z. Wei, H. Guo, Z. Liu, X. Zhang, Q. Liu, Y. Qian, Y. Gong, and C. Shao, “CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop,” Free Radic. Biol. Med. 79, 1–13 (2015).
[Crossref] [PubMed]

H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
[Crossref] [PubMed]

Zhao, H.

H. Zhao, H. D. Halicka, F. Traganos, E. Jorgensen, and Z. Darzynkiewicz, “New biomarkers probing depth of cell senescence assessed by laser scanning cytometry,” Cytometry A 77A(11), 999–1007 (2010).
[Crossref] [PubMed]

Zhao, M.

Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
[Crossref] [PubMed]

H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
[Crossref] [PubMed]

Zheng, W.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, “Autofluorescence of epithelial tissue: single-photon versus two-photon excitation,” J. Biomed. Opt. 13(5), 054010 (2008).
[Crossref] [PubMed]

Zonios, G.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Müller, Q. Zhang, G. Zonios, E. Kline, J. A. McGilligan, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406(6791), 35–36 (2000).
[Crossref] [PubMed]

Ageing Res. Rev. (1)

E. Sikora, T. Arendt, M. Bennett, and M. Narita, “Impact of cellular senescence signature on ageing research,” Ageing Res. Rev. 10(1), 146–152 (2011).
[Crossref] [PubMed]

Aging Cell (1)

H. Guo, Z. Liu, B. Xu, H. Hu, Z. Wei, Q. Liu, X. Zhang, X. Ding, Y. Wang, M. Zhao, Y. Gong, and C. Shao, “Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage,” Aging Cell 12(6), 1110–1121 (2013).
[Crossref] [PubMed]

Appl. Opt. (1)

Bioinformatics (1)

T. S. Furey, N. Cristianini, N. Duffy, D. W. Bednarski, M. Schummer, and D. Haussler, “Support vector machine classification and validation of cancer tissue samples using microarray expression data,” Bioinformatics 16(10), 906–914 (2000).
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Biomed. Opt. Express (4)

Biophys. J. (1)

A. Wax, C. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, and M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82(4), 2256–2264 (2002).
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Cell (1)

M. Narita, S. Nũnez, E. Heard, M. Narita, A. W. Lin, S. A. Hearn, D. L. Spector, G. J. Hannon, and S. W. Lowe, “Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence,” Cell 113(6), 703–716 (2003).
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Cell. Mol. Life Sci. (1)

E. S. Hwang, G. Yoon, and H. T. Kang, “A comparative analysis of the cell biology of senescence and aging,” Cell. Mol. Life Sci. 66(15), 2503–2524 (2009).
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Cytometry A (3)

H. Zhao, H. D. Halicka, F. Traganos, E. Jorgensen, and Z. Darzynkiewicz, “New biomarkers probing depth of cell senescence assessed by laser scanning cytometry,” Cytometry A 77A(11), 999–1007 (2010).
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L. Xie, Y. Yang, X. Sun, X. Qiao, Q. Liu, K. Song, B. Kong, and X. Su, “2D light scattering static cytometry for label-free single cell analysis with submicron resolution,” Cytometry A 87(11), 1029–1037 (2015).
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K. Fišer, T. Sieger, A. Schumich, B. Wood, J. Irving, E. Mejstříková, and M. N. Dworzak, “Detection and monitoring of normal and leukemic cell populations with hierarchical clustering of flow cytometry data,” Cytometry A 81A(1), 25–34 (2012).
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Data Min. Knowl. Discov. (1)

C. J. Burges, “A tutorial on support vector machines for pattern recognition,” Data Min. Knowl. Discov. 2(2), 121–167 (1998).
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Free Radic. Biol. Med. (1)

Z. Wei, H. Guo, Z. Liu, X. Zhang, Q. Liu, Y. Qian, Y. Gong, and C. Shao, “CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop,” Free Radic. Biol. Med. 79, 1–13 (2015).
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IEEE J. Sel. Top. Quantum Electron. (1)

V. Backman, R. Gurjar, K. Badizadegan, L. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5(4), 1019–1026 (1999).
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J. Biomed. Opt. (2)

X. T. Su, K. Singh, C. Capjack, J. Petrácek, C. Backhouse, and W. Rozmus, “Measurements of light scattering in an integrated microfluidic waveguide cytometer,” J. Biomed. Opt. 13(2), 024024 (2008).
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W. Zheng, Y. Wu, D. Li, and J. Y. Qu, “Autofluorescence of epithelial tissue: single-photon versus two-photon excitation,” J. Biomed. Opt. 13(5), 054010 (2008).
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J. Biophotonics (1)

S. Saghafi, K. Becker, C. Hahn, and H. U. Dodt, “3D-ultramicroscopy utilizing aspheric optics,” J. Biophotonics 7(1-2), 117–125 (2014).
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Mol. Cancer Ther. (1)

Q. Liu, X. Xu, M. Zhao, Z. Wei, X. Li, X. Zhang, Z. Liu, Y. Gong, and C. Shao, “Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway,” Mol. Cancer Ther. 14(2), 355–363 (2015).
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Nat. Commun. (1)

B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
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Nat. Med. (1)

B. G. Childs, M. Durik, D. J. Baker, and J. M. van Deursen, “Cellular senescence in aging and age-related disease: from mechanisms to therapy,” Nat. Med. 21(12), 1424–1435 (2015).
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Nat. Methods (1)

M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10(5), 413–420 (2013).
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Nat. Protoc. (1)

F. Debacq-Chainiaux, J. D. Erusalimsky, J. Campisi, and O. Toussaint, “Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo,” Nat. Protoc. 4(12), 1798–1806 (2009).
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Nat. Rev. Mol. Cell Biol. (1)

