Abstract

We present a phase derivative microscopy technique referred to as gradient field microscopy (GFM), which provides the first-order derivatives of the phase associated with an optical field passing through a transparent specimen. GFM utilizes spatial light modulation at the Fourier plane of a bright field microscope to optically obtain the derivatives of the phase and increase the contrast of the final image. The controllable spatial modulation pattern allows us to obtain both one component of the field gradient (derivative along one direction) and the gradient intensity, which offers some advantages over the regular differential interference contrast (DIC) microscopy. Most importantly, unlike DIC, GFM does not use polarizing optics and, thus, it is applicable to birefringent samples. We demonstrate these features of GFM with studies of static and dynamic biological cells (HeLa cells and red blood cells). We show that GFM is capable of qualitatively providing information about cell membrane fluctuations. Specifically, we captured the disappearance of the bending mode of fluctuations in osmotically swollen red blood cells.

© 2012 OSA

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  1. G. Popescu, Quantitative phase imaging of cells and tissues (McGraw-Hill, 2011).
  2. “Milestones in light microscopy,” Nat. Cell Biol. 11(10), 1165–1165 (2009).
    [CrossRef] [PubMed]
  3. F. Zernike, “How I discovered phase contrast,” Science 121(3141), 345–349 (1955).
    [CrossRef] [PubMed]
  4. M. G. Nomarski, “Microinterferometre differentiel a ondes polarisees,” J. Phys. (Paris) 16, S9–S13 (1955).
  5. D. K. Hamilton and C. J. R. Sheppard, “Differential phase-contrast in scanning optical microscopy,” J Microsc. (Oxford) 133(1), 27–39 (1984).
    [CrossRef]
  6. T. Wilson, “Enhanced differential phase-contrast imaging in scanning microscopy using a quadrant detector,” Optik (Stuttg.) 80, 167–170 (1988).
  7. A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer,” Appl. Opt. 44(7), 1188–1190 (2005).
    [CrossRef] [PubMed]
  8. C. H. Yang, A. Wax, I. Georgakoudi, E. B. Hanlon, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Interferometric phase-dispersion microscopy,” Opt. Lett. 25(20), 1526–1528 (2000).
    [CrossRef] [PubMed]
  9. C. K. Hitzenberger and A. F. Fercher, “Differential phase contrast in optical coherence tomography,” Opt. Lett. 24(9), 622–624 (1999).
    [CrossRef] [PubMed]
  10. M. Lew, X. Q. Cui, X. Heng, and C. H. Yang, “Interference of a four-hole aperture for on-chip quantitative two-dimensional differential phase imaging,” Opt. Lett. 32(20), 2963–2965 (2007).
    [CrossRef] [PubMed]
  11. C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, “Spatial refractive index determination of single cells using differential phase optical low-coherence reflectometry,” Lasers Surg. Med., 5–5 (2003).
  12. T. J. McIntyre, C. Maurer, S. Bernet, and M. Ritsch-Marte, “Differential interference contrast imaging using a spatial light modulator,” Opt. Lett. 34(19), 2988–2990 (2009).
    [CrossRef] [PubMed]
  13. S. H. Lee and D. P. Casasent, Optical Information Processing: Fundamentals (Springer-Verlag, 1981).
  14. T. Kim and G. Popescu, “Laplace field microscopy for label-free imaging of dynamic biological structures,” Opt. Lett. 36(23), 4704–4706 (2011).
    [CrossRef] [PubMed]
  15. W. C. Stewart, “Differential phase-contrast with an extended illumination source,” J. Opt. Soc. Am. 66(8), 813–818 (1976).
    [CrossRef]
  16. B. Kachar, “Asymmetric illumination contrast: a method of image formation for video light microscopy,” Science 227(4688), 766–768 (1985).
    [CrossRef] [PubMed]
  17. S. B. Mehta and C. J. R. Sheppard, “Quantitative phase-gradient imaging at high resolution with asymmetric illumination-based differential phase contrast,” Opt. Lett. 34(13), 1924–1926 (2009).
    [CrossRef] [PubMed]
  18. R. Yi, K. K. Chu, and J. Mertz, “Graded-field microscopy with white light,” Opt. Express 14(12), 5191–5200 (2006).
    [CrossRef] [PubMed]
  19. G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt. 11(4), 040503 (2006).
    [CrossRef] [PubMed]
  20. G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
    [CrossRef] [PubMed]
  21. H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
    [CrossRef] [PubMed]
  22. Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
    [CrossRef] [PubMed]
  23. Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
    [CrossRef] [PubMed]
  24. Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
    [CrossRef] [PubMed]
  25. Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
    [CrossRef] [PubMed]
  26. N. Gov, A. G. Zilman, and S. Safran, “Cytoskeleton confinement and tension of red blood cell membranes,” Phys. Rev. Lett. 90(22), 228101 (2003).
    [CrossRef] [PubMed]

