Abstract

We suggest a new multimodal imaging technique for quantitatively measuring the integral (thickness-average) refractive index of the nuclei of live biological cells in suspension. For this aim, we combined quantitative phase microscopy with simultaneous 2-D fluorescence microscopy. We used 2-D fluorescence microscopy to localize the nucleus inside the quantitative phase map of the cell, as well as for measuring the nucleus radii. As verified offline by both 3-D confocal fluorescence microscopy and 2-D fluorescence microscopy while rotating the cells during flow, the nucleus of cells in suspension that are not during division can be assumed to be an ellipsoid. The entire shape of a cell in suspension can be assumed to be a sphere. Then, the cell and nucleus 3-D shapes can be evaluated based on their in-plain radii available from the 2-D phase and fluorescent measurements, respectively. Finally, the nucleus integral refractive index profile is calculated. We demonstrate the new technique on cancer cells, obtaining nucleus refractive index values that are lower than those of the cytoplasm, coinciding with recent findings. We believe that the proposed technique has the potential to be used for flow cytometry, where full 3-D refractive index tomography is too slow to be implemented during flow.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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2018 (1)

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

2017 (4)

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Z. A. Steelman, W. J. Eldridge, J. B. Weintraub, and A. Wax, “Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies,” J. Biophotonics 10(12), 1714–1722 (2017).
[Crossref] [PubMed]

M. Balberg, M. Levi, K. Kalinowski, I. Barnea, S. K. Mirsky, and N. T. Shaked, “Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry,” J. Biophotonics 10(10), 1305–1314 (2017).
[Crossref] [PubMed]

S. Chowdhury, W. J. Eldridge, A. Wax, and J. A. Izatt, “Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy,” Biomed. Opt. Express 8(5), 2496–2518 (2017).
[Crossref] [PubMed]

2016 (1)

M. Schürmann, J. Scholze, P. Müller, J. Guck, and C. J. Chan, “Cell nuclei have lower refractive index and mass density than cytoplasm,” J. Biophotonics 9(10), 1068–1076 (2016).
[Crossref] [PubMed]

2015 (3)

M. M. Villone, G. D’Avino, M. A. Hulsen, and P. L. Maffettone, “Dynamics of prolate spheroidal elastic particles in confined shear flow,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 92(6), 062303 (2015).
[Crossref] [PubMed]

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

E. Zlotek-Zlotkiewicz, S. Monnier, G. Cappello, M. Le Berre, and M. Piel, “Optical volume and mass measurements show that mammalian cells swell during mitosis,” J. Cell Biol. 211(4), 765–774 (2015).
[Crossref] [PubMed]

2014 (1)

2013 (2)

A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

P. Girshovitz and N. T. Shaked, “Compact and portable low-coherence interferometer with off-axis geometry for quantitative phase microscopy and nanoscopy,” Opt. Express 21(5), 5701–5714 (2013).
[Crossref] [PubMed]

2012 (1)

2011 (2)

N. Cardenas, N. Ingle, L. Yu, and S. Mohanty, “Development of a digital holographic microscopy system integrated with atomic force microscope,” Proc. SPIE 7904, 790409 (2011).
[Crossref]

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

2010 (1)

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

2008 (4)

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

B. Rappaz, F. Charrière, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium,” Opt. Lett. 33(7), 744–746 (2008).
[Crossref] [PubMed]

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

2007 (2)

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[Crossref] [PubMed]

2006 (3)

2005 (2)

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

B. Rappaz, P. Marquet, E. Cuche, Y. Emery, C. Depeursinge, and P. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express 13(23), 9361–9373 (2005).
[Crossref] [PubMed]

Achouri, S.

A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

Allman, B. E.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Badizadegan, K.

Balberg, M.

M. Balberg, M. Levi, K. Kalinowski, I. Barnea, S. K. Mirsky, and N. T. Shaked, “Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry,” J. Biophotonics 10(10), 1305–1314 (2017).
[Crossref] [PubMed]

Barbul, A.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

Barnea, I.

