Abstract

A novel, noninvasive measurement technique for quantitative cellular analysis is presented that utilizes the forces generated by an optical beam to evaluate the physical properties of live cells in suspension. In this analysis, a focused, near-infrared laser line with a high cross-sectional intensity gradient is rapidly scanned across a field of cells, and the interaction of those cells with the beam is monitored. The response of each cell to the laser depends on its size, structure, morphology, composition, and surface membrane properties; therefore, with this technique, cell populations of different type, treatment, or biological state can be compared. To demonstrate the utility of this cell analysis platform, we evaluated the early stages of apoptosis induced in the U937 cancer cell line by the drug camptothecin and compared the results with established reference assays. Measurements on our platform show detection of cellular changes earlier than either of the fluorescence-based Annexin V or caspase assays. Because no labeling or additional cell processing is required and because accurate assays can be performed with a small number of cells, this measurement technique may find suitable applications in cell research, medical diagnostics, and drug discovery.

© 2003 Optical Society of America

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  29. H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
    [CrossRef] [PubMed]
  30. K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
    [CrossRef] [PubMed]
  31. Y. Liu, G. J. Sonek, M. W. Berns, B. J. Tromberg, “Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry,” Biophys. J. 71, 2158–2167 (1996).
    [CrossRef] [PubMed]
  32. Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
    [CrossRef] [PubMed]
  33. A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

2001 (2)

J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, I. J. Reynolds, “MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants,” J. Neurosci. Methods 104, 165–176 (2001).
[CrossRef] [PubMed]

Z. Darzynkiewicz, X. Li, E. Bedner, “Use of flow and laser-scanning cytometry in analysis of cell death,” Methods Cell Biol. 66, 69–109 (2001).
[CrossRef] [PubMed]

2000 (3)

G. Liminga, P. Martinsson, B. Jonsson, P. Nygren, R. Larsson, “Apoptosis induced by calcein acetoxymethyl ester in the human histiocytic lymphoma cell line U-937 GTB,” Biochem. Pharmacol. 60, 1751–1759 (2000).
[CrossRef] [PubMed]

J. C. Reed, “Mechanisms of apoptosis,” Am. J. Pathol. 157, 1415–1430 (2000).
[CrossRef] [PubMed]

P. Patrizio, Y. Liu, G. J. Sonek, M. W. Berns, Y. Tadir, “Effect of pentoxifylline on the intrinsic swimming forces of human sperm assessed by optical tweezers,” J. Androl. 21, 753–756 (2000).
[PubMed]

1999 (4)

J. Sleep, D. Wilson, R. Simmons, W. Gratzer, “Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study,” Biophys. J. 77, 3085–3095 (1999).
[CrossRef] [PubMed]

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
[CrossRef] [PubMed]

R. Drezek, A. Dunn, R. Richards-Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt. 38, 3651–3661 (1999).
[CrossRef]

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
[CrossRef] [PubMed]

1998 (3)

M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, C. P. Reuteling-Sperger, “Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure,” Cytometry 31, 1–9 (1998).
[CrossRef] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37, 3586–3593 (1998).
[CrossRef]

M. W. Berns, “Laser scissors and tweezers,” Sci. Am. 278, 62–67 (1998).
[CrossRef] [PubMed]

1997 (2)

M. D. Wang, H. Yin, R. Landick, J. Gelles, S. M. Block, “Stretching DNA with optical tweezers,” Biophys. J. 72, 1335–1346 (1997).
[CrossRef] [PubMed]

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
[CrossRef] [PubMed]

1996 (4)

Y. Harada, T. Asakura, “Radiation forces on a dielectric sphere in the Rayleigh scattering regime,” Opt. Commun. 124, 529–541 (1996).
[CrossRef]

A. Fraser, G. Evan, “A License to kill,” Cell 85, 781–784 (1996).
[CrossRef] [PubMed]

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

Y. Liu, G. J. Sonek, M. W. Berns, B. J. Tromberg, “Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry,” Biophys. J. 71, 2158–2167 (1996).
[CrossRef] [PubMed]

