Abstract

We have developed a Linnik-type interference microscope provided with a low-coherent light source to obtain topographic images of an intact cellular membrane on a nanometer scale. Our technique is based on measurement of the interference between light reflected from the cell surface and a reference beam. The results show full field surface topography of cultured cells and reveal an intrinsic membrane motion of tens of nanometers.

©2008 Optical Society of America

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  1. P. C. Zhang, A. M. Keleshian, and F. Sachs, “Voltage-induced membrane movement,” Nature 413, 428–432 (2001).
    [Crossref] [PubMed]
  2. C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, “Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer,” Opt. Lett. 29, 2028–2030 (2004).
    [Crossref] [PubMed]
  3. G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
    [Crossref] [PubMed]
  4. S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3, 413–438 (2007).
    [Crossref] [PubMed]
  5. L. Weiss, “Biomechanical interactions of cancer cells with the microvasculature during hematogenous metastasis,” Cancer Metastasis Rev. 11, 227–235 (1992).
    [Crossref] [PubMed]
  6. J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
    [Crossref] [PubMed]
  7. M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
    [Crossref] [PubMed]
  8. J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
    [Crossref] [PubMed]
  9. B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
    [Crossref] [PubMed]
  10. H. Iwai, C. Fang-Yen, G. Popescu, A. Wax, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Quantitative phase imaging using actively stabilized phase-shifting low-coherence interferometry,” Opt. Lett. 29, 2399–2401 (2004).
    [Crossref] [PubMed]
  11. T. Yamauchi, H Iwai, M. Miwa, and Y. Yamashita, “Measurement of topographic phase image of living cells by white-light phase-shifting microscope with active stabilization of optical path difference,” Proc.SPIE 6429,  61 (2007).
    [Crossref]
  12. C. Fang-Yen, M. C. Chu, S. Oh, H. S. Seung, R. R. Dasari, and M. S. Feld, “Probe-based and bifocal approaches for phase-referenced low coherence interferometry,” in OSA Optics and Photonics Topical Meetings/Biomedical Optics, Technical Digest (CD) (Optical Society of America, 2006), paper TuH5.
  13. K. Hibino, B. F. Oreb, D. I. Farrant, and K. G. Larkin, “Phase shifting for nonsinusoidal waveforms with phase-shift errors,” J. Opt. Soc. Am. A 12, 761–768 (1995).
    [Crossref]
  14. D. C. Ghiglia and M. D. Pritt, Two-Dimensional phase unwrapping: theory, algorithm, and software (John Wiley & Sons, Inc., Hoboken, NJ, 1998). Chap. 4.
  15. C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
    [PubMed]
  16. B. Rappaz, P. Marquet, E Cuche, Y. Emery, C. Depeursinge, and P. J. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express 13, 9361–9373 (2005).
    [Crossref] [PubMed]
  17. N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett. 31, 2759–2761 (2006).
    [Crossref] [PubMed]
  18. R. Barer, “Refractometry and interferometry of living cells”, J. Opt. Soc. Am. 47, 545–556 (1957).
    [Crossref] [PubMed]

2007 (2)

S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3, 413–438 (2007).
[Crossref] [PubMed]

T. Yamauchi, H Iwai, M. Miwa, and Y. Yamashita, “Measurement of topographic phase image of living cells by white-light phase-shifting microscope with active stabilization of optical path difference,” Proc.SPIE 6429,  61 (2007).
[Crossref]

2006 (2)

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett. 31, 2759–2761 (2006).
[Crossref] [PubMed]

2005 (4)

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

B. Rappaz, P. Marquet, E Cuche, Y. Emery, C. Depeursinge, and P. J. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express 13, 9361–9373 (2005).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

2004 (2)

2002 (1)

B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
[Crossref] [PubMed]

2001 (1)

P. C. Zhang, A. M. Keleshian, and F. Sachs, “Voltage-induced membrane movement,” Nature 413, 428–432 (2001).
[Crossref] [PubMed]

1999 (1)

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

1995 (1)

1992 (1)

L. Weiss, “Biomechanical interactions of cancer cells with the microvasculature during hematogenous metastasis,” Cancer Metastasis Rev. 11, 227–235 (1992).
[Crossref] [PubMed]

1957 (1)

Allman, B. E.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Ananthakrishnan, R.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Badizadegan, K.

Baker, J. Jr.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Barer, R.