M. Balberg, M. Levi, K. Kalinowski, I. Barnea, S. K. Mirsky, and N. T. Shaked, “Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry,” J. Biophotonics 10(10), 1305–1314 (2017).
[Crossref] [PubMed]

Bashir, R.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Bauwens, A.

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

Bednarz, M.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Bellair, C. J.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Benke, A.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

Boss, D.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

Bredebusch, I.

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

Bryant, C. E.

A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

Cappello, G.

E. Zlotek-Zlotkiewicz, S. Monnier, G. Cappello, M. Le Berre, and M. Piel, “Optical volume and mass measurements show that mammalian cells swell during mitosis,” J. Cell Biol. 211(4), 765–774 (2015).
[Crossref] [PubMed]

Cardenas, N.

N. Cardenas, N. Ingle, L. Yu, and S. Mohanty, “Development of a digital holographic microscopy system integrated with atomic force microscope,” Proc. SPIE 7904, 790409 (2011).
[Crossref]

Chalut, K. J.

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

Chan, C. J.

M. Schürmann, J. Scholze, P. Müller, J. Guck, and C. J. Chan, “Cell nuclei have lower refractive index and mass density than cytoplasm,” J. Biophotonics 9(10), 1068–1076 (2016).
[Crossref] [PubMed]

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

Charrière, F.

Choi, W.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[Crossref] [PubMed]

Chowdhury, S.

Cojoc, G.

M. Schürmann, G. Cojoc, S. Girardo, E. Ulbricht, J. Guck, and P. Müller, “Three-dimensional correlative single-cell imaging utilizing fluorescence and refractive index tomography,” J. Biophotonicse201700145 (2017).
[Crossref] [PubMed]

Colomb, T.

Cuche, E.

Curl, C. L.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

D’Avino, G.

M. M. Villone, G. D’Avino, M. A. Hulsen, and P. L. Maffettone, “Dynamics of prolate spheroidal elastic particles in confined shear flow,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 92(6), 062303 (2015).
[Crossref] [PubMed]

D’ippolito, G.

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Dasari, R. R.

Delbridge, L. M.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Depeursinge, C.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

B. Rappaz, F. Charrière, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium,” Opt. Lett. 33(7), 744–746 (2008).
[Crossref] [PubMed]

F. Charrière, A. Marian, F. Montfort, J. Kuehn, T. Colomb, E. Cuche, P. Marquet, and C. Depeursinge, “Cell refractive index tomography by digital holographic microscopy,” Opt. Lett. 31(2), 178–180 (2006).
[Crossref] [PubMed]

B. Rappaz, P. Marquet, E. Cuche, Y. Emery, C. Depeursinge, and P. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express 13(23), 9361–9373 (2005).
[Crossref] [PubMed]

Domschke, W.

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

Ekpenyong, A. E.

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

Eldridge, W. J.

Z. A. Steelman, W. J. Eldridge, J. B. Weintraub, and A. Wax, “Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies,” J. Biophotonics 10(12), 1714–1722 (2017).
[Crossref] [PubMed]

S. Chowdhury, W. J. Eldridge, A. Wax, and J. A. Izatt, “Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy,” Biomed. Opt. Express 8(5), 2496–2518 (2017).
[Crossref] [PubMed]

Emery, Y.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

B. Rappaz, P. Marquet, E. Cuche, Y. Emery, C. Depeursinge, and P. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express 13(23), 9361–9373 (2005).
[Crossref] [PubMed]

Fang-Yen, C.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[Crossref] [PubMed]

Feld, M. S.

Ferraro, P.

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Filippova, N. A.

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

Fontana, A.

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Gambale, A.

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Girardo, S.

M. Schürmann, G. Cojoc, S. Girardo, E. Ulbricht, J. Guck, and P. Müller, “Three-dimensional correlative single-cell imaging utilizing fluorescence and refractive index tomography,” J. Biophotonicse201700145 (2017).
[Crossref] [PubMed]

Girshovitz, P.