1995 (3)

Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
[CrossRef] [PubMed]

S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
[CrossRef] [PubMed]

C. B. Thompson, “Apoptosis in the pathogenesis and treatment of disease,” Science 267, 1456–1462 (1995).
[CrossRef] [PubMed]

1994 (1)

D. L. Vaux, G. Haecker, A. Strasser, “An evolutionary perspective on apoptosis,” Cell 76, 777–779 (1994).
[CrossRef] [PubMed]

1993 (2)

K. Svoboda, C. F. Schmidt, B. J. Schnapp, S. M. Block, “Direct observation of kinesin stepping by optical trapping interferometry,” Nature (London) 365, 721–727 (1993).
[CrossRef]

J. Yuan, S. Shaham, S. Ledoux, H. M. Ellis, H. R. Horvitz, “The C elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme,” Cell 75, 641–652 (1993).
[CrossRef] [PubMed]

1992 (2)

J. A. Hickman, “Apoptosis induced by anticancer drugs,” Cancer Metastasis Rev. 11, 121–139 (1992).
[CrossRef] [PubMed]

K. Svoboda, C. F. Schmidt, D. Branton, S. M. Block, “Conformation and elasticity of the isolated red blood cell membrane skeleton,” Biophys. J. 63, 784–793 (1992).
[CrossRef] [PubMed]

1991 (1)

L. Graziadei, P. Burfeind, D. Bar-Sagi, “Introduction of unlabeled proteins into living cells by electroporation and isolation of viable protein-loaded cells using dextran-fluorescein isothiocyanate as a marker for protein uptake,” Anal. Biochem. 194, 198–203 (1991).
[CrossRef] [PubMed]

1990 (1)

Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, “Force generated by human sperm correlated to velocity and determined using a laser generated optical trap,” Fertil. Steril. 53, 944–947 (1990).
[PubMed]

1987 (1)

A. Ashkin, J. M. Dziedzic, T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature (London) 330, 769–771 (1987).
[CrossRef]

1986 (1)

1972 (1)

J. F. Kerr, A. H. Wyllie, A. R. Currie, “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics,” Br. J. Cancer 26, 239–257 (1972).
[CrossRef] [PubMed]

Asakura, T.

Y. Harada, T. Asakura, “Radiation forces on a dielectric sphere in the Rayleigh scattering regime,” Opt. Commun. 124, 529–541 (1996).
[CrossRef]

Asch, R. H.

Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, “Force generated by human sperm correlated to velocity and determined using a laser generated optical trap,” Fertil. Steril. 53, 944–947 (1990).
[PubMed]

Ashkin, A.

A. Ashkin, J. M. Dziedzic, T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature (London) 330, 769–771 (1987).
[CrossRef]

A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11, 288–290 (1986).
[CrossRef] [PubMed]

Bar-Sagi, D.

L. Graziadei, P. Burfeind, D. Bar-Sagi, “Introduction of unlabeled proteins into living cells by electroporation and isolation of viable protein-loaded cells using dextran-fluorescein isothiocyanate as a marker for protein uptake,” Anal. Biochem. 194, 198–203 (1991).
[CrossRef] [PubMed]

Bedner, E.

Z. Darzynkiewicz, X. Li, E. Bedner, “Use of flow and laser-scanning cytometry in analysis of cell death,” Methods Cell Biol. 66, 69–109 (2001).
[CrossRef] [PubMed]

Bergman, K.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
[CrossRef] [PubMed]

Berns, M. W.

