Abstract

We present Laplace field microscopy as a method for generating intrinsic contrast of transparent specimens. This technique uses a spatial light modulator to perform the Laplacian of the field in the Fourier plane of a microscope image. The resulting image incorporates phase information and thus renders high contrast images from phase objects. We demonstrate the potential of the method by imaging index-matched beads, unlabeled tissue slices, and dynamic live cells.

© 2011 Optical Society of America

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  1. M. Pluta, Advanced Light Microscopy (Polish Scientific Publishers, Warszawa, 1988).
  2. Nat. Cell Biol. 11, 1165 (2009).
    [PubMed]
  3. D. K. Hamilton and C. J. R. Sheppard, J. Microsc. 133, 27 (1984).
    [CrossRef]
  4. T. Wilson, Optik 80, 167 (1988).
  5. C. K. Hitzenberger and A. F. Fercher, Opt. Lett. 24, 622 (1999).
    [CrossRef]
  6. C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, Lasers Surg. Med. 32, 5(2003).
  7. M. Lew, X. Q. Cui, X. Heng, and C. H. Yang, Opt. Lett. 32, 2963 (2007).
    [CrossRef] [PubMed]
  8. C. H. Yang, A. Wax, I. Georgakoudi, E. B. Hanlon, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Lett. 25, 1526 (2000).
    [CrossRef]
  9. A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Appl. Opt. 44, 1188 (2005).
    [CrossRef] [PubMed]
  10. F. Zernike, Science 121, 345 (1955).
    [CrossRef] [PubMed]
  11. G. Nomarski, J. Phys. Radium 16, 9S (1955).
  12. Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, Opt. Express 19, 1016 (2011).
    [CrossRef] [PubMed]
  13. Z. Wang and G. Popescu, Appl. Phys. Lett. 96, 051117(2010).
    [CrossRef]
  14. G. Popescu, Quantitative Phase Imaging of Cells and Tissues (McGraw-Hill, New York, 2011).
  15. Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
    [CrossRef]
  16. Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
    [CrossRef] [PubMed]
  17. Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
    [CrossRef] [PubMed]
  18. R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
    [CrossRef] [PubMed]

2011

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, Opt. Express 19, 1016 (2011).
[CrossRef] [PubMed]

2010

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

Z. Wang and G. Popescu, Appl. Phys. Lett. 96, 051117(2010).
[CrossRef]

2009

Nat. Cell Biol. 11, 1165 (2009).
[PubMed]

2007

2005

2003

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, Lasers Surg. Med. 32, 5(2003).

2000

1999

1988

T. Wilson, Optik 80, 167 (1988).

1984

D. K. Hamilton and C. J. R. Sheppard, J. Microsc. 133, 27 (1984).
[CrossRef]

1955

F. Zernike, Science 121, 345 (1955).
[CrossRef] [PubMed]

G. Nomarski, J. Phys. Radium 16, 9S (1955).

Ahn, A.

Badizadegan, K.

Bashir, R.

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

Best, C. A.

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

Chan, V.

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

Cui, X. Q.

Dasari, R. R.

Diller, K. R.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, Lasers Surg. Med. 32, 5(2003).

Ding, H.

Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, Opt. Express 19, 1016 (2011).
[CrossRef] [PubMed]

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

Fang-Yen, C.

Feld, M. S.

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Appl. Opt. 44, 1188 (2005).
[CrossRef] [PubMed]

C. H. Yang, A. Wax, I. Georgakoudi, E. B. Hanlon, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Lett. 25, 1526 (2000).
[CrossRef]

Fercher, A. F.

Georgakoudi, I.

Gillette, M. U.

Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, Opt. Express 19, 1016 (2011).
[CrossRef] [PubMed]

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Hamilton, D. K.

D. K. Hamilton and C. J. R. Sheppard, J. Microsc. 133, 27 (1984).
[CrossRef]

Hanlon, E. B.

Heng, X.

Henle, M. L.

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

Hitzenberger, C. K.

Kuriabova, T.

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

Leigh, J.

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Levine, A. J.

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

Lew, M.

Millet, L.

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

Millet, L. J.

Milner, T. E.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, Lasers Surg. Med. 32, 5(2003).

Mir, M.

Nomarski, G.

G. Nomarski, J. Phys. Radium 16, 9S (1955).

Park, Y. K.

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

Pluta, M.

M. Pluta, Advanced Light Microscopy (Polish Scientific Publishers, Warszawa, 1988).

Popescu, G.

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, Opt. Express 19, 1016 (2011).
[CrossRef] [PubMed]

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Z. Wang and G. Popescu, Appl. Phys. Lett. 96, 051117(2010).
[CrossRef]

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

A. Ahn, C. H. Yang, A. Wax, G. Popescu, C. Fang-Yen, K. Badizadegan, R. R. Dasari, and M. S. Feld, Appl. Opt. 44, 1188 (2005).
[CrossRef] [PubMed]

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

Rogers, J. A.

