Abstract

High-resolution fluorescence imaging is essential in nanoscience and biological sciences. Due to the diffraction limit, conventional imaging systems can only resolve structures larger than 200 nm. Here, we introduce a new fluorescence imaging method that enhances the resolution by using a high-index scattering medium as an imaging lens. Simultaneously, we achieve a wide field of view. We develop a new image reconstruction algorithm that converges even for complex object structures. We collect two-dimensional fluorescence images of a collection of 100 nm diameter dye-doped nanospheres, and demonstrate a deconvolved Abbe resolution of 116 nm with a field of view of 10μm×10μm. Our method is robust against optical aberrations and stage drifts, and therefore is well suited to image nanostructures with high resolution under ambient conditions.

© 2015 Optical Society of America

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2015 (1)

Y. Shechtman, Y. Eldar, O. Cohen, H. Chapman, J. Miao, M. Segev, “Phase retrieval with application to optical imaging: a contemporary overview,” IEEE Sig. Process. Mag. 32(3), 87–109 (2015).

2014 (4)

O. Katz, P. Heidmann, M. Fink, S. Gigan, “Non-invasive single-shot imaging through scattering layers and around corners via speckle correlations,” Nat. Photonics 8, 784–790 (2014).
[Crossref]

K. Wicker, R. Heintzmann, “Resolving a misconception about structured illumination,” Nat. Photonics 8, 342–344 (2014).
[Crossref]

X. Yang, Y. Pu, D. Psaltis, “Imaging blood cells through scattering biological tissue using speckle scanning microscopy,” Opt. Express 22, 3405–3413 (2014).
[Crossref]

S. Dong, P. Nanda, R. Shiradkar, K. Guo, G. Zheng, “High-resolution fluorescence imaging via pattern-illuminated Fourier ptychography,” Opt. Express 22, 20856–20870 (2014).
[Crossref]

2013 (3)

H. He, Y. Guan, J. Zhou, “Image restoration through thin turbid layers by correlation with a known object,” Opt. Express 21, 12539–12545 (2013).
[Crossref]

J.-H. Park, C. Park, H. S. Yu, J. Park, S. Han, J. Shin, S. H. Ko, K. T. Nam, Y.-H. Cho, Y. Park, “Subwavelength light focusing using random nanoparticles,” Nat. Photonics 7, 454–458 (2013).
[Crossref]

G. Zheng, R. Horstmeyer, C. Yang, “Wide-field, high-resolution Fourier ptychographic microscopy,” Nat. Photonics 7, 739–745 (2013).
[Crossref]

2012 (4)

A. Szameit, Y. Shechtman, E. Osherovich, E. Bullkitch, P. Sidorenko, H. Dana, S. Steiner, E. B. Kley, S. Gazit, T. Cohen-Hymas, S. Shoham, M. Zibulevsky, I. Yavneh, Y. C. Eldar, O. Cohen, M. Segev, “Sparsity-based single-shot sub-wavelength coherent diffractive imaging,” Nat. Mater. 11, 455–459 (2012).
[Crossref]

E. Mudry, K. Belkebir, J. Girard, J. Savatier, E. Le Moal, C. Nicoletti, M. Allain, A. Sentenac, “Structured illumination microscopy using unknown speckle patterns,” Nat. Photonics 6, 312–315 (2012).
[Crossref]

O. Katz, E. Small, Y. Silberberg, “Looking around corners and through thin turbid layers in real time with scattered incoherent light,” Nat. Photonics 6, 549–553 (2012).
[Crossref]

J. Bertolotti, E. G. van Putten, C. Blum, A. Lagendijk, W. L. Vos, A. P. Mosk, “Non-invasive imaging through opaque scattering layers,” Nature 491, 232–234 (2012).
[Crossref]

2011 (2)

