Abstract

Dark-field microscopy is a well-known technique used to exclude the bright background of unscattered photons from a measurement. We show that by choosing an appropriate illumination angle, the background of unwanted scattered light can also be suppressed. The collected flux of scattered photons is calculated in the Mie scattering regime for various particle sizes and objectives over a range of illumination angles. In the case that the dark-field measurement is limited by background scattering, we find that the sensitivity can be improved by lowering the objective numerical aperture. The collected photon flux is calculated for an exemplary dark-field microscopy experiment in which lipid granules were studied within yeast cells. Our model suggests that the signal-to-noise ratio was over three-orders-of-magnitude higher than it would have been with an equivalent bright-field setup.

© 2013 Optical Society of America

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2013 (2)

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

M. A. Taylor, J. Knittel, and W. P. Bowen, “Fundamental constraints on particle tracking with optical tweezers,” New J. Phys. 15, 023018 (2013).
[CrossRef]

2012 (1)

2011 (1)

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

2010 (1)

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

2009 (1)

2008 (1)

N. Noda and S. Kamimura, “A new microscope optics for laser dark-field illumination applied to high precision two dimensional measurement of specimen displacement,” Rev. Sci. Instrum. 79, 023704 (2008).
[CrossRef]

2007 (3)

A. R. Dunn and J. A. Spudich, “Dynamics of the unbound head during myosin V processive translocation,” Nat. Struct. Mol. Biol. 14, 246–248 (2007).
[CrossRef]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4, 717–719 (2007).
[CrossRef]

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

2006 (1)

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

2005 (2)

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

J. D. Wilson and T. H. Foster, “Mie theory interpretations of light scattering from intact cells,” Opt. Lett. 30, 2442–2444 (2005).
[CrossRef]

2004 (2)

I. M. Tolić-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, “Anomalous diffusion in living yeast cells,” Phys. Rev. Lett. 93, 078102 (2004).
[CrossRef]

R. Thar and M. Kühl, “Propagation of electromagnetic radiation in mitochondria?” J. Theor. Biol. 230, 261–270 (2004).
[CrossRef]

2001 (2)

M. Nishiyama, E. Muto, Y. Inoue, T. Yanagida, and H. Higuchi, “Substeps within the 8 nm step of the ATPase cycle of single kinesin molecules,” Nat. Cell Biol. 3, 425–428 (2001).
[CrossRef]

R. Yasuda, H. Noji, M. Yoshida, K. Kinosita, and H. Itoh, “Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase,” Nature 410, 898–904 (2001).
[CrossRef]

2000 (1)

S. Schultz, D. R. Smith, J. J. Mock, and D. A. Schultz, “Single-target molecule detection with nonbleaching multicolor optical immunolabels,” Proc. Natl. Acad. Sci. USA 97, 996–1001 (2000).
[CrossRef]

1999 (1)

1998 (2)

1996 (2)

A. Dunn and R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef]

1995 (1)

1994 (2)

J. S. Maier, S. A. Walker, S. Fantini, M. A. Franceschini, and E. Gratton, “Possible correlation between blood glucose concentration and the reduced scattering coefficient of tissues in the near infrared,” Opt. Lett. 19, 2062–2064 (1994).
[CrossRef]

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef]

1990 (1)

S. Kudo, Y. Magariyama, and S. I. Aizawa, “Abrupt changes in flagellar rotation observed by laser dark-field microscopy,” Nature 346, 677–680 (1990).
[CrossRef]

1974 (1)

A. Brunsting and P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef]

Aizawa, S. I.

S. Kudo, Y. Magariyama, and S. I. Aizawa, “Abrupt changes in flagellar rotation observed by laser dark-field microscopy,” Nature 346, 677–680 (1990).
[CrossRef]

Allman, B. E.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Antolini, R.

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

Bachor, H.-A.

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

Badizadegan, K.

Beauvoit, B.

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef]

Bellair, C. J.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Berg-Sørensen, K.

I. M. Tolić-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, “Anomalous diffusion in living yeast cells,” Phys. Rev. Lett. 93, 078102 (2004).
[CrossRef]

Beuthan, J.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef]

Bohren, C. F.

D. R. Huffman and C. F. Bohren, Absorption and Scattering of Light by Small Particles (Wiley-VCH, 2008).

Bowen, W. P.

