Abstract

We use optical Fourier processing based on two dimensional (2D) Gabor filters to obtain size-encoded images which depict with 20nm sensitivity to size while preserving a 0.36μm spatial resolution, the spatial distribution of structural features within transparent objects. The size of the object feature measured at each pixel in the encoded image is determined by the optimal Gabor filter period, Smax, that maximizes the scattering signal from that location in the object. We show that Smax (in μm) depends linearly on feature size (also in μm) over a size range from 0.11μm to 2μm. This linear response remains largely unchanged when the refractive index ratio is varied and can be predicted from numerical simulations of Gabor-filtered light scattering. Pixel histograms of the size-encoded images of isolated spheres and diatoms were used to generate highly resolved size distributions (“size spectra”) exhibiting sharp peaks characterizing the known major structural features within the studied objects. Dynamic signal associated with changes in selected feature sizes within living cells is also demonstrated. Taken together, our data suggest that a label-free, direct and objective measurement of sample structure is enabled by the size-encoded images and associated pixel histograms generated from a calibrated optical processing microscope based on Gabor filtering.

© 2012 OSA

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    [CrossRef] [PubMed]
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2009 (3)

2008 (1)

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

2007 (3)

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

C. S. Mulvey, A. L. Curtis, S. K. Singh, and I. J. Bigio, “Elastic scattering spectroscopy as a diagnostic tool for apoptosis in cell cultures,” IEEE J. Sel. Top. Quantum Electron.13(6), 1663–1670 (2007).
[CrossRef]

W. J. Cottrell, J. D. Wilson, and T. H. Foster, “Microscope enabling multimodality imaging, angle-resolved scattering, and scattering spectroscopy,” Opt. Lett.32(16), 2348–2350 (2007).
[CrossRef] [PubMed]

2006 (1)

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

2005 (1)

2003 (1)

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

2002 (1)

N. N. Boustany, R. Drezek, and N. V. Thakor, “Calcium-Induced Alterations in Mitochondrial Morphology Quantified in Situ with Optical Scatter Imaging,” Biophys. J.83(3), 1691–1700 (2002).
[CrossRef] [PubMed]

1985 (1)

Andersson, C.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Backman, V.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Berciaud, S.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Bigio, I.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Bigio, I. J.

C. S. Mulvey, A. L. Curtis, S. K. Singh, and I. J. Bigio, “Elastic scattering spectroscopy as a diagnostic tool for apoptosis in cell cultures,” IEEE J. Sel. Top. Quantum Electron.13(6), 1663–1670 (2007).
[CrossRef]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Boustany, N. N.

Capoglu, I. R.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Chalut, K. J.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Cipolloni, P. B.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Cognet, L.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Cottrell, W. J.

Curtis, A. L.

C. S. Mulvey, A. L. Curtis, S. K. Singh, and I. J. Bigio, “Elastic scattering spectroscopy as a diagnostic tool for apoptosis in cell cultures,” IEEE J. Sel. Top. Quantum Electron.13(6), 1663–1670 (2007).
[CrossRef]

Daugman, J. G.

Drezek, R.

N. N. Boustany, R. Drezek, and N. V. Thakor, “Calcium-Induced Alterations in Mitochondrial Morphology Quantified in Situ with Optical Scatter Imaging,” Biophys. J.83(3), 1691–1700 (2002).
[CrossRef] [PubMed]

Fang, H.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Foster, T. H.

Freedman, S. D.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Ghiran, I. C.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Giacomelli, M. G.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Hanlon, E. B.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Heifetz, A.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Itzkan, I.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Kimerer, L. M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Kunte, D.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Lasne, D.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Li, X.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Lim, K. H.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Lippitz, M.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Liu, Y.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Lounis, B.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Metaxas, D. N.

Modell, M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Mulvey, C. S.

C. S. Mulvey, A. L. Curtis, S. K. Singh, and I. J. Bigio, “Elastic scattering spectroscopy as a diagnostic tool for apoptosis in cell cultures,” IEEE J. Sel. Top. Quantum Electron.13(6), 1663–1670 (2007).
[CrossRef]

Ollero, M.

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Orrit, M.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Ostrander, J. H.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Pasternack, R. M.

Perelman, L. T.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Pradhan, P.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Qian, Z.

Qiu, L.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Rogers, J. D.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Roy, H. K.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Sachs, B. P.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Salahuddin, S.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Singh, S. K.

C. S. Mulvey, A. L. Curtis, S. K. Singh, and I. J. Bigio, “Elastic scattering spectroscopy as a diagnostic tool for apoptosis in cell cultures,” IEEE J. Sel. Top. Quantum Electron.13(6), 1663–1670 (2007).
[CrossRef]

Subramanian, H.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Taflove, A.

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Tchebotareva, A. L.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Thakor, N. V.

N. N. Boustany, R. Drezek, and N. V. Thakor, “Calcium-Induced Alterations in Mitochondrial Morphology Quantified in Situ with Optical Scatter Imaging,” Biophys. J.83(3), 1691–1700 (2002).
[CrossRef] [PubMed]

van Dijk, M. A.

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Virkin, E.

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Vitkin, E.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

Wax, A.

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

Wilson, J. D.

Zaman, M. M.