E. G. van Putten, D. Akbulut, J. Bertolotti, W. L. Vos, A. Lagendijk, A. P. Mosk, “Scattering lens resolves sub-100  nm structures with visible light,” Phys. Rev. Lett. 106, 193905 (2011).
[Crossref]

Y. Choi, T. D. Yang, C. Fang-Yen, P. Kang, K. J. Lee, R. R. Dasari, M. S. Feld, W. Choi, “Overcoming the diffraction limit using multiple light scattering in a highly disordered medium,” Phys. Rev. Lett. 107, 023902 (2011).
[Crossref]

2010 (5)

2009 (1)

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, J. Enderlein, “Fast, background-free, 3D super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. U.S.A. 106, 22287–22292 (2009).

2007 (3)

S. W. Hell, “Far-field optical nanoscopy,” Science 316, 1153–1158 (2007).
[Crossref]

G. Lerosey, J. de Rosny, A. Tourin, M. Fink, “Focusing beyond the diffraction limit with far-field time reversal,” Science 315, 1120–1122 (2007).
[Crossref]

J. M. Rodenburg, A. C. Hurst, A. G. Cullis, B. R. Dobson, F. Pfeiffer, O. Bunk, C. David, K. Jefimovs, I. Johnson, “Hard-x-ray lensless imaging of extended objects,” Phys. Rev. Lett. 98, 034801 (2007).
[Crossref]

2006 (2)

M. J. Rust, M. Bates, X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3, 793–796 (2006).
[Crossref]

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

2005 (2)

M. G. L. Gustafsson, “Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution,” Proc. Natl. Acad. Sci. U.S.A. 102, 13081–13086 (2005).

J. García, Z. Zalevsky, D. Fixler, “Synthetic aperture superresolution by speckle pattern projection,” Opt. Express 13, 6073–6078 (2005).
[Crossref]

2004 (1)

H. M. L. Faulkner, J. M. Rodenburg, “Movable aperture lensless transmission microscopy: a novel phase retrieval algorithm,” Phys. Rev. Lett. 93, 023903 (2004).
[Crossref]

2003 (1)

A. Derode, A. Tourin, J. de Rosny, M. Tanter, S. Yon, M. Fink, “Taking advantage of multiple scattering to communicate with time-reversal antennas,” Phys. Rev. Lett. 90, 014301 (2003).
[Crossref]

2000 (1)

M. G. L. Gustafsson, “Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy,” J. Microsc. 198, 82–87 (2000).
[Crossref]

1999 (2)

R. Heintzmann, C. Cremer, “Lateral modulated excitation microscopy: improvement of resolution by using a diffraction grating,” Proc. SPIE 3568, 185–196 (1999).

F. J. P. Schuurmans, D. Vanmaekelbergh, J. van de Lagemaat, A. Lagendijk, “Strongly photonic macroporous gallium phosphide networks,” Science 284, 141–143 (1999).
[Crossref]

1994 (1)

1990 (2)

R. P. Millane, “Phase retrieval in crystallography and optics,” J. Opt. Soc. Am. A 7, 394–411 (1990).
[Crossref]

I. Freund, “Correlation imaging through multiply scattering media,” Phys. Lett. A 147, 502–506 (1990).
[Crossref]

1988 (2)

I. Freund, M. Rosenbluh, S. Feng, “Memory effects in propagation of optical waves through disordered media,” Phys. Rev. Lett. 61, 2328–2331 (1988).
[Crossref]

S. Feng, C. Kane, P. A. Lee, A. D. Stone, “Correlations and fluctuations of coherent wave transmission through disordered media,” Phys. Rev. Lett. 61, 834–837 (1988).
[Crossref]

1986 (2)

E. Betzig, A. Lewis, A. Harootunian, M. Isaacson, E. Kratschmer, “Near field scanning optical microscopy (NSOM): development and biophysical applications,” Biophys. J. 49, 269–279 (1986).
[Crossref]

J. R. Fienup, C. C. Wackerman, “Phase-retrieval stagnation problems and solutions,” J. Opt. Soc. Am. A 3, 1897–1907 (1986).
[Crossref]

1982 (1)

1978 (1)

1970 (1)

A. Labeyrie, “Attainment of diffraction limited resolution in large telescopes by Fourier analysing speckle patterns in star images,” Astron. Astrophys. 6, 85–87 (1970).

