Abstract

Detecting and characterizing single nanoparticles and airborne viruses are of paramount importance for disease control and diagnosis, for environmental monitoring, and for understanding size dependent properties of nanoparticles for developing innovative products. Although single particle and virus detection have been demonstrated in various platforms, single-shot size measurement of each detected particle has remained a significant challenge. Here, we present a nanoparticle size spectrometry scheme for label-free, real-time and continuous detection and sizing of single Influenza A virions, polystyrene and gold nanoparticles using split whispering-gallery-modes (WGMs) in an ultra-high-Q resonator. We show that the size of each particle and virion can be measured as they continuously bind to the resonator one-by-one, eliminating the need for ensemble measurements, stochastic analysis or imaging techniques employed in previous works. Moreover, we show that our scheme has the ability to identify the components of particle mixtures.

©2011 Optical Society of America

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  1. E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
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  4. F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105, 20701–20704 (2008).
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  6. A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
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  7. S. Arnold, S. I. Shopova, and S. Holler, “Whispering gallery mode bio-sensor for label-free detection of single molecules: thermo-optic vs. reactive mechanism,” Opt. Express 18, 281–287 (2010).
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  8. T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
    [Crossref] [PubMed]
  9. T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
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  17. D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultrahigh-Q toroid microcavity on a chip,” Nature 421, 925–928 (2003).
    [Crossref] [PubMed]
  18. A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
    [Crossref] [PubMed]
  19. L. Chantada, N. I. Nikolaev, A. L. Ivanov, P. Borri, and W. Langbein, “Optical resonances in microcylinders: response to perturbations for biosensing,” J. Opt. Soc. Am. B 25, 1312–1321 (2008).
    [Crossref]
  20. J. Zhu, S. K. Ozdemir, L. He, and L. Yang, “Controlled manipulation of mode splitting in an optical microcavity by two Rayleigh scatterers,” Opt. Express 18, 23535–23543 (2010).
    [Crossref] [PubMed]
  21. X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
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    [Crossref]
  24. K. R. Hiremath and V. N. Astratov, “Perturbations of whispering gallery modes by nanoparticles embedded in microcavities,” Opt. Express 16, 5421–5426 (2008)
    [Crossref] [PubMed]
  25. H.-C. Ren, F. Vollmer, S. Arnold, and A. Libchaber, “High-Q microsphere biosensor—analysis for adsorption of rodlike bacteria,” Opt. Express 15, 17410–17423 (2007)
    [Crossref] [PubMed]
  26. W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
    [Crossref]
  27. M. Noto, D. Keng, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys J. 92, 4466–4472 (2007).
    [Crossref] [PubMed]
  28. I. Teraoka and S. Arnold, “Theory on resonance shifts in TE and TM whispering gallery modes by non-radial perturbations for sensing applications,” J. Opt. Soc. Am. B. 23, 1381–1389 (2006).
    [Crossref]
  29. J. Knittel, T. G. McRae, K. H. Lee, and W. P. Bowen, “Interferometric detection of mode splitting for whispering gallery mode biosensors,” Appl. Phys. Lett. 97, 123704 (2010).
    [Crossref]
  30. M. Noto, D. Kenga, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys. J. 92, 3366–4472 (2007).
    [Crossref]
  31. X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
    [Crossref]
  32. L. He, S. K. Ozdemir, J. Zhu, and L. Yang, “Ultrasensitive detection of mode splitting in active optical microcavities,” Phys. Rev. A 82, 053810 (2010).
    [Crossref]

2011 (3)

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A 83, 033817 (2011).
[Crossref]

2010 (9)

W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
[Crossref]

J. Knittel, T. G. McRae, K. H. Lee, and W. P. Bowen, “Interferometric detection of mode splitting for whispering gallery mode biosensors,” Appl. Phys. Lett. 97, 123704 (2010).
[Crossref]

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[Crossref] [PubMed]

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

L. He, S. K. Ozdemir, J. Zhu, and L. Yang, “Ultrasensitive detection of mode splitting in active optical microcavities,” Phys. Rev. A 82, 053810 (2010).
[Crossref]

S. Arnold, S. I. Shopova, and S. Holler, “Whispering gallery mode bio-sensor for label-free detection of single molecules: thermo-optic vs. reactive mechanism,” Opt. Express 18, 281–287 (2010).
[Crossref] [PubMed]