P. Patrizio, Y. Liu, G. J. Sonek, M. W. Berns, Y. Tadir, “Effect of pentoxifylline on the intrinsic swimming forces of human sperm assessed by optical tweezers,” J. Androl. 21, 753–756 (2000).
[PubMed]

M. W. Berns, “Laser scissors and tweezers,” Sci. Am. 278, 62–67 (1998).
[CrossRef] [PubMed]

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

Y. Liu, G. J. Sonek, M. W. Berns, B. J. Tromberg, “Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry,” Biophys. J. 71, 2158–2167 (1996).
[CrossRef] [PubMed]

Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
[CrossRef] [PubMed]

Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, “Force generated by human sperm correlated to velocity and determined using a laser generated optical trap,” Fertil. Steril. 53, 944–947 (1990).
[PubMed]

Bjorkholm, J. E.

Block, S. M.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
[CrossRef] [PubMed]

M. D. Wang, H. Yin, R. Landick, J. Gelles, S. M. Block, “Stretching DNA with optical tweezers,” Biophys. J. 72, 1335–1346 (1997).
[CrossRef] [PubMed]

K. Svoboda, C. F. Schmidt, B. J. Schnapp, S. M. Block, “Direct observation of kinesin stepping by optical trapping interferometry,” Nature (London) 365, 721–727 (1993).
[CrossRef]

K. Svoboda, C. F. Schmidt, D. Branton, S. M. Block, “Conformation and elasticity of the isolated red blood cell membrane skeleton,” Biophys. J. 63, 784–793 (1992).
[CrossRef] [PubMed]

Branton, D.

K. Svoboda, C. F. Schmidt, D. Branton, S. M. Block, “Conformation and elasticity of the isolated red blood cell membrane skeleton,” Biophys. J. 63, 784–793 (1992).
[CrossRef] [PubMed]

Buckman, J. F.

J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, I. J. Reynolds, “MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants,” J. Neurosci. Methods 104, 165–176 (2001).
[CrossRef] [PubMed]

Burfeind, P.

L. Graziadei, P. Burfeind, D. Bar-Sagi, “Introduction of unlabeled proteins into living cells by electroporation and isolation of viable protein-loaded cells using dextran-fluorescein isothiocyanate as a marker for protein uptake,” Anal. Biochem. 194, 198–203 (1991).
[CrossRef] [PubMed]

Butler, W. F.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Chachisvilis, M.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Chadd, E. H.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
[CrossRef] [PubMed]

Chapman, C. F.

Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
[CrossRef] [PubMed]

Cheng, D. K.

Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
[CrossRef] [PubMed]

Chu, S.

Chung, T. D. Y.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Currie, A. R.

J. F. Kerr, A. H. Wyllie, A. R. Currie, “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics,” Br. J. Cancer 26, 239–257 (1972).
[CrossRef] [PubMed]

Darzynkiewicz, Z.

Z. Darzynkiewicz, X. Li, E. Bedner, “Use of flow and laser-scanning cytometry in analysis of cell death,” Methods Cell Biol. 66, 69–109 (2001).
[CrossRef] [PubMed]

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
[CrossRef] [PubMed]

Deslandes, E.

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
[CrossRef] [PubMed]

Drezek, R.

Dunn, A.

Dziedzic, J. M.

A. Ashkin, J. M. Dziedzic, T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature (London) 330, 769–771 (1987).
[CrossRef]

A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11, 288–290 (1986).
[CrossRef] [PubMed]

Eick, A. A.

Ellis, H. M.

J. Yuan, S. Shaham, S. Ledoux, H. M. Ellis, H. R. Horvitz, “The C elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme,” Cell 75, 641–652 (1993).
[CrossRef] [PubMed]

Esener, S. C.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Evan, G.

A. Fraser, G. Evan, “A License to kill,” Cell 85, 781–784 (1996).
[CrossRef] [PubMed]

Forster, A. H.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Fraser, A.

A. Fraser, G. Evan, “A License to kill,” Cell 85, 781–784 (1996).
[CrossRef] [PubMed]

Freyer, J. P.

Gauduchon, P.

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
[CrossRef] [PubMed]

Gelles, J.

M. D. Wang, H. Yin, R. Landick, J. Gelles, S. M. Block, “Stretching DNA with optical tweezers,” Biophys. J. 72, 1335–1346 (1997).
[CrossRef] [PubMed]

Godard, T.

