Abstract

Using the decomposition of an image field in two spatial components that can be controllably shifted in phase with respect to each other, a new quantitative-phase microscope has been developed. The new instrument, referred to as the fast Fourier phase microscope (f-FPM), provides a factor of 100 higher acquisition rate compared with our previously reported Fourier phase microscope. The resulting quantitative-phase images are characterized by diffraction limited transverse resolution and path-length stability better than 2 nm at acquisition rates of 10 frames/s or more. These features make the f-FPM particularly appealing for investigating the structure and dynamics of live cells over a broad range of time scales. In addition, we demonstrate the possibility of examining subcellular structures by digitally processing the amplitude and phase information provided by the instrument. Thus we developed software that can emulate phase contrast and differential interference contrast microscopy images by numerically processing FPM images. This approach adds the flexibility of digitally varying the phase shift between the two interfering beams. The images obtained appear as if they were recorded by variable phase contrast or differential interference contrast microscopes that deliver an enhanced view to the subcellular structure when compared with the typical commercial microscope.

© 2007 Optical Society of America

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    [CrossRef]
  2. F. H. Smith, "Microscopic interferometry," Research (London) 8, 385-395 (1955).
  3. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
    [CrossRef]
  4. C. G. Rylander, D. P. Dave, T. Akkin, T. E. Milner, K. R. Diller, and A. J. Welch, "Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy," Opt. Lett. 29, 1509-1511 (2004).
    [CrossRef]
  5. T. Akkin, D. P. Dave, T. E. Milner, and H. G. Rylander, "Detection of neural activity using phase-sensitive optical low-coherence reflectometry," Opt. Express 12, 2377-2386 (2004).
    [CrossRef]
  6. C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, "Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer," Opt. Lett. 29, 2028-2030 (2004).
    [CrossRef]
  7. M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, "Spectral-domain phase microscopy," Opt. Lett. 30, 1162-1164 (2005).
    [CrossRef]
  8. C. H. Yang, A. Wax, R. R. Dasari, and M. S. Feld, "Phase-dispersion optical tomography," Opt. Lett. 26, 686-688 (2001).
  9. 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, 1526-1528 (2000).
  10. C. Yang, A. Wax, M. S. Hahn, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics, Opt. Lett. 26, 1271-1273 (2001).
  11. G. A. Dunn and D. Zicha, eds., Using DRIMAPS System of Transmission Interference Microscopy to Study Cell Behavior (Academic, 1997).
  12. D. Zicha and G. A. Dunn, "An image-processing system for cell behavior studies in subconfluent cultures," J. Microsc. 179, 11-21 (1995).
  13. D. Zicha, E. Genot, G. A. Dunn, and I. M. Kramer, "TGF beta 1 induces a cell-cycle-dependent increase in motility of epithelial cells," J. Cell Sci. 112, 447-454 (1999).
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  17. T. Zhang and I. Yamaguchi, "Three-dimensional microscopy with phase-shifting digital holography," Opt. Lett. 23, 1221-1223 (1998).
  18. P. Marquet, B. Rappaz, P. J. Magistretti, E. Cuche, Y. Emery, T. Colomb, and C. Depeursinge, "Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy," Opt. Lett. 30, 468-470 (2005).
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    [CrossRef]
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    [CrossRef]
  21. G. Popescu, L. P. Deflores, J. C. Vaughan, K. Badizadegan, H. Iwai, R. R. Dasari, and M. S. Feld, "Fourier phase microscopy for investigation of biological structures and dynamics," Opt. Lett. 29, 2503-2505 (2004).
    [CrossRef]
  22. T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, "Hilbert phase microscopy for investigating fast dynamics in transparent systems," Opt. Lett. 30, 1165-1168 (2005).
    [CrossRef]
  23. G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, "Diffraction phase microscopy for quantifying cell structure and dynamics," Opt. Lett. 31, 775-777 (2006).
    [CrossRef]
  24. G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Erythrocyte structure and dynamics quantified by Hilbert phase microscopy," J. Biomed. Opt. Lett. 10, 060503 (2005).
    [CrossRef]
  25. H. Kadono, M. Ogusu, and S.Toyooka, "Phase-shifting common-path interferometer using a liquid-crystal modulator," Opt. Commun. 110, 391-400 (1994).
    [CrossRef]
  26. J. Gluckstad and P. C. Mogensen, "Optimal phase contrast in common-path interferometry," Appl. Opt. 40, 268-282 (2001).

2006 (2)

2005 (5)

2004 (4)

2001 (3)

2000 (1)

1999 (1)

D. Zicha, E. Genot, G. A. Dunn, and I. M. Kramer, "TGF beta 1 induces a cell-cycle-dependent increase in motility of epithelial cells," J. Cell Sci. 112, 447-454 (1999).