J. Zhu, S. K. Ozdemir, L. He, and L. Yang, “Controlled manipulation of mode splitting in an optical microcavity by two Rayleigh scatterers,” Opt. Express 18, 23535–23543 (2010).
[Crossref] [PubMed]

2009 (1)

A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng, and M. L. Roukes, “Towards single-molecule nanomechanical mass spectrometry,” Nat. Nanotechnol. 4, 445C450 (2009).
[Crossref]

2008 (4)

K. R. Hiremath and V. N. Astratov, “Perturbations of whispering gallery modes by nanoparticles embedded in microcavities,” Opt. Express 16, 5421–5426 (2008)
[Crossref] [PubMed]

L. Chantada, N. I. Nikolaev, A. L. Ivanov, P. Borri, and W. Langbein, “Optical resonances in microcylinders: response to perturbations for biosensing,” J. Opt. Soc. Am. B 25, 1312–1321 (2008).
[Crossref]

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Meth. 5, 591–596 (2008).
[Crossref]

F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105, 20701–20704 (2008).
[Crossref] [PubMed]

2007 (6)

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

M. Noto, D. Kenga, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys. J. 92, 3366–4472 (2007).
[Crossref]

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
[Crossref]

M. Noto, D. Keng, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys J. 92, 4466–4472 (2007).
[Crossref] [PubMed]

H.-C. Ren, F. Vollmer, S. Arnold, and A. Libchaber, “High-Q microsphere biosensor—analysis for adsorption of rodlike bacteria,” Opt. Express 15, 17410–17423 (2007)
[Crossref] [PubMed]

2006 (2)

I. M. White, H. Oveys, and X. Fan, “Liquid-core optical ring-resonator sensors,” Opt. Lett. 31, 1319–1321 (2006).
[Crossref] [PubMed]

I. Teraoka and S. Arnold, “Theory on resonance shifts in TE and TM whispering gallery modes by non-radial perturbations for sensing applications,” J. Opt. Soc. Am. B. 23, 1381–1389 (2006).
[Crossref]

2004 (1)

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

2003 (1)

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultrahigh-Q toroid microcavity on a chip,” Nature 421, 925–928 (2003).
[Crossref] [PubMed]

2000 (1)

1995 (1)

1991 (1)

E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
[Crossref] [PubMed]

1989 (1)

R. G. Knollenberg, “The measurement of latex particle sizes using scattering ratios in the rayleigh scattering size range,” J. Aerosol Sci. 20, 331–345 (1989).
[Crossref]

Armani, A. M.

A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
[Crossref]

Armani, D. K.

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultrahigh-Q toroid microcavity on a chip,” Nature 421, 925–928 (2003).
[Crossref] [PubMed]

Arnold, S.

S. Arnold, S. I. Shopova, and S. Holler, “Whispering gallery mode bio-sensor for label-free detection of single molecules: thermo-optic vs. reactive mechanism,” Opt. Express 18, 281–287 (2010).
[Crossref] [PubMed]

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Meth. 5, 591–596 (2008).
[Crossref]

F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105, 20701–20704 (2008).
[Crossref] [PubMed]

H.-C. Ren, F. Vollmer, S. Arnold, and A. Libchaber, “High-Q microsphere biosensor—analysis for adsorption of rodlike bacteria,” Opt. Express 15, 17410–17423 (2007)
[Crossref] [PubMed]

M. Noto, D. Kenga, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys. J. 92, 3366–4472 (2007).
[Crossref]

M. Noto, D. Keng, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys J. 92, 4466–4472 (2007).
[Crossref] [PubMed]

I. Teraoka and S. Arnold, “Theory on resonance shifts in TE and TM whispering gallery modes by non-radial perturbations for sensing applications,” J. Opt. Soc. Am. B. 23, 1381–1389 (2006).
[Crossref]

Astratov, V. N.

Babcock, K.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Benson, O

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

Betzig, E.

E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
[Crossref] [PubMed]

Borri, P.

Bowen, W. P.

J. Knittel, T. G. McRae, K. H. Lee, and W. P. Bowen, “Interferometric detection of mode splitting for whispering gallery mode biosensors,” Appl. Phys. Lett. 97, 123704 (2010).
[Crossref]

Burg, T. P.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Carlson, G.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Chantada, L.

