Abstract

Recently, we have proposed a method to image fluorescent structures behind turbid layers at diffraction limited resolution using wave-front shaping and the memory effect. However, this was limited to a raster scanning of the wave-front shaped focus to a two dimensional plane. In applications, it can however be of great importance to be able to scan a three dimensional volume. Here we show that this can be implemented in the same setup. This is achieved by the addition of a parabolic phase shift to the shaped wave-front. Via the memory effect, this phase shift leads to a shift of the interference based focus in the z-direction, thus opening the possibility of three dimensional imaging using scattered light fluorescence microscopy. Here, we show an example of such a three dimensional image of fluorescent nano-beads taken behind a turbid layer more than 10 mean free paths thick. Finally, we discuss the differences of the scanning in the z-direction with that in the x–y plane and the corresponding possibilities and limitations of the technique.

© 2012 OSA

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References

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2012 (1)

2011 (3)

2010 (8)

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

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

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4, 320–322 (2010).
[CrossRef]

I. M. Vellekoop and C. M. Aegerter, “Scattered light fluorescence microscopy: imaging through turbid media,” Opt. Lett. 35, 1245–1247 (2010).
[CrossRef] [PubMed]

C. L. Hsieh, Y. Pu, R. Grange, G. Laporte, and D. Psaltis, “Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle,” Opt. Express 18, 20723–20731 (2010).
[CrossRef] [PubMed]

M. Cui, E. J. McDowell, and C. Yang, “An in vivo study of turbidity suppression by optical phase conjugation (TSOPC) on rabbit ear,” Opt. Express 18, 25–30 (2010).
[CrossRef] [PubMed]

M. Cui and C. Yang, “Implementation of a digital optical phase conjugation system and its application to study the robustness of turbidity suppression by phase conjugation,” Opt. Express 18, 3444–3455 (2010).
[CrossRef] [PubMed]

I. M. Vellekoop and C. M. Aegerter, “Focusing light through living tissue,” Proc. SPIE 7554, 755430 (2010).
[CrossRef]

2008 (4)

C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45–47 (2008).
[CrossRef]

Z. Yaqoob, D. Psaltis, M. S. Feld, and C. Yang, “Optical phase conjugation for turbidity suppression in biological samples,” Nat. Photonics 2, 110–115 (2008).
[CrossRef] [PubMed]

I. M. Vellekoop and A. P. Mosk, “Universal optimal transmission of light through disordered materials,” Phys. Rev. Lett. 101, 120601 (2008).
[CrossRef] [PubMed]

I. M. Vellekoop, E. G. van Putten, A. Lagendijk, and A. P. Mosk, “Demixing light paths inside disordered metamaterials,” Opt. Express 16, 67–80 (2008).
[CrossRef] [PubMed]

2007 (3)

M. Wolf, M. Ferrari, and V. Quaresima, “Progress of near-infrared spectroscopy and topography for brain and muscle clinical applications,” J. Biomed. Opt. 12, 062104 (2007).
[CrossRef]

I. M. Vellekoop and A. P. Mosk, “Focusing coherent light through opaque strongly scattering media,” Opt. Lett. 32, 2309–2311 (2007).
[CrossRef] [PubMed]

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

2005 (1)

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2, 932–940 (2005).
[CrossRef] [PubMed]

1997 (1)

M. Fink, “Time reversed acoustics,” Phys. Today 50, 34–40 (1997).
[CrossRef]

1996 (1)

J. L. Thomas, F. Wu, and M. Fink, “Time reversal focusing applied to lithotripsy,” Ultras. Imag. 18, 106–121 (1996).
[CrossRef]

1988 (2)

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

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

1982 (1)

Aegerter, C. M.

Akbulut, D.

Boccara, A.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

Boccara, A. C.

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

Caravaca-Aguirre, A. M.

Carminati, R.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

Conkey, D. B.

Cui, M.

de Rosny, J.

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

Denk, W.

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2, 932–940 (2005).
[CrossRef] [PubMed]

Feld, M. S.

Z. Yaqoob, D. Psaltis, M. S. Feld, and C. Yang, “Optical phase conjugation for turbidity suppression in biological samples,” Nat. Photonics 2, 110–115 (2008).
[CrossRef] [PubMed]

Feng, S.

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

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

Ferrari, M.

M. Wolf, M. Ferrari, and V. Quaresima, “Progress of near-infrared spectroscopy and topography for brain and muscle clinical applications,” J. Biomed. Opt. 12, 062104 (2007).
[CrossRef]

Fink, M.

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

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

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

M. Fink, “Time reversed acoustics,” Phys. Today 50, 34–40 (1997).
[CrossRef]

J. L. Thomas, F. Wu, and M. Fink, “Time reversal focusing applied to lithotripsy,” Ultras. Imag. 18, 106–121 (1996).
[CrossRef]

Freund, I.

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

Fried, D. L.

Gigan, S.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

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

Grange, R.

Helmchen, F.

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2, 932–940 (2005).
[CrossRef] [PubMed]

Hsieh, C. L.

Huisman, T. J.

