Abstract

Quantitative phase imaging systems using white light illumination can exhibit lower noise figures than laser-based systems. However, they can also suffer from object-dependent artifacts, such as halos, which prevent accurate reconstruction of the surface topography. In this work, we show that white light diffraction phase microscopy using a standard halogen lamp can produce accurate height maps of even the most challenging structures provided that there is proper spatial filtering at: 1) the condenser to ensure adequate spatial coherence and 2) the output Fourier plane to produce a uniform reference beam. We explain that these object-dependent artifacts are a high-pass filtering phenomenon, establish design guidelines to reduce the artifacts, and then apply these guidelines to eliminate the halo effect. Since a spatially incoherent source requires significant spatial filtering, the irradiance is lower and proportionally longer exposure times are needed. To circumvent this tradeoff, we demonstrate that a supercontinuum laser, due to its high radiance, can provide accurate measurements with reduced exposure times, allowing for fast dynamic measurements.

© 2014 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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2013 (10)

C. Edwards, K. Wang, R. Zhou, B. Bhaduri, G. Popescu, L. L. Goddard, “Digital projection photochemical etching defines gray-scale features,” Opt. Express 21(11), 13547–13554 (2013).
[CrossRef] [PubMed]

R. Zhou, G. Popescu, L. L. Goddard, “22 nm node wafer inspection using diffraction phase microscopy and image post-processing,” Proc. SPIE 8681, 8610G (2013).

P. Girshovitz, N. T. Shaked, “Compact and portable low-coherence interferometer with off-axis geometry for quantitative phase microscopy and nanoscopy,” Opt. Express 21(5), 5701–5714 (2013).
[CrossRef] [PubMed]

H. V. Pham, B. Bhaduri, K. Tangella, C. Best-Popescu, G. Popescu, “Real time blood testing using quantitative phase imaging,” PLoS ONE 8(2), e55676 (2013).
[CrossRef] [PubMed]

T. Slabý, P. Kolman, Z. Dostál, M. Antoš, M. Lošťák, R. Chmelík, “Off-axis setup taking full advantage of incoherent illumination in coherence-controlled holographic microscope,” Opt. Express 21(12), 14747–14762 (2013).
[CrossRef] [PubMed]

H. V. Pham, C. Edwards, L. L. Goddard, G. Popescu, “Fast phase reconstruction in white light diffraction phase microscopy,” Appl. Opt. 52(1), A97–A101 (2013).
[CrossRef] [PubMed]

T. Kim, R. Zhu, T. H. Nguyen, R. Zhou, C. Edwards, L. L. Goddard, G. Popescu, “Deterministic signal associated with a random field,” Opt. Express 21(18), 20806–20820 (2013).
[CrossRef] [PubMed]

B. Bhaduri, D. Wickland, R. Wang, V. Chan, R. Bashir, G. Popescu, “Cardiomyocyte Imaging Using Real-Time Spatial Light Interference Microscopy (SLIM),” PLoS ONE 8(2), e56930 (2013).
[CrossRef] [PubMed]

B. Bhaduri, K. Tangella, G. Popescu, “Fourier phase microscopy with white light,” Biomed. Opt. Express 4(8), 1434–1441 (2013).
[CrossRef] [PubMed]

T. H. Nguyen, G. Popescu, “Spatial Light Interference Microscopy (SLIM) using twisted-nematic liquid-crystal modulation,” Biomed. Opt. Express 4(9), 1571–1583 (2013).
[CrossRef] [PubMed]

2012 (4)

2011 (4)

2010 (3)

M. T. Rinehart, N. T. Shaked, N. J. Jenness, R. L. Clark, A. Wax, “Simultaneous two-wavelength transmission quantitative phase microscopy with a color camera,” Opt. Lett. 35(15), 2612–2614 (2010).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, 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, 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 (1)

2008 (3)