Aegerter, C.

Akbulut, D.

E. G. van Putten, D. Akbulut, J. Bertolotti, W. L. Vos, A. Lagendijk, A. P. Mosk, “Scattering lens resolves sub-100  nm structures with visible light,” Phys. Rev. Lett. 106, 193905 (2011).
[Crossref]

Allain, M.

E. Mudry, K. Belkebir, J. Girard, J. Savatier, E. Le Moal, C. Nicoletti, M. Allain, A. Sentenac, “Structured illumination microscopy using unknown speckle patterns,” Nat. Photonics 6, 312–315 (2012).
[Crossref]

Bates, M.

M. J. Rust, M. Bates, X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3, 793–796 (2006).
[Crossref]

Belkebir, K.

E. Mudry, K. Belkebir, J. Girard, J. Savatier, E. Le Moal, C. Nicoletti, M. Allain, A. Sentenac, “Structured illumination microscopy using unknown speckle patterns,” Nat. Photonics 6, 312–315 (2012).
[Crossref]

Bertolotti, J.

J. Bertolotti, E. G. van Putten, C. Blum, A. Lagendijk, W. L. Vos, A. P. Mosk, “Non-invasive imaging through opaque scattering layers,” Nature 491, 232–234 (2012).
[Crossref]

E. G. van Putten, D. Akbulut, J. Bertolotti, W. L. Vos, A. Lagendijk, A. P. Mosk, “Scattering lens resolves sub-100  nm structures with visible light,” Phys. Rev. Lett. 106, 193905 (2011).
[Crossref]

Betzig, E.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

E. Betzig, A. Lewis, A. Harootunian, M. Isaacson, E. Kratschmer, “Near field scanning optical microscopy (NSOM): development and biophysical applications,” Biophys. J. 49, 269–279 (1986).
[Crossref]

Blum, C.

J. Bertolotti, E. G. van Putten, C. Blum, A. Lagendijk, W. L. Vos, A. P. Mosk, “Non-invasive imaging through opaque scattering layers,” Nature 491, 232–234 (2012).
[Crossref]

Boccara, A. C.

S. Popoff, G. Lerosey, M. Fink, A. C. Boccara, S. Gigan, “Image transmission through an opaque material,” Nat. Commun. 1, 81 (2010).
[Crossref]

Bonifacino, J. S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

Bullkitch, E.

A. Szameit, Y. Shechtman, E. Osherovich, E. Bullkitch, P. Sidorenko, H. Dana, S. Steiner, E. B. Kley, S. Gazit, T. Cohen-Hymas, S. Shoham, M. Zibulevsky, I. Yavneh, Y. C. Eldar, O. Cohen, M. Segev, “Sparsity-based single-shot sub-wavelength coherent diffractive imaging,” Nat. Mater. 11, 455–459 (2012).
[Crossref]

Bunk, O.

J. M. Rodenburg, A. C. Hurst, A. G. Cullis, B. R. Dobson, F. Pfeiffer, O. Bunk, C. David, K. Jefimovs, I. Johnson, “Hard-x-ray lensless imaging of extended objects,” Phys. Rev. Lett. 98, 034801 (2007).
[Crossref]

Chapman, H.

Y. Shechtman, Y. Eldar, O. Cohen, H. Chapman, J. Miao, M. Segev, “Phase retrieval with application to optical imaging: a contemporary overview,” IEEE Sig. Process. Mag. 32(3), 87–109 (2015).

Cho, Y.-H.