2011 (2)

T. Kim and G. Popescu, “Laplace field microscopy for label-free imaging of dynamic biological structures,” Opt. Lett. 36(23), 4704–4706 (2011).
[CrossRef] [PubMed]

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

2010 (2)

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

2009 (3)

2008 (2)

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
[CrossRef] [PubMed]

2007 (1)

2006 (3)

R. Yi, K. K. Chu, and J. Mertz, “Graded-field microscopy with white light,” Opt. Express 14(12), 5191–5200 (2006).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt. 11(4), 040503 (2006).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

2005 (1)

2003 (2)

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, “Spatial refractive index determination of single cells using differential phase optical low-coherence reflectometry,” Lasers Surg. Med., 5–5 (2003).

N. Gov, A. G. Zilman, and S. Safran, “Cytoskeleton confinement and tension of red blood cell membranes,” Phys. Rev. Lett. 90(22), 228101 (2003).
[CrossRef] [PubMed]

2000 (1)

1999 (1)

1988 (1)

T. Wilson, “Enhanced differential phase-contrast imaging in scanning microscopy using a quadrant detector,” Optik (Stuttg.) 80, 167–170 (1988).

1985 (1)

B. Kachar, “Asymmetric illumination contrast: a method of image formation for video light microscopy,” Science 227(4688), 766–768 (1985).
[CrossRef] [PubMed]

1984 (1)

D. K. Hamilton and C. J. R. Sheppard, “Differential phase-contrast in scanning optical microscopy,” J Microsc. (Oxford) 133(1), 27–39 (1984).
[CrossRef]

1976 (1)

1955 (2)

F. Zernike, “How I discovered phase contrast,” Science 121(3141), 345–349 (1955).
[CrossRef] [PubMed]

M. G. Nomarski, “Microinterferometre differentiel a ondes polarisees,” J. Phys. (Paris) 16, S9–S13 (1955).

Ahn, A.

Auth, T.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Badizadegan, K.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt. 11(4), 040503 (2006).
[CrossRef] [PubMed]

A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer,” Appl. Opt. 44(7), 1188–1190 (2005).
[CrossRef] [PubMed]

C. H. Yang, A. Wax, I. Georgakoudi, E. B. Hanlon, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Interferometric phase-dispersion microscopy,” Opt. Lett. 25(20), 1526–1528 (2000).
[CrossRef] [PubMed]

Bernet, S.

Best, C. A.

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Best-Popescu, C. A.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

Boppart, S. A.

H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
[CrossRef] [PubMed]

Choi, W. S.

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Chu, K. K.

Cui, X. Q.

Dasari, R. R.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt. 11(4), 040503 (2006).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer,” Appl. Opt. 44(7), 1188–1190 (2005).
[CrossRef] [PubMed]

C. H. Yang, A. Wax, I. Georgakoudi, E. B. Hanlon, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Interferometric phase-dispersion microscopy,” Opt. Lett. 25(20), 1526–1528 (2000).
[CrossRef] [PubMed]

Diez-Silva, M.

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Diller, K. R.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, “Spatial refractive index determination of single cells using differential phase optical low-coherence reflectometry,” Lasers Surg. Med., 5–5 (2003).

Ding, H. F.

H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
[CrossRef] [PubMed]

Fang-Yen, C.

Feld, M. S.

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt. 11(4), 040503 (2006).
[CrossRef] [PubMed]

A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer,” Appl. Opt. 44(7), 1188–1190 (2005).
[CrossRef] [PubMed]

C. H. Yang, A. Wax, I. Georgakoudi, E. B. Hanlon, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Interferometric phase-dispersion microscopy,” Opt. Lett. 25(20), 1526–1528 (2000).
[CrossRef] [PubMed]

Fercher, A. F.