N. Lue, W. Choi, K. Badizadegan, R. R. Dasari, M. S. Feld, G. Popescu, “Confocal diffraction phase microscopy of live cells,” Opt. Lett. 33(18), 2074–2076 (2008).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, 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]

C. J. Mann, P. R. Bingham, V. C. Paquit, K. W. Tobin, “Quantitative phase imaging by three-wavelength digital holography,” Opt. Express 16(13), 9753–9764 (2008).
[CrossRef] [PubMed]

2006 (2)

2003 (1)

1981 (1)

T. Wilson, C. J. R. Sheppard, “The halo effect of image processing by spatial frequency filtering,” Optik (Stuttg.) 59(1), 19–23 (1981).

Antoš, M.

Arbabi, A.

C. Edwards, A. Arbabi, G. Popescu, L. L. Goddard, “Optically monitoring and controlling nanoscale topography during semiconductor etching,” Light Sci. Appl. 1(9), e30 (2012).
[CrossRef]

Auth, T.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, 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, 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]

N. Lue, W. Choi, K. Badizadegan, R. R. Dasari, M. S. Feld, G. Popescu, “Confocal diffraction phase microscopy of live cells,” Opt. Lett. 33(18), 2074–2076 (2008).
[CrossRef] [PubMed]

Y. Park, G. Popescu, K. Badizadegan, R. R. Dasari, M. S. Feld, “Diffraction phase and fluorescence microscopy,” Opt. Express 14(18), 8263–8268 (2006).
[CrossRef] [PubMed]

Barman, I.

Bashir, R.

B. Bhaduri, D. Wickland, R. Wang, V. Chan, R. Bashir, G. Popescu, “Cardiomyocyte Imaging Using Real-Time Spatial Light Interference Microscopy (SLIM),” PLoS ONE 8(2), e56930 (2013).
[CrossRef] [PubMed]

Best, C. A.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, 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, 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]

Best-Popescu, C.

H. V. Pham, B. Bhaduri, K. Tangella, C. Best-Popescu, G. Popescu, “Real time blood testing using quantitative phase imaging,” PLoS ONE 8(2), e55676 (2013).
[CrossRef] [PubMed]

Bhaduri, B.

Bingham, P. R.

Chan, V.

B. Bhaduri, D. Wickland, R. Wang, V. Chan, R. Bashir, G. Popescu, “Cardiomyocyte Imaging Using Real-Time Spatial Light Interference Microscopy (SLIM),” PLoS ONE 8(2), e56930 (2013).
[CrossRef] [PubMed]

Chmelík, R.

Choi, W.

Clark, R. L.

Dakoff, A.

Dasari, R.

Dasari, R. R.

Diez-Silva, M.

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, 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]

Ding, H.

Dingari, N. C.

Dostál, Z.

Edwards, C.

Feld, M. S.

J. W. Kang, N. Lue, C.-R. Kong, I. Barman, N. C. Dingari, S. J. Goldfless, J. C. Niles, R. R. Dasari, M. S. Feld, “Combined confocal Raman and quantitative phase microscopy system for biomedical diagnosis,” Biomed. Opt. Express 2(9), 2484–2492 (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, 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, 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. Park, T. Yamauchi, W. Choi, R. Dasari, M. S. Feld, “Spectroscopic phase microscopy for quantifying hemoglobin concentrations in intact red blood cells,” Opt. Lett. 34(23), 3668–3670 (2009).
[CrossRef] [PubMed]

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, 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]

N. Lue, W. Choi, K. Badizadegan, R. R. Dasari, M. S. Feld, G. Popescu, “Confocal diffraction phase microscopy of live cells,” Opt. Lett. 33(18), 2074–2076 (2008).
[CrossRef] [PubMed]

Y. Park, G. Popescu, K. Badizadegan, R. R. Dasari, M. S. Feld, “Diffraction phase and fluorescence microscopy,” Opt. Express 14(18), 8263–8268 (2006).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, R. R. Dasari, M. S. Feld, “Diffraction phase microscopy for quantifying cell structure and dynamics,” Opt. Lett. 31(6), 775–777 (2006).
[CrossRef] [PubMed]

Gao, P.