Beals, J.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Bellair, C. J.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Best-Popescu, C. A.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

Bielinska, A.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Bilby, C.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Budor, A.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Chu, M. C.

C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, “Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer,” Opt. Lett. 29, 2028–2030 (2004).
[Crossref] [PubMed]

C. Fang-Yen, M. C. Chu, S. Oh, H. S. Seung, R. R. Dasari, and M. S. Feld, “Probe-based and bifocal approaches for phase-referenced low coherence interferometry,” in OSA Optics and Photonics Topical Meetings/Biomedical Optics, Technical Digest (CD) (Optical Society of America, 2006), paper TuH5.

Cuche, E

Curl, C. L.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Dasari, R. R.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett. 31, 2759–2761 (2006).
[Crossref] [PubMed]

H. Iwai, C. Fang-Yen, G. Popescu, A. Wax, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Quantitative phase imaging using actively stabilized phase-shifting low-coherence interferometry,” Opt. Lett. 29, 2399–2401 (2004).
[Crossref] [PubMed]

C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, “Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer,” Opt. Lett. 29, 2028–2030 (2004).
[Crossref] [PubMed]

C. Fang-Yen, M. C. Chu, S. Oh, H. S. Seung, R. R. Dasari, and M. S. Feld, “Probe-based and bifocal approaches for phase-referenced low coherence interferometry,” in OSA Optics and Photonics Topical Meetings/Biomedical Optics, Technical Digest (CD) (Optical Society of America, 2006), paper TuH5.

Delbridge, L. M.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Depeursinge, C.

Ebert, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Emery, Y.

Erickson, H. M.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Fang-Yen, C.

Farrant, D. I.

Feld, M. S.

N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett. 31, 2759–2761 (2006).
[Crossref] [PubMed]

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, “Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer,” Opt. Lett. 29, 2028–2030 (2004).
[Crossref] [PubMed]

H. Iwai, C. Fang-Yen, G. Popescu, A. Wax, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Quantitative phase imaging using actively stabilized phase-shifting low-coherence interferometry,” Opt. Lett. 29, 2399–2401 (2004).
[Crossref] [PubMed]

C. Fang-Yen, M. C. Chu, S. Oh, H. S. Seung, R. R. Dasari, and M. S. Feld, “Probe-based and bifocal approaches for phase-referenced low coherence interferometry,” in OSA Optics and Photonics Topical Meetings/Biomedical Optics, Technical Digest (CD) (Optical Society of America, 2006), paper TuH5.

Ghiglia, D. C.

D. C. Ghiglia and M. D. Pritt, Two-Dimensional phase unwrapping: theory, algorithm, and software (John Wiley & Sons, Inc., Hoboken, NJ, 1998). Chap. 4.

Gil, D.

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

Goda, K.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

Guck, J.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Harris, P. J.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Harris, T.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Hessler, J. A.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Hibino, K.

Holl, M. M. B.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Hrynkiewicz, A. Z.

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

Ikeda, T.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett. 31, 2759–2761 (2006).
[Crossref] [PubMed]

Iwai, H

T. Yamauchi, H Iwai, M. Miwa, and Y. Yamashita, “Measurement of topographic phase image of living cells by white-light phase-shifting microscope with active stabilization of optical path difference,” Proc.SPIE 6429,  61 (2007).
[Crossref]

Iwai, H.

Kas, J.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Keleshian, A. M.

P. C. Zhang, A. M. Keleshian, and F. Sachs, “Voltage-induced membrane movement,” Nature 413, 428–432 (2001).
[Crossref] [PubMed]

Környei, Z.

B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
[Crossref] [PubMed]

Laidler, P.

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

Laposata, M.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

Larkin, K. G.

Lekka, M.

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

Lekki, J.

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

Lenz, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Lincoln, B.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Lue, N.

Madarász, E.

B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
[Crossref] [PubMed]

Magistretti, P. J.

Manley, S.

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

Marquet, P.

Mecke, A.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Mitchell, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Miwa, M.

T. Yamauchi, H Iwai, M. Miwa, and Y. Yamashita, “Measurement of topographic phase image of living cells by white-light phase-shifting microscope with active stabilization of optical path difference,” Proc.SPIE 6429,  61 (2007).
[Crossref]

Nugent, K. A.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Oh, S.