Golding, I.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Guck, J.

M. Schürmann, J. Scholze, P. Müller, J. Guck, and C. J. Chan, “Cell nuclei have lower refractive index and mass density than cytoplasm,” J. Biophotonics 9(10), 1068–1076 (2016).
[Crossref] [PubMed]

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

M. Schürmann, G. Cojoc, S. Girardo, E. Ulbricht, J. Guck, and P. Müller, “Three-dimensional correlative single-cell imaging utilizing fluorescence and refractive index tomography,” J. Biophotonicse201700145 (2017).
[Crossref] [PubMed]

Harris, P. J.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Harris, T.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Hulsen, M. A.

M. M. Villone, G. D’Avino, M. A. Hulsen, and P. L. Maffettone, “Dynamics of prolate spheroidal elastic particles in confined shear flow,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 92(6), 062303 (2015).
[Crossref] [PubMed]

Ikeda, T.

Ingle, N.

N. Cardenas, N. Ingle, L. Yu, and S. Mohanty, “Development of a digital holographic microscopy system integrated with atomic force microscope,” Proc. SPIE 7904, 790409 (2011).
[Crossref]

Iolascon, A.

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Izatt, J. A.

Jourdain, P.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

Kalinowski, K.

M. Balberg, M. Levi, K. Kalinowski, I. Barnea, S. K. Mirsky, and N. T. Shaked, “Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry,” J. Biophotonics 10(10), 1305–1314 (2017).
[Crossref] [PubMed]

Kemper, B.

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

Klemyashov, I. V.

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

Korenstein, R.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

Kosmeier, S.

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

Kretushev, A. V.

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

Kuehn, J.

Kühn, J.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

Langehanenberg, P.

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

Le Berre, M.

E. Zlotek-Zlotkiewicz, S. Monnier, G. Cappello, M. Le Berre, and M. Piel, “Optical volume and mass measurements show that mammalian cells swell during mitosis,” J. Cell Biol. 211(4), 765–774 (2015).
[Crossref] [PubMed]

Levi, M.

M. Balberg, M. Levi, K. Kalinowski, I. Barnea, S. K. Mirsky, and N. T. Shaked, “Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry,” J. Biophotonics 10(10), 1305–1314 (2017).
[Crossref] [PubMed]

Lue, N.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[Crossref] [PubMed]

N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett. 31(18), 2759–2761 (2006).
[Crossref] [PubMed]

Maffettone, P. L.

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

M. M. Villone, G. D’Avino, M. A. Hulsen, and P. L. Maffettone, “Dynamics of prolate spheroidal elastic particles in confined shear flow,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 92(6), 062303 (2015).
[Crossref] [PubMed]

Magistretti, P.

Magistretti, P. J.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

B. Rappaz, F. Charrière, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium,” Opt. Lett. 33(7), 744–746 (2008).
[Crossref] [PubMed]

Man, S. M.

A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

Marian, A.

Marquet, P.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

B. Rappaz, F. Charrière, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium,” Opt. Lett. 33(7), 744–746 (2008).
[Crossref] [PubMed]

F. Charrière, A. Marian, F. Montfort, J. Kuehn, T. Colomb, E. Cuche, P. Marquet, and C. Depeursinge, “Cell refractive index tomography by digital holographic microscopy,” Opt. Lett. 31(2), 178–180 (2006).
[Crossref] [PubMed]

B. Rappaz, P. Marquet, E. Cuche, Y. Emery, C. Depeursinge, and P. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express 13(23), 9361–9373 (2005).
[Crossref] [PubMed]

Memmolo, P.

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Merola, F.

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Miccio, L.

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Mir, M.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Mirsky, S. K.

M. Balberg, M. Levi, K. Kalinowski, I. Barnea, S. K. Mirsky, and N. T. Shaked, “Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry,” J. Biophotonics 10(10), 1305–1314 (2017).
[Crossref] [PubMed]

Mohanty, S.

