Abstract

It has recently been shown that quantitative phase imaging methods can provide clinically relevant parameters for red blood cell analysis with unprecedented detail and sensitivity. Since the quantitative phase information is dependent on both the thickness and refractive index, a major limitation to clinical translation has been a simple and practical approach to measure both simultaneously. Here we demonstrate both theoretically and experimentally that, by combining quantitative phase with a single absorption measurement, it is possible to measure both quantities at the single cell level. We validate this approach by comparing our results to those acquired using a clinical blood analyzer. This approach to decouple the thickness and refractive index for red blood cells may be used with any quantitative phase imaging method that can operate in tandem with bright field microscopy at the Soret-band wavelength.

© 2011 OSA

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  1. B. J. Bain, Blood Cells A Practical Guide, 3rd ed. (Blackwell Science, London, 2002).
  2. B. J. Bain, “Diagnosis from the blood smear,” N. Engl. J. Med.353(5), 498–507 (2005).
    [CrossRef] [PubMed]
  3. H. H. Billett, M. E. Fabry, and R. L. Nagel, “Hemoglobin distribution width: a rapid assessment of dense red cells in the steady state and during painful crisis in sickle cell anemia,” J. Lab. Clin. Med.112(3), 339–344 (1988).
    [PubMed]
  4. M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
    [CrossRef] [PubMed]
  5. G. Rusciano, “Experimental analysis of Hb oxy-deoxy transition in single optically stretched red blood cells,” Phys. Med.26(4), 233–239 (2010).
    [CrossRef] [PubMed]
  6. S. Winoto-Morbach, W. Müller-Ruchholtz, and V. Tchikov, “Magnetophoresis: II. Quantification of iron and hemoglobin content at the single erythrocyte level,” J. Clin. Lab. Anal.9(1), 42–46 (1995).
    [CrossRef] [PubMed]
  7. A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
    [CrossRef] [PubMed]
  8. K. A. Sem’yanov, P. A. Tarasov, J. T. Soini, A. K. Petrov, and V. P. Maltsev, “Calibration-free method to determine the size and hemoglobin concentration of individual red blood cells from light scattering,” Appl. Opt.39(31), 5884–5889 (2000).
    [CrossRef] [PubMed]
  9. M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
    [CrossRef] [PubMed]
  10. M. Mir, Z. Wang, K. Tangella, and G. Popescu, “Diffraction phase cytometry: blood on a CD-ROM,” Opt. Express17(4), 2579–2585 (2009).
    [CrossRef] [PubMed]
  11. Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
    [CrossRef] [PubMed]
  12. Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
    [CrossRef] [PubMed]
  13. Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
    [CrossRef] [PubMed]
  14. G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
    [CrossRef] [PubMed]
  15. G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
    [CrossRef] [PubMed]
  16. G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt.11(4), 040503 (2006).
    [CrossRef] [PubMed]
  17. S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
    [CrossRef] [PubMed]
  18. S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
    [CrossRef] [PubMed]
  19. N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
    [CrossRef] [PubMed]
  20. A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).
  21. M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
    [CrossRef] [PubMed]
  22. B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
    [CrossRef] [PubMed]
  23. B. Rappaz, F. Charrière, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium,” Opt. Lett.33(7), 744–746 (2008).
    [CrossRef] [PubMed]
  24. B. Rappaz, P. Marquet, E. Cuche, Y. Emery, C. Depeursinge, and P. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express13(23), 9361–9373 (2005).
    [CrossRef] [PubMed]
  25. Y. K. 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).
    [CrossRef] [PubMed]
  26. Z. Wang, L. Millet, M. Mir, H. Ding, S. Unarunotai, J. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express19(2), 1016–1026 (2011).
    [CrossRef] [PubMed]
  27. Z. Wang and G. Popescu, “Quantitative phase imaging with broadband fields,” Appl. Phys. Lett.96(5), 051117 (2010).
    [CrossRef]
  28. R. Barer, “Refractometry and interferometry of living cells,” J. Opt. Soc. Am.47(6), 545–556 (1957).
    [CrossRef] [PubMed]
  29. R. Barer, J. B. Howie, K. F. Ross, and S. Tkaczyk, “Applications of refractometry in haematology,” J. Physiol.120(4), 67P–68P (1953).
    [PubMed]
  30. R. Barer and K. A. Ross, “Refractometry of living cells,” J. Physiol.118(2), 38P–39P (1952).
    [PubMed]
  31. R. Barer and S. Tkaczyk, “Refractive index of concentrated protein solutions,” Nature173(4409), 821–822 (1954).
    [CrossRef] [PubMed]
  32. Z. Wang, I. S. Chun, X. Li, Z. Y. Ong, E. Pop, L. Millet, M. U. Gillette, and G. Popescu, “Topography and refractometry of nanostructures using spatial light interference microscopy,” Opt. Lett.35(2), 208–210 (2010).
    [CrossRef] [PubMed]
  33. S. Prahl, “Tabulated molar extinction coefficient for hemoglobin in water” (1998), http://omlc.ogi.edu/spectra/hemoglobin/summary.html .

