Abstract

We demonstrate a common-path tomographic diffractive microscopy technique for three-dimensional (3D) refractive-index (RI) imaging of unstained living cells. A diffraction grating is utilized to generate a reference beam that traverses a blank region of the sample in a common-path off-axis interferometry setup. Single-shot phase images captured at multiple illumination angles are used for 3D RI reconstruction based on optical diffraction tomography. The common-path configuration shows lower temporal phase fluctuations and better RI resolution than a Mach–Zehnder configuration. 3D subcellular RI distributions of live HeLa cells are quantified.

© 2014 Optical Society of America

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  1. W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
    [CrossRef]
  2. N. Lue, W. Choi, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 16, 16240 (2008).
    [CrossRef]
  3. Y. Sung, W. Choi, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 17, 266 (2009).
    [CrossRef]
  4. C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
    [CrossRef]
  5. Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
    [CrossRef]
  6. J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
    [CrossRef]
  7. H. Iwai, C. Fang-Yen, G. Popescu, A. Wax, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Lett. 29, 2399 (2004).
    [CrossRef]
  8. M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
    [CrossRef]
  9. Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
    [CrossRef]
  10. G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, Opt. Lett. 31, 775 (2006).
    [CrossRef]
  11. Z. Wang, D. L. Marks, P. S. Carney, L. J. Millet, M. U. Gillette, A. Mihi, P. V. Braun, Z. Shen, S. G. Prasanth, and G. Popescu, Opt. Express 19, 19907 (2011).
    [CrossRef]
  12. T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, Opt. Lett. 30, 1165 (2005).
    [CrossRef]
  13. N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Phys. Chem. A 113, 13327 (2009).
    [CrossRef]
  14. B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
    [CrossRef]
  15. B. Bhaduri, H. Pham, M. Mir, and G. Popescu, Opt. Lett. 37, 1094 (2012).
    [CrossRef]
  16. W.-C. Hsu, J.-W. Su, C.-C. Chang, and K.-B. Sung, Proc. SPIE 8553, 85531O (2012).
    [CrossRef]

2013 (2)

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
[CrossRef]

2012 (3)

Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
[CrossRef]

B. Bhaduri, H. Pham, M. Mir, and G. Popescu, Opt. Lett. 37, 1094 (2012).
[CrossRef]

W.-C. Hsu, J.-W. Su, C.-C. Chang, and K.-B. Sung, Proc. SPIE 8553, 85531O (2012).
[CrossRef]

2011 (3)

B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
[CrossRef]

Z. Wang, D. L. Marks, P. S. Carney, L. J. Millet, M. U. Gillette, A. Mihi, P. V. Braun, Z. Shen, S. G. Prasanth, and G. Popescu, Opt. Express 19, 19907 (2011).
[CrossRef]

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
[CrossRef]

2009 (2)

Y. Sung, W. Choi, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 17, 266 (2009).
[CrossRef]

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Phys. Chem. A 113, 13327 (2009).
[CrossRef]

2008 (2)

M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
[CrossRef]

N. Lue, W. Choi, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 16, 16240 (2008).
[CrossRef]

2007 (1)

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
[CrossRef]

2006 (1)

2005 (1)

2004 (1)

Badizadegan, K.

Bhaduri, B.

Boss, D.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Braun, P. V.

Carney, P. S.

Chang, C.-C.

W.-C. Hsu, J.-W. Su, C.-C. Chang, and K.-B. Sung, Proc. SPIE 8553, 85531O (2012).
[CrossRef]

Chang, C.-H.

J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
[CrossRef]

Choi, W.

Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
[CrossRef]

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
[CrossRef]

Y. Sung, W. Choi, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 17, 266 (2009).
[CrossRef]

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Phys. Chem. A 113, 13327 (2009).
[CrossRef]

N. Lue, W. Choi, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 16, 16240 (2008).
[CrossRef]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
[CrossRef]

Chou, C.-Y.

J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
[CrossRef]

Cotte, Y.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Dasari, R. R.

Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
[CrossRef]

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
[CrossRef]

Y. Sung, W. Choi, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 17, 266 (2009).
[CrossRef]

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Phys. Chem. A 113, 13327 (2009).
[CrossRef]

N. Lue, W. Choi, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 16, 16240 (2008).
[CrossRef]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
[CrossRef]

G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, Opt. Lett. 31, 775 (2006).
[CrossRef]

T. Ikeda, G. Popescu, R. R. Dasari, and M. S. Feld, Opt. Lett. 30, 1165 (2005).
[CrossRef]

H. Iwai, C. Fang-Yen, G. Popescu, A. Wax, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Lett. 29, 2399 (2004).
[CrossRef]

Debailleul, M.

M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
[CrossRef]

Depeursinge, C.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Fang-Yen, C.

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
[CrossRef]

Y. Sung, W. Choi, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 17, 266 (2009).
[CrossRef]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
[CrossRef]

H. Iwai, C. Fang-Yen, G. Popescu, A. Wax, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Lett. 29, 2399 (2004).
[CrossRef]

Feld, M. S.

Georges, V.

M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
[CrossRef]

Gillette, M. U.

Haeberlé, O.

M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
[CrossRef]

Holbrow, C. J.

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
[CrossRef]

Hsu, W.-C.