J.-H. Park, C. Park, H. S. Yu, J. Park, S. Han, J. Shin, S. H. Ko, K. T. Nam, Y.-H. Cho, Y. Park, “Subwavelength light focusing using random nanoparticles,” Nat. Photonics 7, 454–458 (2013).
[Crossref]

Choi, W.

Y. Choi, T. D. Yang, C. Fang-Yen, P. Kang, K. J. Lee, R. R. Dasari, M. S. Feld, W. Choi, “Overcoming the diffraction limit using multiple light scattering in a highly disordered medium,” Phys. Rev. Lett. 107, 023902 (2011).
[Crossref]

Choi, Y.

Y. Choi, T. D. Yang, C. Fang-Yen, P. Kang, K. J. Lee, R. R. Dasari, M. S. Feld, W. Choi, “Overcoming the diffraction limit using multiple light scattering in a highly disordered medium,” Phys. Rev. Lett. 107, 023902 (2011).
[Crossref]

Cohen, O.

Y. Shechtman, Y. Eldar, O. Cohen, H. Chapman, J. Miao, M. Segev, “Phase retrieval with application to optical imaging: a contemporary overview,” IEEE Sig. Process. Mag. 32(3), 87–109 (2015).

A. Szameit, Y. Shechtman, E. Osherovich, E. Bullkitch, P. Sidorenko, H. Dana, S. Steiner, E. B. Kley, S. Gazit, T. Cohen-Hymas, S. Shoham, M. Zibulevsky, I. Yavneh, Y. C. Eldar, O. Cohen, M. Segev, “Sparsity-based single-shot sub-wavelength coherent diffractive imaging,” Nat. Mater. 11, 455–459 (2012).
[Crossref]

Cohen-Hymas, T.

A. Szameit, Y. Shechtman, E. Osherovich, E. Bullkitch, P. Sidorenko, H. Dana, S. Steiner, E. B. Kley, S. Gazit, T. Cohen-Hymas, S. Shoham, M. Zibulevsky, I. Yavneh, Y. C. Eldar, O. Cohen, M. Segev, “Sparsity-based single-shot sub-wavelength coherent diffractive imaging,” Nat. Mater. 11, 455–459 (2012).
[Crossref]

Colyer, R.

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, J. Enderlein, “Fast, background-free, 3D super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. U.S.A. 106, 22287–22292 (2009).

Cremer, C.

R. Heintzmann, C. Cremer, “Lateral modulated excitation microscopy: improvement of resolution by using a diffraction grating,” Proc. SPIE 3568, 185–196 (1999).

Cullis, A. G.

J. M. Rodenburg, A. C. Hurst, A. G. Cullis, B. R. Dobson, F. Pfeiffer, O. Bunk, C. David, K. Jefimovs, I. Johnson, “Hard-x-ray lensless imaging of extended objects,” Phys. Rev. Lett. 98, 034801 (2007).
[Crossref]

Dainty, J. C.

J. C. Dainty, Laser Speckle and Related Phenomena (Springer, 1984).

Dana, H.

A. Szameit, Y. Shechtman, E. Osherovich, E. Bullkitch, P. Sidorenko, H. Dana, S. Steiner, E. B. Kley, S. Gazit, T. Cohen-Hymas, S. Shoham, M. Zibulevsky, I. Yavneh, Y. C. Eldar, O. Cohen, M. Segev, “Sparsity-based single-shot sub-wavelength coherent diffractive imaging,” Nat. Mater. 11, 455–459 (2012).
[Crossref]

Dasari, R. R.

Y. Choi, T. D. Yang, C. Fang-Yen, P. Kang, K. J. Lee, R. R. Dasari, M. S. Feld, W. Choi, “Overcoming the diffraction limit using multiple light scattering in a highly disordered medium,” Phys. Rev. Lett. 107, 023902 (2011).
[Crossref]

David, C.