Gass, J.

Gillette, M. U.

Girshovitz, P.

Goddard, L.

T. Nguyen, C. Edwards, L. Goddard, G. Popescu, “Quantitative phase imaging with partially coherent illumination,” (to be submitted).

Goddard, L. L.

Goldfless, S. J.

Gov, N. S.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, 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]

Groot, M. L.

Harder, I.

Henle, M. L.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, 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]

Ikeda, T.

Jenness, N. J.

Kang, J. W.

Kim, M. K.

Kim, T.

Kolman, P.

Kong, C.-R.

Kuriabova, T.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, 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]

Levine, A. J.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, 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]

Lindlein, N.

Lošták, M.

Lue, N.

Lykotrafitis, G.

Y. K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, 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]

Mann, C. J.

Mansvelder, H. D.

Millet, L.

Mir, M.

Nguyen, T.

T. Nguyen, C. Edwards, L. Goddard, G. Popescu, “Quantitative phase imaging with partially coherent illumination,” (to be submitted).

Nguyen, T. H.

Niles, J. C.

Paquit, V. C.

Park, Y.

Park, Y. K.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, 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, 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. Choi, M. S. Feld, 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]

Pham, H.

Pham, H. V.

H. V. Pham, B. Bhaduri, K. Tangella, C. Best-Popescu, G. Popescu, “Real time blood testing using quantitative phase imaging,” PLoS ONE 8(2), e55676 (2013).
[CrossRef] [PubMed]

H. V. Pham, C. Edwards, L. L. Goddard, G. Popescu, “Fast phase reconstruction in white light diffraction phase microscopy,” Appl. Opt. 52(1), A97–A101 (2013).
[CrossRef] [PubMed]

Plauska, A.

Popescu, G.

R. Zhou, G. Popescu, L. L. Goddard, “22 nm node wafer inspection using diffraction phase microscopy and image post-processing,” Proc. SPIE 8681, 8610G (2013).

C. Edwards, K. Wang, R. Zhou, B. Bhaduri, G. Popescu, L. L. Goddard, “Digital projection photochemical etching defines gray-scale features,” Opt. Express 21(11), 13547–13554 (2013).
[CrossRef] [PubMed]

H. V. Pham, C. Edwards, L. L. Goddard, G. Popescu, “Fast phase reconstruction in white light diffraction phase microscopy,” Appl. Opt. 52(1), A97–A101 (2013).
[CrossRef] [PubMed]

H. V. Pham, B. Bhaduri, K. Tangella, C. Best-Popescu, G. Popescu, “Real time blood testing using quantitative phase imaging,” PLoS ONE 8(2), e55676 (2013).
[CrossRef] [PubMed]

B. Bhaduri, K. Tangella, G. Popescu, “Fourier phase microscopy with white light,” Biomed. Opt. Express 4(8), 1434–1441 (2013).
[CrossRef] [PubMed]

T. H. Nguyen, G. Popescu, “Spatial Light Interference Microscopy (SLIM) using twisted-nematic liquid-crystal modulation,” Biomed. Opt. Express 4(9), 1571–1583 (2013).
[CrossRef] [PubMed]

B. Bhaduri, D. Wickland, R. Wang, V. Chan, R. Bashir, G. Popescu, “Cardiomyocyte Imaging Using Real-Time Spatial Light Interference Microscopy (SLIM),” PLoS ONE 8(2), e56930 (2013).
[CrossRef] [PubMed]

T. Kim, R. Zhu, T. H. Nguyen, R. Zhou, C. Edwards, L. L. Goddard, G. Popescu, “Deterministic signal associated with a random field,” Opt. Express 21(18), 20806–20820 (2013).
[CrossRef] [PubMed]

