Abstract

A microscopy technique, spatial-domain low-coherence quantitative phase microscopy (SL-QPM) is proposed for speckle-free, quantitative phase imaging of subcellular structures with subnanometer sensitivity. We quantified, for the first time to our knowledge, the refractive index of the cell nuclei on original unmodified histology specimens. We demonstrate that the refractive index of cell nucleus is highly sensitive in detecting cancer, especially in histologically normal-appearing cells from cancer patients. Because this technique is sensitive and does not require special sample processing, it can be disseminated to all clinical settings.

© 2010 Optical Society of America

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References

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2008 (1)

2006 (1)

2005 (2)

2004 (1)

2003 (1)

2001 (1)

Akkin, T.

Backman, V.

Badizadegan, K.

Cense, B.

Choi, W.

Chu, M. C.

Dasari, R. R.

de Boer, J. F.

Fang-Yen, C.

Feld, M. S.

Indebetouw, G.

Izatt, J. A.

Joo, C.

Kim, Y. L.

Klysubun, P.

Li, X.

Liu, Y.

Lue, N.

Naser-Kolahzadeh, Z. P.

Z. P. Naser-Kolahzadeh and J. G. Stavrianopoulos, “Mounting medium for microscope slide preparations,” U.S. patent 5,492,837 (February 20, 1996).

Park, B. H.

Popescu, G.

Sarunic, M. V.

Seung, H. S.

Stavrianopoulos, J. G.

Z. P. Naser-Kolahzadeh and J. G. Stavrianopoulos, “Mounting medium for microscope slide preparations,” U.S. patent 5,492,837 (February 20, 1996).

Wax, A.

Weinberg, S.

Yang, C.

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Figures (3)

Fig. 1
Fig. 1

Signal processing steps of SL-QPM system. The spectrum from each pixel (bandwidth from 500 to 620 nm ) is interpolated, windowed prior to performing fast Fourier transform. The predominant peak corresponding to the depth of interest is chosen for phase processing. The two-dimensional quantitative phase map can be obtained by repeating these steps pixel by pixel. The scale bar indicates 5 μm .

Fig. 2
Fig. 2

(a) Depth profile of USAF resolution target showing elements of group 7. The color bar represents the unit of nanometer. (b) Phase map of a 5 μm polystyrene microsphere. The color bar represents the phase in radians. Phase unwrapping program is used to correct the phase jump of 2 π .

Fig. 3
Fig. 3

(a) Representative histology images and the corresponding refractive index maps of cell nuclei from (a) normal, (b) uninvolved, and (c) malignant cells. The scale bar indicates 5 μm . (b) By analyzing approximately 30 cell nuclei per group, the average refractive indices of malignant and uninvolved cell nuclei are significantly increased when compared to the normal cell nuclei (t-test, two-sided P value < 0.001 ).

Equations (4)

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I ( x , y , k ) = | E r ( x , y , k ) | 2 + | E s ( x , y , k ) | 2 + 2 | E r ( x , y , k ) | | E s ( x , y , k ) | cos ( φ ( x , y ) ) ,
φ ( z ) | ( x , y ) = tan 1 { Im ( F ( z ) ) / Re ( F ( z ) ) }
δ ( OPL ) = [ λ 0 φ ( x , y ) ] / ( 4 π ) ,
OPL ( x , y ) = n ( x , y ) L ( x , y ) ,

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