J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
[CrossRef]

W.-C. Hsu, J.-W. Su, C.-C. Chang, and K.-B. Sung, Proc. SPIE 8553, 85531O (2012).
[CrossRef]

Ikeda, T.

Iwai, H.

Jourdain, P.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Kemper, B.

B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
[CrossRef]

Lauer, V.

M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
[CrossRef]

Lue, N.

Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
[CrossRef]

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Phys. Chem. A 113, 13327 (2009).
[CrossRef]

N. Lue, W. Choi, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 16, 16240 (2008).
[CrossRef]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
[CrossRef]

Magistretti, P.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Marks, D. L.

Marquet, P.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Mihi, A.

Millet, L. J.

Mir, M.

Oh, S.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
[CrossRef]

Pavillon, N.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Pham, H.

Popescu, G.

Prasanth, S. G.

Rommel, C. E.

B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
[CrossRef]

Schnekenburger, J.

B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
[CrossRef]

Shen, Z.

Simon, B.

M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
[CrossRef]

Su, J.-W.

J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
[CrossRef]

W.-C. Hsu, J.-W. Su, C.-C. Chang, and K.-B. Sung, Proc. SPIE 8553, 85531O (2012).
[CrossRef]

Sung, K.-B.

J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
[CrossRef]

W.-C. Hsu, J.-W. Su, C.-C. Chang, and K.-B. Sung, Proc. SPIE 8553, 85531O (2012).
[CrossRef]

Sung, Y.

Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
[CrossRef]

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
[CrossRef]

Y. Sung, W. Choi, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 17, 266 (2009).
[CrossRef]

Toy, F.

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Vollmer, A.

B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
[CrossRef]

von Bally, G.

B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
[CrossRef]

Wang, Z.

Wax, A.

Yaqoob, Z.

Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
[CrossRef]

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Phys. Chem. A 113, 13327 (2009).
[CrossRef]

J. Biomed. Opt. (2)

C. Fang-Yen, W. Choi, Y. Sung, C. J. Holbrow, R. R. Dasari, and M. S. Feld, J. Biomed. Opt. 16, 011005 (2011).
[CrossRef]

B. Kemper, A. Vollmer, C. E. Rommel, J. Schnekenburger, and G. von Bally, J. Biomed. Opt. 16, 026014 (2011).
[CrossRef]

J. Biophotonics (1)

J.-W. Su, W.-C. Hsu, C.-Y. Chou, C.-H. Chang, and K.-B. Sung, J. Biophotonics 6, 416 (2013).
[CrossRef]

J. Phys. Chem. A (1)

N. Lue, W. Choi, G. Popescu, Z. Yaqoob, K. Badizadegan, R. R. Dasari, and M. S. Feld, J. Phys. Chem. A 113, 13327 (2009).
[CrossRef]

Meas. Sci. Technol. (1)

M. Debailleul, B. Simon, V. Georges, O. Haeberlé, and V. Lauer, Meas. Sci. Technol. 19, 074009 (2008).
[CrossRef]

Nat. Methods (1)

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, Nat. Methods 4, 717 (2007).
[CrossRef]

Nat. Photonics (1)

Y. Cotte, F. Toy, P. Jourdain, N. Pavillon, D. Boss, P. Magistretti, P. Marquet, and C. Depeursinge, Nat. Photonics 7, 113 (2013).
[CrossRef]

Opt. Express (3)

Opt. Lett. (4)

PLoS One (1)

Y. Sung, W. Choi, N. Lue, R. R. Dasari, and Z. Yaqoob, PLoS One 7, e49502 (2012).
[CrossRef]

Proc. SPIE (1)

W.-C. Hsu, J.-W. Su, C.-C. Chang, and K.-B. Sung, Proc. SPIE 8553, 85531O (2012).
[CrossRef]

Supplementary Material (2)

» Media 1: AVI (480 KB)     
» Media 2: AVI (480 KB)     

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Figures (4)

Fig. 1.
Fig. 1.

Schematic diagram of the cTDM setup. BS, beam splitter; GM, galvanometer mirror; L1, L2, L3, and L4, lenses; OL, objective lens; G, grating; IP1 and IP2, image planes; FP1 and FP2, Fourier planes.

Fig. 2.
Fig. 2.

Single-shot phase images of a 10 μm polystyrene bead obtained with the (a) common-path and (b) Mach–Zehnder configuration. The color bar represents phase in radians (rad). (c) Histograms of pixel-wise phase fluctuations over 5.7 s for pixels in the empty regions in (a) and (b).

Fig. 3.
Fig. 3.

XY slices of reconstructed RI tomograms of a 10 μm polystyrene bead near the focal plane obtained by the (a) cTDM and (b) Mach–Zehnder configuration. The color bars represent RI values.

Fig. 4.
Fig. 4.

(a) RI tomogram (Media 1) of a living HeLa cell with a grid size of 8 μm. The color bar represents RI values. (b)–(g) Selected XY slices of the RI tomogram in (a). (h) Segmentation of three cellular components in (d). The nucleoli, nucleus excluding the nucleoli, and cytoplasm are marked as 1, 2, and 3, respectively.

Equations (1)

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I(x)=IS(x)+IB(x)+2[IS(x)IB(x)]1/2cos[kx+ϕ(x)],

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