1998 (1)

1995 (3)

1994 (1)

H. Kadono, M. Ogusu, and S.Toyooka, "Phase-shifting common-path interferometer using a liquid-crystal modulator," Opt. Commun. 110, 391-400 (1994).
[CrossRef]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

1955 (1)

F. Zernike, "How I discovered phase contrast," Science 121, 345-349 (1955).
[CrossRef]

1948 (1)

D. Gabor, "A new microscopic principle," Nature 161, 777-778 (1948).

Akkin, T.

Badizadegan, K.

Best, C. A.

G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Erythrocyte structure and dynamics quantified by Hilbert phase microscopy," J. Biomed. Opt. Lett. 10, 060503 (2005).
[CrossRef]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Charriere, F.

Choma, M. A.

Chu, M. C.

Colomb, T.

Creazzo, T. L.

Cuche, E.

Dasari, R. R.

G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, "Diffraction phase microscopy for quantifying cell structure and dynamics," Opt. Lett. 31, 775-777 (2006).
[CrossRef]

G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Erythrocyte structure and dynamics quantified by Hilbert phase microscopy," J. Biomed. Opt. Lett. 10, 060503 (2005).
[CrossRef]

T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, "Hilbert phase microscopy for investigating fast dynamics in transparent systems," Opt. Lett. 30, 1165-1168 (2005).
[CrossRef]

G. Popescu, L. P. Deflores, J. C. Vaughan, K. Badizadegan, H. Iwai, R. R. Dasari, and M. S. Feld, "Fourier phase microscopy for investigation of biological structures and dynamics," Opt. Lett. 29, 2503-2505 (2004).
[CrossRef]

C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, "Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer," Opt. Lett. 29, 2028-2030 (2004).
[CrossRef]

C. H. Yang, A. Wax, R. R. Dasari, and M. S. Feld, "Phase-dispersion optical tomography," Opt. Lett. 26, 686-688 (2001).

C. Yang, A. Wax, M. S. Hahn, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics, Opt. Lett. 26, 1271-1273 (2001).

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, 1526-1528 (2000).

Dave, D. P.

Deflores, L. P.

Depeursinge, C.

Diller, K. R.

Dunn, G. A.

D. Zicha, E. Genot, G. A. Dunn, and I. M. Kramer, "TGF beta 1 induces a cell-cycle-dependent increase in motility of epithelial cells," J. Cell Sci. 112, 447-454 (1999).

D. Zicha and G. A. Dunn, "An image-processing system for cell behavior studies in subconfluent cultures," J. Microsc. 179, 11-21 (1995).

G. A. Dunn and D. Zicha, eds., Using DRIMAPS System of Transmission Interference Microscopy to Study Cell Behavior (Academic, 1997).

Ellerbee, A. K.

Emery, Y.

Fang-Yen, C.

Feld, M. S.

G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, "Diffraction phase microscopy for quantifying cell structure and dynamics," Opt. Lett. 31, 775-777 (2006).
[CrossRef]

T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, "Hilbert phase microscopy for investigating fast dynamics in transparent systems," Opt. Lett. 30, 1165-1168 (2005).
[CrossRef]

G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Erythrocyte structure and dynamics quantified by Hilbert phase microscopy," J. Biomed. Opt. Lett. 10, 060503 (2005).
[CrossRef]

C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, "Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer," Opt. Lett. 29, 2028-2030 (2004).
[CrossRef]

G. Popescu, L. P. Deflores, J. C. Vaughan, K. Badizadegan, H. Iwai, R. R. Dasari, and M. S. Feld, "Fourier phase microscopy for investigation of biological structures and dynamics," Opt. Lett. 29, 2503-2505 (2004).
[CrossRef]

C. H. Yang, A. Wax, R. R. Dasari, and M. S. Feld, "Phase-dispersion optical tomography," Opt. Lett. 26, 686-688 (2001).

C. Yang, A. Wax, M. S. Hahn, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics, Opt. Lett. 26, 1271-1273 (2001).

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, 1526-1528 (2000).

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Fujimoto, J. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Gabor, D.

D. Gabor, "A new microscopic principle," Nature 161, 777-778 (1948).

Genot, E.

D. Zicha, E. Genot, G. A. Dunn, and I. M. Kramer, "TGF beta 1 induces a cell-cycle-dependent increase in motility of epithelial cells," J. Cell Sci. 112, 447-454 (1999).

Georgakoudi, I.

Gluckstad, J.

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Gureyev, T. E.

Hahn, M. S.

Hanlon, E. B.

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Ikeda, T.

Iwai, H.

Izatt, J. A.

Kadono, H.

H. Kadono, M. Ogusu, and S.Toyooka, "Phase-shifting common-path interferometer using a liquid-crystal modulator," Opt. Commun. 110, 391-400 (1994).
[CrossRef]

Kramer, I. M.

D. Zicha, E. Genot, G. A. Dunn, and I. M. Kramer, "TGF beta 1 induces a cell-cycle-dependent increase in motility of epithelial cells," J. Cell Sci. 112, 447-454 (1999).

Kuehn, J.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Magistretti, P. J.

Marian, A.

Marquet, P.

Milner, T. E.

Mogensen, P. C.

Montfort, F.

Nugent, K. A.

Ogusu, M.

H. Kadono, M. Ogusu, and S.Toyooka, "Phase-shifting common-path interferometer using a liquid-crystal modulator," Opt. Commun. 110, 391-400 (1994).
[CrossRef]

Popescu, G.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Rappaz, B.

Roberts, A.

Rylander, C. G.

Rylander, H. G.

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Seung, H. S.

Smith, F. H.

F. H. Smith, "Microscopic interferometry," Research (London) 8, 385-395 (1955).

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Toyooka, S.

H. Kadono, M. Ogusu, and S.Toyooka, "Phase-shifting common-path interferometer using a liquid-crystal modulator," Opt. Commun. 110, 391-400 (1994).
[CrossRef]

Vaughan, J. C.

Wax, A.

Welch, A. J.

Yamaguchi, I.

Yang, C.

Yang, C. H.

Zernike, F.

F. Zernike, "How I discovered phase contrast," Science 121, 345-349 (1955).
[CrossRef]

Zhang, T.

Zicha, D.

D. Zicha, E. Genot, G. A. Dunn, and I. M. Kramer, "TGF beta 1 induces a cell-cycle-dependent increase in motility of epithelial cells," J. Cell Sci. 112, 447-454 (1999).

D. Zicha and G. A. Dunn, "An image-processing system for cell behavior studies in subconfluent cultures," J. Microsc. 179, 11-21 (1995).

G. A. Dunn and D. Zicha, eds., Using DRIMAPS System of Transmission Interference Microscopy to Study Cell Behavior (Academic, 1997).

Appl. Opt. (1)

J. Biomed. Opt. Lett. (1)

G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Erythrocyte structure and dynamics quantified by Hilbert phase microscopy," J. Biomed. Opt. Lett. 10, 060503 (2005).
[CrossRef]

J. Cell Sci. (1)

D. Zicha, E. Genot, G. A. Dunn, and I. M. Kramer, "TGF beta 1 induces a cell-cycle-dependent increase in motility of epithelial cells," J. Cell Sci. 112, 447-454 (1999).

J. Microsc. (1)

D. Zicha and G. A. Dunn, "An image-processing system for cell behavior studies in subconfluent cultures," J. Microsc. 179, 11-21 (1995).

J. Opt. Soc. Am. A (2)

Nature (1)

D. Gabor, "A new microscopic principle," Nature 161, 777-778 (1948).

Opt. Commun. (1)

H. Kadono, M. Ogusu, and S.Toyooka, "Phase-shifting common-path interferometer using a liquid-crystal modulator," Opt. Commun. 110, 391-400 (1994).
[CrossRef]

Opt. Express (2)

Opt. Lett. (12)

F. Charriere, 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, 178-180 (2006).
[CrossRef]

G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, "Diffraction phase microscopy for quantifying cell structure and dynamics," Opt. Lett. 31, 775-777 (2006).
[CrossRef]

C. H. Yang, A. Wax, R. R. Dasari, and M. S. Feld, "Phase-dispersion optical tomography," Opt. Lett. 26, 686-688 (2001).

C. Yang, A. Wax, M. S. Hahn, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics, Opt. Lett. 26, 1271-1273 (2001).

C. G. Rylander, D. P. Dave, T. Akkin, T. E. Milner, K. R. Diller, and A. J. Welch, "Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy," Opt. Lett. 29, 1509-1511 (2004).
[CrossRef]

C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, "Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer," Opt. Lett. 29, 2028-2030 (2004).
[CrossRef]

G. Popescu, L. P. Deflores, J. C. Vaughan, K. Badizadegan, H. Iwai, R. R. Dasari, and M. S. Feld, "Fourier phase microscopy for investigation of biological structures and dynamics," Opt. Lett. 29, 2503-2505 (2004).
[CrossRef]

P. Marquet, B. Rappaz, P. J. Magistretti, E. Cuche, Y. Emery, T. Colomb, and C. Depeursinge, "Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy," Opt. Lett. 30, 468-470 (2005).
[CrossRef]

M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, "Spectral-domain phase microscopy," Opt. Lett. 30, 1162-1164 (2005).
[CrossRef]

T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, "Hilbert phase microscopy for investigating fast dynamics in transparent systems," Opt. Lett. 30, 1165-1168 (2005).
[CrossRef]

T. Zhang and I. Yamaguchi, "Three-dimensional microscopy with phase-shifting digital holography," Opt. Lett. 23, 1221-1223 (1998).

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, 1526-1528 (2000).

Science (2)

F. Zernike, "How I discovered phase contrast," Science 121, 345-349 (1955).
[CrossRef]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef]

Other (2)

G. A. Dunn and D. Zicha, eds., Using DRIMAPS System of Transmission Interference Microscopy to Study Cell Behavior (Academic, 1997).

F. H. Smith, "Microscopic interferometry," Research (London) 8, 385-395 (1955).

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