Chen, D.-R.

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

Chen, T.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Chen, Y.-L.

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

Deutsch, B.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[Crossref] [PubMed]

Dykes, C.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[Crossref] [PubMed]

Fan, X.

Feng, X. L.

A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng, and M. L. Roukes, “Towards single-molecule nanomechanical mass spectrometry,” Nat. Nanotechnol. 4, 445C450 (2009).
[Crossref]

Flagan, R. C.

A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
[Crossref]

Flagand, R. C.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Foster, J. S.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Fraser, S. E.

A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
[Crossref]

Frasera, S. E.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Godin, M.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Gong, Q.

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Gorodetsky, M. L.

Gotzinger, S

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

Hanay, M. S.

A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng, and M. L. Roukes, “Towards single-molecule nanomechanical mass spectrometry,” Nat. Nanotechnol. 4, 445C450 (2009).
[Crossref]

Hare, J.

Haroche, S.

Harris, T. D.

E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
[Crossref] [PubMed]

Hayden, O.

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

He, L.

S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A 83, 033817 (2011).
[Crossref]

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

L. He, S. K. Ozdemir, J. Zhu, and L. Yang, “Ultrasensitive detection of mode splitting in active optical microcavities,” Phys. Rev. A 82, 053810 (2010).
[Crossref]

J. Zhu, S. K. Ozdemir, L. He, and L. Yang, “Controlled manipulation of mode splitting in an optical microcavity by two Rayleigh scatterers,” Opt. Express 18, 23535–23543 (2010).
[Crossref] [PubMed]

W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
[Crossref]

Herchakb, S.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Hiebert, W. K.

A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng, and M. L. Roukes, “Towards single-molecule nanomechanical mass spectrometry,” Nat. Nanotechnol. 4, 445C450 (2009).
[Crossref]

Hiremath, K. R.

Holler, S.

Huanga, X.

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

Ignatovich, F.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[Crossref] [PubMed]

Ilchenko, V. S.

Ivanov, A. L.

Keng, D.

F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105, 20701–20704 (2008).
[Crossref] [PubMed]

M. Noto, D. Keng, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys J. 92, 4466–4472 (2007).
[Crossref] [PubMed]

Kenga, D.

M. Noto, D. Kenga, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys. J. 92, 3366–4472 (2007).
[Crossref]

Kim, J.-H.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Kim, W.

W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
[Crossref]

Kippenberg, T. J.

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultrahigh-Q toroid microcavity on a chip,” Nature 421, 925–928 (2003).
[Crossref] [PubMed]

Knittel, J.

J. Knittel, T. G. McRae, K. H. Lee, and W. P. Bowen, “Interferometric detection of mode splitting for whispering gallery mode biosensors,” Appl. Phys. Lett. 97, 123704 (2010).
[Crossref]

Knollenberg, R. G.

R. G. Knollenberg, “The measurement of latex particle sizes using scattering ratios in the rayleigh scattering size range,” J. Aerosol Sci. 20, 331–345 (1989).
[Crossref]

Knudsen, S. M.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Kostelak, R. L.

E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
[Crossref] [PubMed]

Kulkarni, R. P.

A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
[Crossref]

Lakadamyali, M.

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

Langbein, W.

Lee, H.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Lee, K. H.

J. Knittel, T. G. McRae, K. H. Lee, and W. P. Bowen, “Interferometric detection of mode splitting for whispering gallery mode biosensors,” Appl. Phys. Lett. 97, 123704 (2010).
[Crossref]

Lefevre-Seguin, V.

Li, B.-B.

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Li, L.

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

Li, Y.

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Libchaber, A.

Lid, J.

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

Lieber, C. M.

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

Liu, Y.-C.

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Liu, Z.-P.

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Lu, T.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Lua, J.

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

Manalis, S. R.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Mazzei, A

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

McRae, T. G.

J. Knittel, T. G. McRae, K. H. Lee, and W. P. Bowen, “Interferometric detection of mode splitting for whispering gallery mode biosensors,” Appl. Phys. Lett. 97, 123704 (2010).
[Crossref]

Menezes, L De S

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

Mitra, A.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[Crossref] [PubMed]

Naik, A. K.