2011

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
[CrossRef] [PubMed]

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Z. Wang, L. Millet, M. Mir, H. Ding, S. Unarunotai, J. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express19(2), 1016–1026 (2011).
[CrossRef] [PubMed]

2010

Z. Wang, I. S. Chun, X. Li, Z. Y. Ong, E. Pop, L. Millet, M. U. Gillette, and G. Popescu, “Topography and refractometry of nanostructures using spatial light interference microscopy,” Opt. Lett.35(2), 208–210 (2010).
[CrossRef] [PubMed]

Z. Wang and G. Popescu, “Quantitative phase imaging with broadband fields,” Appl. Phys. Lett.96(5), 051117 (2010).
[CrossRef]

G. Rusciano, “Experimental analysis of Hb oxy-deoxy transition in single optically stretched red blood cells,” Phys. Med.26(4), 233–239 (2010).
[CrossRef] [PubMed]

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

2009

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
[CrossRef] [PubMed]

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

M. Mir, Z. Wang, K. Tangella, and G. Popescu, “Diffraction phase cytometry: blood on a CD-ROM,” Opt. Express17(4), 2579–2585 (2009).
[CrossRef] [PubMed]

Y. K. 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).
[CrossRef] [PubMed]

2008

B. Rappaz, F. Charrière, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium,” Opt. Lett.33(7), 744–746 (2008).
[CrossRef] [PubMed]

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

2007

G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
[CrossRef] [PubMed]

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

2006

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt.11(4), 040503 (2006).
[CrossRef] [PubMed]

2005

2000

1995

S. Winoto-Morbach, W. Müller-Ruchholtz, and V. Tchikov, “Magnetophoresis: II. Quantification of iron and hemoglobin content at the single erythrocyte level,” J. Clin. Lab. Anal.9(1), 42–46 (1995).
[CrossRef] [PubMed]

1988

H. H. Billett, M. E. Fabry, and R. L. Nagel, “Hemoglobin distribution width: a rapid assessment of dense red cells in the steady state and during painful crisis in sickle cell anemia,” J. Lab. Clin. Med.112(3), 339–344 (1988).
[PubMed]

1957

1954

R. Barer and S. Tkaczyk, “Refractive index of concentrated protein solutions,” Nature173(4409), 821–822 (1954).
[CrossRef] [PubMed]

1953

R. Barer, J. B. Howie, K. F. Ross, and S. Tkaczyk, “Applications of refractometry in haematology,” J. Physiol.120(4), 67P–68P (1953).
[PubMed]

1952

R. Barer and K. A. Ross, “Refractometry of living cells,” J. Physiol.118(2), 38P–39P (1952).
[PubMed]

Auth, T.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Badizadegan, K.

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt.11(4), 040503 (2006).
[CrossRef] [PubMed]

Bain, B. J.

B. J. Bain, “Diagnosis from the blood smear,” N. Engl. J. Med.353(5), 498–507 (2005).
[CrossRef] [PubMed]

Bannister, L. H.

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Barbul, A.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
[CrossRef] [PubMed]

Barer, R.

R. Barer, “Refractometry and interferometry of living cells,” J. Opt. Soc. Am.47(6), 545–556 (1957).
[CrossRef] [PubMed]

R. Barer and S. Tkaczyk, “Refractive index of concentrated protein solutions,” Nature173(4409), 821–822 (1954).
[CrossRef] [PubMed]

R. Barer, J. B. Howie, K. F. Ross, and S. Tkaczyk, “Applications of refractometry in haematology,” J. Physiol.120(4), 67P–68P (1953).
[PubMed]

R. Barer and K. A. Ross, “Refractometry of living cells,” J. Physiol.118(2), 38P–39P (1952).
[PubMed]

Barman, I.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Bashir, R.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Bednarz, M.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Best, C. A.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Best-Popescu, C.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

Billett, H. H.

