Abstract

Digital holographic microscopy enables a quantitative phase contrast metrology that is suitable for the investigation of reflective surfaces as well as for the marker-free analysis of living cells. The digital holographic feature of (subsequent) numerical focus adjustment makes possible applications for multifocus imaging. An overview of digital holographic microscopy methods is described. Applications of digital holographic microscopy are demonstrated by results obtained from livings cells and engineered surfaces.

© 2008 Optical Society of America

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    [CrossRef] [PubMed]

2007 (5)

J. A. Herrera Ramírez and J. Garcia-Sucerquia, "Digital off-axis holography without zero-order diffraction via phase manipulation," Opt. Commun. 277, 259-263 (2007).
[CrossRef]

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. De Petrocellis, and S. De Nicola, "Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram," Appl. Phys. Lett. 90, 041104 (2007).
[CrossRef]

P. Langehanenberg, B. Kemper, and G. von Bally, "Autofocus algorithms for digital-holographic microscopy," Proc SPIE 6633, 66330E (2007).
[CrossRef]

P. Marquet, B. Rappaz, F. Charrière, Y. Emery, C. Depeursinge, and P. Magistretti, "Analysis of cellular structure and dynamics with digital holographic microscopy," Proc SPIE 6633, 66330F (2007).
[CrossRef]

F. Charrière, B. Rappaz, J. Kühn, T. Colomb, P. Marquet, and C. Depeursinge, "Influence of shot noise on phase measurement accuracy in digital holographic microscopy," Opt. Express 15, 8818-8831 (2007).
[CrossRef] [PubMed]

2006 (12)

B. Kemper, D. D. Carl, J. Schnekenburger, I. Bredebusch, M. Schäfer, W. Domschke, and G. von Bally, "Investigation of living pancreas tumor cells by digital holographic microscopy," J. Biomed. Opt. 11, 034005 (2006).
[CrossRef]

B. Kemper, D. Carl, A. Höink, G. von Bally, I. Bredebusch, and J. Schnekenburger, "Modular digital holographic microscopy system for marker-free quantitative phase contrast imaging of living cells," Proc. SPIE 6191, 61910T (2006).
[CrossRef]

F. Charrière, A. Marian, F. Montfort, J. Kühn, T. Colomb, E. Cuche, P. Marquet, and C. Depeursinge, "Cell refractive index tomography by digital holographic microscopy," Opt. Lett. 31, 178-180 (2006).
[CrossRef] [PubMed]

T. Colomb, E. Cuche, F. Charrière, J. Kühn, N. Aspert, F. Montfort, P. Marquet, and C. Depeursinge, "Automatic procedure for aberration compensation in digital holographic microscopy and applications to specimen shape compensation," Appl. Opt. 45, 851-863 (2006).
[CrossRef] [PubMed]

P. Ferraro, D. Alferi, S. De Nicola, L. De Petrocellis, A. Finizio, and G. Pierattini, "Quantitative phase-contrast microscopy by a lateral shear approach to digital holographic image reconstruction," Opt. Lett. 31, 1405-1407 (2006).
[CrossRef] [PubMed]

T. Colomb, J. Kühn, F. Charrière, C. Depeursinge, P. Marquet, and N. Aspert, "Total aberrations compensation in digital holographic microscopy with a reference conjugated hologram," Opt. Express 14, 4300-4306 (2006).
[CrossRef] [PubMed]

F. Dubois, C. Schockaert, N. Callens, and C. Yourassowsky, "Focus plane detection criteria in digital holography microscopy by amplitude analysis," Opt. Express 14, 5895-5908 (2006).
[CrossRef] [PubMed]

F. Charrière, N. Pavillon, T. Colomb, C. Depeursinge, T. J. Heger, E. A. D. Mitchell, P. Marquet, and B. Rappaz, "Living specimen tomography by digital holographic microscopy: morphometry of testate amoeba," Opt. Express 14, 7005-7013 (2006).
[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, 2759-2761 (2006).
[CrossRef] [PubMed]

Y. Park, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Diffraction phase and fluorescence microscopy," Opt. Express 14, 8263-8268 (2006).
[CrossRef] [PubMed]

F. Charrière, T. Colomb, F. Montfort, E. Cuche, P. Marquet, and C. Depeursinge, "Shot-noise influence on the reconstructed phase image signal-to-noise ratio in digital holographic microscopy," Appl. Opt. 45, 7667-7673 (2006).
[CrossRef] [PubMed]

T. Colomb, F. Montfort, J. Kühn, N. Aspert, E. Cuche, A. Marian, F. Charrière, S. Bourquin, P. Marquet, and C. Depeursinge, "Numerical parametric lens for shifting, magnification, and complete aberration compensation in digital holographic microscopy," J. Opt. Soc. Am. A 23, 3177-3190 (2006).
[CrossRef]