A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng, and M. L. Roukes, “Towards single-molecule nanomechanical mass spectrometry,” Nat. Nanotechnol. 4, 445C450 (2009).
[Crossref]

Nikolaev, N. I.

Noto, M.

M. Noto, D. Kenga, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys. J. 92, 3366–4472 (2007).
[Crossref]

M. Noto, D. Keng, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys J. 92, 4466–4472 (2007).
[Crossref] [PubMed]

Novotny, L.

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[Crossref] [PubMed]

Oveys, H.

Ozdemir, S. K.

S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A 83, 033817 (2011).
[Crossref]

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

L. He, S. K. Ozdemir, J. Zhu, and L. Yang, “Ultrasensitive detection of mode splitting in active optical microcavities,” Phys. Rev. A 82, 053810 (2010).
[Crossref]

W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
[Crossref]

J. Zhu, S. K. Ozdemir, L. He, and L. Yang, “Controlled manipulation of mode splitting in an optical microcavity by two Rayleigh scatterers,” Opt. Express 18, 23535–23543 (2010).
[Crossref] [PubMed]

Patela, U.

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

Patolsky, F.

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

Pryamikov, A. D.

Raimond, J.-M.

Ren, H.-C.

Roukes, M. L.

A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng, and M. L. Roukes, “Towards single-molecule nanomechanical mass spectrometry,” Nat. Nanotechnol. 4, 445C450 (2009).
[Crossref]

Sandoghdar, V

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

Sandoghdar, V.

Shana, X.

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

Shen, W.

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

Shopova, S. I.

Spillane, S. M.

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultrahigh-Q toroid microcavity on a chip,” Nature 421, 925–928 (2003).
[Crossref] [PubMed]

Tao, N.

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

Teraoka, I.

M. Noto, D. Keng, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys J. 92, 4466–4472 (2007).
[Crossref] [PubMed]

M. Noto, D. Kenga, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys. J. 92, 3366–4472 (2007).
[Crossref]

I. Teraoka and S. Arnold, “Theory on resonance shifts in TE and TM whispering gallery modes by non-radial perturbations for sensing applications,” J. Opt. Soc. Am. B. 23, 1381–1389 (2006).
[Crossref]

Trautmann, J. K.

E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
[Crossref] [PubMed]

Vahala, K.

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

Vahala, K. J.

A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
[Crossref]

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultrahigh-Q toroid microcavity on a chip,” Nature 421, 925–928 (2003).
[Crossref] [PubMed]

Vollmer, F.

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Meth. 5, 591–596 (2008).
[Crossref]

F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105, 20701–20704 (2008).
[Crossref] [PubMed]

H.-C. Ren, F. Vollmer, S. Arnold, and A. Libchaber, “High-Q microsphere biosensor—analysis for adsorption of rodlike bacteria,” Opt. Express 15, 17410–17423 (2007)
[Crossref] [PubMed]

Wang, S.

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

Weiner, J. S.

E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
[Crossref] [PubMed]

Weiss, D. S.

White, I. M.

Xiao, Y.-F.

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Yang, L.

S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A 83, 033817 (2011).
[Crossref]

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

L. He, S. K. Ozdemir, J. Zhu, and L. Yang, “Ultrasensitive detection of mode splitting in active optical microcavities,” Phys. Rev. A 82, 053810 (2010).
[Crossref]

J. Zhu, S. K. Ozdemir, L. He, and L. Yang, “Controlled manipulation of mode splitting in an optical microcavity by two Rayleigh scatterers,” Opt. Express 18, 23535–23543 (2010).
[Crossref] [PubMed]

W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
[Crossref]

Yi, X.

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Zheng, G.

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

Zhu, J.

S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A 83, 033817 (2011).
[Crossref]

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

L. He, S. K. Ozdemir, J. Zhu, and L. Yang, “Ultrasensitive detection of mode splitting in active optical microcavities,” Phys. Rev. A 82, 053810 (2010).
[Crossref]

J. Zhu, S. K. Ozdemir, L. He, and L. Yang, “Controlled manipulation of mode splitting in an optical microcavity by two Rayleigh scatterers,” Opt. Express 18, 23535–23543 (2010).
[Crossref] [PubMed]

W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
[Crossref]

Zhuang, X.