H. H. Billett, M. E. Fabry, and R. L. Nagel, “Hemoglobin distribution width: a rapid assessment of dense red cells in the steady state and during painful crisis in sickle cell anemia,” J. Lab. Clin. Med.112(3), 339–344 (1988).
[PubMed]

Bishara, W.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

Brazhe, A. R.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Brazhe, N. A.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Brohee, D.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

Brysgalova, N. Y.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Charrière, F.

Choi, W.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Y. K. 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).
[CrossRef] [PubMed]

Chun, I. S.

Cuche, E.

Dasari, R.

Dasari, R. R.

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt.11(4), 040503 (2006).
[CrossRef] [PubMed]

Deflores, L.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

Depeursinge, C.

Diez-Silva, M.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Ding, H.

Z. Wang, L. Millet, M. Mir, H. Ding, S. Unarunotai, J. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express19(2), 1016–1026 (2011).
[CrossRef] [PubMed]

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

Emery, Y.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
[CrossRef] [PubMed]

B. Rappaz, P. Marquet, E. Cuche, Y. Emery, C. Depeursinge, and P. Magistretti, “Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy,” Opt. Express13(23), 9361–9373 (2005).
[CrossRef] [PubMed]

Erlinger, A.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
[CrossRef] [PubMed]

Esposito, A.

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Fabry, M. E.

H. H. Billett, M. E. Fabry, and R. L. Nagel, “Hemoglobin distribution width: a rapid assessment of dense red cells in the steady state and during painful crisis in sickle cell anemia,” J. Lab. Clin. Med.112(3), 339–344 (1988).
[PubMed]

Feld, M. S.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Y. K. 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).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt.11(4), 040503 (2006).
[CrossRef] [PubMed]

Fu, D.

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Gillette, M. U.

Golding, I.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Gov, N. S.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Henle, M. L.

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Howie, J. B.

R. Barer, J. B. Howie, K. F. Ross, and S. Tkaczyk, “Applications of refractometry in haematology,” J. Physiol.120(4), 67P–68P (1953).
[PubMed]

Isikman, S. O.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

Kaminski, C. F.

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Korenstein, R.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
[CrossRef] [PubMed]

Kuriabova, T.

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Levin, G. G.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Levine, A. J.

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

Lew, V. L.

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Li, X.

Lomakin, A. G.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Lue, N.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

Magistretti, P.

Magistretti, P. J.

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
[CrossRef] [PubMed]

B. Rappaz, F. Charrière, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium,” Opt. Lett.33(7), 744–746 (2008).
[CrossRef] [PubMed]

Maksimov, G. V.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Maltsev, V. P.

Marquet, P.

Mauritz, J. M.

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Millet, L.

Mir, M.

Z. Wang, L. Millet, M. Mir, H. Ding, S. Unarunotai, J. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express19(2), 1016–1026 (2011).
[CrossRef] [PubMed]

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

M. Mir, Z. Wang, K. Tangella, and G. Popescu, “Diffraction phase cytometry: blood on a CD-ROM,” Opt. Express17(4), 2579–2585 (2009).
[CrossRef] [PubMed]

Mudanyali, O.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

Müller-Ruchholtz, W.

S. Winoto-Morbach, W. Müller-Ruchholtz, and V. Tchikov, “Magnetophoresis: II. Quantification of iron and hemoglobin content at the single erythrocyte level,” J. Clin. Lab. Anal.9(1), 42–46 (1995).
[CrossRef] [PubMed]

Nagel, R. L.

H. H. Billett, M. E. Fabry, and R. L. Nagel, “Hemoglobin distribution width: a rapid assessment of dense red cells in the steady state and during painful crisis in sickle cell anemia,” J. Lab. Clin. Med.112(3), 339–344 (1988).
[PubMed]

Ong, Z. Y.

Ozcan, A.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
[CrossRef] [PubMed]

Park, Y.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
[CrossRef] [PubMed]

Park, Y. K.

Parshina, E. Y.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Petrov, A. K.

Piagnerelli, M.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

Piro, P.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

Pop, E.

