OSA's Digital Library

Applied Optics

Applied Optics


  • Vol. 42, Iss. 28 — Oct. 1, 2003
  • pp: 5765–5773

Optical Forces for Noninvasive Cellular Analysis

Mark M. Wang, Catherine A. Schnabel, Mirianas Chachisvilis, Rong Yang, Michael J. Paliotti, Laura A. Simons, Laura McMullin, Norbert Hagen, Kristie Lykstad, Eugene Tu, Luis M. Pestana, Sudipto Sur, Haichuan Zhang, William F. Butler, Ilona Kariv, and Philippe J. Marchand  »View Author Affiliations

Applied Optics, Vol. 42, Issue 28, pp. 5765-5773 (2003)

View Full Text Article

Acrobat PDF (1265 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



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

OCIS Codes
(170.1530) Medical optics and biotechnology : Cell analysis
(170.4520) Medical optics and biotechnology : Optical confinement and manipulation

Mark M. Wang, Catherine A. Schnabel, Mirianas Chachisvilis, Rong Yang, Michael J. Paliotti, Laura A. Simons, Laura McMullin, Norbert Hagen, Kristie Lykstad, Eugene Tu, Luis M. Pestana, Sudipto Sur, Haichuan Zhang, William F. Butler, Ilona Kariv, and Philippe J. Marchand, "Optical Forces for Noninvasive Cellular Analysis," Appl. Opt. 42, 5765-5773 (2003)

Sort:  Author  |  Year  |  Journal  |  Reset


  1. M. W. Berns, “Laser scissors and tweezers,” Sci. Am. 278, 62–67 (1998).
  2. A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, and S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles,” Opt. Lett. 11, 288–290 (1986).
  3. A. Ashkin, J. M. Dziedzic, and T. Yamane, “Optical trapping and manipulation of single cells using infrared laser beams,” Nature (London) 330, 769–771 (1987).
  4. K. Svoboda, C. F. Schmidt, B. J. Schnapp, and S. M. Block, “Direct observation of kinesin stepping by optical trapping interferometry,” Nature (London) 365, 721–727 (1993).
  5. M. D. Wang, H. Yin, R. Landick, J. Gelles, and S. M. Block, “Stretching DNA with optical tweezers,” Biophys. J. 72, 1335–1346 (1997).
  6. Y. Tadir, W. H. Wright, O. Vafa, T. Ord, R. H. Asch, and 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).
  7. P. Patrizio, Y. Liu, G. J. Sonek, M. W. Berns, and Y. Tadir, “Effect of pentoxifylline on the intrinsic swimming forces of human sperm assessed by optical tweezers,” J. Androl. 21, 753–756 (2000).
  8. K. Svoboda, C. F. Schmidt, D. Branton, and S. M. Block, “Conformation and elasticity of the isolated red blood cell membrane skeleton,” Biophys. J. 63, 784–793 (1992).
  9. J. Sleep, D. Wilson, R. Simmons, and W. Gratzer, “Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study,” Biophys. J. 77, 3085–3095 (1999).
  10. G. Liminga, P. Martinsson, B. Jonsson, P. Nygren, and R. Larsson, “Apoptosis induced by calcein acetoxymethyl ester in the human histiocytic lymphoma cell line U-937 GTB,” Biochem. Pharmacol. 60, 1751–1759 (2000).
  11. J. F. Buckman, H. Hernandez, G. J. Kress, T. V. Votyakova, S. Pal, and 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).
  12. L. Graziadei, P. Burfeind, and 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).
  13. H. M. Shapiro, Practical Flow Cytometry (Wiley-Liss, New York, 1995).
  14. J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37, 3586–3593 (1998).
  15. J. F. Kerr, A. H. Wyllie, and A. R. Currie, “Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics,” Br. J. Cancer 26, 239–257 (1972).
  16. C. B. Thompson, “Apoptosis in the pathogenesis and treatment of disease,” Science 267, 1456–1462 (1995).
  17. J. C. Reed, “Mechanisms of apoptosis,” Am. J. Pathol. 157, 1415–1430 (2000).
  18. D. L. Vaux, G. Haecker, and A. Strasser, “An evolutionary perspective on apoptosis,” Cell 76, 777–779 (1994).
  19. Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, and F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry 27, 1–20 (1997).
  20. Z. Darzynkiewicz, X. Li, and E. Bedner, “Use of flow and laser-scanning cytometry in analysis of cell death,” Methods Cell Biol. 66, 69–109 (2001).
  21. T. Godard, E. Deslandes, P. Lebailly, C. Vigreux, F. Sichel, J. M. Poul, and P. Gauduchon, “Early detection of staurosporine-induced apoptosis by comet and annexin V assays,” Histochem. Cell Biol. 112, 155–161 (1999).
  22. J. A. Hickman, “Apoptosis induced by anticancer drugs,” Cancer Metastasis Rev. 11, 121–139 (1992).
  23. R. Drezek, A. Dunn, and R. Richards-Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt. 38, 3651–3661 (1999).
  24. Y. Harada and T. Asakura, “Radiation forces on a dielectric sphere in the Rayleigh scattering regime,” Opt. Commun. 124, 529–541 (1996).
  25. J. Yuan, S. Shaham, S. Ledoux, H. M. Ellis, and 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).
  26. A. Fraser and G. Evan, “A License to kill,” Cell 85, 781–784 (1996).
  27. S. J. Martin, C. P. Reutelingsperger, A. J. McGahon, J. A. Rader, R. C. van Schie, D. M. LaFace, and 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).
  28. M. van Engeland, L. J. Nieland, F. C. Ramaekers, B. Schutte, and C. P. Reuteling-Sperger, “Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure,” Cytometry 31, 1–9 (1998).
  29. H. Liang, K. T. Vu, P. Krishnan, T. C. Trang, D. Shin, S. Kimel, and M. W. Berns, “Wavelength dependence of cell cloning efficiency after optical trapping,” Biophys. J. 70, 1529–1533 (1996).
  30. K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, “Characterization of photodamage to escherichia coli in optical traps,” Biophys. J. 77, 2856–2863 (1999).
  31. Y. Liu, G. J. Sonek, M. W. Berns, and 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).
  32. Y. Liu, D. K. Cheng, G. J. Sonek, M. W. Berns, C. F. Chapman, and B. J. Tromberg, “Evidence for localized cell heating induced by infrared optical tweezers,” Biophys. J. 68, 2137–2144 (1995).
  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, and I. Kariv, “Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model,” submitted for publication.

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited