Abstract

We describe a heterodyne Mach–Zehnder interferometric microscope capable of quantitative phase imaging of biological samples with subnanometer sensitivity and frame rates up to 10kHz. We use the microscope to image cultured neurons and measure nanometer-scale voltage-dependent motions in cells expressing the membrane motor protein prestin.

© 2007 Optical Society of America

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2006

2005

2004

2002

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, J. Microsc. 206, 194 (2002).
[CrossRef] [PubMed]

P. Dallos and B. Fakler, Nat. Rev. Mol. Cell Biol. 3, 104 (2002).
[CrossRef] [PubMed]

2001

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

2000

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

1998

1995

G. A. Dunn and D. Zicha, J. Cell. Sci. 108, 1239 (1995).
[PubMed]

1988

R. M. Goldstein, H. A. Zebker, and C. L. Werner, Radio Sci. 23, 713 (1988).
[CrossRef]

1955

G. Nomarski, J. Phys. Radium 16, 9S (1955).

1942

F. Zernike, Physica 9, 686 (1942).
[CrossRef]

Akkin, T.

Badizadegan, K.

Barone-Nugent, E. D.

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, J. Microsc. 206, 194 (2002).
[CrossRef] [PubMed]

Barty, A.

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, J. Microsc. 206, 194 (2002).
[CrossRef] [PubMed]

A. Barty, K. A. Nugent, D. Paganin, and A. Roberts, Opt. Lett. 23, 817 (1998).
[CrossRef]

Best, C. A.

G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 10, (2005).
[CrossRef]

Bredebusch, I.

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

Carl, D.

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

Choi, J.

A. Starovoytov, J. Choi, and H. S. Seung, J. Neurophysiol. 93, 1090 (2005).
[CrossRef]

Choma, M. A.

Chu, M. C.

Creazzo, T. L.

Cuche, E.

Dallos, P.

P. Dallos and B. Fakler, Nat. Rev. Mol. Cell Biol. 3, 104 (2002).
[CrossRef] [PubMed]

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

Dasari, R. R.

Dave, D. P.

Deflores, L. P.

Depeursinge, C.

Domschke, W.

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

Dunn, G. A.

G. A. Dunn and D. Zicha, J. Cell. Sci. 108, 1239 (1995).
[PubMed]

Ellerbee, A. K.

Emery, Y.

Fakler, B.

P. Dallos and B. Fakler, Nat. Rev. Mol. Cell Biol. 3, 104 (2002).
[CrossRef] [PubMed]

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

Fang-Yen, C.

Feld, M. S.

Frank, G.

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

Goldstein, R. M.

R. M. Goldstein, H. A. Zebker, and C. L. Werner, Radio Sci. 23, 713 (1988).
[CrossRef]

Gummer, A. W.

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

He, D. Z.

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

Hiruma, T.

Ikeda, T.

Iwai, H.

Izatt, J. A.

Kemper, B.

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

Klocker, N.

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

Li, X. H.

Long, K. B.

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

Ludwig, J.

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

Lue, N.

Madison, L. D.

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

Magistretti, P. J.

Marquet, P.

Milner, T. E.

Nomarski, G.

G. Nomarski, J. Phys. Radium 16, 9S (1955).

Nugent, K. A.

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, J. Microsc. 206, 194 (2002).
[CrossRef] [PubMed]

A. Barty, K. A. Nugent, D. Paganin, and A. Roberts, Opt. Lett. 23, 817 (1998).
[CrossRef]

Oliver, D.

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

Paganin, D.

Popescu, G.

Rappaz, B.

Roberts, A.

Rylander, H. G.

Schafer, M.

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

Schnekenburger, J.

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

Seung, H. S.

Shen, W.

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

Starovoytov, A.

A. Starovoytov, J. Choi, and H. S. Seung, J. Neurophysiol. 93, 1090 (2005).
[CrossRef]

Vaughan, J. C.

von Bally, G.

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

Wax, A.

Werner, C. L.