Rylander, C.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, Lasers Surg. Med. 32, 5(2003).

Sheppard, C. J. R.

D. K. Hamilton and C. J. R. Sheppard, J. Microsc. 133, 27 (1984).
[CrossRef]

Sobh, N.

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Unarunotai, S.

Wang, R.

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Wang, Z.

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

Z. Wang, L. J. Millet, M. Mir, H. Ding, S. Unarunotai, J. A. Rogers, M. U. Gillette, and G. Popescu, Opt. Express 19, 1016 (2011).
[CrossRef] [PubMed]

Z. Wang and G. Popescu, Appl. Phys. Lett. 96, 051117(2010).
[CrossRef]

Wax, A.

Welch, A. J.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, Lasers Surg. Med. 32, 5(2003).

Wilson, T.

T. Wilson, Optik 80, 167 (1988).

Yang, C. H.

Zernike, F.

F. Zernike, Science 121, 345 (1955).
[CrossRef] [PubMed]

Appl. Opt.

Appl. Phys. Lett.

Z. Wang and G. Popescu, Appl. Phys. Lett. 96, 051117(2010).
[CrossRef]

J. Biomed. Opt.

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, J. Biomed. Opt. 16, 026019 (2011).
[CrossRef] [PubMed]

J. Microsc.

D. K. Hamilton and C. J. R. Sheppard, J. Microsc. 133, 27 (1984).
[CrossRef]

J. Phys. Condens. Matter

R. Wang, Z. Wang, J. Leigh, N. Sobh, L. Millet, M. U. Gillette, A. J. Levine, and G. Popescu, J. Phys. Condens. Matter 23, 374107 (2011).
[CrossRef] [PubMed]

J. Phys. Radium

G. Nomarski, J. Phys. Radium 16, 9S (1955).

Lasers Surg. Med.

C. Rylander, T. E. Milner, K. R. Diller, and A. J. Welch, Lasers Surg. Med. 32, 5(2003).

Nat. Cell Biol.

Nat. Cell Biol. 11, 1165 (2009).
[PubMed]

Opt. Express

Opt. Lett.

Optik

T. Wilson, Optik 80, 167 (1988).

Phys. Rev. E

Y. K. Park, C. A. Best, T. Kuriabova, M. L. Henle, M. S. Feld, A. J. Levine, and G. Popescu, Phys. Rev. E 83, 0519252011).
[CrossRef]

Proc. Nat. Acad. Sci.

Y. K. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, Proc. Nat. Acad. Sci. 107, 6731 (2010).
[CrossRef] [PubMed]

Science

F. Zernike, Science 121, 345 (1955).
[CrossRef] [PubMed]

Other

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

M. Pluta, Advanced Light Microscopy (Polish Scientific Publishers, Warszawa, 1988).

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Figures (4)

Fig. 1
Fig. 1

LFM setup built as a module added on to Olympus IX70 bright field microscope. L 1 and L 2 has focal length of 75 mm and 150 mm , respectively. Inset: parabola modulation profile on SLM.

Fig. 2
Fig. 2

3 μm polystyrene beads ( n = 1.59 ) immersed in oil ( n = 1.516 ) measured with bright field and LFM. (a) Bright field (BF) image of the bead. (b) LFM image of the bead. (c) Horizontal profile of each measurement (scatters) and simulated result using Eq. (4).

Fig. 3
Fig. 3

Bright field and LFM images of tissue samples. (a), (b) Images of gut section taken with BF and LFM. (c) Histogram of (a) and (b) (semilog plot). (d), (e) Images of kidney section taken with BF and LFM. (e) Histogram of (d) and (e) (semilog plot).

Fig. 4
Fig. 4

(a) Bright field image of a HeLa cell. (b) LFM image of the same cell as in (a), but a few minutes later. (c) Dynamic measurement of a HeLa cell using LFM.

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

I ( x , y ) = A | e i ϕ ( x , y ) + e i [ ϕ ( x + δ x , y ) + α ] | 2 = 2 A { 1 + cos [ δ ϕ x ( x , y ) + α ] } .
δ ϕ x ( x , y ) = ϕ ( x + δ x , y ) ϕ ( x , y ) ϕ ( x , y ) x .
U i ( x , y ) = a I [ ( k x 2 + k y 2 ) U ˜ ( k x , k y ) ] = a 2 U ( x , y ) .
I ( x , y ) [ 2 ϕ ( x , y ) ] 2 + [ ( ϕ ( x , y ) x ) 2 + ( ϕ ( x , y ) y ) 2 ] 2 .

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