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

M. A. Taylor, J. Knittel, and W. P. Bowen, “Fundamental constraints on particle tracking with optical tweezers,” New J. Phys. 15, 023018 (2013).
[CrossRef]

Branczyk, A. M.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

Brunsting, A.

A. Brunsting and P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef]

Chance, B.

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef]

Choi, W.

Curl, C. L.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

D’Amico, M.

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

Daria, V.

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

Dasari, R. R.

Delbridge, L. M. D.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Drezek, R.

Drubin, D. G.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Dunn, A.

R. Drezek, A. Dunn, and R. Richards-Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt. 38, 3651–3661 (1999).
[CrossRef]

A. Dunn and R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

Dunn, A. K.

A. K. Dunn, “Light scattering properties of cells,” Doctoral dissertation (University of Texas at Austin, 1997).

Dunn, A. R.

A. R. Dunn and J. A. Spudich, “Dynamics of the unbound head during myosin V processive translocation,” Nat. Struct. Mol. Biol. 14, 246–248 (2007).
[CrossRef]

Eick, A. A.

Fang-Yen, C.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4, 717–719 (2007).
[CrossRef]

Fantini, S.

Feld, M. S.

Foster, T. H.

Franceschini, M. A.

Freyer, J. P.

Gratton, E.

Hage, B.

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

Harris, P. J.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Harris, T.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Heckenberg, N. R.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

Helfmann, J.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef]

Herrig, M.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef]

Hielscher, A. H.

Higuchi, H.

M. Nishiyama, E. Muto, Y. Inoue, T. Yanagida, and H. Higuchi, “Substeps within the 8 nm step of the ATPase cycle of single kinesin molecules,” Nat. Cell Biol. 3, 425–428 (2001).
[CrossRef]

Huffman, D. R.

D. R. Huffman and C. F. Bohren, Absorption and Scattering of Light by Small Particles (Wiley-VCH, 2008).

Iino, R.

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

Inoue, Y.

M. Nishiyama, E. Muto, Y. Inoue, T. Yanagida, and H. Higuchi, “Substeps within the 8 nm step of the ATPase cycle of single kinesin molecules,” Nat. Cell Biol. 3, 425–428 (2001).
[CrossRef]

Itoh, H.

R. Yasuda, H. Noji, M. Yoshida, K. Kinosita, and H. Itoh, “Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase,” Nature 410, 898–904 (2001).
[CrossRef]

Jacques, S. L.

Janousek, J.

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

Johnson, T. M.

Kalashnikov, M.

Kamimura, S.

N. Noda and S. Kamimura, “A new microscope optics for laser dark-field illumination applied to high precision two dimensional measurement of specimen displacement,” Rev. Sci. Instrum. 79, 023704 (2008).
[CrossRef]

Kinosita, K.

R. Yasuda, H. Noji, M. Yoshida, K. Kinosita, and H. Itoh, “Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase,” Nature 410, 898–904 (2001).
[CrossRef]

Kitai, T.

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef]

Knittel, J.

M. A. Taylor, J. Knittel, and W. P. Bowen, “Fundamental constraints on particle tracking with optical tweezers,” New J. Phys. 15, 023018 (2013).
[CrossRef]

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

Knoechel, C.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Knöener, G.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

Kudo, S.

S. Kudo, Y. Magariyama, and S. I. Aizawa, “Abrupt changes in flagellar rotation observed by laser dark-field microscopy,” Nature 346, 677–680 (1990).
[CrossRef]

Kühl, M.

R. Thar and M. Kühl, “Propagation of electromagnetic radiation in mitochondria?” J. Theor. Biol. 230, 261–270 (2004).
[CrossRef]

Kumar, G.

Larabell, C. A.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Le Gros, M. A.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Loke, V. L. Y.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

Lue, N.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4, 717–719 (2007).
[CrossRef]

Magariyama, Y.

S. Kudo, Y. Magariyama, and S. I. Aizawa, “Abrupt changes in flagellar rotation observed by laser dark-field microscopy,” Nature 346, 677–680 (1990).
[CrossRef]

Maier, J. S.

Marina, O. C.

McDermott, G.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Minet, O.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef]

Mock, J. J.

