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Research in Biomedical Optics

Quantitative Microscopy and Tomography of Live Cells

Quantitative Phase Microscopy

Quantitative phase imaging is a new optical approach that promises to revolutionize microscopy studies in cell biology. It provides biologists with a tool to study static and dynamic physical properties of live cells quantitatively, without exogenous contrast agents.  For past several years, there has been considerable work on the development of quantitative phase microscopy (QPM) techniques at the LBRC. This includes, for example, the use of a harmonically-related pair of wavelengths and a phase-referenced interferometer. In the recent past, several QPM techniques have been developed that include:

  • Fourier phase microscopy
  • Heterodyne Mach-Zehnder phase microscopy
  • Hilbert phase microscopy
  • Diffraction phase microscopy
  • Spectroscopic phase microscopy
  • Speckle contrast phase microscopy
  • Quantitative DIC microscopy

These techniques have been employed to determine dry mass, refractive index of live cells and dynamic of cells such as cell’s membrane fluctuations and cell’s motion. Currently, the LBRC is developing advanced transmission and reflection phase microscopes for biological applications:

  • Low coherence diffraction phase microscopy
  • Wide-field dispersion phase microscopy
  • Line-field reflection phase microscopy
  • Wide-field reflection phase microscopy
  1. T. Vo-Dinh, Biomedical Photonics Handbook (CRC Press, 2003).
  2. Popescu G, Deflores LP, Vaughan JC, Badizadegan K, Iwai H, Dasari RR, and Feld MS, "Fourier Phase Microscopy for Investigation of Biological Structure and Dynamics”, Optics Letters 29 (21), 2503-2505 (2004).
  3. Ikeda T, Popescu G, Dasari RR, and Feld MS, “Hilbert Phase Microscopy for Investigating Fast Dynamics in Transparent Systems,” Optics Letters 30 (10), 1165-1167 (2005).
  4. Park YK, Popescu G, Badizadegan K, Dasari RR, Feld MS. Diffraction phase and fluorescence microscopy. Optics Express 14, 8263-8 (2006) PMID: 19529201.
  5. Popescu G, Ikeda T, Goda K, Best-Popescu CA, Laposata M, Manley S, Dasari RR, Badizadegan K, Feld MS. Optical measurement of cell membrane tension. Physical Review Letters. 97,  (2006) PMID: 17155774.
  6. Lue N, Choi W, Popescu G, Ikeda T, Dasari RR, Badizadegan K, Feld MS. Quantitative phase imaging of live cells using fast Fourier phase microscopy. Applied optics. 46, 1836-42 (2007).
  7. Fang-Yen C, Chu MC, Seung HS, Dasari RR, and Feld MS. Phase-referenced probe interferometer for biological surface profiling and displacement measurements. Review of Scientific Instruments 78, 123703 (2007) PMID: 18163733.
  8. Lue N, Choi W, Popescu G, Yaqoob Z, Badizadegan K, Dasari RR, and Feld MS. Live Cell Refractometry Using Hilbert Phase Microscopy and Confocal Reflectance Microscopy. The Journal of Physical Chemistry A 113, 13327-13330 (2009) PMCID: PMC2858636.
  9. Lue N, Choi W, Badizadegan K, Dasari RR, Feld MS and Popescu G. Confocal diffraction phase microscopy of live cells. Optics Letters 33, 2074-2076 (2008) PMCID: PMC2730468.
  10. Y. Park, T. Yamauchi, W. Choi, R. Dasari, and M. S. Feld, “Spectroscopic phase microscopy for quantifying hemoglobin concentrations in intact red blood cells,” Opt. Lett. 34(23), 3668–3670 (2009).
  11. Park YK, Choi W, Yaqoob Z, Dasari RR, Badizadegan K, and Feld MS. Speckle-field digital holographic microscopy. Optics Express 17, 12285-12292 (2009) PMCID2862625.
  12. Fu D, Oh S, Choi W, Yamauchi T, Dorn A, Yaqoob Z, Dasari RR, and Feld MS. Quantitative DIC microscopy using an off-axis self-interference approach. Optics Letters 35, 2370-2372 (2010) PMID: 20634833.
  13. Fu D, Choi W, Sung Y, Oh S, Yaqoob Z, Park YK, Dasari RR, and Feld MS. Ultraviolet refractometry using field-based light scattering spectroscopy. Optics Express 17, 18878-18886 (2009) PMCID: PMC2852178.
  14. D. Fu, W. Choi, Y. Sung, Z. Yaqoob, R. R. Dasari, and M. Feld, “Quantitative dispersion microscopy,” Biomed. Opt. Express 1, 347–353 (2010).
  15. Yaqoob Z, Choi W, Oh S, Lue N, Park Y, Fang-Yen C, Dasari RR, Badizadegan K, Feld MS. Improved phase sensitivity in spectral domain phase microscopy using line-field illumination and self phase-referencing. Optics Express. 17, 10681-7 (2009) PMCID: PMC2844447.