Abstract

We demonstrate a single-shot holographic phase microscope that combines short-coherence laser pulses with an off-axis geometry. By introducing a controlled pulse front tilt, ultrashort pulses are made to interfere over a large field-of-view without loss of fringe contrast. With this microscope, quantitative phase images of live cells can be recorded in a full-field geometry without moving parts. We perform phase imaging of HEK293 cells, to study the dynamics of cell volume regulation in response to an osmotic shock.

© 2012 OSA

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2012

2011

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

2010

2006

Y. Okada, T. Shimizu, E. Maeno, S. Tanabe, X. Wang, and N. Takahashi, “Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death,” J. Membr. Biol.209(1), 21–29 (2006).
[CrossRef] [PubMed]

2005

2004

K. Strange, “Cellular volume homeostasis,” Adv. Physiol. Educ.28(4), 155–159 (2004).
[CrossRef] [PubMed]

2002

G. Pedrini and H. J. Tiziani, “Short-coherence digital microscopy by use of a lensless holographic imaging system,” Appl. Opt.41(22), 4489–4496 (2002).
[CrossRef] [PubMed]

U. Schnars and W. P. O. Jüptner, “Digital recording and numerical reconstruction of holograms,” Meas. Sci. Technol.13(9), R85–R101 (2002).
[CrossRef]

2001

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A.98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, and M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett.26(6), 334–336 (2001).
[CrossRef] [PubMed]

2000

S. Lai, B. King, and M. A. Neifeld, “Wave front reconstruction by means of phase-shifting digital in-line holography,” Opt. Commun.173(1-6), 155–160 (2000).
[CrossRef]

M. Tziraki, R. Jones, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Photorefractive holography for imaging through turbid media using low coherence light,” Appl. Phys. B70(1), 151–154 (2000).
[CrossRef]

E. Cuche, P. Marquet, and C. Depeursinge, “Spatial filtering for zero-order and twin-image elimination in digital off-axis holography,” Appl. Opt.39(23), 4070–4075 (2000).
[CrossRef] [PubMed]

1999

1998

1995

W. E. Crowe, J. Altamirano, L. Huerto, and F. J. Alvarez-Leefmans, “Volume changes in single N1E-115 neuroblastoma cells measured with a fluorescent probe,” Neuroscience69(1), 283–296 (1995).
[CrossRef] [PubMed]

1991

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1990

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

1987

1962

1948

D. Gabor, “A new microscopic principle,” Nature161(4098), 777–778 (1948).
[CrossRef] [PubMed]

Altamirano, J.

W. E. Crowe, J. Altamirano, L. Huerto, and F. J. Alvarez-Leefmans, “Volume changes in single N1E-115 neuroblastoma cells measured with a fluorescent probe,” Neuroscience69(1), 283–296 (1995).
[CrossRef] [PubMed]

Alvarez-Leefmans, F. J.

W. E. Crowe, J. Altamirano, L. Huerto, and F. J. Alvarez-Leefmans, “Volume changes in single N1E-115 neuroblastoma cells measured with a fluorescent probe,” Neuroscience69(1), 283–296 (1995).
[CrossRef] [PubMed]

Ansari, Z.

Bevilacqua, F.

Bhaduri, B.

Boor, I.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

Brussaard, A. B.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

Capdevila-Nortes, X.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Charrière, F.

Chun, I. S.

Crimmins, T. F.

Crowe, W. E.

W. E. Crowe, J. Altamirano, L. Huerto, and F. J. Alvarez-Leefmans, “Volume changes in single N1E-115 neuroblastoma cells measured with a fluorescent probe,” Neuroscience69(1), 283–296 (1995).
[CrossRef] [PubMed]

Cuche, E.

Denk, W.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Depeursinge, C.

Depeursinge, C. D.

Duarri, A.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

Emery, Y.

Estévez, R.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

French, P. M. W.

