Asian Journal of Physics Vol 30, No 12 (2021) 1653-1666

Quantitative interferometric off-axis methods in biomedical microscopy research

N Lue
Lincoln Laboratory, Massachusetts Institute of Technology 244 Wood St, Lexington, MA02421 USA
Dedicated to Prof D V G L N Rao

This review work is a brief communication introducing an off-axis quantitative phase method and its variation for label-free biomedical microscopy applications. Various setups and concepts were explained and discussed, as well as their biomedical.applications: from quantitative phase to refractive index and dry mass, single cells to large number of cells, stationary to flow geometry, single to multiple wavelengths and full field 2D to 3D. © Anita Publications. All rights reserved.
Keywords: Quantitative phase microscopy, Off-axis interferometry.

Peer Review Information
Method: Single- anonymous; Screened for Plagiarism? Yes
Buy this Article in Print © Anita Publications. All rights reserve


  2. Walter J C, Accuracy and precision in quantitative fluorescence microscopy, J Cell Biology, 185(2009)1135–1148.
  3. Zernike F, How I discovered phase contrast, Science, 121(1955)345–349.
  4. Ross K F A, Phase contrast and interference microscopy for cell biologists, (London: Edward Arnold), 1967.
  5. Pluta M, Nomaski’s DIC microscopy: a Review, Proc SPIE, 1846(1994);
  6. Ghiglia D C, Pritt M D, Two-dimensional phase unwrapping: Theory, Algorithm, and Software, (Wiely-Interscience), 1998.
  7. Popescu G, Park Y K, Lue N, Best-Popescu C, Deflores L, Dasari R R, Feld M S , Badizadegan K, Optical imaging of cell mass and growth dynamics, Am J Physiol-Cell Physiol, 295(2008)538–544.
  8. Park Y K, Depeursinge C, Popescu G, Quantitative phase imaging in biomedicine, Nature Photonics, 12(2018), 587–589.
  9. Holden E, Tárnok A, Popescu G. Quantitative phase imaging for label-free cytometry, Cytometry A, 91(2017)407–411.
  10. Marquet P, Rappaz B, Magistretti P J, Cuche E, Emery Y, Colomb T, Depeursinge C, Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy, Opt Lett, 30(2005)468–470.
  11. Trusiak M, Cywińska M, Micó V, Picazo-Bueno J A, Zuo C, Zdańkowski P, Patorski K, Variational Hilbert Quantitative Phase Imaging, Sci Rep, 10(2020)13955.
  12. Ikeda T, Popescu G, Dasari R R, Feld M S, Hilbert phase microscopy for investigating fast dynamics in transparent systems, Opt Lett, 30(2005)1165–1168.
  13. Stagaman G, Forsyth J M, Bright-field microscopy of semitransparent objects, J Opt Soc Am A, 5(1988)647–659.
  14. Popescu G, Quantitative Phase Imaging of Cells and Tissues, (McGraw-Hill, New York), 2011.
  15. Lue N, Choi W, Popescu G, Ikeda T, Dasari R, Badizadegan K, Feld M S, Quantitative phase imaging of live cells using fast Fourier phase microscopy, App Opt, 46(2007)1836–1842.
  16. Lue N, Bewersdorf J, Lessard M, Badizadegan K, Dasari R R, Feld M S, Popescu G, Tissue refractometry using Hilbert phase microscopy, Opt Lett, 32(2007)3522–3524.
  17. Smartt R N, Steel W H, Theory and Application of Point-Diffraction Interferometers, Jpn J Appl Phys, 14(1975). 351; 10.7567/JJAPS.14S1.351.
  18. Popescu G, Ikeda T, Dasari R R, Feld M S, Diffraction phase microscopy for quantifying cell structure and dynamics, Opt Lett, 31(2006)775–777.
  19. Hillman T R, Lue N, Sung Y J, Dasari R R, Yaqoob Z, Near-common-path self-referenced quantitative phase microscopy, IEEE Photon Technol Lett, 24(2012)1812–1814.