N. Cardenas, N. Ingle, L. Yu, and S. Mohanty, “Development of a digital holographic microscopy system integrated with atomic force microscope,” Proc. SPIE 7904, 790409 (2011).
[Crossref]

Monnier, S.

E. Zlotek-Zlotkiewicz, S. Monnier, G. Cappello, M. Le Berre, and M. Piel, “Optical volume and mass measurements show that mammalian cells swell during mitosis,” J. Cell Biol. 211(4), 765–774 (2015).
[Crossref] [PubMed]

Montfort, F.

Moratal, C.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

Mugnano, M.

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Müller, P.

M. Schürmann, J. Scholze, P. Müller, J. Guck, and C. J. Chan, “Cell nuclei have lower refractive index and mass density than cytoplasm,” J. Biophotonics 9(10), 1068–1076 (2016).
[Crossref] [PubMed]

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

M. Schürmann, G. Cojoc, S. Girardo, E. Ulbricht, J. Guck, and P. Müller, “Three-dimensional correlative single-cell imaging utilizing fluorescence and refractive index tomography,” J. Biophotonicse201700145 (2017).
[Crossref] [PubMed]

Nugent, K. A.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Oh, S.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
[Crossref] [PubMed]

Park, Y.

Pavillon, N.

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
[Crossref] [PubMed]

Piel, M.

E. Zlotek-Zlotkiewicz, S. Monnier, G. Cappello, M. Le Berre, and M. Piel, “Optical volume and mass measurements show that mammalian cells swell during mitosis,” J. Cell Biol. 211(4), 765–774 (2015).
[Crossref] [PubMed]

Popescu, G.

Prasanth, S. G.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Raikhlin, N. T.

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

Rappaz, B.

Roberts, A.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Sardo, A.

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Savoia, R.

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
[Crossref]

Schnekenburger, J.

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

Scholze, J.

M. Schürmann, J. Scholze, P. Müller, J. Guck, and C. J. Chan, “Cell nuclei have lower refractive index and mass density than cytoplasm,” J. Biophotonics 9(10), 1068–1076 (2016).
[Crossref] [PubMed]

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

Schürmann, M.

M. Schürmann, J. Scholze, P. Müller, J. Guck, and C. J. Chan, “Cell nuclei have lower refractive index and mass density than cytoplasm,” J. Biophotonics 9(10), 1068–1076 (2016).
[Crossref] [PubMed]

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
[Crossref] [PubMed]

M. Schürmann, G. Cojoc, S. Girardo, E. Ulbricht, J. Guck, and P. Müller, “Three-dimensional correlative single-cell imaging utilizing fluorescence and refractive index tomography,” J. Biophotonicse201700145 (2017).
[Crossref] [PubMed]

Shaked, N. T.

Shen, Z.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Shtil, A. A.

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

Steelman, Z. A.

Z. A. Steelman, W. J. Eldridge, J. B. Weintraub, and A. Wax, “Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies,” J. Biophotonics 10(12), 1714–1722 (2017).
[Crossref] [PubMed]

Stewart, A. G.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Tychinsky, V. P.

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

Ulbricht, E.

M. Schürmann, G. Cojoc, S. Girardo, E. Ulbricht, J. Guck, and P. Müller, “Three-dimensional correlative single-cell imaging utilizing fluorescence and refractive index tomography,” J. Biophotonicse201700145 (2017).
[Crossref] [PubMed]

Villone, M. M.

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

M. M. Villone, G. D’Avino, M. A. Hulsen, and P. L. Maffettone, “Dynamics of prolate spheroidal elastic particles in confined shear flow,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 92(6), 062303 (2015).
[Crossref] [PubMed]

von Bally, G.

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

Vyshenskaya, T. V.

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

Wang, Z.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Wax, A.

Z. A. Steelman, W. J. Eldridge, J. B. Weintraub, and A. Wax, “Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies,” J. Biophotonics 10(12), 1714–1722 (2017).
[Crossref] [PubMed]

S. Chowdhury, W. J. Eldridge, A. Wax, and J. A. Izatt, “Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy,” Biomed. Opt. Express 8(5), 2496–2518 (2017).
[Crossref] [PubMed]

Weintraub, J. B.