H. Pham, B. Bhaduri, H. Ding, G. Popescu, “Spectroscopic diffraction phase microscopy,” Opt. Lett. 37(16), 3438–3440 (2012).
[CrossRef] [PubMed]

B. Bhaduri, H. Pham, M. Mir, G. Popescu, “Diffraction phase microscopy with white light,” Opt. Lett. 37(6), 1094–1096 (2012).
[CrossRef] [PubMed]

C. Edwards, A. Arbabi, G. Popescu, L. L. Goddard, “Optically monitoring and controlling nanoscale topography during semiconductor etching,” Light Sci. Appl. 1(9), e30 (2012).
[CrossRef]

Z. Wang, L. Millet, M. Mir, H. Ding, S. Unarunotai, J. Rogers, M. U. Gillette, G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express 19(2), 1016–1026 (2011).
[CrossRef] [PubMed]

M. Mir, K. Tangella, G. Popescu, “Blood testing at the single cell level using quantitative phase and amplitude microscopy,” Biomed. Opt. Express 2(12), 3259–3266 (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, 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, 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. Choi, M. S. Feld, 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]

N. Lue, W. Choi, K. Badizadegan, R. R. Dasari, M. S. Feld, G. Popescu, “Confocal diffraction phase microscopy of live cells,” Opt. Lett. 33(18), 2074–2076 (2008).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, R. R. Dasari, M. S. Feld, “Diffraction phase microscopy for quantifying cell structure and dynamics,” Opt. Lett. 31(6), 775–777 (2006).
[CrossRef] [PubMed]

Y. Park, G. Popescu, K. Badizadegan, R. R. Dasari, M. S. Feld, “Diffraction phase and fluorescence microscopy,” Opt. Express 14(18), 8263–8268 (2006).
[CrossRef] [PubMed]

T. Nguyen, C. Edwards, L. Goddard, G. Popescu, “Quantitative phase imaging with partially coherent illumination,” (to be submitted).

Ridder, M. C.

Rinehart, M. T.

Rogers, J.

Safran, S. A.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, 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]

Shaked, N. T.

Sheppard, C. J. R.

T. Wilson, C. J. R. Sheppard, “The halo effect of image processing by spatial frequency filtering,” Optik (Stuttg.) 59(1), 19–23 (1981).

Slabý, T.

Suresh, S.

Y. K. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, 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. Choi, M. S. Feld, 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]

Tangella, K.

Tobin, K. W.

Torcal-Milla, F. J.

Unarunotai, S.

van Berge, L.

Wang, K.

Wang, R.

B. Bhaduri, D. Wickland, R. Wang, V. Chan, R. Bashir, G. Popescu, “Cardiomyocyte Imaging Using Real-Time Spatial Light Interference Microscopy (SLIM),” PLoS ONE 8(2), e56930 (2013).
[CrossRef] [PubMed]

Wang, Z.

Wax, A.

Wickland, D.

B. Bhaduri, D. Wickland, R. Wang, V. Chan, R. Bashir, G. Popescu, “Cardiomyocyte Imaging Using Real-Time Spatial Light Interference Microscopy (SLIM),” PLoS ONE 8(2), e56930 (2013).
[CrossRef] [PubMed]

Wilson, T.

T. Wilson, C. J. R. Sheppard, “The halo effect of image processing by spatial frequency filtering,” Optik (Stuttg.) 59(1), 19–23 (1981).

Witte, S.

Yamauchi, T.

Yao, B.

Zhou, R.

Zhu, R.

Appl. Opt. (1)

Biomed. Opt. Express (5)

Light Sci. Appl. (1)

C. Edwards, A. Arbabi, G. Popescu, L. L. Goddard, “Optically monitoring and controlling nanoscale topography during semiconductor etching,” Light Sci. Appl. 1(9), e30 (2012).
[CrossRef]

Opt. Express (7)

Opt. Lett. (8)

Optik (Stuttg.) (1)

T. Wilson, C. J. R. Sheppard, “The halo effect of image processing by spatial frequency filtering,” Optik (Stuttg.) 59(1), 19–23 (1981).