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

Zumofen, G

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

ACS Nano (1)

A. Mitra, B. Deutsch, F. Ignatovich, C. Dykes, and L. Novotny, “Nano-optofluidic detection of single viruses and nanoparticles,” ACS Nano 4, 1305–1312 (2010).
[Crossref] [PubMed]

Appl. Phys. Lett. (3)

W. Kim, S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Demonstration of mode splitting in an optical microcavity in aqueous environment,” Appl. Phys. Lett. 97, 071111 (2010).
[Crossref]

J. Knittel, T. G. McRae, K. H. Lee, and W. P. Bowen, “Interferometric detection of mode splitting for whispering gallery mode biosensors,” Appl. Phys. Lett. 97, 123704 (2010).
[Crossref]

X. Yi, Y.-F. Xiao, Y. Li, Y.-C. Liu, B.-B. Li, Z.-P. Liu, and Q. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett. 97, 203705 (2010).
[Crossref]

Biophys J. (1)

M. Noto, D. Keng, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys J. 92, 4466–4472 (2007).
[Crossref] [PubMed]

Biophys. J. (1)

M. Noto, D. Kenga, I. Teraoka, and S. Arnold, “Detection of protein orientation on the silica microsphere surface using transverse electric/transverse magnetic whispering gallery modes,” Biophys. J. 92, 3366–4472 (2007).
[Crossref]

J. Aerosol Sci. (1)

R. G. Knollenberg, “The measurement of latex particle sizes using scattering ratios in the rayleigh scattering size range,” J. Aerosol Sci. 20, 331–345 (1989).
[Crossref]

J. Opt. Soc. Am. B (2)

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

I. Teraoka and S. Arnold, “Theory on resonance shifts in TE and TM whispering gallery modes by non-radial perturbations for sensing applications,” J. Opt. Soc. Am. B. 23, 1381–1389 (2006).
[Crossref]

Nat. Meth. (1)

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Meth. 5, 591–596 (2008).
[Crossref]

Nat. Nanotechnol. (1)

A. K. Naik, M. S. Hanay, W. K. Hiebert, X. L. Feng, and M. L. Roukes, “Towards single-molecule nanomechanical mass spectrometry,” Nat. Nanotechnol. 4, 445C450 (2009).
[Crossref]

Nat. Photonics (1)

J. Zhu, S. K. Ozdemir, Y.-F. Xiao, L. Li, L. He, D.-R. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics 4, 46–49 (2010).
[Crossref]

Nature (2)

T. P. Burg, M. Godin, S. M. Knudsen, W. Shen, G. Carlson, J. S. Foster, K. Babcock, and S. R. Manalis, “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446, 1066–1069 (2007).
[Crossref] [PubMed]

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultrahigh-Q toroid microcavity on a chip,” Nature 421, 925–928 (2003).
[Crossref] [PubMed]

Opt. Express (4)

Opt. Lett. (2)

Phys. Rev. A (3)

L. He, S. K. Ozdemir, J. Zhu, and L. Yang, “Ultrasensitive detection of mode splitting in active optical microcavities,” Phys. Rev. A 82, 053810 (2010).
[Crossref]

X. Yi, Y.-F. Xiao, Y.-C. Liu, B.-B. Li, Y.-L. Chen, Y. Li, and Q. Gong, “Multiple-Rayleigh-scatterer-induced mode splitting in a high-Q whispering-gallery-mode microresonator,” Phys. Rev. A,  83, 023803 (2011).
[Crossref]

S. K. Ozdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A 83, 033817 (2011).
[Crossref]

Phys. Rev. Lett. (1)

A Mazzei, S Gotzinger, L De S Menezes, G Zumofen, O Benson, and V Sandoghdar, “Controlled coupling of counterpropagating whispering-gallery modes by a single Rayleigh scatterer: a classical problem in a quantum optical light,” Phys. Rev. Lett. 99, 173603 (2007).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (4)

F. Vollmer, S. Arnold, and D. Keng, “Single virus detection from the reactive shift of a whispering-gallery mode,” Proc. Natl. Acad. Sci. U.S.A. 105, 20701–20704 (2008).
[Crossref] [PubMed]

T. Lu, H. Lee, T. Chen, S. Herchakb, J.-H. Kim, S. E. Frasera, R. C. Flagand, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A. 108, 5976–5979 (2011).
[Crossref] [PubMed]