Z. A. Steelman, W. J. Eldridge, J. B. Weintraub, and A. Wax, “Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies,” J. Biophotonics 10(12), 1714–1722 (2017).
[Crossref] [PubMed]

Yu, L.

N. Cardenas, N. Ingle, L. Yu, and S. Mohanty, “Development of a digital holographic microscopy system integrated with atomic force microscope,” Proc. SPIE 7904, 790409 (2011).
[Crossref]

Zlotek-Zlotkiewicz, E.

E. Zlotek-Zlotkiewicz, S. Monnier, G. Cappello, M. Le Berre, and M. Piel, “Optical volume and mass measurements show that mammalian cells swell during mitosis,” J. Cell Biol. 211(4), 765–774 (2015).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

Cytometry A (2)

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A 73(10), 895–903 (2008).
[Crossref] [PubMed]

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

J. Biomed. Opt. (2)

B. Kemper, S. Kosmeier, P. Langehanenberg, G. von Bally, I. Bredebusch, W. Domschke, and J. Schnekenburger, “Integral refractive index determination of living suspension cells by multifocus digital holographic phase contrast microscopy,” J. Biomed. Opt. 12(5), 054009 (2007).
[Crossref] [PubMed]

V. P. Tychinsky, A. V. Kretushev, I. V. Klemyashov, T. V. Vyshenskaya, N. A. Filippova, N. T. Raikhlin, and A. A. Shtil, “Quantitative real-time analysis of nucleolar stress by coherent phase microscopy,” J. Biomed. Opt. 13(6), 064032 (2008).
[Crossref] [PubMed]

J. Biophotonics (5)

N. Pavillon, A. Benke, D. Boss, C. Moratal, J. Kühn, P. Jourdain, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Cell morphology and intracellular ionic homeostasis explored with a multimodal approach combining epifluorescence and digital holographic microscopy,” J. Biophotonics 3(7), 432–436 (2010).
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A. E. Ekpenyong, S. M. Man, S. Achouri, C. E. Bryant, J. Guck, and K. J. Chalut, “Bacterial infection of macrophages induces decrease in refractive index,” J. Biophotonics 6(5), 393–397 (2013).
[Crossref] [PubMed]

Z. A. Steelman, W. J. Eldridge, J. B. Weintraub, and A. Wax, “Is the nuclear refractive index lower than cytoplasm? Validation of phase measurements and implications for light scattering technologies,” J. Biophotonics 10(12), 1714–1722 (2017).
[Crossref] [PubMed]

M. Schürmann, J. Scholze, P. Müller, J. Guck, and C. J. Chan, “Cell nuclei have lower refractive index and mass density than cytoplasm,” J. Biophotonics 9(10), 1068–1076 (2016).
[Crossref] [PubMed]

M. Balberg, M. Levi, K. Kalinowski, I. Barnea, S. K. Mirsky, and N. T. Shaked, “Localized measurements of physical parameters within human sperm cells obtained with wide-field interferometry,” J. Biophotonics 10(10), 1305–1314 (2017).
[Crossref] [PubMed]

J. Cell Biol. (1)

E. Zlotek-Zlotkiewicz, S. Monnier, G. Cappello, M. Le Berre, and M. Piel, “Optical volume and mass measurements show that mammalian cells swell during mitosis,” J. Cell Biol. 211(4), 765–774 (2015).
[Crossref] [PubMed]

Lab Chip (1)

M. M. Villone, P. Memmolo, F. Merola, M. Mugnano, L. Miccio, P. L. Maffettone, and P. Ferraro, “Full-angle tomographic phase microscopy of flowing quasi-spherical cells,” Lab Chip 18(1), 126–131 (2018).
[Crossref] [PubMed]

Light Sci. Appl. (1)