C. Fang-Yen, M. C. Chu, S. Oh, H. S. Seung, R. R. Dasari, and M. S. Feld, “Probe-based and bifocal approaches for phase-referenced low coherence interferometry,” in OSA Optics and Photonics Topical Meetings/Biomedical Optics, Technical Digest (CD) (Optical Society of America, 2006), paper TuH5.

Oreb, B. F.

Orr, B. G.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Popescu, G.

Pritt, M. D.

D. C. Ghiglia and M. D. Pritt, Two-Dimensional phase unwrapping: theory, algorithm, and software (John Wiley & Sons, Inc., Hoboken, NJ, 1998). Chap. 4.

Putchakayala, K.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Rappaz, B.

Rieger, D.

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Roberts, A.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Romeyke, M.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Rozlosnik, N.

B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
[Crossref] [PubMed]

Sachs, F.

P. C. Zhang, A. M. Keleshian, and F. Sachs, “Voltage-induced membrane movement,” Nature 413, 428–432 (2001).
[Crossref] [PubMed]

Schinkinger, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Selmeczi, D.

B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
[Crossref] [PubMed]

Seung, H. S.

C. Fang-Yen, M. C. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, “Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer,” Opt. Lett. 29, 2028–2030 (2004).
[Crossref] [PubMed]

C. Fang-Yen, M. C. Chu, S. Oh, H. S. Seung, R. R. Dasari, and M. S. Feld, “Probe-based and bifocal approaches for phase-referenced low coherence interferometry,” in OSA Optics and Photonics Topical Meetings/Biomedical Optics, Technical Digest (CD) (Optical Society of America, 2006), paper TuH5.

Stachura, Z.

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

Stewart, A. G.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Suresh, S.

S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3, 413–438 (2007).
[Crossref] [PubMed]

Szabó, B.

B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
[Crossref] [PubMed]

Ulvick, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Wax, A.

Weiss, L.

L. Weiss, “Biomechanical interactions of cancer cells with the microvasculature during hematogenous metastasis,” Cancer Metastasis Rev. 11, 227–235 (1992).
[Crossref] [PubMed]

Wottawah, F.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Yamashita, Y.

T. Yamauchi, H Iwai, M. Miwa, and Y. Yamashita, “Measurement of topographic phase image of living cells by white-light phase-shifting microscope with active stabilization of optical path difference,” Proc.SPIE 6429,  61 (2007).
[Crossref]

Yamauchi, T.

T. Yamauchi, H Iwai, M. Miwa, and Y. Yamashita, “Measurement of topographic phase image of living cells by white-light phase-shifting microscope with active stabilization of optical path difference,” Proc.SPIE 6429,  61 (2007).
[Crossref]

Zhang, P. C.

P. C. Zhang, A. M. Keleshian, and F. Sachs, “Voltage-induced membrane movement,” Nature 413, 428–432 (2001).
[Crossref] [PubMed]

Acta Biomater. (1)

S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3, 413–438 (2007).
[Crossref] [PubMed]

Biophys. J. (1)

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophys. J. 88, 3689–3698 (2005).
[Crossref] [PubMed]

Cancer Metastasis Rev. (1)

L. Weiss, “Biomechanical interactions of cancer cells with the microvasculature during hematogenous metastasis,” Cancer Metastasis Rev. 11, 227–235 (1992).
[Crossref] [PubMed]

Cytometry A (1)

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65, 88–92 (2005).
[PubMed]

Eur. Biophys. J. (1)

M. Lekka, P. Laidler, D. Gil, J. Lekki, Z. Stachura, and A. Z. Hrynkiewicz, ”Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy,” Eur. Biophys. J. 28, 312–316 (1999).
[Crossref] [PubMed]

J. Opt. Soc. Am. (1)

J. Opt. Soc. Am. A (1)

Langmuir. (1)

J. A. Hessler, A. Budor, K. Putchakayala, A. Mecke, D. Rieger, M. M. B. Holl, B. G. Orr, A. Bielinska, J. Beals, and J. Jr. Baker, “Atomic force microscopy study of early morphological changes during apoptosis,” Langmuir. 21, 9280–9286 (2005).
[Crossref] [PubMed]

Nature (1)

P. C. Zhang, A. M. Keleshian, and F. Sachs, “Voltage-induced membrane movement,” Nature 413, 428–432 (2001).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (3)

Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. (1)

B. Szabó, D. Selmeczi, Z. Környei, E. Madarász, and N. Rozlosnik, “Atomic force microscopy of height fluctuations of fibroblast cells,” Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 65, 041910 (2002).
[Crossref] [PubMed]

