Abstract

We report on a novel algorithm for high-resolution quantitative phase imaging in a new concept of lensless holographic microscope based on single-shot multi-wavelength illumination. This new microscope layout, reported by Noom et al. along the past year and named by us as MISHELF (initials incoming from Multi-Illumination Single-Holographic-Exposure Lensless Fresnel) microscopy, rises from the simultaneous illumination and recording of multiple diffraction patterns in the Fresnel domain. In combination with a novel and fast iterative phase retrieval algorithm, MISHELF microscopy is capable of high-resolution (micron range) phase-retrieved (twin image elimination) biological imaging of dynamic events. In this contribution, MISHELF microscopy is demonstrated through qualitative concept description, algorithm implementation, and experimental validation using both a synthetic object (resolution test target) and a biological sample (swine sperm sample) for the case of three (RGB) illumination wavelengths. The proposed method becomes in an alternative instrument improving the capabilities of existing lensless microscopes.

© 2015 Optical Society of America

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References

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2014 (4)

B. Perucho and V. Micó, “Wavefront holoscopy: application of digital in-line holography for the inspection of engraved marks in progressive addition lenses,” J. Biomed. Opt. 19(1), 016017 (2014).
[Crossref] [PubMed]

S. Witte, V. T. Tenner, D. W. E. Noom, and K. S. E. Eikema, “Lensless diffractive imaging with ultra broad-band table-top sources: from infrared to extreme-ultraviolet wavelengths,” Light Sci. Appl. 3(3), e163 (2014).
[Crossref]

D. W. E. Noom, K. S. E. Eikema, and S. Witte, “Lensless phase contrast microscopy based on multiwavelength Fresnel diffraction,” Opt. Lett. 39(2), 193–196 (2014).
[Crossref] [PubMed]

D. W. E. Noom, D. E. Boonzajer Flaes, E. Labordus, K. S. E. Eikema, and S. Witte, “High-speed multi-wavelength Fresnel diffraction imaging,” Opt. Express 22(25), 30504–30511 (2014).
[Crossref] [PubMed]

2013 (3)

2012 (6)

2011 (2)

J. P. Ryle, S. McDonnell, and J. T. Sheridan, “Lensless multispectral digital in-line holographic microscope,” J. Biomed. Opt. 16(12), 126004 (2011).
[Crossref] [PubMed]

M. Lee, O. Yaglidere, and A. Ozcan, “Field-portable reflection and transmission microscopy based on lensless holography,” Biomed. Opt. Express 2(9), 2721–2730 (2011).
[Crossref] [PubMed]

2010 (5)

2009 (1)

2008 (1)

2006 (1)

S. K. Jericho, J. Garcia-Sucerquia, W. Xu, M. H. Jericho, and H. J. Kreuzer, “Submersible digital in-line holographic microscope,” Rev. Sci. Instrum. 77(4), 043706 (2006).
[Crossref]

2005 (1)

2004 (2)

M. Beleggia, M. A. Schofield, V. V. Volkov, and Y. Zhu, “On the transport of intensity technique for phase retrieval,” Ultramicroscopy 102(1), 37–49 (2004).
[Crossref] [PubMed]

L. Repetto, E. Piano, and C. Pontiggia, “Lensless digital holographic microscope with light-emitting diode illumination,” Opt. Lett. 29(10), 1132–1134 (2004).
[Crossref] [PubMed]

2003 (1)

2001 (1)

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]

1998 (2)

T. Zhang and I. Yamaguchi, “Three-dimensional microscopy with phase-shifting digital holography,” Opt. Lett. 23(15), 1221–1223 (1998).
[Crossref] [PubMed]

D. Paganin and K. Nugent, “Noninterferometric phase imaging with partially coherent light,” Phys. Rev. Lett. 80(12), 2586–2589 (1998).
[Crossref]

1997 (1)

1984 (1)

N. Streibl, “Phase imaging by the transport equation of intensity,” Opt. Commun. 49(1), 6–10 (1984).
[Crossref]

1983 (1)

1952 (1)

G. L. Rogers, “Experiments in diffraction microscopy,” Proc. - R. Soc. Edinburgh, Sect. A: Math. 63, 193–221 (1952).

1948 (1)

D. Gabor, “A new microscopic principle,” Nature 161(4098), 777–778 (1948).
[Crossref] [PubMed]

Akbari, N.

Andrés, P.

Bao, P.

Barbastathis, G.

Beleggia, M.

M. Beleggia, M. A. Schofield, V. V. Volkov, and Y. Zhu, “On the transport of intensity technique for phase retrieval,” Ultramicroscopy 102(1), 37–49 (2004).
[Crossref] [PubMed]

Bishara, W.

