Abstract

A spectroscopic microscope, configured to detect interference spectra of backscattered light in the far zone, quantifies the statistics of refractive-index (RI) distribution via the spectral variance (Σ˜2) of the acquired bright-field image. Its sensitivity to subtle structural changes within weakly scattering, label-free media at subdiffraction scales shows great promise in fields from material science to medical diagnostics. We further investigate the length-scale sensitivity of Σ˜ and reveal that, in theory, it can detect RI fluctuations at any spatial frequency whatsoever. Based on a 5% noise floor, Σ˜ detects scales from 22 to 200–700 nm (exact values depend on sample structure and thickness). In an example involving mass-density distribution characteristic of biological cell nuclei, we suggest the level of chromatin organization, which can be quantified via Σ˜.

© 2014 Optical Society of America

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  1. L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
    [CrossRef]
  2. H. G. Davies, M. H. F. Wilkins, J. Chayen, and L. F. La Cour, Q. J. Microsc. Sci. s3–95, 271 (1954).
  3. G. C. Crossmon, Stain Technol. 24, 241 (1949).
  4. A. J. Radosevich, J. Yi, J. D. Rogers, and V. Backman, Opt. Lett. 37, 5220 (2012).
    [CrossRef]
  5. L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).
  6. H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, Opt. Lett. 34, 518 (2009).
    [CrossRef]

2014 (1)

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

2013 (1)

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

2012 (1)

2009 (1)

1954 (1)

H. G. Davies, M. H. F. Wilkins, J. Chayen, and L. F. La Cour, Q. J. Microsc. Sci. s3–95, 271 (1954).

1949 (1)

G. C. Crossmon, Stain Technol. 24, 241 (1949).

Backman, V.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

A. J. Radosevich, J. Yi, J. D. Rogers, and V. Backman, Opt. Lett. 37, 5220 (2012).
[CrossRef]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, Opt. Lett. 34, 518 (2009).
[CrossRef]

Bianchi, L. K.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

Brand, R. E.

Capoglu, I.

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

Capoglu, I. R.

Chayen, J.

H. G. Davies, M. H. F. Wilkins, J. Chayen, and L. F. La Cour, Q. J. Microsc. Sci. s3–95, 271 (1954).

Cherkezyan, L.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

Crossmon, G. C.

G. C. Crossmon, Stain Technol. 24, 241 (1949).

Damania, D.

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

Davies, H. G.

H. G. Davies, M. H. F. Wilkins, J. Chayen, and L. F. La Cour, Q. J. Microsc. Sci. s3–95, 271 (1954).

Dela Cruz, M.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

Goldberg, M. J.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

La Cour, L. F.

H. G. Davies, M. H. F. Wilkins, J. Chayen, and L. F. La Cour, Q. J. Microsc. Sci. s3–95, 271 (1954).

Liu, Y.

Pradhan, P.

Radosevich, A. J.

Rogers, J. D.

Roy, H. K.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, Opt. Lett. 34, 518 (2009).
[CrossRef]

Stypula-Cyrus, Y.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

Subramanian, H.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, J. D. Rogers, H. K. Roy, R. E. Brand, and V. Backman, Opt. Lett. 34, 518 (2009).
[CrossRef]

Taflove, A.

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

Wali, R. K.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

White, C.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

Wilkins, M. H. F.

H. G. Davies, M. H. F. Wilkins, J. Chayen, and L. F. La Cour, Q. J. Microsc. Sci. s3–95, 271 (1954).

Yi, J.

BMC Cancer (1)

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, BMC Cancer 14, 189 (2014).

Opt. Lett. (2)

Phys. Rev. Lett. (1)

L. Cherkezyan, I. Capoglu, H. Subramanian, J. D. Rogers, D. Damania, A. Taflove, and V. Backman, Phys. Rev. Lett. 111, 033903 (2013).
[CrossRef]

Q. J. Microsc. Sci. (1)

H. G. Davies, M. H. F. Wilkins, J. Chayen, and L. F. La Cour, Q. J. Microsc. Sci. s3–95, 271 (1954).

Stain Technol. (1)

G. C. Crossmon, Stain Technol. 24, 241 (1949).

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Figures (5)

Fig. 1.
Fig. 1.

(a) Cross section of a single spatial-frequency medium with n1/kLS of 100 nm. (b) Cross section of nΔ(r) with an exponential SCF and the corresponding (c) nΔl(r) and (d) nΔh(r) for W=100nm.

Fig. 2.
Fig. 2.

(a) Cross section of PSD of nΔ(r) (red) with kLS>2k2, and the PSD of the abridged sample nΔ(r) (blue). (b) Σ˜/σnΓ012 as a function of the spatial frequency of RI fluctuations for samples with different thicknesses (all wavenumbers evaluated inside the sample). Γ012 denotes (n0n1)2/(n0+n1)2.

Fig. 3.
Fig. 3.

Decrease in Σ˜ measured from samples with different thicknesses when (a) low and (b) high LS are perturbed. Data shown for RI correlation length of 100 nm. Dotted horizontal line indicates the threshold of a 5% change in Σ˜.

Fig. 4.
Fig. 4.

Dependence of (a) rmin and (b) rmax corresponding to the 5% threshold on L and lc. Black dashed lines indicate rmin=22nm and rmax=171nm corresponding to L=.

Fig. 5.
Fig. 5.

Relative change in Σ˜ when (a) lower (Σ˜l/Σ˜) and (b) higher (Σ˜h/Σ˜) LS are perturbed. Calculation performed for samples with SCF, which is experimentally measured from TEM images (blue markers for samples with thickness 1.5 μm and green for 6.0 μm) and analytically defined as exponential (blue solid line for L=1.5 and green-dashed for L=6.0μm).

Equations (2)

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

Σ˜2=Γ2kc2LΔkT3DΦnΔ(k)d3k,
Σ˜l2=Γ2kc2LΔkT3D|F{nΔ}F{G}F{TL}|2d3k,Σ˜h2=Γ2kc2LΔkT3D|F{nΔ}[1F{G}]F{TL}|2d3k.

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