Abstract

We report a practical method for label-free quantification of specific molecules using spectroscopic imaging of sample-induced phase shifts. Diffraction phase microscopy equipped with various wavelengths of light source is used to record wavelength-dependent phase images. We first perform dispersion measurements on pure solutions of single molecular species present in the cells, such as albumin and hemoglobin (Hb). With this prior calibration of molecular specific dispersion, we demonstrate the extraction of Hb concentration from individual human red blood cells. The end point of this study is noninvasive monitoring of physiological states of intact living cells.

© 2009 Optical Society of America

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2009 (2)

2008 (5)

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

G. Popescu, Y. Park, W. Choi, R. Dasari, M. Feld, and K. Badizadegan, Blood Cells Mol. Dis. 41, 10 (2008).
[CrossRef] [PubMed]

B. Kemper and G. von Bally, Appl. Opt. 47, 52 (2008).
[CrossRef]

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

B. Rappaz, F. Charriere, C. Depeursinge, P. J. Magistretti, and P. Marquet, Opt. Lett. 33, 744 (2008).
[CrossRef] [PubMed]

2006 (3)

2005 (1)

2004 (1)

2000 (1)

1999 (1)

1998 (1)

1990 (1)

P. Schiebener, J. Straub, J. Sengers, and J. Gallagher, J. Phys. Chem. Ref. Data 19, 677 (1990).
[CrossRef]

1974 (1)

M. Andersen, L. Painter, and S. Nir, Biopolymers 13, 1261 (1974).
[CrossRef]

1953 (1)

R. Barer, Nature 172, 1097 (1953).
[CrossRef] [PubMed]

Akkin, T.

Andersen, M.

M. Andersen, L. Painter, and S. Nir, Biopolymers 13, 1261 (1974).
[CrossRef]

Badizadegan, K.

Barer, R.

R. Barer, Nature 172, 1097 (1953).
[CrossRef] [PubMed]

Barty, A.

Best-Popescu, C.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

Bevilacqua, F.

Charriere, F.

Choi, W.

Y. Park, W. Choi, Z. Yaqoob, R. Dasari, K. Badizadegan, and M. Feld, Opt. Express 17, 12285 (2009).
[CrossRef] [PubMed]

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, W. Choi, R. Dasari, M. Feld, and K. Badizadegan, Blood Cells Mol. Dis. 41, 10 (2008).
[CrossRef] [PubMed]

Cuche, E.

Dasari, R.

Y. Park, W. Choi, Z. Yaqoob, R. Dasari, K. Badizadegan, and M. Feld, Opt. Express 17, 12285 (2009).
[CrossRef] [PubMed]

G. Popescu, Y. Park, W. Choi, R. Dasari, M. Feld, and K. Badizadegan, Blood Cells Mol. Dis. 41, 10 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

C. Yang, A. Wax, I. Georgakoudi, E. Hanlon, K. Badizadegan, R. Dasari, and M. Feld, Opt. Lett. 25, 1526 (2000).
[CrossRef]

Dasari, R. R.

Davé, D. P.

Deflores, L.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

Depeursinge, C.

Diez-Silva, M.

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

Diller, K. R.

Emery, Y.

Feld, M.

Y. Park, W. Choi, Z. Yaqoob, R. Dasari, K. Badizadegan, and M. Feld, Opt. Express 17, 12285 (2009).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

G. Popescu, Y. Park, W. Choi, R. Dasari, M. Feld, and K. Badizadegan, Blood Cells Mol. Dis. 41, 10 (2008).
[CrossRef] [PubMed]

C. Yang, A. Wax, I. Georgakoudi, E. Hanlon, K. Badizadegan, R. Dasari, and M. Feld, Opt. Lett. 25, 1526 (2000).
[CrossRef]

Feld, M. S.

Friebel, M.

Gallagher, J.

P. Schiebener, J. Straub, J. Sengers, and J. Gallagher, J. Phys. Chem. Ref. Data 19, 677 (1990).
[CrossRef]

Georgakoudi, I.

Hanlon, E.

Ikeda, T.

Kemper, B.

Lichtman, M.

M. Lichtman, Williams Hematology (McGraw-Hill Professional, 2005).

Lue, N.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

Lykotrafitis, G.