Georgakoudi, I.

Goda, K.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

Gov, N.

N. Gov, A. G. Zilman, and S. Safran, “Cytoskeleton confinement and tension of red blood cell membranes,” Phys. Rev. Lett. 90(22), 228101 (2003).
[CrossRef] [PubMed]

Gov, N. S.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Hamilton, D. K.

D. K. Hamilton and C. J. R. Sheppard, “Differential phase-contrast in scanning optical microscopy,” J Microsc. (Oxford) 133(1), 27–39 (1984).
[CrossRef]

Hanlon, E. B.

Heng, X.

Henle, M. L.

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Hitzenberger, C. K.

Ikeda, T.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

Kachar, B.

B. Kachar, “Asymmetric illumination contrast: a method of image formation for video light microscopy,” Science 227(4688), 766–768 (1985).
[CrossRef] [PubMed]

Kim, T.

Kuriabova, T.

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Laposata, M.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

Levine, A. J.

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Lew, M.

Lykotrafitis, G.

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Manley, S.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

Maurer, C.

McIntyre, T. J.

Mehta, S. B.

Mertz, J.

Milner, T. E.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, “Spatial refractive index determination of single cells using differential phase optical low-coherence reflectometry,” Lasers Surg. Med., 5–5 (2003).

Nguyen, F.

H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
[CrossRef] [PubMed]

Nomarski, M. G.

M. G. Nomarski, “Microinterferometre differentiel a ondes polarisees,” J. Phys. (Paris) 16, S9–S13 (1955).

Park, Y.

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

Park, Y. K.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Popescu, G.

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

T. Kim and G. Popescu, “Laplace field microscopy for label-free imaging of dynamic biological structures,” Opt. Lett. 36(23), 4704–4706 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt. 11(4), 040503 (2006).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer,” Appl. Opt. 44(7), 1188–1190 (2005).
[CrossRef] [PubMed]

Ritsch-Marte, M.

Rylander, C.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, “Spatial refractive index determination of single cells using differential phase optical low-coherence reflectometry,” Lasers Surg. Med., 5–5 (2003).

Safran, S.

N. Gov, A. G. Zilman, and S. Safran, “Cytoskeleton confinement and tension of red blood cell membranes,” Phys. Rev. Lett. 90(22), 228101 (2003).
[CrossRef] [PubMed]

Safran, S. A.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Sheppard, C. J. R.

Stewart, W. C.

Suresh, S.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Wang, Z.

H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
[CrossRef] [PubMed]

Wax, A.

Welch, A. J.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, “Spatial refractive index determination of single cells using differential phase optical low-coherence reflectometry,” Lasers Surg. Med., 5–5 (2003).

Wilson, T.

T. Wilson, “Enhanced differential phase-contrast imaging in scanning microscopy using a quadrant detector,” Optik (Stuttg.) 80, 167–170 (1988).

Yang, C. H.

Yi, R.

Zernike, F.

F. Zernike, “How I discovered phase contrast,” Science 121(3141), 345–349 (1955).
[CrossRef] [PubMed]

Zilman, A. G.

N. Gov, A. G. Zilman, and S. Safran, “Cytoskeleton confinement and tension of red blood cell membranes,” Phys. Rev. Lett. 90(22), 228101 (2003).
[CrossRef] [PubMed]

Appl. Opt. (1)

J Microsc. (Oxford) (1)

D. K. Hamilton and C. J. R. Sheppard, “Differential phase-contrast in scanning optical microscopy,” J Microsc. (Oxford) 133(1), 27–39 (1984).
[CrossRef]

J. Biomed. Opt. (1)

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt. 11(4), 040503 (2006).
[CrossRef] [PubMed]

J. Opt. Soc. Am. (1)

J. Phys. (Paris) (1)

M. G. Nomarski, “Microinterferometre differentiel a ondes polarisees,” J. Phys. (Paris) 16, S9–S13 (1955).

Lasers Surg. Med. (1)

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, “Spatial refractive index determination of single cells using differential phase optical low-coherence reflectometry,” Lasers Surg. Med., 5–5 (2003).