S. Schultz, D. R. Smith, J. J. Mock, and D. A. Schultz, “Single-target molecule detection with nonbleaching multicolor optical immunolabels,” Proc. Natl. Acad. Sci. USA 97, 996–1001 (2000).
[CrossRef]

Mourant, J. R.

Mullaney, P.

A. Brunsting and P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef]

Müller, G.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef]

Munteanu, E.-L.

I. M. Tolić-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, “Anomalous diffusion in living yeast cells,” Phys. Rev. Lett. 93, 078102 (2004).
[CrossRef]

Muto, E.

M. Nishiyama, E. Muto, Y. Inoue, T. Yanagida, and H. Higuchi, “Substeps within the 8 nm step of the ATPase cycle of single kinesin molecules,” Nat. Cell Biol. 3, 425–428 (2001).
[CrossRef]

Nieminen, T. A.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

Nishikawa, S.

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

Nishiyama, M.

M. Nishiyama, E. Muto, Y. Inoue, T. Yanagida, and H. Higuchi, “Substeps within the 8 nm step of the ATPase cycle of single kinesin molecules,” Nat. Cell Biol. 3, 425–428 (2001).
[CrossRef]

Noda, N.

N. Noda and S. Kamimura, “A new microscope optics for laser dark-field illumination applied to high precision two dimensional measurement of specimen displacement,” Rev. Sci. Instrum. 79, 023704 (2008).
[CrossRef]

Noji, H.

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

R. Yasuda, H. Noji, M. Yoshida, K. Kinosita, and H. Itoh, “Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase,” Nature 410, 898–904 (2001).
[CrossRef]

Nugent, K. A.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Oddershede, L.

I. M. Tolić-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, “Anomalous diffusion in living yeast cells,” Phys. Rev. Lett. 93, 078102 (2004).
[CrossRef]

Oh, S.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4, 717–719 (2007).
[CrossRef]

Olivotto, M.

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

Parkinson, D.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Pavone, F. S.

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

Richards-Kortum, R.

R. Drezek, A. Dunn, and R. Richards-Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt. 38, 3651–3661 (1999).
[CrossRef]

A. Dunn and R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

Roberts, A.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Rubinsztein-Dunlop, H.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

Sacconi, L.

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

Saidi, I. S.

Sakakihara, S.

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

Sanders, C. K.

Schmitt, J. M.

Schultz, D. A.

S. Schultz, D. R. Smith, J. J. Mock, and D. A. Schultz, “Single-target molecule detection with nonbleaching multicolor optical immunolabels,” Proc. Natl. Acad. Sci. USA 97, 996–1001 (2000).
[CrossRef]

Schultz, S.

S. Schultz, D. R. Smith, J. J. Mock, and D. A. Schultz, “Single-target molecule detection with nonbleaching multicolor optical immunolabels,” Proc. Natl. Acad. Sci. USA 97, 996–1001 (2000).
[CrossRef]

Shen, D.

Smith, D. R.

S. Schultz, D. R. Smith, J. J. Mock, and D. A. Schultz, “Single-target molecule detection with nonbleaching multicolor optical immunolabels,” Proc. Natl. Acad. Sci. USA 97, 996–1001 (2000).
[CrossRef]

Spudich, J. A.

A. R. Dunn and J. A. Spudich, “Dynamics of the unbound head during myosin V processive translocation,” Nat. Struct. Mol. Biol. 14, 246–248 (2007).
[CrossRef]

Stewart, A. G.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

Stilgoe, A. B.

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

Sun, Y.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Sung, Y.

Tabata, K. V.

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

Taylor, M. A.

M. A. Taylor, J. Knittel, and W. P. Bowen, “Fundamental constraints on particle tracking with optical tweezers,” New J. Phys. 15, 023018 (2013).
[CrossRef]

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

Thar, R.

R. Thar and M. Kühl, “Propagation of electromagnetic radiation in mitochondria?” J. Theor. Biol. 230, 261–270 (2004).
[CrossRef]

Thon, G.

I. M. Tolić-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, “Anomalous diffusion in living yeast cells,” Phys. Rev. Lett. 93, 078102 (2004).
[CrossRef]

Tittel, F. K.

Tolic-Nørrelykke, I. M.

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

I. M. Tolić-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, “Anomalous diffusion in living yeast cells,” Phys. Rev. Lett. 93, 078102 (2004).
[CrossRef]

Uchida, M.