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

Magistretti, P. J.

Marquet, M.

Marquet, P.

Meinke, M.

Milner, T. E.

Nir, S.

M. Andersen, L. Painter, and S. Nir, Biopolymers 13, 1261 (1974).
[CrossRef]

Nugent, K.

Paganin, D.

Painter, L.

M. Andersen, L. Painter, and S. Nir, Biopolymers 13, 1261 (1974).
[CrossRef]

Park, Y.

Y. Park, W. Choi, Z. Yaqoob, R. Dasari, K. Badizadegan, and M. Feld, Opt. Express 17, 12285 (2009).
[CrossRef] [PubMed]

G. Popescu, Y. Park, W. Choi, R. Dasari, M. Feld, and K. Badizadegan, Blood Cells Mol. Dis. 41, 10 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

Park, Y. K.

Park, Y.-K.

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

Popescu, G.

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

G. Popescu, Y. Park, W. Choi, R. Dasari, M. Feld, and K. Badizadegan, Blood Cells Mol. Dis. 41, 10 (2008).
[CrossRef] [PubMed]

Y. K. Park, G. Popescu, K. Badizadegan, R. R. Dasari, and M. S. Feld, Opt. Express 14, 8263 (2006).
[CrossRef] [PubMed]

G. Popescu, T. Ikeda, R. R. Dasari, and M. S. Feld, Opt. Lett. 31, 775 (2006).
[CrossRef] [PubMed]

Rappaz, B.

Reinhart, M.

Roberts, A.

Rylander, C. G.

Schiebener, P.

P. Schiebener, J. Straub, J. Sengers, and J. Gallagher, J. Phys. Chem. Ref. Data 19, 677 (1990).
[CrossRef]

Sengers, J.

P. Schiebener, J. Straub, J. Sengers, and J. Gallagher, J. Phys. Chem. Ref. Data 19, 677 (1990).
[CrossRef]

Shaked, N.

Straub, J.

P. Schiebener, J. Straub, J. Sengers, and J. Gallagher, J. Phys. Chem. Ref. Data 19, 677 (1990).
[CrossRef]

Suresh, S.

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

von Bally, G.

Wax, A.

Welch, A. J.

Yang, C.

Yaqoob, Z.

Am. J. Physiol.: Cell Physiol. (1)

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. Dasari, M. Feld, and K. BadizadeganAm. J. Physiol.: Cell Physiol. 295, C538 (2008).
[CrossRef]

Appl. Opt. (2)

Biopolymers (1)

M. Andersen, L. Painter, and S. Nir, Biopolymers 13, 1261 (1974).
[CrossRef]

Blood Cells Mol. Dis. (1)

G. Popescu, Y. Park, W. Choi, R. Dasari, M. Feld, and K. Badizadegan, Blood Cells Mol. Dis. 41, 10 (2008).
[CrossRef] [PubMed]

J. Phys. Chem. Ref. Data (1)

P. Schiebener, J. Straub, J. Sengers, and J. Gallagher, J. Phys. Chem. Ref. Data 19, 677 (1990).
[CrossRef]

Nature (1)

R. Barer, Nature 172, 1097 (1953).
[CrossRef] [PubMed]

Opt. Express (3)

Opt. Lett. (7)

Proc. Natl. Acad. Sci. USA (1)

Y.-K. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, Proc. Natl. Acad. Sci. USA 105, 13730 (2008).
[CrossRef] [PubMed]

Other (1)

M. Lichtman, Williams Hematology (McGraw-Hill Professional, 2005).

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Figures (3)

Fig. 1
Fig. 1

Experimental setup.

Fig. 2
Fig. 2

(a)–(c) Interferograms of PDMS channel filled with Hb solution. (d)–(f) Corresponding quantitative phase maps. (g) RIs of PDMS, BSA, and water. RIs of water are adopted from [16]. Inset, RI difference between BSA solution and water. (h) Measured dispersion of Hb solutions (symbols) and comparison with [18] (lines). Error bars indicate standard deviations.

Fig. 3
Fig. 3

(a)–(c) Quantitative phase maps of an RBC at three different wavelengths. (d) Retrieved Hb concentration. Histogram of (e) Hb concentration and (f) mean cell volumes ( N = 25 ) .

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