Nat. Cell Biol. (1)

“Milestones in light microscopy,” Nat. Cell Biol. 11(10), 1165–1165 (2009).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (6)

Optik (Stuttg.) (1)

T. Wilson, “Enhanced differential phase-contrast imaging in scanning microscopy using a quadrant detector,” Optik (Stuttg.) 80, 167–170 (1988).

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

Y. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, “Measurement of the nonlinear elasticity of red blood cell membranes,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 83(5), 051925 (2011).
[CrossRef] [PubMed]

Phys. Rev. Lett. (3)

N. Gov, A. G. Zilman, and S. Safran, “Cytoskeleton confinement and tension of red blood cell membranes,” Phys. Rev. Lett. 90(22), 228101 (2003).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97(21), 218101 (2006).
[CrossRef] [PubMed]

H. F. Ding, Z. Wang, F. Nguyen, S. A. Boppart, and G. Popescu, “Fourier transform light scattering of inhomogeneous and dynamic structures,” Phys. Rev. Lett. 101(23), 238102 (2008).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (3)

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A. 107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A. 107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. S. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A. 105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Science (2)

B. Kachar, “Asymmetric illumination contrast: a method of image formation for video light microscopy,” Science 227(4688), 766–768 (1985).
[CrossRef] [PubMed]

F. Zernike, “How I discovered phase contrast,” Science 121(3141), 345–349 (1955).
[CrossRef] [PubMed]

Other (2)

G. Popescu, Quantitative phase imaging of cells and tissues (McGraw-Hill, 2011).

S. H. Lee and D. P. Casasent, Optical Information Processing: Fundamentals (Springer-Verlag, 1981).

Supplementary Material (2)

» Media 1: AVI (1212 KB)     
» Media 2: AVI (15858 KB)     

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Figures (4)

Fig. 1
Fig. 1

GFM setup: L1 and L2 have focal length of 75mm and 150mm, respectively. The spatial light modulator (SLM) with contrast ratio of 400/1 and pixel size 13μm is obtained from Epson Powerlite S5 commercial projector. Andor iXon + EMCCD is used for the detection. Inset: modulation filters projected on SLM for sine-GFM (top) and linear-GFM (bottom).

Fig. 2
Fig. 2

Same HeLa cells under (a) bright field, (b) linear-GFM, and (c) sine-GFM;40x, 0.6NA objective. (d)-(i) HeLa cells imaged with different period sine modulation All images are taken using a 40x, 0.6NA objective. Insets of (d)-(i) show the modulation filters used for the HeLa cell image. (Media 1) The movie contains another field of view in the HeLa cell sample with varying filter period.

Fig. 3
Fig. 3

(a)-(b) comparison between BF and commercially available DIC on the same field of view, indicating a modest increase in contrast. (c)-(d) Comparison between BF and sine-GFM at the same field of view. Evident contrast enhancement is observed for the cells indicated by arrows.

Fig. 4
Fig. 4

Dynamic measurement of red blood cell (RBC) membrane fluctuations. (Media 2) The movie shows a time-lapse measurement of a blood smear sample. (a) One frame from a time-lapse measurement of a blood smear on a glass slide imaged by sine-GFM. (b) 2D (space-time) power spectrum associated with the time-lapse displacement. (c) spatial power spectrum that shows the sine function applied by the SLM. (d) MSD vs. k after sine removal, for normal RBCs (errors indicated standard deviation for N = 20 cells). k−2 and k−4 power laws are indicated as a green and red line, respectively. (e) MSD vs. k for osmotically swollen spherocyte (errors indicated standard deviation for N = 20 cells). k−2 power law is indicated as a green line. (f) comparison between the average MSDs for the normal and swollen RBCs.

Equations (4)

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[ 1+sin( a k y ) ]U( k x , k y )[ δ( x,y )+ δ( x,ya )δ( x,y+a ) 2i ]*U( x,y ) =U( x,y )+ia U( x,y ) y
I( x,y )= | e iϕ( x,y ) a ϕ( x,y ) y e iϕ( x,y ) | 2 12a ϕ( x,y ) y
I( r )= | FT[ | k r |U( k r ) ] | 2 | ϕ( r ) r | 2 ,
Δ u 2 ( k )= k B T κ k 4 +σ k 2

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