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Ueno, H.

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

Vanzi, F.

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

Walker, S. A.

Wilson, J. D.

Yanagida, T.

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

M. Nishiyama, E. Muto, Y. Inoue, T. Yanagida, and H. Higuchi, “Substeps within the 8 nm step of the ATPase cycle of single kinesin molecules,” Nat. Cell Biol. 3, 425–428 (2001).
[CrossRef]

Yasuda, R.

R. Yasuda, H. Noji, M. Yoshida, K. Kinosita, and H. Itoh, “Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase,” Nature 410, 898–904 (2001).
[CrossRef]

Yoshida, M.

R. Yasuda, H. Noji, M. Yoshida, K. Kinosita, and H. Itoh, “Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase,” Nature 410, 898–904 (2001).
[CrossRef]

Yu, C.-C.

Appl. Opt. (4)

Biomed. Opt. Express (1)

Biophys. J. (3)

A. Brunsting and P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef]

H. Ueno, S. Nishikawa, R. Iino, K. V. Tabata, S. Sakakihara, T. Yanagida, and H. Noji, “Simple dark-field microscopy with nanometer spatial precision and microsecond temporal resolution,” Biophys. J. 98, 2014–2023 (2010).
[CrossRef]

B. Beauvoit, T. Kitai, and B. Chance, “Contribution of the mitochondrial compartment to the optical properties of the rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef]

Cell Biochem. Biophys. (1)

L. Sacconi, I. M. Tolic-Nørrelykke, M. D’Amico, F. Vanzi, M. Olivotto, R. Antolini, and F. S. Pavone, “Cell imaging and manipulation by nonlinear optical microscopy,” Cell Biochem. Biophys. 45, 289–302 (2006).
[CrossRef]

Cytometry Part A (1)

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry Part A 65, 88–92 (2005).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron. (1)

A. Dunn and R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

J. Opt. A (1)

T. A. Nieminen, V. L. Y. Loke, A. B. Stilgoe, G. Knöener, A. M. Branczyk, N. R. Heckenberg, and H. Rubinsztein-Dunlop, “Optical tweezers computational toolbox,” J. Opt. A 9, S196–S203 (2007).
[CrossRef]

J. Theor. Biol. (1)

R. Thar and M. Kühl, “Propagation of electromagnetic radiation in mitochondria?” J. Theor. Biol. 230, 261–270 (2004).
[CrossRef]

Nat. Cell Biol. (1)

M. Nishiyama, E. Muto, Y. Inoue, T. Yanagida, and H. Higuchi, “Substeps within the 8 nm step of the ATPase cycle of single kinesin molecules,” Nat. Cell Biol. 3, 425–428 (2001).
[CrossRef]

Nat. Methods (1)

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods 4, 717–719 (2007).
[CrossRef]

Nat. Photonics (1)

M. A. Taylor, J. Janousek, V. Daria, J. Knittel, B. Hage, H.-A. Bachor, and W. P. Bowen, “Biological measurement beyond the quantum limit,” Nat. Photonics 7, 229–233 (2013).
[CrossRef]

Nat. Struct. Mol. Biol. (1)

A. R. Dunn and J. A. Spudich, “Dynamics of the unbound head during myosin V processive translocation,” Nat. Struct. Mol. Biol. 14, 246–248 (2007).
[CrossRef]

Nature (2)

S. Kudo, Y. Magariyama, and S. I. Aizawa, “Abrupt changes in flagellar rotation observed by laser dark-field microscopy,” Nature 346, 677–680 (1990).
[CrossRef]

R. Yasuda, H. Noji, M. Yoshida, K. Kinosita, and H. Itoh, “Resolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase,” Nature 410, 898–904 (2001).
[CrossRef]

New J. Phys. (1)

M. A. Taylor, J. Knittel, and W. P. Bowen, “Fundamental constraints on particle tracking with optical tweezers,” New J. Phys. 15, 023018 (2013).
[CrossRef]

Opt. Express (1)

Opt. Lett. (2)

Phys. Med. Biol. (1)

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, and G. Müller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef]

Phys. Rev. Lett. (1)

I. M. Tolić-Nørrelykke, E.-L. Munteanu, G. Thon, L. Oddershede, and K. Berg-Sørensen, “Anomalous diffusion in living yeast cells,” Phys. Rev. Lett. 93, 078102 (2004).
[CrossRef]

