Abstract

Existing optical imaging techniques offer us powerful tools to directly visualize the cellular structure at the microscale; however, their capability of nanoscale sensitivity is restricted by the diffraction-limited resolution. We show that the mesoscopic light transport theory analysis of the spectra of partial waves propagating within a weakly disordered medium, such as biological cells [i.e., partial wave spectroscopy (PWS)] quantifies refractive index fluctuations at subdiffractional length scales. We validate this nanoscale sensitivity of PWS using experiments with nanostructured models. We also demonstrate the potential of this technique to detect nanoscale alterations in cells from patients with pancreatic cancer who are otherwise classified as normal by conventional microscopic histopathology.

© 2009 Optical Society of America

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  1. K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
    [CrossRef] [PubMed]
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    [CrossRef]
  4. R. Rammal and B. Doucot, J. Phys. (Paris) 48, 509 (1987).
    [CrossRef]
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    [CrossRef] [PubMed]
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2008 (1)

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

2007 (1)

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

2006 (1)

M. Bartek, X. Wang, W. Wells, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 11, 064007 (2006).
[CrossRef]

2005 (2)

K. Chen, A. Taflove, Y. L. Kim, and V. Backman, Appl. Phys. Lett. 86, 033101 (2005).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, Opt. Lett. 30, 2445 (2005).
[CrossRef] [PubMed]

1994 (2)

1992 (1)

S. B. Haley and P. Erdos, Phys. Rev. B 45, 8572 (1992).
[CrossRef]

1987 (1)

R. Rammal and B. Doucot, J. Phys. (Paris) 48, 509 (1987).
[CrossRef]

Backman, V.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

K. Chen, A. Taflove, Y. L. Kim, and V. Backman, Appl. Phys. Lett. 86, 033101 (2005).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, Opt. Lett. 30, 2445 (2005).
[CrossRef] [PubMed]

Baird, M.

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

Bartek, M.

M. Bartek, X. Wang, W. Wells, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 11, 064007 (2006).
[CrossRef]

Capoglu, I. R.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Chalut, K. J.

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

Chen, K.

K. Chen, A. Taflove, Y. L. Kim, and V. Backman, Appl. Phys. Lett. 86, 033101 (2005).
[CrossRef]

Doucot, B.

R. Rammal and B. Doucot, J. Phys. (Paris) 48, 509 (1987).
[CrossRef]

Erdos, P.

S. B. Haley and P. Erdos, Phys. Rev. B 45, 8572 (1992).
[CrossRef]

Haley, S. B.

S. B. Haley and P. Erdos, Phys. Rev. B 45, 8572 (1992).
[CrossRef]

Heifetz, A.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Kim, Y. L.

K. Chen, A. Taflove, Y. L. Kim, and V. Backman, Appl. Phys. Lett. 86, 033101 (2005).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, Opt. Lett. 30, 2445 (2005).
[CrossRef] [PubMed]

Kresty, L. A.

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

Kumar, N.

P. Pradhan and N. Kumar, Phys. Rev. B 50, 9644 (1994).
[CrossRef]

Kunte, D.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Lam, S.

Li, X.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, Opt. Lett. 30, 2445 (2005).
[CrossRef] [PubMed]

Liu, Y.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, Opt. Lett. 30, 2445 (2005).
[CrossRef] [PubMed]

Macaulay, C.

Nines, R.

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

Palcic, B.

Paulsen, K. D.

M. Bartek, X. Wang, W. Wells, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 11, 064007 (2006).
[CrossRef]

Pogue, B. W.

M. Bartek, X. Wang, W. Wells, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 11, 064007 (2006).
[CrossRef]

Pradhan, P.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

P. Pradhan and N. Kumar, Phys. Rev. B 50, 9644 (1994).
[CrossRef]

Pyhtila, J. W.

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

Qu, J. N.

Rammal, R.

R. Rammal and B. Doucot, J. Phys. (Paris) 48, 509 (1987).
[CrossRef]

Rodgers, J. D.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Roy, H. K.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Steele, V. E.

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

Subramanian, H.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

Taflove, A.

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

K. Chen, A. Taflove, Y. L. Kim, and V. Backman, Appl. Phys. Lett. 86, 033101 (2005).
[CrossRef]

Wang, X.

M. Bartek, X. Wang, W. Wells, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 11, 064007 (2006).
[CrossRef]

Wax, A.

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

Wells, W.

M. Bartek, X. Wang, W. Wells, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 11, 064007 (2006).
[CrossRef]

Appl. Opt. (1)

Appl. Phys. Lett. (1)

K. Chen, A. Taflove, Y. L. Kim, and V. Backman, Appl. Phys. Lett. 86, 033101 (2005).
[CrossRef]

Cancer Epidemiol. Biomarkers Prev. (1)

K. J. Chalut, L. A. Kresty, J. W. Pyhtila, R. Nines, M. Baird, V. E. Steele, and A. Wax, Cancer Epidemiol. Biomarkers Prev. 16, 223 (2007).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

M. Bartek, X. Wang, W. Wells, K. D. Paulsen, and B. W. Pogue, J. Biomed. Opt. 11, 064007 (2006).
[CrossRef]

J. Phys. (Paris) (1)

R. Rammal and B. Doucot, J. Phys. (Paris) 48, 509 (1987).
[CrossRef]

Opt. Lett. (1)

Phys. Rev. B (2)

P. Pradhan and N. Kumar, Phys. Rev. B 50, 9644 (1994).
[CrossRef]

S. B. Haley and P. Erdos, Phys. Rev. B 45, 8572 (1992).
[CrossRef]

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

H. Subramanian, P. Pradhan , Y. Liu, I. R. Capoglu, X. Li, J. D. Rodgers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, Proc. Natl. Acad. Sci. USA 105, 20124 (2008).
[CrossRef]

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Figures (3)

Fig. 1
Fig. 1

(a) Normalized backscattering spectrum I ( λ ) from a single pixel of a biological cell (solid blue) and a pure glass slide (dashed red) with the I p ( λ ) (black). (b) The corresponding spectrum R ( λ ) obtained from a biological cell (solid blue) and from a pure glass slide (dashed red).

Fig. 2
Fig. 2

Validation of the nanoscale sensitivity of L d using experimental nanostructured model media.

Fig. 3
Fig. 3

(a) Representative bright field image and (b) corresponding pseudocolor L d map recorded from three different cell types: N, C, and CN. (c) and (d) L d ( c ) and σ ( c ) for different cell types. Error bars are the standard errors of the mean.

Equations (1)

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L d = B n 0 2 2 k 2 R ( Δ k ) 2 ln ( C ( Δ k ) ) ,

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