Popescu, G.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Z. Wang, L. Millet, M. Mir, H. Ding, S. Unarunotai, J. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express19(2), 1016–1026 (2011).
[CrossRef] [PubMed]

Z. Wang, I. S. Chun, X. Li, Z. Y. Ong, E. Pop, L. Millet, M. U. Gillette, and G. Popescu, “Topography and refractometry of nanostructures using spatial light interference microscopy,” Opt. Lett.35(2), 208–210 (2010).
[CrossRef] [PubMed]

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Z. Wang and G. Popescu, “Quantitative phase imaging with broadband fields,” Appl. Phys. Lett.96(5), 051117 (2010).
[CrossRef]

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

M. Mir, Z. Wang, K. Tangella, and G. Popescu, “Diffraction phase cytometry: blood on a CD-ROM,” Opt. Express17(4), 2579–2585 (2009).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt.11(4), 040503 (2006).
[CrossRef] [PubMed]

Prasanth, S. G.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Rappaz, B.

Reedy, J.

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

Rogers, J.

Ross, K. A.

R. Barer and K. A. Ross, “Refractometry of living cells,” J. Physiol.118(2), 38P–39P (1952).
[PubMed]

Ross, K. F.

R. Barer, J. B. Howie, K. F. Ross, and S. Tkaczyk, “Applications of refractometry in haematology,” J. Physiol.120(4), 67P–68P (1953).
[PubMed]

Rusciano, G.

G. Rusciano, “Experimental analysis of Hb oxy-deoxy transition in single optically stretched red blood cells,” Phys. Med.26(4), 233–239 (2010).
[CrossRef] [PubMed]

Safran, S. A.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Satterwhite, L. L.

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
[CrossRef] [PubMed]

Schlachter, S.

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Sem’yanov, K. A.

Sencan, I.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

Seo, S.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
[CrossRef] [PubMed]

Shaked, N. T.

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
[CrossRef] [PubMed]

Shen, Z.

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Soini, J. T.

Su, T. W.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
[CrossRef] [PubMed]

Suresh, S.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

Tangella, K.

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

M. Mir, Z. Wang, K. Tangella, and G. Popescu, “Diffraction phase cytometry: blood on a CD-ROM,” Opt. Express17(4), 2579–2585 (2009).
[CrossRef] [PubMed]

Tarasov, P. A.

Tchikov, V.

S. Winoto-Morbach, W. Müller-Ruchholtz, and V. Tchikov, “Magnetophoresis: II. Quantification of iron and hemoglobin content at the single erythrocyte level,” J. Clin. Lab. Anal.9(1), 42–46 (1995).
[CrossRef] [PubMed]

Telen, M. J.

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
[CrossRef] [PubMed]

Tiffert, T.

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Tkaczyk, S.

R. Barer and S. Tkaczyk, “Refractive index of concentrated protein solutions,” Nature173(4409), 821–822 (1954).
[CrossRef] [PubMed]

R. Barer, J. B. Howie, K. F. Ross, and S. Tkaczyk, “Applications of refractometry in haematology,” J. Physiol.120(4), 67P–68P (1953).
[PubMed]

Truskey, G. A.

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
[CrossRef] [PubMed]

Tseng, D. K.

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
[CrossRef] [PubMed]

Unarunotai, S.

Vanhaeverbeek, M.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

Vereerstraeten, A.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

Vincent, J.-L.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

Wang, Z.

Z. Wang, L. Millet, M. Mir, H. Ding, S. Unarunotai, J. Rogers, M. U. Gillette, and G. Popescu, “Spatial light interference microscopy (SLIM),” Opt. Express19(2), 1016–1026 (2011).
[CrossRef] [PubMed]

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Z. Wang, I. S. Chun, X. Li, Z. Y. Ong, E. Pop, L. Millet, M. U. Gillette, and G. Popescu, “Topography and refractometry of nanostructures using spatial light interference microscopy,” Opt. Lett.35(2), 208–210 (2010).
[CrossRef] [PubMed]

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

Z. Wang and G. Popescu, “Quantitative phase imaging with broadband fields,” Appl. Phys. Lett.96(5), 051117 (2010).
[CrossRef]

M. Mir, Z. Wang, K. Tangella, and G. Popescu, “Diffraction phase cytometry: blood on a CD-ROM,” Opt. Express17(4), 2579–2585 (2009).
[CrossRef] [PubMed]

Wax, A.

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
[CrossRef] [PubMed]

Winoto-Morbach, S.