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
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Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
[CrossRef] [PubMed]

Gratzer, W.

J. Sleep, D. Wilson, R. Simmons, W. Gratzer, “Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study,” Biophys. J. 77, 3085–3095 (1999).
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L. Graziadei, P. Burfeind, D. Bar-Sagi, “Introduction of unlabeled proteins into living cells by electroporation and isolation of viable protein-loaded cells using dextran-fluorescein isothiocyanate as a marker for protein uptake,” Anal. Biochem. 194, 198–203 (1991).
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S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
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Haecker, G.

D. L. Vaux, G. Haecker, A. Strasser, “An evolutionary perspective on apoptosis,” Cell 76, 777–779 (1994).
[CrossRef] [PubMed]

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A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

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J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, I. J. Reynolds, “MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants,” J. Neurosci. Methods 104, 165–176 (2001).
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J. A. Hickman, “Apoptosis induced by anticancer drugs,” Cancer Metastasis Rev. 11, 121–139 (1992).
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Horvitz, H. R.

J. Yuan, S. Shaham, S. Ledoux, H. M. Ellis, H. R. Horvitz, “The C elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme,” Cell 75, 641–652 (1993).
[CrossRef] [PubMed]

Johnson, T. M.

Jonsson, B.

G. Liminga, P. Martinsson, B. Jonsson, P. Nygren, R. Larsson, “Apoptosis induced by calcein acetoxymethyl ester in the human histiocytic lymphoma cell line U-937 GTB,” Biochem. Pharmacol. 60, 1751–1759 (2000).
[CrossRef] [PubMed]

Juan, G.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
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A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

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Kimel, S.

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

Kress, G. J.

J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, I. J. Reynolds, “MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants,” J. Neurosci. Methods 104, 165–176 (2001).
[CrossRef] [PubMed]

Krishnan, P.

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

LaFace, D. M.

S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
[CrossRef] [PubMed]

Landick, R.

M. D. Wang, H. Yin, R. Landick, J. Gelles, S. M. Block, “Stretching DNA with optical tweezers,” Biophys. J. 72, 1335–1346 (1997).
[CrossRef] [PubMed]

Larsson, R.

G. Liminga, P. Martinsson, B. Jonsson, P. Nygren, R. Larsson, “Apoptosis induced by calcein acetoxymethyl ester in the human histiocytic lymphoma cell line U-937 GTB,” Biochem. Pharmacol. 60, 1751–1759 (2000).
[CrossRef] [PubMed]

Lebailly, P.

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
[CrossRef] [PubMed]

Ledoux, S.

J. Yuan, S. Shaham, S. Ledoux, H. M. Ellis, H. R. Horvitz, “The C elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme,” Cell 75, 641–652 (1993).
[CrossRef] [PubMed]

Li, X.

Z. Darzynkiewicz, X. Li, E. Bedner, “Use of flow and laser-scanning cytometry in analysis of cell death,” Methods Cell Biol. 66, 69–109 (2001).
[CrossRef] [PubMed]

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
[CrossRef] [PubMed]

Liang, H.

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

Liminga, G.

G. Liminga, P. Martinsson, B. Jonsson, P. Nygren, R. Larsson, “Apoptosis induced by calcein acetoxymethyl ester in the human histiocytic lymphoma cell line U-937 GTB,” Biochem. Pharmacol. 60, 1751–1759 (2000).
[CrossRef] [PubMed]

Liou, G. F.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
[CrossRef] [PubMed]

Liu, Y.

P. Patrizio, Y. Liu, G. J. Sonek, M. W. Berns, Y. Tadir, “Effect of pentoxifylline on the intrinsic swimming forces of human sperm assessed by optical tweezers,” J. Androl. 21, 753–756 (2000).
[PubMed]

Y. Liu, G. J. Sonek, M. W. Berns, B. J. Tromberg, “Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry,” Biophys. J. 71, 2158–2167 (1996).
[CrossRef] [PubMed]

Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
[CrossRef] [PubMed]

Lykstad, K.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Marchand, P. J.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Martin, S. J.