2005 (6)

2004 (4)

2003 (1)

2002 (1)

C. Liu, Y. Li, X. Cheng, Z. Liu, F. Bo, and J. Zhu, "Elimination of zero-order diffraction in digital holography," Opt. Eng. 41, 2434-2437 (2002).
[CrossRef]

2001 (2)

W. Avenhaus, B. Kemper, G. von Bally, and W. Domschke, "Gastric wall elasticity assessed by dynamic holographic endoscopy: ex vivo investigations in the porcine stomach," Gastrointest. Endosc. 54, 496-500 (2001).
[CrossRef] [PubMed]

I. Yamaguchi, J. Kato, S. Ohta, and J. Mizuno, "Image formation in phase-shifting digital holography and applications to microscopy," Appl. Opt. 40, 6177-6186 (2001).
[CrossRef]

2000 (4)

1999 (2)

1997 (2)

I. Yamaguchi and T. Zhang, "Phase-shifting digital holography," Opt. Lett. 22, 1268-1270 (1997).
[CrossRef] [PubMed]

T. M. Kreis, M. Adams, and W. P. O. Jüptner, "Methods of digital holography: a comparison," Proc. SPIE 3098, 224-233 (1997).
[CrossRef]

1994 (1)

1992 (1)

H. P. Elsässer, U. Lehr, B. Agricola, and H. F. Kern, "Establishment and characterization of two cell lines with different grade of differentiation derived from one primary human pancreatic adenocarcinoma," Virchows Arch. B. Cell Pathol. Incl. Mol. Pathol. 61, 295-306 (1992).
[CrossRef] [PubMed]

1974 (1)

1965 (1)

1964 (1)

1963 (1)

1962 (1)

1960 (1)

T. H. Maiman, "Stimulated optical radiation in ruby," Nature 187, 493-494 (1960).
[CrossRef]

1948 (1)

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

Appl. Opt. (12)

Y. Takaki, H. Kawai, and H. Ohzu, "Hybrid holographic microscopy free of conjugate and zero-order images," Appl. Opt. 38, 4990-4996 (1999).
[CrossRef]

E. Cuche, P. Marquet, and C. Depeursinge, "Simultaneous amplitude-contrast and quantitative phase-contrast microscopy by numerical reconstruction of Fresnel off-axis holograms," Appl. Opt. 38, 6994-7001 (1999).
[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, 4070-4075 (2000).
[CrossRef]

S. Schedin, G. Pedrini, and H. J. Tiziani, "Pulsed digital holography for deformation measurements on biological tissues," Appl. Opt. 39, 2853-2857 (2000).
[CrossRef]

B. Kemper, D. Dirksen, W. Avenhaus, A. Merker, and G. von Bally, "Endoscopic double-pulse electronic-speckle-pattern interferometer for technical and medical intracavity inspection," Appl. Opt. 39, 3899-3905 (2000).
[CrossRef]

I. Yamaguchi, J. Kato, S. Ohta, and J. Mizuno, "Image formation in phase-shifting digital holography and applications to microscopy," Appl. Opt. 40, 6177-6186 (2001).
[CrossRef]

P. Ferraro, S. De Nicola, A. Finizio, G. Coppola, S. Grilli, C. Magro, and G. Pierattini, "Compensation of the inherent wave front curvature in digital holographic coherent microscopy for quantitative phase-contrast imaging," Appl. Opt. 42, 1938-1946 (2003).
[CrossRef] [PubMed]

T. H. Demetrakopoulos and R. Mittra, "Digital and optical reconstruction of images from suboptical diffraction patterns," Appl. Opt. 13, 665-670 (1974).
[CrossRef] [PubMed]

U. Schnars and W. Jüptner, "Direct recording of holograms by a CCD target and numerical reconstruction," Appl. Opt. 33, 179-181 (1994).
[CrossRef] [PubMed]

D. Carl, B. Kemper, G. Wernicke, and G. von Bally, "Parameter-optimized digital holographic microscope for high-resolution living-cell analysis," Appl. Opt. 43, 6536-6544 (2004).
[CrossRef]

T. Colomb, E. Cuche, F. Charrière, J. Kühn, N. Aspert, F. Montfort, P. Marquet, and C. Depeursinge, "Automatic procedure for aberration compensation in digital holographic microscopy and applications to specimen shape compensation," Appl. Opt. 45, 851-863 (2006).
[CrossRef] [PubMed]

F. Charrière, T. Colomb, F. Montfort, E. Cuche, P. Marquet, and C. Depeursinge, "Shot-noise influence on the reconstructed phase image signal-to-noise ratio in digital holographic microscopy," Appl. Opt. 45, 7667-7673 (2006).
[CrossRef] [PubMed]

Appl. Phys. Lett. (1)