F. Merola, P. Memmolo, L. Miccio, R. Savoia, M. Mugnano, A. Fontana, G. D’ippolito, A. Sardo, A. Iolascon, A. Gambale, and P. Ferraro, “Tomographic flow cytometry by digital holography,” Light Sci. Appl. 6(4), e16241 (2017).
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Methods Cell Biol. (1)

M. Schürmann, J. Scholze, P. Müller, C. J. Chan, A. E. Ekpenyong, K. J. Chalut, and J. Guck, “Refractive index measurements of single, spherical cells using digital holographic microscopy,” Methods Cell Biol. 125, 143–159 (2015).
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Nat. Methods (1)

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4(9), 717–719 (2007).
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Opt. Express (3)

Opt. Lett. (5)

Phys. Rev. E Stat. Nonlin. Soft Matter Phys. (1)

M. M. Villone, G. D’Avino, M. A. Hulsen, and P. L. Maffettone, “Dynamics of prolate spheroidal elastic particles in confined shear flow,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 92(6), 062303 (2015).
[Crossref] [PubMed]

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

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A. 108(32), 13124–13129 (2011).
[Crossref] [PubMed]

Proc. SPIE (2)

S. Kosmeier, B. Kemper, P. Langehanenberg, I. Bredebusch, J. Schnekenburger, A. Bauwens, and G. von Bally, “Determination of the integral refractive index of cells in suspension by digital holographic phase contrast microscopy,” Proc. SPIE 6991, 699110 (2008).
[Crossref]

N. Cardenas, N. Ingle, L. Yu, and S. Mohanty, “Development of a digital holographic microscopy system integrated with atomic force microscope,” Proc. SPIE 7904, 790409 (2011).
[Crossref]

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N. T. Shaked, L. L. Satterwhite, M. T. Rinehart, and A. Wax, “Quantitative Analysis of Biological Cells Using Digital Holographic Microscopy,” In Holography, Research and Technologies, J. Rosen Ed., (InTech, 2011), 219–236.

M. Schürmann, G. Cojoc, S. Girardo, E. Ulbricht, J. Guck, and P. Müller, “Three-dimensional correlative single-cell imaging utilizing fluorescence and refractive index tomography,” J. Biophotonicse201700145 (2017).
[Crossref] [PubMed]

C. M. Vest, Holographic Interferometry (Wiley, New York, 1979).

R. A. Lotufo and E. R. Dougherty, Hands-on Morphological Image Processing (SPIE, Washington, 2003).

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Supplementary Material (1)

NameDescription
» Visualization 1       Stained nuclei rotation during flow

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Figures (7)