Boonzajer Flaes, D. E.

Calabuig, A.

Camacho, L.

Coskun, A. F.

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

Eikema, K. S. E.

Feizi, A.

Fienup, J. R.

Frentz, Z.

Z. Frentz, S. Kuehn, D. Hekstra, and S. Leibler, “Microbial population dynamics by digital in-line holographic microscopy,” Rev. Sci. Instrum. 81(8), 084301 (2010).
[Crossref] [PubMed]

Gabor, D.

D. Gabor, “A new microscopic principle,” Nature 161(4098), 777–778 (1948).
[Crossref] [PubMed]

García, J.

Garcia-Sucerquia, J.

Göröcs, Z.

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

Greenbaum, A.

Guizar-Sicairos, M.

Hekstra, D.

Z. Frentz, S. Kuehn, D. Hekstra, and S. Leibler, “Microbial population dynamics by digital in-line holographic microscopy,” Rev. Sci. Instrum. 81(8), 084301 (2010).
[Crossref] [PubMed]

Isikman, S. O.

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

Javidi, B.

Jericho, M. H.

S. K. Jericho, J. Garcia-Sucerquia, W. Xu, M. H. Jericho, and H. J. Kreuzer, “Submersible digital in-line holographic microscope,” Rev. Sci. Instrum. 77(4), 043706 (2006).
[Crossref]

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]

Jericho, S. K.

S. K. Jericho, J. Garcia-Sucerquia, W. Xu, M. H. Jericho, and H. J. Kreuzer, “Submersible digital in-line holographic microscope,” Rev. Sci. Instrum. 77(4), 043706 (2006).
[Crossref]

Kou, S. S.

Kreuzer, H. J.

S. K. Jericho, J. Garcia-Sucerquia, W. Xu, M. H. Jericho, and H. J. Kreuzer, “Submersible digital in-line holographic microscope,” Rev. Sci. Instrum. 77(4), 043706 (2006).
[Crossref]

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]

Kuehn, S.

Z. Frentz, S. Kuehn, D. Hekstra, and S. Leibler, “Microbial population dynamics by digital in-line holographic microscopy,” Rev. Sci. Instrum. 81(8), 084301 (2010).
[Crossref] [PubMed]

Labordus, E.

Lancis, J.

Lee, M.

Leibler, S.

Z. Frentz, S. Kuehn, D. Hekstra, and S. Leibler, “Microbial population dynamics by digital in-line holographic microscopy,” Rev. Sci. Instrum. 81(8), 084301 (2010).
[Crossref] [PubMed]

Luo, W.

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

McDonnell, S.

J. P. Ryle, S. McDonnell, and J. T. Sheridan, “Lensless multispectral digital in-line holographic microscope,” J. Biomed. Opt. 16(12), 126004 (2011).
[Crossref] [PubMed]

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]

Mendoza-Yero, O.

Micó, V.

Mudanyali, O.

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

Noom, D. W. E.

Nugent, K.

D. Paganin and K. Nugent, “Noninterferometric phase imaging with partially coherent light,” Phys. Rev. Lett. 80(12), 2586–2589 (1998).
[Crossref]

Osten, W.

Ozcan, A.

Paganin, D.

D. Paganin and K. Nugent, “Noninterferometric phase imaging with partially coherent light,” Phys. Rev. Lett. 80(12), 2586–2589 (1998).
[Crossref]

Pedrini, G.

Perucho, B.

B. Perucho and V. Micó, “Wavefront holoscopy: application of digital in-line holography for the inspection of engraved marks in progressive addition lenses,” J. Biomed. Opt. 19(1), 016017 (2014).
[Crossref] [PubMed]

Piano, E.

Pontiggia, C.

Repetto, L.

Rogers, G. L.

G. L. Rogers, “Experiments in diffraction microscopy,” Proc. - R. Soc. Edinburgh, Sect. A: Math. 63, 193–221 (1952).

Ryle, J. P.

J. P. Ryle, S. McDonnell, and J. T. Sheridan, “Lensless multispectral digital in-line holographic microscope,” J. Biomed. Opt. 16(12), 126004 (2011).
[Crossref] [PubMed]

Schofield, M. A.

M. Beleggia, M. A. Schofield, V. V. Volkov, and Y. Zhu, “On the transport of intensity technique for phase retrieval,” Ultramicroscopy 102(1), 37–49 (2004).
[Crossref] [PubMed]

Sheppard, C. J. R.

Sheridan, J. T.