S. Winoto-Morbach, W. Müller-Ruchholtz, and V. Tchikov, “Magnetophoresis: II. Quantification of iron and hemoglobin content at the single erythrocyte level,” J. Clin. Lab. Anal.9(1), 42–46 (1995).
[CrossRef] [PubMed]

Yamauchi, T.

Yusipovich, A. I.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

Zouaoui Boudjeltia, K.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

Am. J. Physiol. Cell Physiol.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

Anal. Chem.

S. Seo, S. O. Isikman, I. Sencan, O. Mudanyali, T. W. Su, W. Bishara, A. Erlinger, and A. Ozcan, “High-throughput lens-free blood analysis on a chip,” Anal. Chem.82(11), 4621–4627 (2010).
[CrossRef] [PubMed]

Appl. Opt.

Appl. Phys. Lett.

Z. Wang and G. Popescu, “Quantitative phase imaging with broadband fields,” Appl. Phys. Lett.96(5), 051117 (2010).
[CrossRef]

Cytometry A

B. Rappaz, A. Barbul, Y. Emery, R. Korenstein, C. Depeursinge, P. J. Magistretti, and P. Marquet, “Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer,” Cytometry A73A(10), 895–903 (2008).
[CrossRef] [PubMed]

J. Appl. Phys.

A. R. Brazhe, A. I. Yusipovich, E. Y. Parshina, N. Y. Brysgalova, N. A. Brazhe, A. G. Lomakin, G. G. Levin, and G. V. Maksimov, “Laser interference microscopy in erythrocyte study,” J. Appl. Phys.105, 102037(2009).

J. Biomed. Opt.

M. Mir, H. Ding, Z. Wang, J. Reedy, K. Tangella, and G. Popescu, “Blood screening using diffraction phase cytometry,” J. Biomed. Opt.15(2), 027016 (2010).
[CrossRef] [PubMed]

N. T. Shaked, L. L. Satterwhite, M. J. Telen, G. A. Truskey, and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry,” J. Biomed. Opt.16(3), 030506 (2011).
[CrossRef] [PubMed]

G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Observation of dynamic subdomains in red blood cells,” J. Biomed. Opt.11(4), 040503 (2006).
[CrossRef] [PubMed]

Y. Park, M. Diez-Silva, D. Fu, G. Popescu, W. Choi, I. Barman, S. Suresh, and M. S. Feld, “Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells,” J. Biomed. Opt.15(2), 020506 (2010).
[CrossRef] [PubMed]

J. Clin. Lab. Anal.

S. Winoto-Morbach, W. Müller-Ruchholtz, and V. Tchikov, “Magnetophoresis: II. Quantification of iron and hemoglobin content at the single erythrocyte level,” J. Clin. Lab. Anal.9(1), 42–46 (1995).
[CrossRef] [PubMed]

J. Clin. Pathol.

M. Piagnerelli, K. Zouaoui Boudjeltia, D. Brohee, A. Vereerstraeten, P. Piro, J.-L. Vincent, and M. Vanhaeverbeek, “Assessment of erythrocyte shape by flow cytometry techniques,” J. Clin. Pathol.60(5), 549–554 (2007).
[CrossRef] [PubMed]

J. Lab. Clin. Med.

H. H. Billett, M. E. Fabry, and R. L. Nagel, “Hemoglobin distribution width: a rapid assessment of dense red cells in the steady state and during painful crisis in sickle cell anemia,” J. Lab. Clin. Med.112(3), 339–344 (1988).
[PubMed]

J. Opt. Soc. Am.

J. Physiol.

R. Barer, J. B. Howie, K. F. Ross, and S. Tkaczyk, “Applications of refractometry in haematology,” J. Physiol.120(4), 67P–68P (1953).
[PubMed]

R. Barer and K. A. Ross, “Refractometry of living cells,” J. Physiol.118(2), 38P–39P (1952).
[PubMed]

Lab Chip

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip9(6), 777–787 (2009).
[CrossRef] [PubMed]

N. Engl. J. Med.

B. J. Bain, “Diagnosis from the blood smear,” N. Engl. J. Med.353(5), 498–507 (2005).
[CrossRef] [PubMed]

Nature

R. Barer and S. Tkaczyk, “Refractive index of concentrated protein solutions,” Nature173(4409), 821–822 (1954).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Phys. Med.

G. Rusciano, “Experimental analysis of Hb oxy-deoxy transition in single optically stretched red blood cells,” Phys. Med.26(4), 233–239 (2010).
[CrossRef] [PubMed]

Phys. Rev. E Stat. Nonlin. Soft Matter Phys.