J. M. Rodenburg, A. C. Hurst, A. G. Cullis, B. R. Dobson, F. Pfeiffer, O. Bunk, C. David, K. Jefimovs, I. Johnson, “Hard-x-ray lensless imaging of extended objects,” Phys. Rev. Lett. 98, 034801 (2007).
[Crossref]

Davidson, M. W.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
[Crossref]

de Rosny, J.

G. Lerosey, J. de Rosny, A. Tourin, M. Fink, “Focusing beyond the diffraction limit with far-field time reversal,” Science 315, 1120–1122 (2007).
[Crossref]

A. Derode, A. Tourin, J. de Rosny, M. Tanter, S. Yon, M. Fink, “Taking advantage of multiple scattering to communicate with time-reversal antennas,” Phys. Rev. Lett. 90, 014301 (2003).
[Crossref]

Derode, A.

A. Derode, A. Tourin, J. de Rosny, M. Tanter, S. Yon, M. Fink, “Taking advantage of multiple scattering to communicate with time-reversal antennas,” Phys. Rev. Lett. 90, 014301 (2003).
[Crossref]

Dertinger, T.

T. Dertinger, R. Colyer, G. Iyer, S. Weiss, J. Enderlein, “Fast, background-free, 3D super-resolution optical fluctuation imaging (SOFI),” Proc. Natl. Acad. Sci. U.S.A. 106, 22287–22292 (2009).

Dobson, B. R.

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Supplementary Material (1)

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Figures (4)

Fig. 1.
Fig. 1.

Concept of wide-field, high-resolution speckle scanning microscopy. A beam of coherent light illuminates a scattering layer on a gallium phosphide (GaP) substrate. The scattered light generates a speckle pattern that enables high-resolution imaging on the object plane. The incident beam is tilted by angles θ x and θ y , and as a result the speckle pattern is scanned across the sample. Fluorescent nanospheres on the object plane are imaged on a CCD camera. With parallel speckle detection, the field of view is wider than the single speckle-scan range. d denotes the thickness of the scattering layer; L denotes the thickness of the substrate.

Fig. 2.
Fig. 2.

Data analysis procedure on a single sub-datacube. (a) Datacube I ( x , y , δ x , δ y ) . (b) Standard resolution subimage J m ( x , y ) obtained by summing the sub-datacube shown by the square non-grayed-out area over δ x and δ y . (c) Speckle-scan matrix K m ( δ x , δ y ) obtained by summing the sub-datacube shown by the square non-grayed-out area over x and y . (d) Magnitude of the Fourier components of J m ( x , y ) . (e) Phase of the Fourier components of J m ( x , y ) . (f) Magnitude of the Fourier components of K m ( δ x , δ y ) . (g) Phase of the Fourier components of K m ( δ x , δ y ) .

Fig. 3.
Fig. 3.

Phase retrieval in the Fourier domain. (a) Phase of the Fourier components of the object. (b) Magnitude of the Fourier components of the object. (c) Gerchberg–Saxton-type algorithm. (d) Retrieved phase of high-frequency Fourier components of the object. Phase data comes from Fig. 2(e) and the magnitude data comes from Fig. 2(f). Color bars are as in Fig. 2.

Fig. 4.
Fig. 4.

Wide-field images of fluorescent nanospheres with diameter of 100 nm. (a) Wide-field image by conventional microscopy. (b) Zoomed image of (a). (c) Cross-section of (b) represented by the white line. (d) Wide-field image by SCORE microscopy. (e) Zoomed image of (d). (f) Cross-section of (e) represented by the white line. In (c), a single nanosphere is apparent while in (f), two smaller nanospheres are apparent with a center-to-center distance of 146 nm.

Equations (2)

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K m ( δ x , δ y ) = x , y I ( x , y , δ x , δ y ) W m ( x , y ) = x , y O ( x , y ) S ( x δ x , y δ y ) W m ( x , y ) = [ ( O · W m ) * S ] ( δ x , δ y ) ,
| F { K m } | = | F { O · W m } | · | F { S } | = C | F { O · W m } | ,

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