PLoS ONE (2)

B. Bhaduri, D. Wickland, R. Wang, V. Chan, R. Bashir, G. Popescu, “Cardiomyocyte Imaging Using Real-Time Spatial Light Interference Microscopy (SLIM),” PLoS ONE 8(2), e56930 (2013).
[CrossRef] [PubMed]

H. V. Pham, B. Bhaduri, K. Tangella, C. Best-Popescu, G. Popescu, “Real time blood testing using quantitative phase imaging,” PLoS ONE 8(2), e55676 (2013).
[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, 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, 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. Choi, M. S. Feld, 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]

Proc. SPIE (1)

R. Zhou, G. Popescu, L. L. Goddard, “22 nm node wafer inspection using diffraction phase microscopy and image post-processing,” Proc. SPIE 8681, 8610G (2013).

Other (6)

G. Popescu, Quantitative Phase Imaging of Cells and Tissues, McGraw-Hill biophotonics (McGraw-Hill, 2011).

J. W. Goodman, “Statistical properties of laser speckle patterns,” in Laser Speckle and Related Phenomena (Springer, 1975).

J. W. Goodman, Introduction to Fourier Optics (Roberts & Company, 2005).

B. E. A. Saleh and M. C. Teich, Fundamentals of Photonics (Wiley, 2013).

M. Born and E. Wolf, Principles of optics, 7th (expanded) ed. (Pergamon Press, 1999).

T. Nguyen, C. Edwards, L. Goddard, G. Popescu, “Quantitative phase imaging with partially coherent illumination,” (to be submitted).

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Figures (9)

Fig. 1
Fig. 1

wDPM imaging system. A diffraction grating, 4f lens system, and a spatial light modulator (SLM) are used to achieve interference. The SLM performs spatial filtering and one order can be gray-scaled in order to match intensities and optimize the fringe visibility. The interferogram captured by the CCD is a spatially modulated signal, which allows us to extract the phase information via a Hilbert transform and reconstruct the surface topography.

Fig. 2
Fig. 2

Spatial coherence of the wDPM imaging system. (a) Angular spectrum of the source showing the full-width at half-maximum (FWHM) approximation. (b) Horizontal slice taken through the origin in (a). The radius of the unscattered light circle is approximately k0NAcon. (c) Autocorrelation function computed from (a). (d) Horizontal slice taken through origin in (c). The spatial coherence radius is ρc = 4.0 μm.

Fig. 3
Fig. 3

DPM image formation. (a) Simulation of the ideal height map for a 3 μm diameter polystyrene microbead in immersion oil. (b) Simulated height from the cancellation field under non-ideal conditions. (c) Simulation of recovered height, which is the difference between (a) and (b). (d) Horizontal slice taken through origin showing (a-c). Note that cancellation field in (b) contains residues of the structure which results in the observed halo effect and a reduction in the measured height. (e-h) Corresponding simulations for a red blood cell in Coulter solution showing a reduction in the measured height as well as a halo and a negative dimple.

Fig. 4
Fig. 4

The effects of spatial filtering in DPM. (a) Log-log plot showing the investigated parameter space of SLM pinhole filter diameter (D) and condenser numerical aperture (NAcon). The solid line represents the matched filter condition. Labels b-k correspond to the operating point for subsequent subfigures. (b-k) 0th order reference amplitude images, recovered height images, and corresponding height cross-sections. The cross-section figures show the wDPM profile in red and the Alpha Step profile in blue. The spatial noise (σs) and exposure times (texp) are also listed for each subfigure. Both adequate spatial coherence and proper spatial filtering are required in order to properly reconstruct the height maps using wDPM. As both the condenser NA and the SLM pinhole diameter are reduced, aberrations such as halo and shade-off are reduced and the pillar heights converge to their proper value (h = 123 nm) as verified with the Alpha Step IQ Profilometer. † denotes a physical pinhole in the SLM plane, and ‡ denotes a physical pinhole with SLM attenuation to better match intensities. * indicates a gain setting of 2 on the Zeiss AxioCam MRm CCD.