L. Miccio, D. Alfieri, S. Grilli, P. Ferraro, A. Finizio, L. De Petrocellis, and S. De Nicola, "Direct full compensation of the aberrations in quantitative phase microscopy of thin objects by a single digital hologram," Appl. Phys. Lett. 90, 041104 (2007).
[CrossRef]

Gastrointest. Endosc. (1)

W. Avenhaus, B. Kemper, G. von Bally, and W. Domschke, "Gastric wall elasticity assessed by dynamic holographic endoscopy: ex vivo investigations in the porcine stomach," Gastrointest. Endosc. 54, 496-500 (2001).
[CrossRef] [PubMed]

Gut (1)

J. Schnekenburger, J. Mayerle, B. Krüger, I. Buchwalow, F. U. Weiss, E. Albrecht, V. E. Samoilova, W. Domschke, and M. M. Lerch, "Protein tyrosine phosphatase κ and SHP-1 are involved in the regulation of cell-cell contacts at adherens junctions in the exocrine pancreas," Gut 54, 1445-1455 (2005).
[CrossRef] [PubMed]

J. Biomed. Opt. (2)

B. Kemper, D. D. Carl, J. Schnekenburger, I. Bredebusch, M. Schäfer, W. Domschke, and G. von Bally, "Investigation of living pancreas tumor cells by digital holographic microscopy," J. Biomed. Opt. 11, 034005 (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. 10, 060503 (2005).
[CrossRef]

J. Opt. Soc. Am. (4)

J. Opt. Soc. Am. A (3)

Nature (2)

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

T. H. Maiman, "Stimulated optical radiation in ruby," Nature 187, 493-494 (1960).
[CrossRef]

Opt. Commun. (2)

Y. Zhang, Q. Lü, and B. Ge, "Elimination of zero-order diffraction in digital off-axis holography," Opt. Commun. 240, 261-267 (2004).
[CrossRef]

J. A. Herrera Ramírez and J. Garcia-Sucerquia, "Digital off-axis holography without zero-order diffraction via phase manipulation," Opt. Commun. 277, 259-263 (2007).
[CrossRef]

Opt. Eng. (1)

C. Liu, Y. Li, X. Cheng, Z. Liu, F. Bo, and J. Zhu, "Elimination of zero-order diffraction in digital holography," Opt. Eng. 41, 2434-2437 (2002).
[CrossRef]

Opt. Express (7)

F. Charrière, B. Rappaz, J. Kühn, T. Colomb, P. Marquet, and C. Depeursinge, "Influence of shot noise on phase measurement accuracy in digital holographic microscopy," Opt. Express 15, 8818-8831 (2007).
[CrossRef] [PubMed]

Y. Park, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Diffraction phase and fluorescence microscopy," Opt. Express 14, 8263-8268 (2006).
[CrossRef] [PubMed]

C. Mann, L. Yu, C.-M. Lo, and M. Kim, "High-resolution quantitative phase-contrast microscopy by digital holography," Opt. Express 13, 8693-8698 (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 morphotometry of living cells with digital holographic microscopy," Opt. Express 13, 9361-9373 (2005).
[CrossRef] [PubMed]

T. Colomb, J. Kühn, F. Charrière, C. Depeursinge, P. Marquet, and N. Aspert, "Total aberrations compensation in digital holographic microscopy with a reference conjugated hologram," Opt. Express 14, 4300-4306 (2006).
[CrossRef] [PubMed]

F. Dubois, C. Schockaert, N. Callens, and C. Yourassowsky, "Focus plane detection criteria in digital holography microscopy by amplitude analysis," Opt. Express 14, 5895-5908 (2006).
[CrossRef] [PubMed]

F. Charrière, N. Pavillon, T. Colomb, C. Depeursinge, T. J. Heger, E. A. D. Mitchell, P. Marquet, and B. Rappaz, "Living specimen tomography by digital holographic microscopy: morphometry of testate amoeba," Opt. Express 14, 7005-7013 (2006).
[CrossRef] [PubMed]

Opt. Lasers Eng. (1)

M.-A. Beeck and W. Hentschel, "Laser metrology--a diagnostic tool in automotive development processes," Opt. Lasers Eng. 34, 101-120 (2000).
[CrossRef]

Opt. Lett. (6)

Proc SPIE (2)

P. Langehanenberg, B. Kemper, and G. von Bally, "Autofocus algorithms for digital-holographic microscopy," Proc SPIE 6633, 66330E (2007).
[CrossRef]

P. Marquet, B. Rappaz, F. Charrière, Y. Emery, C. Depeursinge, and P. Magistretti, "Analysis of cellular structure and dynamics with digital holographic microscopy," Proc SPIE 6633, 66330F (2007).
[CrossRef]

Proc. SPIE (2)

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Figures (9)

Fig. 1
Fig. 1

(Color online) Schematic of digital holographic microscopy: (a) inverse transmission setup and (b) incident light (reflective) setup; HP at z = z 0 ; z IP , image plane; Δz, propagation distance.