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

Zheng, J.-Y.

Biophys. J. (1)

N. N. Boustany, R. Drezek, and N. V. Thakor, “Calcium-Induced Alterations in Mitochondrial Morphology Quantified in Situ with Optical Scatter Imaging,” Biophys. J.83(3), 1691–1700 (2002).
[CrossRef] [PubMed]

Cancer Res. (1)

K. J. Chalut, J. H. Ostrander, M. G. Giacomelli, and A. Wax, “Light scattering measurements of subcellular structure provide noninvasive early detection of chemotherapy-induced apoptosis,” Cancer Res.69(3), 1199–1204 (2009).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (2)

H. Fang, M. Ollero, E. Virkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron.9(2), 267–276 (2003).
[CrossRef]

C. S. Mulvey, A. L. Curtis, S. K. Singh, and I. J. Bigio, “Elastic scattering spectroscopy as a diagnostic tool for apoptosis in cell cultures,” IEEE J. Sel. Top. Quantum Electron.13(6), 1663–1670 (2007).
[CrossRef]

J. Opt. Soc. Am. A (1)

Opt. Express (2)

Opt. Lett. (2)

Phys. Chem. Chem. Phys. (1)

M. A. van Dijk, A. L. Tchebotareva, M. Orrit, M. Lippitz, S. Berciaud, D. Lasne, L. Cognet, and B. Lounis, “Absorption and scattering microscopy of single metal nanoparticles,” Phys. Chem. Chem. Phys.8(30), 3486–3495 (2006).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

I. Itzkan, L. Qiu, H. Fang, M. M. Zaman, E. Vitkin, I. C. Ghiran, S. Salahuddin, M. Modell, C. Andersson, L. M. Kimerer, P. B. Cipolloni, K. H. Lim, S. D. Freedman, I. Bigio, B. P. Sachs, E. B. Hanlon, and L. T. Perelman, “Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels,” Proc. Natl. Acad. Sci. U.S.A.104(44), 17255–17260 (2007).
[CrossRef] [PubMed]

H. Subramanian, P. Pradhan, Y. Liu, I. R. Capoglu, X. Li, J. D. Rogers, A. Heifetz, D. Kunte, H. K. Roy, A. Taflove, and V. Backman, “Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20118–20123 (2008).
[CrossRef] [PubMed]

Other (1)

D. B. Murphy, Fundamentals of Light Microscopy and Electronic Imaging (Wiley, New York) (2001).

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Figures (5)

Fig. 1
Fig. 1

(a) The object scattering pattern (colormap) is sequentially filtered by a set of Gabor filters (2D gray Gaussians) in Fourier space. (b) A dark-field image stack of the object is collected in which each filtered image corresponds to the application of a different Gabor filter in Fourier space. (c) and (d) The first analysis consisted of segmenting filtered sphere images and analyzing the signal from each whole sphere segment as a function of Gabor filter period. Data in (d) show the measured (red line) and simulated (blue line) signal for a 0.86µm diameter sphere segment, and Smax(segment), the Gabor period at which the maximum signal occurs. (e) and (f), the second analysis consisted of finding Smax, the optimum Gabor period resulting in maximum signal, at each pixel within the filtered image stack. A profile of Smax, is shown in (f) for a line of pixels taken across the center of a 0.11µm sphere within the Smax-encoded image shown in (e).

Fig. 2
Fig. 2

Gabor filter period Smax(segment) giving maximum signal plotted against sphere diameter. The signal was measured within image segments encompassing a whole sphere. Experimental data for spheres suspended in an aqueous gel (filled black circles) or immersion oil (filled red circles) are shown along with theoretical predictions based on Mie theory (connected open black and red circles for suspensions in gel and oil respectively). The solid red and black lines are linear fits to the experimental data and have a slope of 2.23. Experimental data are mean +/− standard deviation for measurements from 10 isolated sphere segments. Simulated data from a cube with its side oriented perpendicular to the incident field are also shown (connected green open squares).

Fig. 3
Fig. 3

(a): Size-encoded images of two samples of PMMA spheres with 0.71µm and 0.73µm diameter suspended in gel. At each pixel, the color scale encodes Smax, the Gabor filter period giving maximum signal. For clarity only a limited field of view ~36µm × 36µm (156pixels × 156pixels) is shown. (b): Pixel histograms of the size-encoded images of the two sphere samples.

Fig. 4
Fig. 4

Size-encoded images of pleurosigma angulatum diatom and associated pixel histograms shown for Gabor filter orientations at φ = 0 (left panels) and φ = 90° (right panels). The colorscale in the images encodes Smax, the Gabor filter period resulting in maximum signal at each pixel. The inset in the top right panels depicts the expected arrangement of the holes in the diatom’s frustule. For clarity, histograms show only the pixels values below 0.7µm.

Fig. 5
Fig. 5

(a) Size-encoded images of an endothelial cell at different time-points during migration on a glass coverslip under normal growth conditions. At each pixel, the colorscale encodes the Gabor filter period Smax which maximizes the filtered image signal. Only 13 selected Gabor filter periods were used. (b) Average pixel value within the cell region plotted as a function of time.

Equations (1)

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R i =| u v O(u,v) G i (u,v) |

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