J. P. Ryle, S. McDonnell, and J. T. Sheridan, “Lensless multispectral digital in-line holographic microscope,” J. Biomed. Opt. 16(12), 126004 (2011).
[Crossref] [PubMed]

Situ, G.

Streibl, N.

N. Streibl, “Phase imaging by the transport equation of intensity,” Opt. Commun. 49(1), 6–10 (1984).
[Crossref]

Su, T.-W.

T.-W. Su, L. Xue, and A. Ozcan, “High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories,” Proc. Natl. Acad. Sci. U.S.A. 109(40), 16018–16022 (2012).
[Crossref] [PubMed]

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

Tajahuerce, E.

Teague, M. R.

Tenner, V. T.

S. Witte, V. T. Tenner, D. W. E. Noom, and K. S. E. Eikema, “Lensless diffractive imaging with ultra broad-band table-top sources: from infrared to extreme-ultraviolet wavelengths,” Light Sci. Appl. 3(3), e163 (2014).
[Crossref]

Tiziani, H.

Volkov, V. V.

M. Beleggia, M. A. Schofield, V. V. Volkov, and Y. Zhu, “On the transport of intensity technique for phase retrieval,” Ultramicroscopy 102(1), 37–49 (2004).
[Crossref] [PubMed]

Waller, L.

Witte, S.

Xu, W.

S. K. Jericho, J. Garcia-Sucerquia, W. Xu, M. H. Jericho, and H. J. Kreuzer, “Submersible digital in-line holographic microscope,” Rev. Sci. Instrum. 77(4), 043706 (2006).
[Crossref]

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]

Xue, L.

T.-W. Su, L. Xue, and A. Ozcan, “High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories,” Proc. Natl. Acad. Sci. U.S.A. 109(40), 16018–16022 (2012).
[Crossref] [PubMed]

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

Yaglidere, O.

Yamaguchi, I.

Zalevsky, Z.

Zhang, F.

Zhang, T.

Zhang, Y.

Zhu, H.

Zhu, Y.

M. Beleggia, M. A. Schofield, V. V. Volkov, and Y. Zhu, “On the transport of intensity technique for phase retrieval,” Ultramicroscopy 102(1), 37–49 (2004).
[Crossref] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (1)

J. Biomed. Opt. (2)

B. Perucho and V. Micó, “Wavefront holoscopy: application of digital in-line holography for the inspection of engraved marks in progressive addition lenses,” J. Biomed. Opt. 19(1), 016017 (2014).
[Crossref] [PubMed]

J. P. Ryle, S. McDonnell, and J. T. Sheridan, “Lensless multispectral digital in-line holographic microscope,” J. Biomed. Opt. 16(12), 126004 (2011).
[Crossref] [PubMed]

J. Opt. Soc. Am. (1)

J. Opt. Soc. Am. A (1)

Light Sci. Appl. (1)

S. Witte, V. T. Tenner, D. W. E. Noom, and K. S. E. Eikema, “Lensless diffractive imaging with ultra broad-band table-top sources: from infrared to extreme-ultraviolet wavelengths,” Light Sci. Appl. 3(3), e163 (2014).
[Crossref]

Nat. Methods (1)

A. Greenbaum, W. Luo, T.-W. Su, Z. Göröcs, L. Xue, S. O. Isikman, A. F. Coskun, O. Mudanyali, and A. Ozcan, “Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy,” Nat. Methods 9(9), 889–895 (2012).
[Crossref] [PubMed]

Nature (1)

D. Gabor, “A new microscopic principle,” Nature 161(4098), 777–778 (1948).
[Crossref] [PubMed]

Opt. Commun. (1)

N. Streibl, “Phase imaging by the transport equation of intensity,” Opt. Commun. 49(1), 6–10 (1984).
[Crossref]

Opt. Express (7)

Opt. Lett. (11)

J. Garcia-Sucerquia, “Color lensless digital holographic microscopy with micrometer resolution,” Opt. Lett. 37(10), 1724–1726 (2012).
[Crossref] [PubMed]

V. Micó and J. García, “Common-path phase-shifting lensless holographic microscopy,” Opt. Lett. 35(23), 3919–3921 (2010).
[Crossref] [PubMed]

O. Mendoza-Yero, E. Tajahuerce, J. Lancis, and J. Garcia-Sucerquia, “Diffractive digital lensless holographic microscopy with fine spectral tuning,” Opt. Lett. 38(12), 2107–2109 (2013).
[Crossref] [PubMed]

O. Mendoza-Yero, A. Calabuig, E. Tajahuerce, J. Lancis, P. Andrés, and J. Garcia-Sucerquia, “Femtosecond digital lensless holographic microscopy to image biological samples,” Opt. Lett. 38(17), 3205–3207 (2013).
[Crossref] [PubMed]