Fig. 5
Fig. 5

Required spatial coherence for a given object size. Cross-sections were taken of square micropillars of different widths for various condenser numerical apertures using the optimum SLM pinhole filter size for each case. (a-d) 5, 10, 20, and 40 μm wide square pillars respectively. As the condenser NA is reduced and the SLM filter is optimized, the recovered structure becomes more quantitatively correct. Halo and shade-off disappear simultaneously as the pillar height converges to the proper value. Larger objects require more spatial coherence (smaller NAcon) to image properly. The 5, 10, and 20 μm wide pillars image properly for NAcon ≤ 0.014, 0.0072, and 0.0036, respectively. The 40 μm wide pillar will require an even smaller NAcon to image properly.

Fig. 6
Fig. 6

Halo reduction in 3 μm diameter polystyrene microbeads in immersion oil. wDPM height map of microbeads for (a) closed condenser (NAcon = 0.09), (b) a 1mm iris placed in the condenser (NAcon = 0.036), and (c) a 100 μm pinhole placed in the condenser (NAcon = 0.0036). (d) Overlay showing cross-sections of a diagonal slice taken through the center of both beads. Closing the condenser beyond the conventional limit of NAcon = 0.09 to NAcon = 0.036 allows the heights to converge to their proper values, while additional spatial coherence using NAcon = 0.0036 is needed to remove the halo. Residual ringing is due to the Gibbs’ phenomenon.

Fig. 7
Fig. 7

Halo reduction in red blood cells (RBCs). (a) wDPM height map of live RBCs in Coulter solution with a closed condenser (NAcon = 0.09). (b) Cropped image showing a single RBC from (a). (c) Horizontal slice of the RBC in (b) showing the halo and negative dimple. (d-f) Corresponding images for a 100 µm pinhole placed in the condenser (NAcon = 0.0036) show a reduction in the halo and the removal of the negative dimple. Note that a small halo remains, which is attributed to the Gibbs’ phenomenon.

Fig. 8
Fig. 8

DPM using an SCL with a 750nm shortpass filter. (a) Spectrum of the SCL source with power-equivalent bandwidth (PEB) approximation. The mean wavelength is 599.6 nm. (b) 0th order reference amplitude image is uniform. (c-f) Recovered height images and corresponding cross-sections for 5, 10, 20, and 40 μm wide square pillars, respectively. The cross-section figure shows wDPM profile in red and the Alpha Step profile in blue. † denotes a physical pinhole in the SLM plane.

Fig. 9
Fig. 9

Temporal coherence of the wDPM imaging system. (a) Spectrum of the HAL 100 halogen lamp showing the power-equivalent bandwidth (PEB) approximation. The center wavelength at a color temperature of 3200 K is 574 nm. This wavelength is used to convert the measured phase to height. (b) Temporal autocorrelation function and its envelope obtained via a Hilbert transform. The temporal coherence length obtained from the envelope is 2.1 μm.

Equations (3)

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| g ( x 1 , x 2 , y 1 , y 2 ) | = | 2 J 1 ( π ρ θ s / λ ) π ρ θ s / λ |
I ( r ) = | U 0 ( r , t ) + U 1 ( r , t ) | 2 T = I 0 ( r ) + I 1 ( r ) + 2 { U 0 * ( r , t ) U 1 ( r , t ) T }
ϕ ( r ) = arg [ T ( r ) ] arg [ ( Γ i l l u m * ( r ) Π ˜ s l m ( r ) ) T ( r ) ]

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