R. M. Goldstein, H. A. Zebker, and C. L. Werner, Radio Sci. 23, 713 (1988).
[CrossRef]

Yamashita, Y.

Yamauchi, T.

Yang, C. H.

Zebker, H. A.

R. M. Goldstein, H. A. Zebker, and C. L. Werner, Radio Sci. 23, 713 (1988).
[CrossRef]

Zernike, F.

F. Zernike, Physica 9, 686 (1942).
[CrossRef]

Zhang, H. J.

Zheng, J.

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

Zicha, D.

G. A. Dunn and D. Zicha, J. Cell. Sci. 108, 1239 (1995).
[PubMed]

J. Biomed. Opt.

G. Popescu, T. Ikeda, C. A. Best, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 10, (2005).
[CrossRef]

B. Kemper, D. Carl, J. Schnekenburger, I. Bredebusch, M. Schafer, W. Domschke, and G. von Bally, J. Biomed. Opt. 11, 34005 (2006).
[CrossRef] [PubMed]

J. Cell. Sci.

G. A. Dunn and D. Zicha, J. Cell. Sci. 108, 1239 (1995).
[PubMed]

J. Microsc.

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, J. Microsc. 206, 194 (2002).
[CrossRef] [PubMed]

J. Neurophysiol.

A. Starovoytov, J. Choi, and H. S. Seung, J. Neurophysiol. 93, 1090 (2005).
[CrossRef]

J. Phys. Radium

G. Nomarski, J. Phys. Radium 16, 9S (1955).

Nat. Rev. Mol. Cell Biol.

P. Dallos and B. Fakler, Nat. Rev. Mol. Cell Biol. 3, 104 (2002).
[CrossRef] [PubMed]

Nature

J. Zheng, W. Shen, D. Z. He, K. B. Long, L. D. Madison, and P. Dallos, Nature 405, 149 (2000).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Physica

F. Zernike, Physica 9, 686 (1942).
[CrossRef]

Proc. Natl. Acad. Sci. U.S.A.

J. Ludwig, D. Oliver, G. Frank, N. Klocker, A. W. Gummer, and B. Fakler, Proc. Natl. Acad. Sci. U.S.A. 98, 4178 (2001).
[CrossRef] [PubMed]

Radio Sci.

R. M. Goldstein, H. A. Zebker, and C. L. Werner, Radio Sci. 23, 713 (1988).
[CrossRef]

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Figures (3)

Fig. 1
Fig. 1

Heterodyne Mach–Zehnder phase microscope. HeNe, helium–neon laser; solid line, laser beam; dashed line, bright-field illumination beam. In the sample path: S, sample; OBJ, objective lens ( f = f 1 ) ; DBS, dichroic beam splitter; TL, tube lenses ( f = f 2 ) ; LED, light-emitting diode bright-field illuminator (removed during interferometry measurements); CCD, camera for bright-field and fluorescence imaging. In the reference path: AOM1,2, acousto-optic modulators; BE, beam expander; SF, spatial filter; CMOS, camera for interferometric imaging. Not shown: mercury lamp fluorescence illuminator and filter cube in the bright-field illumination path.

Fig. 2
Fig. 2

Phase image of a cultured rat hippocampal neuron. Phase in radians.

Fig. 3
Fig. 3

(a) Phase image of prestin-transfected HEK 293 cell in a micropipette. Squares, regions of interest (ROI) labeled 1–3 and reference region R. Phase in radians. (b) Map of the in-phase component of fast Fourier transform at stimulus frequency 217 Hz . ROIs are denoted by circles. (c). Power spectra of the phase signals from ROIs 1–3. (d) Solid line, time trace of phase of ROI-1 referenced by ROI-R; dashed line, 217 Hz , 20 mrad peak-to-peak amplitude sine wave.

Equations (1)

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I ( x , y , t ) = I S ( x , y ) + I R ( x , y ) + 2 I S ( x , y ) I R ( x , y ) cos [ ϕ S ( x , y , t ) + Ω t ] ,

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