Fig. 2
Fig. 2

(a) Digital hologram of living human erythrocytes (human red blood cells); the enlarged area shows a part of the carrier fringe pattern that is generated by the holographic off-axis arrangement. (b) Reconstructed holographic amplitude image; (c) reconstructed phase contrast image modulo 2π; (d) unwrapped phase distribution; (e) pseudo-three-dimensional representation of the phase distribution with a cross section through a cell.

Fig. 3
Fig. 3

(a) Digital holographic reconstructed amplitude image of a negative U.S. Air Force 1951 resolution test chart recorded with a 40 × microscope lens ( 0.6 NA ) ; (b) enlarged area of (a); (c) topography calculated from the phase distribution of a nanostructured gold-coated surface (pure phase object, cooperation: Nano+Bio Center Technical University, Kaiserslautern, Germany); (d) 256 gray level coded pseudo-three-dimensional representation of the phase data in (c).

Fig. 4
Fig. 4

(a) Amplitude in the hologram plane reconstructed from a slightly out-of-focus recorded hologram of a semitransparent U.S. Air Force 1951 test chart (illumination in transmission, 40× microscope optic, 0.6 NA ); (b) numerically refocused holographic amplitude reconstructed by variation of the propagation distance; (c), (d) corresponding results obtained from investigation of a living adherent grown human pancreas tumor cell (Patu8988S) in culture medium ( 100 × oil immersion microscope lens, 1.3 NA ).

Fig. 5
Fig. 5

Reconstruction of a spherical living pancreas tumor cell (Patu8988T) in suspension ( 63 × microscope lens, 0.75 NA ) for different focal planes and propagation distances Δz. Left column, amplitude images; middle column, phase distributions modulo 2π; right, unwrapped phase contrast images.

Fig. 6
Fig. 6

Monitoring of living PaTu8988T cells after the addition of Taxol to the cell culture medium. Gray level coded unwrapped phase distributions at t = 0 , t = 3.5   h , t = 8.3   h , and t = 14.2   h after the addition of Taxol.

Fig. 7
Fig. 7

Temporal dependence of the maximum phase contrast Δ φ s , max and related cell thickness d c e l l for the cells that are marked in Fig. 6 by A, B, C.

Fig. 8
Fig. 8

Cross sections through the phase data Δ φ s marked by dashed white lines in Fig. 6 and corresponding cell thickness d cell .

Fig. 9
Fig. 9

Characterization of engineered surfaces (incident light arrangement): (a)–(c) topography measurement of a silicon sensor ( 25 × microscope lens, 0.4 NA ). (a) Unwrapped phase distribution coded to 256 gray levels; (b) rendered pseudo-three-dimensional representation of (a); (c) profile calculated from the cross section that is marked in (a) by a dashed line. (d)–(f) Topography measurement of a reflective microstructured silicon surface: (d) unwrapped phase distribution coded to 256 gray levels; (e) rendered pseudo-three-dimensional representation of (d); (f) profile calculated from the cross section that is marked in (d) by a dotted line.

Equations (7)

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I HP ( x , y , z 0 ) = O ( x , y , z 0 ) O * ( x , y , z 0 ) + R ( x , y , z 0 ) R * ( x , y , z 0 ) + O ( x , y , z 0 ) R * ( x , y , z 0 ) + R ( x , y , z 0 ) O * ( x , y , z 0 ) = I O ( x , y , z 0 ) + I R ( x , y , z 0 ) + 2 I O ( x , y , z 0 ) I R ( x , y , z 0 ) × cos Δ ϕ HP ( x , y , z 0 ) ,
Δ ϕ HP ( x , y , z 0 ) = ϕ R ( x , y , z 0 ) ϕ O 0 ( x , y , z 0 ) = 2 π ( K x x 2 + K y y 2 + L x x + L y y ) .
O ( x , y , z IP = z 0 + Δ z ) = F 1 { F { O ( x , y , z 0 ) }
× exp [ i π λ Δ z ( v 2 + μ 2 ) ] } .
Δ φ S ( x , y , z IP ) = ϕ O ( x , y , z IP ) ϕ O 0 ( x , y , z IP ) = arctan Im { O ( x , y , z IP ) } Re { O ( x , y , z IP ) } ( mod 2 π ) .
z s ( x , y , z IP ) = 2 λ Δ φ s ( x , y , z IP ) 2 π = λ π Δ φ s ( x , y , z IP ) ,
d cell ( x , y , z IP ) = λ Δ φ cell ( x , y , z IP ) 2 π 1 n cell n medium .

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