Abstract

We describe a new scanning microscopy technique, phase-dispersion microscopy (PDM). The technique is based on measuring the phase difference between the fundamental and the second-harmonic light in a novel interferometer. PDM is highly sensitive to subtle refractive-index differences that are due to dispersion (differential optical path sensitivity, 5 nm). We apply PDM to measure minute amounts of DNA in solution and to study biological tissue sections. We demonstrate that PDM performs better than conventional phase-contrast microscopy in imaging dispersive and weakly scattering samples.

© 2000 Optical Society of America

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2000

1999

1998

A. Wax and J. E. Thomas, J. Opt. Soc. Am. A 15, 1896 (1998).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

1994

H. Matsumoto, Rev. Sci. Instrum. 65, 2894 (1994).
[CrossRef]

H. Matsumoto and L. Zeng, Opt. Commun. 104, 241 (1994).
[CrossRef]

An, K.

Backman, V.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Bevilacqua, F.

Carlson, A. B.

A. B. Carlson, Communication Systems, 3rd ed. (McGraw-Hill, New York, 1986).

Chen, Z.

Crawford, J. M.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Cuche, E.

Dasari, R. R.

de Boer, J. F.

Despeursinge, C.

Drexler, W.

Feld, M. S.

C. Yang, K. An, L. T. Perelman, R. R. Dasari, and M. S. Feld, J. Opt. Soc. Am. A 16, 866 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

C. Yang, A. Wax, and M. S. Feld are preparing a manuscript to be called “Measurement of anomalous phase velocity of ballistic light in a random medium using a novel interferometer.”

Fercher, A. F.

Fornaro, G.

Franceschetti, G.

Fujimoto, J. G.

Hamamo, T.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Hitzenberger, C. K.

Ippen, E. P.

Itzkan, I.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Kartner, F. X.

Lanari, R.

Lee, S. L.

K. M. Yung, S. L. Lee, and J. M. Schmitt, J. Biomed. Opt. 4, 125 (1999).
[CrossRef] [PubMed]

Li, X. D.

Lima, C.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Manohanan, R.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Matsumoto, H.

H. Matsumoto, Rev. Sci. Instrum. 65, 2894 (1994).
[CrossRef]

H. Matsumoto and L. Zeng, Opt. Commun. 104, 241 (1994).
[CrossRef]

Morgner, U.

Nelson, J. S.

Nusrat, A.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Perelman, L. T.

C. Yang, K. An, L. T. Perelman, R. R. Dasari, and M. S. Feld, J. Opt. Soc. Am. A 16, 866 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Pitris, C.

Ross, K. F. A.

K. F. A. Ross, Phase Contrast and Interference Microscopy for Cell Biologists (St. Martin’s, New York, 1967).

Sansosti, E.

Saxer, C.

Schmitt, J. M.

K. M. Yung, S. L. Lee, and J. M. Schmitt, J. Biomed. Opt. 4, 125 (1999).
[CrossRef] [PubMed]

Seiler, M.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Shields, S.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Thomas, J. E.

Van Dam, J.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Wallace, M.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Wax, A.

A. Wax and J. E. Thomas, J. Opt. Soc. Am. A 15, 1896 (1998).
[CrossRef]

C. Yang, A. Wax, and M. S. Feld are preparing a manuscript to be called “Measurement of anomalous phase velocity of ballistic light in a random medium using a novel interferometer.”

Xiang, S.

Yang, C.

C. Yang, K. An, L. T. Perelman, R. R. Dasari, and M. S. Feld, J. Opt. Soc. Am. A 16, 866 (1999).
[CrossRef]

C. Yang, A. Wax, and M. S. Feld are preparing a manuscript to be called “Measurement of anomalous phase velocity of ballistic light in a random medium using a novel interferometer.”

Yung, K. M.

K. M. Yung, S. L. Lee, and J. M. Schmitt, J. Biomed. Opt. 4, 125 (1999).
[CrossRef] [PubMed]

Zeng, L.

H. Matsumoto and L. Zeng, Opt. Commun. 104, 241 (1994).
[CrossRef]

Zhao, Y.

Zonios, G.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

J. Biomed. Opt.

K. M. Yung, S. L. Lee, and J. M. Schmitt, J. Biomed. Opt. 4, 125 (1999).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A

Opt. Commun.

H. Matsumoto and L. Zeng, Opt. Commun. 104, 241 (1994).
[CrossRef]

Opt. Lett.

Phys. Rev. Lett.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manohanan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamamo, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Rev. Sci. Instrum.

H. Matsumoto, Rev. Sci. Instrum. 65, 2894 (1994).
[CrossRef]

Other

K. F. A. Ross, Phase Contrast and Interference Microscopy for Cell Biologists (St. Martin’s, New York, 1967).

C. Yang, A. Wax, and M. S. Feld are preparing a manuscript to be called “Measurement of anomalous phase velocity of ballistic light in a random medium using a novel interferometer.”

A. B. Carlson, Communication Systems, 3rd ed. (McGraw-Hill, New York, 1986).

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Figures (3)

Fig. 1
Fig. 1

Experimental setup: M1, M2, mirrors (M1 is the moving reference mirror); BS, beam splitter; O1–O4, microscope objectives; D1, D2, photodetectors; DM, 400–800-nm dichroic mirror; ADC, analog–digital converter.

Fig. 2
Fig. 2

Comparison of images from (top) PCM and (bottom) PDM of a drop of water and a drop of 1.0% DNA solution sandwiched between two coverslips. We measure the refractive-index dispersion Δn400 nm-Δn800 nm of the DNA solution to be 1.3±0.2×10-4.

Fig. 3
Fig. 3

Images of a white matter–gray matter interface in a 16µm-thick brain sample. A, PCM image; B, PDM image; C, an adjacent frozen section stained with hemotoxylin and eosin.

Equations (2)

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ΔOLk2,k1=Ψ2-2Ψ1/k2.
Δn400 nm-Δn800 nm=ΔOLk2,k1/L,

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