Fig. 1
Fig. 1 A scheme of the cell and nucleus shape model: n n , n c and n m are the RIs of the nucleus, cytoplasm and medium, respectively. R 1 , n and R 2 , n   are the radii in the x-y projection cast by the nucleus, and R 3 , n is the radius of the nucleus in the z dimension; R 1 , c and R 2 , c are the radii in the x-y projection cast by the entire cell, and R 3 , c is the radius of the entire cell in the z dimension. The radii in the x-y projection are extracted from the OPD image and fluorescence image for the cytoplasm and the nucleus, respectively, and the radius in the z dimension is estimated to be their average. (a) Nucleus modeled as a tilted ellipsoid. (b) Nucleus modeled as an ellipsoid with main axes aligned with Cartesian coordinates, with identical R 1 , n ,   R 2 , n ,   R 3 , n . The red and blue circles denote the center of mass of the cytoplasm and nucleus, respectively. The Cartesian coordinate system indicates directions, where light propagates in the z direction.
Fig. 2
Fig. 2 Assessment of error due to assuming tilted versus untitled ellipsoid as the nucleus model. Red curve: cross section through the center of the thickness distribution of an ellipsoid tilted in 40 ° relative to the z axis, as shown schematically in Fig. 1(a). Blue curve: cross section through the center of the thickness distribution of an ellipsoid with axes aligned relative to the Cartesian coordinate system, as shown schematically in Fig. 1(b). Both ellipsoids have identical R 1 , n ,   R 2 , n   and R 3 , n .
Fig. 3
Fig. 3 3-D rendering of a representative SW480 cancer cell nucleus, using 3-D fluorescence confocal microscopy, where the cell nucleus is labeled with Hoechst and the cell is not attached to the substrate. The numbers on the axes indicate length in µm.
Fig. 4
Fig. 4 2-D fluorescent tracking of the nucleus of a representative SW480 cell during flow.
Fig. 5
Fig. 5 Thickness distribution for worst orientation scenarios in using ellipsoid model, for a normalized representative cell nucleus. (a,c,e,g) Case 1, corresponding to the first row in Table 2. (b,d,f,h) Case 2, corresponding to the second row in Table 2. (a,b) True thickness distribution. (c,d) Evaluated thickness distribution. (e,f) Absolute value of error in thickness evaluation. (g,h) Absolute value of error in inverse thickness evaluation.
Fig. 6
Fig. 6 Scheme of the combined IPM-epifluorescence setup used for imaging. IPM beams appear in red; The fluorescent excitation beam appears in green; The fluorescent emission beam appears in blue. Ex, excitation filter; DM, dichroic mirror; Em, emission filter; AOTF, acousto optical tunable filter; BS1, BS2, beam splitters; M1, M2, mirrors; RR, retroreflector; S, sample; MO1, microscope objective; TL1, TL2, L1, L2, L3, L4, lenses; LP, long-pass filter; Camera1, Camera2, digital cameras.
Fig. 7
Fig. 7 Steps in extraction of the integral RI profile of a cell nucleus from the combined IPM/fluorescence measurement for an SW480 cell in suspension. (a) Reconstructed OPD image. (b) Fluorescence image of the labeled nucleus. (c) Reconstructed OPD image with nucleus boundary shown by broken line, as found from the fluorescence image. (d) Estimated thickness distribution for the cytoplasm. (e) Estimated thickness distribution for the nucleus. (f) Integral RI estimation for the cytoplasm only area. (g) The resulting integral RI profile of the cell nucleus.

Tables (2)

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Table 1 Mean values for 30 SW480 nuclei. R 1 , R 2 and R 3 are the main axis radii of the estimated ellipsoids.

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Table 2 Worst scenarios for using the ellipsoid model, calculated for a normalized representative nucleus. All lengths are given normalized [AU]. The absolute values are given by multiplying by the size of the smallest axis.

Equations (12)

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φ ( x , y ) = 2 π λ O P D ( x , y ) ,
O P D ( x , y ) = 0 h ( x , y ) [ n ( x , y , z ) n m ] d z ,
O P D ( i , j ) = k = 1 N ( i , j ) [ n ( i , j , k ) n m ] Δ k ,
Δ k = Δ C C D M ,
O P D ( i , j ) = h ( i , j ) [ n c e l l ( i , j ) n m ] ,
O P D ( i , j ) = h n ( i , j ) [ n n ( i , j ) n m ] + h c ( i , j ) [ n c ( i , j ) n m ] , ( i , j ) nucleus ,
n n ( i , j ) = O P D ( i , j ) h c ( i , j ) [ n c ( i , j ) n m ] h n ( i , j ) + n m , ( i , j ) nucleus ,
n c ( i , j ) = O P D ( i , j ) h c ( i , j ) + n m , ( i , j ) cytoplasm .
n c , a v g = i , j n c ( i , j ) h c ( i , j ) i , j h c ( i , j ) , ( i , j ) cytoplasm .
h ( i , j ) = Δ k k V ( i , j , k ) ,
Δ n ( i , j ) = n ( i , j ) n e ( i , j ) = O P D ( i , j ) h ( i , j ) + n m [ O P D ( i , j ) h e ( i , j ) + n m ] ,
Δ n ( i , j ) = O P D ( i , j ) [ 1 h ( i , j ) 1 h e ( i , j ) ] .

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