S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
[CrossRef] [PubMed]

Martinsson, P.

G. Liminga, P. Martinsson, B. Jonsson, P. Nygren, R. Larsson, “Apoptosis induced by calcein acetoxymethyl ester in the human histiocytic lymphoma cell line U-937 GTB,” Biochem. Pharmacol. 60, 1751–1759 (2000).
[CrossRef] [PubMed]

McGahon, A. J.

S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
[CrossRef] [PubMed]

Mercer, E. M.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Mourant, J. R.

Murakami, T.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
[CrossRef] [PubMed]

Neuman, K. C.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
[CrossRef] [PubMed]

Nieland, L. J.

M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, C. P. Reuteling-Sperger, “Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure,” Cytometry 31, 1–9 (1998).
[CrossRef] [PubMed]

Nygren, P.

G. Liminga, P. Martinsson, B. Jonsson, P. Nygren, R. Larsson, “Apoptosis induced by calcein acetoxymethyl ester in the human histiocytic lymphoma cell line U-937 GTB,” Biochem. Pharmacol. 60, 1751–1759 (2000).
[CrossRef] [PubMed]

Ord, T.

Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, “Force generated by human sperm correlated to velocity and determined using a laser generated optical trap,” Fertil. Steril. 53, 944–947 (1990).
[PubMed]

Pal, S.

J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, I. J. Reynolds, “MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants,” J. Neurosci. Methods 104, 165–176 (2001).
[CrossRef] [PubMed]

Patrizio, P.

P. Patrizio, Y. Liu, G. J. Sonek, M. W. Berns, Y. Tadir, “Effect of pentoxifylline on the intrinsic swimming forces of human sperm assessed by optical tweezers,” J. Androl. 21, 753–756 (2000).
[PubMed]

Pestana, L. M.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Poul, J. M.

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
[CrossRef] [PubMed]

Rader, J. A.

S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
[CrossRef] [PubMed]

Ramaekers, F. C.

M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, C. P. Reuteling-Sperger, “Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure,” Cytometry 31, 1–9 (1998).
[CrossRef] [PubMed]

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J. C. Reed, “Mechanisms of apoptosis,” Am. J. Pathol. 157, 1415–1430 (2000).
[CrossRef] [PubMed]

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S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
[CrossRef] [PubMed]

Reuteling-Sperger, C. P.

M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, C. P. Reuteling-Sperger, “Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure,” Cytometry 31, 1–9 (1998).
[CrossRef] [PubMed]

Reynolds, I. J.

J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, I. J. Reynolds, “MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants,” J. Neurosci. Methods 104, 165–176 (2001).
[CrossRef] [PubMed]

Richards-Kortum, R.

Schmidt, C. F.

K. Svoboda, C. F. Schmidt, B. J. Schnapp, S. M. Block, “Direct observation of kinesin stepping by optical trapping interferometry,” Nature (London) 365, 721–727 (1993).
[CrossRef]

K. Svoboda, C. F. Schmidt, D. Branton, S. M. Block, “Conformation and elasticity of the isolated red blood cell membrane skeleton,” Biophys. J. 63, 784–793 (1992).
[CrossRef] [PubMed]

Schnapp, B. J.

K. Svoboda, C. F. Schmidt, B. J. Schnapp, S. M. Block, “Direct observation of kinesin stepping by optical trapping interferometry,” Nature (London) 365, 721–727 (1993).
[CrossRef]

Schutte, B.

M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, C. P. Reuteling-Sperger, “Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure,” Cytometry 31, 1–9 (1998).
[CrossRef] [PubMed]

Shaham, S.

J. Yuan, S. Shaham, S. Ledoux, H. M. Ellis, H. R. Horvitz, “The C elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme,” Cell 75, 641–652 (1993).
[CrossRef] [PubMed]

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H. M. Shapiro, Practical Flow Cytometry (Wiley-Liss, New York, 1995).