D. W. E. Noom, K. S. E. Eikema, and S. Witte, “Lensless phase contrast microscopy based on multiwavelength Fresnel diffraction,” Opt. Lett. 39(2), 193–196 (2014).
[Crossref] [PubMed]

L. Repetto, E. Piano, and C. Pontiggia, “Lensless digital holographic microscope with light-emitting diode illumination,” Opt. Lett. 29(10), 1132–1134 (2004).
[Crossref] [PubMed]

G. Pedrini, W. Osten, and Y. Zhang, “Wave-front reconstruction from a sequence of interferograms recorded at different planes,” Opt. Lett. 30(8), 833–835 (2005).
[Crossref] [PubMed]

P. Bao, F. Zhang, G. Pedrini, and W. Osten, “Phase retrieval using multiple illumination wavelengths,” Opt. Lett. 33(4), 309–311 (2008).
[Crossref] [PubMed]

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Supplementary Material (2)

NameDescription
» Visualization 1: MOV (5217 KB)      Twin image removal validation: B channel image (see Visualization 1) at the plane where twin image is located
» Visualization 2: MOV (3934 KB)      Twin image removal validation: final image provided by MISHELF microscopy (see Visualization 2) at the plane where twin image is located

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Figures (10)

Fig. 1
Fig. 1

Experimental setup: (a) scheme and (b) picture from the lab.

Fig. 2
Fig. 2

Flow diagram of the MISHELF algorithm. After RGB illumination of the sample, the process starts with the recording at the CCD plane of a single RGB hologram (dashed red line frame). Then, arrows guide the way of reading (clockwise direction) until the Nth final iteration where the sample’s complex information is retrieved (solid red line frame). The variables I, A, U, O in the chart are (x, y)-spatially dependent.

Fig. 3
Fig. 3

Schematic chart of the proposed digital stage processing in MISHELF microscopy for the USAF test target. The included images are represented by their intensity in order to allow direct comparison among them.

Fig. 4
Fig. 4

Intensity image comparison for the USAF test target in the low NA setup: (a) conventional single-wavelength (blue channel) LHM, (b) same than in (a) after image equalization stage, (c) image retrieved after the first object spectrum synthesis, and (d) the final image after 2 iterations of the phase retrieval algorithm. Images in (e) to (h) are the central magnified areas of (a) to (d), respectively. Scale bar in the lower-right corner of (d) is 50 μm in length.

Fig. 5
Fig. 5

Intensity and phase image comparison for the USAF test target in the low NA setup with full frame recording area: (a) and (b) are the intensity and phase images using conventional single-wavelength (blue channel) LHM, respectively, and (c) and (d) are the intensity and phase images retrieved after 2 iterations of the phase retrieval algorithm, respectively. Images in (e) to (h) are the central magnified areas of (a) to (d), respectively.

Fig. 6
Fig. 6

Twin image removal validation: (a) B channel image (see Visualization 1) and (b) final image provided by MISHELF microscopy (see Visualization 2) at the plane where twin image is located.

Fig. 7
Fig. 7

Intensity biosample results: (a)-(b) are the holograms and (c)-(d) includes the final intensity images of the framed areas (solid white line squares) included in (a)-(b), respectively, for the proposed MISHELF microscope and the conventional single-wavelength (B channel) LHM case. Scale bars in the images are 100 μm in length.

Fig. 8
Fig. 8

Phase visualizations of the biosample: (a)-(d) and (e)-(h) are positive and negative phase contrast images, respectively obtained from MISHELF microscopy [(a) and (e)], B-LHM [(b) and (f)], G-LHM [(c) and (g)] and R-LHM [(d) and (h)]. Images in (i) and (j) represent a 3D view of the phase unwrapped distributions incoming from the MISHELF microscope and for the conventional B-LHM, respectively, where gray scale bars represents optical phase in radians. Scale bars in (a)-(d) images are 100 μm in length.

Fig. 9
Fig. 9

Phase visualizations of the biosample: (a) and (b) represent a 3D plot of the phase unwrapped distributions incoming from the MISHELF microscope and for the conventional B-LHM, respectively. Gray scale bars represent optical phase in radians. The dotted black line rectangles are used to compare STD values of the background.

Fig. 10
Fig. 10

Digital post-processing biosamples images from the MISHELF recovered complex amplitude distribution: (a) darkfield image, (b) and (c) DIC images in the horizontal and vertical directions, respectively, and (d) spiral phase contrast image.

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