Kane, C.

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

Lagendijk, A.

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4, 320–322 (2010).
[CrossRef]

I. M. Vellekoop, E. G. van Putten, A. Lagendijk, and A. P. Mosk, “Demixing light paths inside disordered metamaterials,” Opt. Express 16, 67–80 (2008).
[CrossRef] [PubMed]

Laporte, G.

Lee, P. A.

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

Leonhardt, U.

Y. G. Ma, S. Sahebdivan, C. K. Ong, T. Tyc, and U. Leonhardt, “Evidence for subwavelength imaging with positive refraction,” New J. Phys. 13, 033016 (2011).
[CrossRef]

Lerosey, G.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

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

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

Ma, Y. G.

Y. G. Ma, S. Sahebdivan, C. K. Ong, T. Tyc, and U. Leonhardt, “Evidence for subwavelength imaging with positive refraction,” New J. Phys. 13, 033016 (2011).
[CrossRef]

McDowell, E. J.

Mosk, A. P.

Ntziachristos, V.

C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45–47 (2008).
[CrossRef]

Ong, C. K.

Y. G. Ma, S. Sahebdivan, C. K. Ong, T. Tyc, and U. Leonhardt, “Evidence for subwavelength imaging with positive refraction,” New J. Phys. 13, 033016 (2011).
[CrossRef]

Perrimon, N.

C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45–47 (2008).
[CrossRef]

Piestun, R.

Pitsouli, C.

C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45–47 (2008).
[CrossRef]

Popoff, S. M.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

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

Psaltis, D.

Pu, Y.

Quaresima, V.

M. Wolf, M. Ferrari, and V. Quaresima, “Progress of near-infrared spectroscopy and topography for brain and muscle clinical applications,” J. Biomed. Opt. 12, 062104 (2007).
[CrossRef]

Razansky, D.

C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45–47 (2008).
[CrossRef]

Rosenbluh, M.

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

Sahebdivan, S.

Y. G. Ma, S. Sahebdivan, C. K. Ong, T. Tyc, and U. Leonhardt, “Evidence for subwavelength imaging with positive refraction,” New J. Phys. 13, 033016 (2011).
[CrossRef]

Stone, A. D.

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

Thomas, J. L.

J. L. Thomas, F. Wu, and M. Fink, “Time reversal focusing applied to lithotripsy,” Ultras. Imag. 18, 106–121 (1996).
[CrossRef]

Tourin, A.

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

Tyc, T.

Y. G. Ma, S. Sahebdivan, C. K. Ong, T. Tyc, and U. Leonhardt, “Evidence for subwavelength imaging with positive refraction,” New J. Phys. 13, 033016 (2011).
[CrossRef]

van Putten, E. G.

Vellekoop, I. M.

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4, 320–322 (2010).
[CrossRef]

I. M. Vellekoop and C. M. Aegerter, “Scattered light fluorescence microscopy: imaging through turbid media,” Opt. Lett. 35, 1245–1247 (2010).
[CrossRef] [PubMed]

I. M. Vellekoop and C. M. Aegerter, “Focusing light through living tissue,” Proc. SPIE 7554, 755430 (2010).
[CrossRef]

I. M. Vellekoop and A. P. Mosk, “Universal optimal transmission of light through disordered materials,” Phys. Rev. Lett. 101, 120601 (2008).
[CrossRef] [PubMed]

I. M. Vellekoop, E. G. van Putten, A. Lagendijk, and A. P. Mosk, “Demixing light paths inside disordered metamaterials,” Opt. Express 16, 67–80 (2008).
[CrossRef] [PubMed]

I. M. Vellekoop and A. P. Mosk, “Focusing coherent light through opaque strongly scattering media,” Opt. Lett. 32, 2309–2311 (2007).
[CrossRef] [PubMed]

Vinegoni, C.

C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45–47 (2008).
[CrossRef]

Vos, W. L.

Wolf, M.

M. Wolf, M. Ferrari, and V. Quaresima, “Progress of near-infrared spectroscopy and topography for brain and muscle clinical applications,” J. Biomed. Opt. 12, 062104 (2007).
[CrossRef]

Wu, F.

J. L. Thomas, F. Wu, and M. Fink, “Time reversal focusing applied to lithotripsy,” Ultras. Imag. 18, 106–121 (1996).
[CrossRef]

Yang, C.

Yaqoob, Z.