Shen, D.

Shin, D.

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

Sichel, F.

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
[CrossRef] [PubMed]

Simmons, R.

J. Sleep, D. Wilson, R. Simmons, W. Gratzer, “Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study,” Biophys. J. 77, 3085–3095 (1999).
[CrossRef] [PubMed]

Sleep, J.

J. Sleep, D. Wilson, R. Simmons, W. Gratzer, “Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study,” Biophys. J. 77, 3085–3095 (1999).
[CrossRef] [PubMed]

Sonek, G. J.

P. Patrizio, Y. Liu, G. J. Sonek, M. W. Berns, Y. Tadir, “Effect of pentoxifylline on the intrinsic swimming forces of human sperm assessed by optical tweezers,” J. Androl. 21, 753–756 (2000).
[PubMed]

Y. Liu, G. J. Sonek, M. W. Berns, B. J. Tromberg, “Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry,” Biophys. J. 71, 2158–2167 (1996).
[CrossRef] [PubMed]

Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
[CrossRef] [PubMed]

Strasser, A.

D. L. Vaux, G. Haecker, A. Strasser, “An evolutionary perspective on apoptosis,” Cell 76, 777–779 (1994).
[CrossRef] [PubMed]

Sur, S.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Svoboda, K.

K. Svoboda, C. F. Schmidt, B. J. Schnapp, S. M. Block, “Direct observation of kinesin stepping by optical trapping interferometry,” Nature (London) 365, 721–727 (1993).
[CrossRef]

K. Svoboda, C. F. Schmidt, D. Branton, S. M. Block, “Conformation and elasticity of the isolated red blood cell membrane skeleton,” Biophys. J. 63, 784–793 (1992).
[CrossRef] [PubMed]

Tadir, Y.

P. Patrizio, Y. Liu, G. J. Sonek, M. W. Berns, Y. Tadir, “Effect of pentoxifylline on the intrinsic swimming forces of human sperm assessed by optical tweezers,” J. Androl. 21, 753–756 (2000).
[PubMed]

Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, “Force generated by human sperm correlated to velocity and determined using a laser generated optical trap,” Fertil. Steril. 53, 944–947 (1990).
[PubMed]

Thompson, C. B.

C. B. Thompson, “Apoptosis in the pathogenesis and treatment of disease,” Science 267, 1456–1462 (1995).
[CrossRef] [PubMed]

Traganos, F.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
[CrossRef] [PubMed]

Trang, T. C.

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

Tromberg, B. J.

Y. Liu, G. J. Sonek, M. W. Berns, B. J. Tromberg, “Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry,” Biophys. J. 71, 2158–2167 (1996).
[CrossRef] [PubMed]

Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
[CrossRef] [PubMed]

Tu, E.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Vafa, O.

Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, “Force generated by human sperm correlated to velocity and determined using a laser generated optical trap,” Fertil. Steril. 53, 944–947 (1990).
[PubMed]

van Engeland, M.

M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, C. P. Reuteling-Sperger, “Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure,” Cytometry 31, 1–9 (1998).
[CrossRef] [PubMed]

van Schie, R. C.

S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, D. R. Green, “Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of bcl-2 and abl,” J. Exp. Med. 182, 1545–1556 (1995).
[CrossRef] [PubMed]

Vaux, D. L.

D. L. Vaux, G. Haecker, A. Strasser, “An evolutionary perspective on apoptosis,” Cell 76, 777–779 (1994).
[CrossRef] [PubMed]

Vigreux, C.

T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
[CrossRef] [PubMed]

Votyakova, T. V.

J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, I. J. Reynolds, “MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants,” J. Neurosci. Methods 104, 165–176 (2001).
[CrossRef] [PubMed]

Vu, K. T.

H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
[CrossRef] [PubMed]

Wang, M. D.