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, and M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett.26(6), 334–336 (2001).
[CrossRef] [PubMed]

M. Tziraki, R. Jones, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Photorefractive holography for imaging through turbid media using low coherence light,” Appl. Phys. B70(1), 151–154 (2000).
[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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Gabor, D.

D. Gabor, “A new microscopic principle,” Nature161(4098), 777–778 (1948).
[CrossRef] [PubMed]

Gillette, M.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Gu, Y.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Huerto, L.

W. E. Crowe, J. Altamirano, L. Huerto, and F. J. Alvarez-Leefmans, “Volume changes in single N1E-115 neuroblastoma cells measured with a fluorescent probe,” Neuroscience69(1), 283–296 (1995).
[CrossRef] [PubMed]

Inoue, H.

H. Inoue, S.-I. Mori, S. Morishima, and Y. Okada, “Volume-sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation,” Eur. J. Neurosci.21(6), 1648–1658 (2005).
[CrossRef] [PubMed]

Jericho, M. H.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A.98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Jones, R.

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, and M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett.26(6), 334–336 (2001).
[CrossRef] [PubMed]

M. Tziraki, R. Jones, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Photorefractive holography for imaging through turbid media using low coherence light,” Appl. Phys. B70(1), 151–154 (2000).
[CrossRef]

Jüptner, W. P. O.

U. Schnars and W. P. O. Jüptner, “Digital recording and numerical reconstruction of holograms,” Meas. Sci. Technol.13(9), R85–R101 (2002).
[CrossRef]

King, B.

S. Lai, B. King, and M. A. Neifeld, “Wave front reconstruction by means of phase-shifting digital in-line holography,” Opt. Commun.173(1-6), 155–160 (2000).
[CrossRef]

Kreuzer, H. J.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A.98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Lai, S.

S. Lai, B. King, and M. A. Neifeld, “Wave front reconstruction by means of phase-shifting digital in-line holography,” Opt. Commun.173(1-6), 155–160 (2000).
[CrossRef]

Leith, E. N.

Li, X.

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Liu, G.

Lodder, J. C.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

Maeno, E.

Y. Okada, T. Shimizu, E. Maeno, S. Tanabe, X. Wang, and N. Takahashi, “Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death,” J. Membr. Biol.209(1), 21–29 (2006).
[CrossRef] [PubMed]

Magistretti, P. J.

Mansvelder, H. D.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

Marquet, P.

Massatsch, P.

Maznev, A. A.

Meinertzhagen, I. A.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A.98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Melloch, M. R.

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, and M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett.26(6), 334–336 (2001).
[CrossRef] [PubMed]

M. Tziraki, R. Jones, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Photorefractive holography for imaging through turbid media using low coherence light,” Appl. Phys. B70(1), 151–154 (2000).
[CrossRef]

Millet, L.

Mir, M.

Mori, S.-I.

H. Inoue, S.-I. Mori, S. Morishima, and Y. Okada, “Volume-sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation,” Eur. J. Neurosci.21(6), 1648–1658 (2005).
[CrossRef] [PubMed]

Morishima, S.

H. Inoue, S.-I. Mori, S. Morishima, and Y. Okada, “Volume-sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation,” Eur. J. Neurosci.21(6), 1648–1658 (2005).
[CrossRef] [PubMed]

Neifeld, M. A.

S. Lai, B. King, and M. A. Neifeld, “Wave front reconstruction by means of phase-shifting digital in-line holography,” Opt. Commun.173(1-6), 155–160 (2000).
[CrossRef]

Nelson, K. A.

Nolte, D. D.

Z. Ansari, Y. Gu, M. Tziraki, R. Jones, P. M. W. French, D. D. Nolte, and M. R. Melloch, “Elimination of beam walk-off in low-coherence off-axis photorefractive holography,” Opt. Lett.26(6), 334–336 (2001).
[CrossRef] [PubMed]

M. Tziraki, R. Jones, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Photorefractive holography for imaging through turbid media using low coherence light,” Appl. Phys. B70(1), 151–154 (2000).
[CrossRef]

Okada, Y.