Z. Yaqoob, D. Psaltis, M. S. Feld, and C. Yang, “Optical phase conjugation for turbidity suppression in biological samples,” Nat. Photonics 2, 110–115 (2008).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

M. Wolf, M. Ferrari, and V. Quaresima, “Progress of near-infrared spectroscopy and topography for brain and muscle clinical applications,” J. Biomed. Opt. 12, 062104 (2007).
[CrossRef]

J. Opt. Soc. Am. (1)

Nat. Commun. (1)

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

Nat. Methods (2)

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2, 932–940 (2005).
[CrossRef] [PubMed]

C. Vinegoni, C. Pitsouli, D. Razansky, N. Perrimon, and V. Ntziachristos, “In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography,” Nat. Methods 5, 45–47 (2008).
[CrossRef]

Nat. Photonics (2)

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4, 320–322 (2010).
[CrossRef]

Z. Yaqoob, D. Psaltis, M. S. Feld, and C. Yang, “Optical phase conjugation for turbidity suppression in biological samples,” Nat. Photonics 2, 110–115 (2008).
[CrossRef] [PubMed]

New J. Phys. (1)

Y. G. Ma, S. Sahebdivan, C. K. Ong, T. Tyc, and U. Leonhardt, “Evidence for subwavelength imaging with positive refraction,” New J. Phys. 13, 033016 (2011).
[CrossRef]

Opt. Express (7)

Opt. Lett. (2)

Phys. Rev. Lett. (4)

I. M. Vellekoop and A. P. Mosk, “Universal optimal transmission of light through disordered materials,” Phys. Rev. Lett. 101, 120601 (2008).
[CrossRef] [PubMed]

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

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

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. Boccara, and S. Gigan, “Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media,” Phys. Rev. Lett. 104, 100601 (2010).
[CrossRef] [PubMed]

Phys. Today (1)

M. Fink, “Time reversed acoustics,” Phys. Today 50, 34–40 (1997).
[CrossRef]

Proc. SPIE (1)

I. M. Vellekoop and C. M. Aegerter, “Focusing light through living tissue,” Proc. SPIE 7554, 755430 (2010).
[CrossRef]

Science (1)

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

Ultras. Imag. (1)

J. L. Thomas, F. Wu, and M. Fink, “Time reversal focusing applied to lithotripsy,” Ultras. Imag. 18, 106–121 (1996).
[CrossRef]

Other (2)

J. B. Pawley ed., Handbook of Biological Confocal Microscopy, 3rd ed. (Springer, Berlin2006).
[CrossRef]

A. Diaspro, ed., Confocal and Two-Photon Microscopy: Foundations, Applications and Advances (Wiley-Liss, New York, 2002).

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Figures (5)

Fig. 1
Fig. 1

Schematic setup of the experiment. The illuminating laser is expanded and reflected from the SLM shown in the figure. The SLM is imaged onto the surface of the turbid layer. In between, the light passes a scanning mirror, which adds a linear phase shift onto the light, which is used for scanning the focus in the xy plane. The sample consists of a turbid layer of ZnO pigment 15 μm thick on a glass cover slide of a thickness of 1 mm. On the other side of the glass slide, fluorescent latex beads of a diameter of 450 nm are placed. This mimics the situation in a natural sample, where a turbid shell hides a structure of interest, which has been labelled fluorescently (see inset). The fluorescent light is captured by a photomultiplier (PM) behind a fluorescent filter.

Fig. 2
Fig. 2

Geometry of scanning in the different directions. The change in angle is limited by the memory effect. a) shows the situation for two-dimensional scanning in the xy plane. The change in angle here is given by Δθ = Δr/a. In the z-direction in contrast, the change in angle is given by Δθ = rΔz/a2.

Fig. 3
Fig. 3

(a)–(i) The fluorescence signal of a 450 nm diameter fluorescent bead hidden behind a turbid layer. The images show the scattered light fluorescence image of the same bead and on the same intensity scale, while the position of the focal plane differs for the images. In (a), the position is at −7 μm behind the bead and consecutively moves forward in steps of 2μm, until it lies 7 μm in front of the bead position in image (i). The center of the bead, which would therefore lie between image (d) and its neighbor has been added as well in part (e). Thus, the difference in z position between parts (d) and (e) as well as (e) and (f) corresponds to only 1 micron. The scan range in this case is a window in the xy plane of 12×12 μm2. The three dimensional structure of the bead can be clearly seen.

Fig. 4
Fig. 4

The point spread function of the scattered light fluorescence microscope in the z-direction. The figure shows the intensity at the position of a fluorescent bead as a function of scanning depth. In contrast to Fig. 3, we show the full scanning range with a step size in the z-direction of 1 μm, giving a better measure of the depth resolution. This shows that the resolution in the z-direction is about 3 μm half width at half maximum, which is somewhat worse than in the xy plane thus showing that the interference focus is asymmetric. The red line shows a Gaussian fit with a standard deviation of 2.6(1) μm.

Fig. 5
Fig. 5

(a)–(c) The fluorescence signal of two 450 nm diameter fluorescent beads hidden behind a turbid layer. The two beads are 55 μm apart in the z-direction and are at positions (−2,−1) and (2,−2) respectively in the (x,y) plane. The images show the scattered light fluorescence image on the same intensity scale, at three different depth. In (a), the position is at the first bead, whereas at (b) the position is 30 μm towards the second particle. Figure (c) finally is at a z position of 55 μm corresponding to the position of the second particle. The scan range in this case is a window in the xy plane of 12×12 μm2. As discussed in the text, the z scan-range is 60 μm explaining the deteriorating quality of the image of the second particle. However, the three dimensional structure of the beads’ positioning can be clearly seen.

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