  20. Beuthan J, Minet O, Helfmann J, Herrig M, Muller G. The spatial variation of the refractive index in biological cells, Physics in Med and Biol, 41(1996)369–382.
  21. Brunstin A, Mullaney P F, Differential Light-Scattering from Spherical Mammalian-Cells, Biophysical J, 14(1974) 439–453.
  22. Lue N, Popescu G, Ikeda T, Badizadegan K, Dasari R R, Feld M S, Live cell refractometry using microfluidic devices, Opt Lett, 31(2006)2759–2761.
  23. Lue N, Choi W, Popescu G, Yaqoob Z, Badizadegan K, Dasari R R, Feld M S, Live cell refractometry using Hilbert phase microscopy and confocal reflectance microscopy, J Phys Chem A, 113(2009)13327–13330.
  24. Davies G, Wilkins M H F, Interference microscopy and mass determination, Nature, 161(1952)541;
  25. Baber R, Interference microscopy and mass determination, Nature, 169(1952)366–367.
  26. Baber R,. Determination of Dry Mass, Thickness, Solid and Water Concentration in Living Cells, Nature, 172 (1953)1097–1098.
  27. Kang J W, Nguyen F T, Lue N, Temporal Imaging of Live Cells by High-Speed Confocal Raman Microscopy, Materials, 14(2021)3732;
  28. Lue N, Kang J W, Hillman T R, Dasari R R, Yaqoob Z, Single-shot quantitative dispersion phase microscopy, Appl Phys Lett, 101(2012)084101;
  29. Hosseini P, Lue N, Yaqoob Z, Dasari R, So P T C, Self-reference line-dispersion interferometry microscopy, Appl Phys Lett, 110(2017)131103;
  30. Jin D, Sung Y J, Lue N, Kim Y H, So P T C, Yaqoob Z, Large Population Cell Characterization using quantitative phase cytometer, Cytometry A, 91(2017)450–459.
  31. Noda T, Kawata S, Miami S, Three-dimensional phase-contrast imaging by a computered-tomorgaphy microscope, Appl Opt, 31(1992)670–675.
  32. Charrière F, Pavillon N, Colomb T, Depeursinge C, Living specimen tomography by digital. holographic microscopy: morphometry of testate amoeba, Opt Express, 14(2006)7005–7013.
  33. Choi W, Fang-Yen C, Oh S, Lue N, Badizadegan K, Dasari R R, Feld M S. Tomography phase microscopy, Nat Methods, 4(2007)717–719.
  34. Sung Y, Choi W, Lue N, Dasari R R, Yaqoob Z, Stain-Free Quantification of Chromosomes in Live Cells Using Regularized Tomographic Phase Microscopy, PLoS One, 7(2012)e49502;
  35. Lue N, Choi W, Popescu G, Badizadegan K, Dasari R R, Feld M S, Synthetic aperture tomographic phase microscopy for 3D imaging of live cells in translational motion, Opt Express, 16(2008)16240–16246.
  36. Sung Y J, Lue N, Hamza B, Martel J, Irimia D, Dasari R R, Choi W, Yaqoob Z, So PTC. Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel, Phys Rev Appl, 1(2014)014002;
  37. Nahamoo D, Pan S X, Kak A C, Synthetic aperture diffraction tomography and its interpolation –free computer implementation, IEEE Transact Sonics and ultrasound, 31(1984)218–229.
  38. Choi H K, Munson D C, Direct-Fourier reconstruction in tomography and synthetic aperture radar, Int J Imag Sys and Tech, 9(1998)1–13.
  39. Choi Y W, Hosseini P, Kang J W, Kang S S, Yang T D, Hyeon M G, So P T C, Yaqoob Zm, Reflection phase microscopy using spatio-temporal coherence of light, Opitca, 5(2018)1468–1473.
  40. Singh V R, Yang Y A, Yu H, Kamm R D, Yaqoob Z, So P T C. Studying nucleic envelope and plasma membrane mechanics of eukaryotic cells using confocal reflectance interferometric microscopy, Nature Commun, 10(2019) 3652;