G. Popescu, Y. Park, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Coherence properties of red blood cell membrane motions,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.76(3), 031902 (2007).
[CrossRef] [PubMed]

PLoS ONE

A. Esposito, T. Tiffert, J. M. Mauritz, S. Schlachter, L. H. Bannister, C. F. Kaminski, and V. L. Lew, “FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells,” PLoS ONE3(11), e3780 (2008).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

Y. Park, C. A. Best, T. Auth, N. S. Gov, S. A. Safran, G. Popescu, S. Suresh, and M. S. Feld, “Metabolic remodeling of the human red blood cell membrane,” Proc. Natl. Acad. Sci. U.S.A.107(4), 1289–1294 (2010).
[CrossRef] [PubMed]

Y. Park, C. A. Best, K. Badizadegan, R. R. Dasari, M. S. Feld, T. Kuriabova, M. L. Henle, A. J. Levine, and G. Popescu, “Measurement of red blood cell mechanics during morphological changes,” Proc. Natl. Acad. Sci. U.S.A.107(15), 6731–6736 (2010).
[CrossRef] [PubMed]

M. Mir, Z. Wang, Z. Shen, M. Bednarz, R. Bashir, I. Golding, S. G. Prasanth, and G. Popescu, “Optical measurement of cycle-dependent cell growth,” Proc. Natl. Acad. Sci. U.S.A.108(32), 13124–13129 (2011).
[CrossRef] [PubMed]

Other

S. Prahl, “Tabulated molar extinction coefficient for hemoglobin in water” (1998), http://omlc.ogi.edu/spectra/hemoglobin/summary.html .

B. J. Bain, Blood Cells A Practical Guide, 3rd ed. (Blackwell Science, London, 2002).

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Figures (3)

Fig. 1
Fig. 1

Experimental setup. The SLIM system is built as an add-on module to a commercial phase contrast microscope. The back focal plane of the objective is projected onto a spatial light modulator which is calibrated to impart a phase shift to the un-scattered light (yellow lines) relative to the scattered light (shown in red). Four intensity images are recorded corresponding to 4 phase shifts in increments of π/2, the quantitative phase map is reconstructed from these 4 intensity images as detailed in Ref. [26]. For the SLIM measurements the illumination type is set to phase contrast and the filter wheel is set to an open position such that the entire spectrum of the halogen lamp is passed. For the absorption measurements the illumination type is set to bright field and a 430 nm filter is used in the filter wheel. The inset for the filter wheel shows the normalized intensity of the white light spectrum, the spectrum of the 430 nm bandpass filter (right axis) and the extinction coefficients of oxygenated and deoxygenated hemoglobin (left axis) as a function of wavelength from Ref. [33].

Fig. 2
Fig. 2

Image analysis (a) Quantitative phase map acquired using SLIM, color bar is in radians. (b) Absorption map acquired at 430 nm, color bar is in 16-bit gray scale values. (a-b) Insets show an example of a single RBC from the maps. (c) Overlay of l line profiles drawn through the center of a single cell, the phase values are shown in red against the left axis and the corresponding intensity from the absorption maps are shown in black against the right axis. (d) Average absorption vs. phase for each of the 7 patients analyzed in this study, a strong linear relationship (dotted line) indicates the feasibility of this method. For the cell shown here the volume and hemoglobin concentration were calculated to be 86.18 fL and 0.3 g/mL respectively.

Fig. 3
Fig. 3

Comparison of measured mean values with clinically reported values. (a) Mean Cell Volume, red error bars correspond to the SD reported by the Clinic and black error bars correspond to SD measured by the QPI and absorption measurements (b) Mean Cell Hemoglobin Concentration, error bars correspond to the measured SD, no SD information on the hemoglobin concentration is available from the Clinic. The dashed black lines have a slope of one.

Equations (6)

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

Δϕ(x,y)= k 0 Δn(x,y)t(x,y)
Δϕ(x,y)= k 0 [ βC(x,y)+Δ n ws ]t(x,y)
A=ln( I I 0 )=σtN
A'(x,y)= log 10 ( I I 0 )= εt(x,y)C(x,y) M
C(x,y)= Δ n ws ε M k 0 Δϕ(x,y) A'(x,y) β
t(x,y)= MA'(x,y) εC(x,y)

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