M. D. Wang, H. Yin, R. Landick, J. Gelles, S. M. Block, “Stretching DNA with optical tweezers,” Biophys. J. 72, 1335–1346 (1997).
[CrossRef] [PubMed]

Wang, M. M.

A. H. Forster, M. M. Wang, W. F. Butler, M. Chachisvilis, T. D. Y. Chung, S. C. Esener, J. M. Hall, O. Kibar, K. Lykstad, P. J. Marchand, E. M. Mercer, L. M. Pestana, S. Sur, E. Tu, R. Yang, H. Zhang, I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Wilson, D.

J. Sleep, D. Wilson, R. Simmons, W. Gratzer, “Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study,” Biophys. J. 77, 3085–3095 (1999).
[CrossRef] [PubMed]

Wright, W. H.

Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, M. W. Berns, “Force generated by human sperm correlated to velocity and determined using a laser generated optical trap,” Fertil. Steril. 53, 944–947 (1990).
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Figures (10)

Fig. 1
Fig. 1

Laser-induced motion of the cells is measured from images taken before and after the scan of the laser. (A) Prior to the scan of the laser, cells are dispersed randomly in the field of view. After the first image is captured, a laser line is generated and scanned across the field of view at a constant velocity. Cells are moved by the laser a certain distance depending on the attractive force of the beam and the fluidic and surface drag forces on the cell. (B) After the laser line scan is finished, a second image is captured and the displacements of all cells are calculated. Lines indicate the trajectory of the particles and circles indicate positions both before and after the scans. Typically, multiple scans of the laser are used to increase the average measured displacement.

Fig. 2
Fig. 2

Experimental setup for the measurement of the position displacement of cells induced by the optical forces of a scanned laser beam.

Fig. 3
Fig. 3

Displacement for 15-μm polystyrene beads as a function of both power (with a constant scanning velocity of 110 μm/s) and scanning velocity (with a constant power of 2.3 W). Five scans of the laser were used in all cases. Each data point represents the average displacement of approximately 30–50 measured beads.

Fig. 4
Fig. 4

Displacement distribution profile of a homogeneous population of 15-μm polystyrene beads. The distribution curve is fit to a binned sampling on 2.4-μm intervals.

Fig. 5
Fig. 5

Mean displacements as a function of particle diameter for polystyrene beads. Approximately 300 particles were measured per sample. Laser power was 2.5 W and the scan velocity was 140 μm/s with seven scans. Error bars indicate three standard errors of the mean.

Fig. 6
Fig. 6

Micrographs of U937 cells stained with DNA-marking DAPI show morphological changes to the nucleus in response to camptothecin treatment. (A) Nuclei of untreated cells exhibit a homogeneous appearance in comparison with the (B) characteristic apoptotic bodies seen in cells treated for 4 h with 4 μg/ml of camptothecin (arrows).

Fig. 7
Fig. 7

Displacement distribution profiles of U937 cells undergoing apoptosis. Camptothecin treatment demonstrates a downward trend in mean displacement that correlates with treatment time. Measurements were taken with a scan velocity of 75 μm/s, six scans, and a laser power of 10 W. The distribution curve is fit to a binned sampling on 3.6-μm intervals.

Fig. 8
Fig. 8

U937 cells treated with camptothecin for specified time intervals analyzed for phosphatidyl serine externalization by Annexin V and propidium iodide fluorescence by flow cytometry. Quantitation of Annexin V-FITC fluorescence indicates percentage of population that is apoptotic.

Fig. 9
Fig. 9

Time course of camptothecin treatment on U937 cells plated at specified densities and assayed for caspase activity with a DEVD-Rhodamine substrate. Representative data are given as relative fluorescence units (RFU) and include each sample measured in triplicate. Error bars represent standard deviations of the triplicate measurements.

Fig. 10
Fig. 10

Detection of apoptosis in U937 cells treated with camptothecin by measurement of displacements induced by optical forces. Measurements were recorded for 300 cells per sample and expressed as mean displacement values. Data presented are the average displacement of three independent experiments with error bars indicating standard deviations of those three experiments.

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