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

S. Schultz, D. R. Smith, J. J. Mock, and D. A. Schultz, “Single-target molecule detection with nonbleaching multicolor optical immunolabels,” Proc. Natl. Acad. Sci. USA 97, 996–1001 (2000).
[CrossRef]

Rev. Sci. Instrum. (1)

N. Noda and S. Kamimura, “A new microscope optics for laser dark-field illumination applied to high precision two dimensional measurement of specimen displacement,” Rev. Sci. Instrum. 79, 023704 (2008).
[CrossRef]

Yeast (1)

M. Uchida, Y. Sun, G. McDermott, C. Knoechel, M. A. Le Gros, D. Parkinson, D. G. Drubin, and C. A. Larabell, “Quantitative analysis of yeast internal architecture using soft x-ray tomography,” Yeast 28, 227–236 (2011).
[CrossRef]

Other (2)

D. R. Huffman and C. F. Bohren, Absorption and Scattering of Light by Small Particles (Wiley-VCH, 2008).

A. K. Dunn, “Light scattering properties of cells,” Doctoral dissertation (University of Texas at Austin, 1997).

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Figures (4)

Fig. 1.
Fig. 1.

We consider a microscopy measurement in which the illuminating light can be incident from any angle θ relative to the objective, as depicted in (a). In this example, the light is incident at the particle 45° from the objective axis, and the resulting scattered field which falls within the objective aperture is collected. The Mie scattering profile for a 1064 nm p-polarized light, striking with a refractive index of 1.4 suspended in water, is shown in (b) for particles with a diameter of 30 nm, 100 nm, 300 nm, 1 μm, and 3 μm. This intensity profile has substantial structure, with numerous maxima and minima for the larger particles, and a single minima at an angle of 90° for the dipole scatterers. In (c), the calculated flux of scattered photons through an NA=1.2 objective is plotted as a function of the angle θ, for an illumination intensity of 10mWμm2 at the particle. Because the optical power is measured over a large aperture, the structure evident in the intensity profile is smooth. Dark-field measurement requires the illumination angle to be between the two dashed lines, where neither the illumination or a back-reflection of the illumination will enter the objective aperture.

Fig. 2.
Fig. 2.

Flux of scattered photons from the particles considered in Fig. 1 is calculated for various objectives as a function of the angle θ, with dark-field measurement requiring the illumination to lie between the dashed lines. The smallest particle with a 30 nm diameter has a photon flux below the plotted range when the objective NA is below 0.6. As the NA drops, the profile of the collected power approaches the intensity profile shown in Fig. 1(b). In the case that the measurement sensitivity is limited by background scatterers, this could provide a way to improve the measurement sensitivity. If large particles are being measured among a background of dipole scatterers, the scattering background can be suppressed by choosing an illumination angle of 90° and a low NA objective. Alternatively, if a 300 nm particle is studied, and the scattering background is produced by larger 1 μm particles, then the optimal measurement angle is around 140°, and the relative strength of the scattering background is reduced by reducing the objective NA.

Fig. 3.
Fig. 3.

Collected photon flux is plotted at four separate illumination angles as a function of particle diameter, for an objective NA of 0.4. For dipole scatterers, the collected photon flux always scales as d6. For larger particles, the side and back scatter photon flux is modulated, but the flux collected at the maxima scale as d2. By contrast, the forward scatter grows far more rapidly than this.

Fig. 4.
Fig. 4.

Measured scattered field is calculated for the experimental parameters in [9], where lipid granule motion within a yeast cell was measured in dark-field particle tracking with s-polarized light and an objective NA of 0.4. (a) The dominant source of the collected scattered field varies with the collection angle from the nucleus, mitochondria, to lipid granules at the largest angles. (b) The SNR of the measurement is plotted here, and is defined as the lipid granule scatter power divided by the scattered power from all other contributions. The illumination angle of [9] was 135°, as indicated by the light vertical line. As in Figs. 1 and 2, dark-field microscopy required the illumination angle to be between the two dashed vertical lines. The slight rise in the SNR around 130° results from a minima in the calculated field for the nucleus. Because the position of such minima in a real measurement is unlikely to be accurately given by our calculations, this maxima is not considered to be physically meaningful.

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