Phys. Rev. Lett. (1)

G. Popescu, T. Ikeda, K. Goda, C. A. Best-Popescu, M. Laposata, S. Manley, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Optical measurement of cell membrane tension,” Phys. Rev. Lett. 97, 218101 (2006).
[Crossref] [PubMed]

Proc.SPIE 6429 (1)

T. Yamauchi, H Iwai, M. Miwa, and Y. Yamashita, “Measurement of topographic phase image of living cells by white-light phase-shifting microscope with active stabilization of optical path difference,” Proc.SPIE 6429,  61 (2007).
[Crossref]

Other (2)

C. Fang-Yen, M. C. Chu, S. Oh, H. S. Seung, R. R. Dasari, and M. S. Feld, “Probe-based and bifocal approaches for phase-referenced low coherence interferometry,” in OSA Optics and Photonics Topical Meetings/Biomedical Optics, Technical Digest (CD) (Optical Society of America, 2006), paper TuH5.

D. C. Ghiglia and M. D. Pritt, Two-Dimensional phase unwrapping: theory, algorithm, and software (John Wiley & Sons, Inc., Hoboken, NJ, 1998). Chap. 4.

Supplementary Material (1)

» Media 1: MOV (1804 KB)     

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Figures (15)

Fig. 1.
Fig. 1.

Experimental setup—BS1, BS2, BS3: non-polarizing beam splitters. L1, L2: identical achromatic lenses. O1, O2: identical objective lenses (Nikon, CFI FLUOR 60XW, NA = 1.0). ND: gelatin neutral density filter. RG695: long-pass filter with a cut-off wavelength of 695 nm. PZT1: high-speed, small-stroke piezoelectric transducer (NEC TOKIN, AE0505D08F). PZT2: large-stroke piezoelectric transducer (Physik Instrumente, P-611.ZS)

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Fig. 2.
Fig. 2.

One-point interferogram of the filtered halogen light seen by a single pixel of the CCD camera.

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Fig. 3.
Fig. 3.

(a). Focal condition for measuring the transmission mode phase image. (b) Focal condition for measuring the reflection mode phase image.

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Fig. 4.
Fig. 4.

Z-estimation error as a function of z-offset.

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Fig. 5.
Fig. 5.

Four consecutive interference images obtained in TM at an OPD interval of λc/4.

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Fig. 6.
Fig. 6.

Wrapped phase image derived from Figs. 5 (a)–5(d).

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Fig. 7.
Fig. 7.

Distribution of optical thickness.

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Fig. 8.
Fig. 8.

Schematic diagram of image processing

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Fig. 9.
Fig. 9.

Examples of four consecutive interference images obtained in RM.

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Fig. 10.
Fig. 10.

(a). Wrapped phase image derived from Figs. 9(a)–9(d). (b) Merged phase image built from ten sectional phase images obtained with an OPD interval of λc.

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Fig. 11.
Fig. 11.

Quantitative topography of a cell surface.

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Fig. 12.
Fig. 12.

Distribution of the mean refractive index.

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Fig. 13.
Fig. 13.

(1.81MB) Movie showing the surface fluctuation of a cell. The pseudo-color of each pixel represents the z-axial displacement corresponding to the scale (nanometer) on the color bar. [Media 1]

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Fig. 14.
Fig. 14.

Histogram of the peak-to-peak amplitude of the cellular surface fluctuation in the 5.1 × 7.0 μm area shown in Fig. 13.

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Fig. 15.
Fig. 15.

Surface fluctuation of a living cell (solid blue) and a 10-μm bead (solid black).

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Equations (8)

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

φ = tan ⁡ − 1 ( I − 3 π 2 − 3 I − π 2 + 3 I π 2 − I 3 π 2 2 ( − I − π + 2 I 0 − I π ) ) ,
OT = ∫ Δ n ( z ) dz = λ c 2 π ∙ φ 2 ,
OT = Δ n ̅ ∙H = λ c 2 π ∙ φ 2 .
H = λ c 2 π ∙ − φ 2 ∙n medium .
φ absolute x y = φ measured x y + Δφ .
n cell ̅ = n medium + OT H ,
Δ n ̅ = n cell ̅ − n medium = OT H ,
Δ n ̅ error = ∣ OT H − ΔH 2 − OT H + ΔH 2 ∣ . ≈ Δ n ̅ ΔH H

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