Y. Okada, T. Shimizu, E. Maeno, S. Tanabe, X. Wang, and N. Takahashi, “Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death,” J. Membr. Biol.209(1), 21–29 (2006).
[CrossRef] [PubMed]

H. Inoue, S.-I. Mori, S. Morishima, and Y. Okada, “Volume-sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation,” Eur. J. Neurosci.21(6), 1648–1658 (2005).
[CrossRef] [PubMed]

Ong, Z.-Y.

Pedrini, G.

Pham, H.

Pop, E.

Popescu, G.

Postma, N. L.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Rappaz, B.

Ridder, M. C.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

Scheper, G. C.

M. C. Ridder, I. Boor, J. C. Lodder, N. L. Postma, X. Capdevila-Nortes, A. Duarri, A. B. Brussaard, R. Estévez, G. C. Scheper, H. D. Mansvelder, and M. S. van der Knaap, “Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation,” Brain134(11), 3342–3354 (2011).
[CrossRef] [PubMed]

Schnars, U.

U. Schnars and W. P. O. Jüptner, “Digital recording and numerical reconstruction of holograms,” Meas. Sci. Technol.13(9), R85–R101 (2002).
[CrossRef]

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Scott, P. D.

Shimizu, T.

Y. Okada, T. Shimizu, E. Maeno, S. Tanabe, X. Wang, and N. Takahashi, “Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death,” J. Membr. Biol.209(1), 21–29 (2006).
[CrossRef] [PubMed]

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Strange, K.

K. Strange, “Cellular volume homeostasis,” Adv. Physiol. Educ.28(4), 155–159 (2004).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

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,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Takahashi, N.

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Figures (4)

Fig. 1
Fig. 1

(a) Setup used for short-coherence off-axis holographic microscopy. A grating in the reference arm introduces a controlled pulse-front-tilt between reference and sample arms, causing short-coherence pulses to overlap over their entire field-of-view despite the finite off-axis angle (lower right inset), in contrast to the normal non-tilted situation (upper right inset). The zero-order reflection is blocked by slightly tilting the grating vertically and placing a beam block (BB) in the returning beam. BS: beam splitter, PCF: photonic crystal fiber, CCD: CCD camera. (b) Hologram of a test sample, measured without pulse front tilt in the reference beam. The limited overlap leads to a strongly reduced field-of-view. (c) Hologram of the same sample, measured with pulse front tilt. A good contrast image is obtained across the entire field-of-view.

Fig. 2
Fig. 2

(a) Single-shot off-axis hologram recorded on the CCD camera. Fine fringes are seen across the entire image. (b) 2D-FFT of the image in (a). The cross-correlation terms containing the electric field information are clearly visible and shifted away from DC because of the off-axis geometry, allowing direct filtering of the area shown in red. (c) Resulting quantitative phase map of a neuron after filtering, inverse 2D-FFT and 2D phase unwrapping.

Fig. 3
Fig. 3

(a) Fluorescence image of GFP-labeled HEK293 cells under normal conditions. (b) Fluorescence image of the same cells after hypo-osmotic shock, showing cell swelling. (c) Measured surface area of two cells as a function of time during a hypo-osmotic shock, using fluorescence images. (d) Phase microscopy image of unlabeled HEK293 cells. (e) Measured surface area of two cells as a function of time during a hypo-osmotic shock, using phase microscopy. (f) Phase signal and cell surface area as a function of time. When assuming isotropic expansion, an estimate for the refractive index change can be calculated as well.

Fig. 4
Fig. 4

(a) Measured phase shift during a hypo-osmotic shock using off-axis phase holography on two HEK293 cells. After initial rapid cell swelling, active cell volume regulation is observed. (b) Measured phase shift during a similar hypo-osmotic shock as in (a), but with Zinc added to the extracellular solution. The Zn2+-ions inhibit Cl- channels in the cell membrane, resulting in an absence of active volume regulation.

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