J. Campisi and F. d’Adda di Fagagna, “Cellular senescence: when bad things happen to good cells,” Nat. Rev. Mol. Cell Biol. 8(9), 729–740 (2007).
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Nature (1)

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Opt. Express (7)

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express 15(17), 10562–10575 (2007).
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X. Su, S. E. Kirkwood, M. Gupta, L. Marquez-Curtis, Y. Qiu, A. Janowska-Wieczorek, W. Rozmus, and Y. Y. Tsui, “Microscope-based label-free microfluidic cytometry,” Opt. Express 19(1), 387–398 (2011).
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J. H. Spille, T. Kaminski, H. P. Königshoven, and U. Kubitscheck, “Dynamic three-dimensional tracking of single fluorescent nanoparticles deep inside living tissue,” Opt. Express 20(18), 19697–19707 (2012).
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J. Wu, J. Li, and R. K. Y. Chan, “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis,” Opt. Express 21(12), 14474–14480 (2013).
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F. O. Fahrbach, F. F. Voigt, B. Schmid, F. Helmchen, and J. Huisken, “Rapid 3D light-sheet microscopy with a tunable lens,” Opt. Express 21(18), 21010–21026 (2013).
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J. Zhang, Y. Feng, M. S. Moran, J. Q. Lu, L. V. Yang, Y. Sa, N. Zhang, L. Dong, and X. H. Hu, “Analysis of cellular objects through diffraction images acquired by flow cytometry,” Opt. Express 21(21), 24819–24828 (2013).
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X. Su, S. Liu, X. Qiao, Y. Yang, K. Song, and B. Kong, “Pattern recognition cytometry for label-free cell classification by 2D light scattering measurements,” Opt. Express 23(21), 27558–27565 (2015).
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Proc. Natl. Acad. Sci. U.S.A. (1)

G. P. Dimri, X. Lee, G. Basile, M. Acosta, G. Scott, C. Roskelley, E. E. Medrano, M. Linskens, I. Rubelj, and O. Pereira-Smith, “A biomarker that identifies senescent human cells in culture and in aging skin in vivo,” Proc. Natl. Acad. Sci. U.S.A. 92(20), 9363–9367 (1995).
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Science (1)

J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. K. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305(5686), 1007–1009 (2004).
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Trends Cell Biol. (1)

J. Campisi, “Cellular senescence as a tumor-suppressor mechanism,” Trends Cell Biol. 11(11), S27–S31 (2001).
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H. M. Shapiro, Practical Flow Cytometry (John Wiley & Sons, 2005).

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Figures (7)

Fig. 1
Fig. 1 Schematic of the light-sheet-based 2D light scattering static cytometer. A collimated laser beam is reshaped by a cylindrical lens to form a light sheet. The sample in a waveguide as shown in the inset is illuminated by the thin light sheet. A CMOS sensor is used to obtain 2D light scattering patterns via a microscope objective with an NA of 0.4. The experimental patterns are sent to computer and are analyzed for particle sizing and cell differentiation.
Fig. 2
Fig. 2 Illustration of the scattered light ray path from a single scatterer excited by a light sheet. The light sheet is with a thickness of d at the beam waist. The 2D light scattering pattern is detected by an optical objective working in positive defocusing mode. The angle θ denotes the scatter polar angle and α is the maximal half-angle of the cone of light that can enter the microscope objective. The refractive index of solution, glass and air are indicated as n1, n2 and n3, respectively. The top and bottom glass layers are both 170 μm in thickness. (Not to scale)
Fig. 3
Fig. 3 Measurements of the light sheet thickness in the 2D light scattering label-free cytometry. (a) shows the image of a light sheet in the Rhodamine 6G solution generated by a cylindrical lens with a focal length of 25.4 mm, and (b) is from a cylindrical lens with a focal length of 150 mm. Scale bar: 50 μm. (c) and (d) show the measured thickness of the light sheets in (a) and (b), respectively.
Fig. 4
Fig. 4 Differentiation of 3.87 μm and 4.19 μm standard polystyrene microspheres by light-sheet-based 2D light scattering cytometry. (a) and (b) are the phase contrast microscope images of 3.87 μm and 4.19 μm microspheres. Scale bar: 10 μm. (c) and (d) are the 2D light scattering patterns of the microspheres in (a) and (b), respectively. (e) and (f) are the Mie theory simulations for 3.87 μm and 4.19 μm microspheres, in the angular range from 72.5° to 107.5°. (g) presents the comparisons between experimental and simulation results by using Fourier analysis.
Fig. 5
Fig. 5 Evaluation of the human fibroblasts senescence rate for the control sample and H2O2 treated sample. (a) is the representative image of the control group and (b) is for the H2O2 treated sample. Scale bar: 100 μm. (c) shows the percentages of SA-β-gal positive cells of the two samples.
Fig. 6
Fig. 6 Representative 2D light scattering patterns of the NHF and SHF obtained with the light-sheet-based label-free cytometry. (a) and (b) are the microscope images of an NHF and an SHF. Scale bar: 20 μm. (c) and (d) show the corresponding 2D light scattering patterns.
Fig. 7
Fig. 7 Differentiation of NHFs and SHFs by light-sheet-based 2D light scattering label-free cytometry. The average area of the speckles in a 2D pattern varying with its speckle number is plotted, as shown in open circle and square signs for NHFs and SHFs, respectively. The solid circle and square signs denote the results of NHF in Fig. 6(a) and SHF in Fig. 6(b), respectively. The mean and SD for the average areas and speckle numbers of the groups of NHFs and SHFs show that these two groups of cells can be differentiated.

Tables (1)

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Table 1 Classification of the NHFs and SHFs by SVM.

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