S. Wang, X. Shana, U. Patela, X. Huanga, J. Lua, J. Lid, and N. Tao, “Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance,” Proc. Natl. Acad. Sci. U.S.A. 107, 16028–16032 (2010).
[Crossref] [PubMed]

F. Patolsky, G. Zheng, O. Hayden, M. Lakadamyali, X. Zhuang, and C. M. Lieber, “Electrical detection of single viruses,” Proc. Natl. Acad. Sci. U.S.A. 101, 14017–14022 (2004).
[Crossref] [PubMed]

Science (2)

E. Betzig, J. K. Trautmann, T. D. Harris, J. S. Weiner, and R. L. Kostelak, “Breaking the diffraction barrier: optical microscopy on a nanometric scale,” Science 251, 1468–1470 (1991).
[Crossref] [PubMed]

A. M. Armani, R. P. Kulkarni, S. E. Fraser, R. C. Flagan, and K. J. Vahala, “Label-free, single-molecule detection with optical microcavities,” Science 10, 783–787 (2007).
[Crossref]

Other (1)

The Universal Database of the International Committee on Taxonomy of Viruses (ICTVdB, http://www.ictvdb.org/ICTVdB/index.htm ).

Supplementary Material (1)

» Media 1: AVI (2241 KB)     

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Figures (5)

Fig. 1
Fig. 1 Experimental Setup (a) Simplified schematic of the virion/nanoparticle size spectrometry system, showing the virion/nanoparticle deposition through a nozzle onto a fiber taper coupled microtoroid resonator. The inset displays the scanning electron micrograph of single InfA virions adsorbed on the surface of a resonator. (b) Typical transmission spectrum of the system showing virion induced mode splitting.

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Fig. 2
Fig. 2 Real-time records of single InfA virion adsorption events using mode splitting phenomenon in a microtoroid optical resonator. (a) Evolution of transmission spectra as the single virions are adsorbed onto the resonator mode volume. The single resonance splits into a doublet with the first virion binding event. The subsequent binding events lead to abrupt changes in the mode splitting spectra. Each abrupt change corresponds to detection of a single virion, and the amount of change depends on the polarizability and the position of the adsorbed virion in the mode volume (see Eqs. (4) and (5)). A video showing the detection of R=100 nm PS particles is also included (Media 1). (b) Frequencies and (c) linewidths of the two split modes extracted from the data in (a) by curve fitting. (d) Sum of the frequency shifts of the two split modes with respect to frequency of the initial single mode resonance mode, δ N + , and (e) sum of the linewidths of the split modes, ρ N +   +   2 γ 0 . Lines are for eye guide. (F) Evolution of splitting quality Q sp   =   2 δ N − / ( ρ N +   +   2 γ 0 ) as a function of time. Note that mode splitting is observable in the transmission spectrum if Q sp > 1. (g) Size of each adsorbed single virion calculated from the data in (d) and (e) using Eqs. (9) and (10). The horizontal line designates the average size. In (d) and (g), the ’*’ signs mark the point of single virus adsorption events, and circles mark the events from which accurate size information could be extracted.

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Fig. 3
Fig. 3 Single virus/nanoparticle size spectrometry using mode splitting in microtoroid resonators. Polarizabilities and sizes are calculated from transmission spectra according to Eqs. (9) and (10). (a) Measured polarizability distributions of InfA virions and 50 nm Au nanoparticles. (b) Measured size distribution of InfA virions with average radius at 53.2 nm. (c) Measured polarizability distributions of 50 nm and 100 nm Au particles. (d) Measured size distrbutions of 100 nm and 135 nm polystyrene (PS) particles. Red curves are Gaussian fits to the experimentally obtained distributions.

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Fig. 4
Fig. 4 Measured polarizability distributions of a homogenous mixture of PS and Au particles with radii 50 nm. Bimodality of the mixture is accurately determined from the processing of mode splitting spectra. Red curves are the Gaussian fits to the experimentally obtained distributions. The left peak corresponds to PS particles and the right peak corresponds to Au particles.

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Fig. 5
Fig. 5 Estimation of the size of InfA virions by applying Eq. (11) on the data in Fig. 2. The fluctuations in size estimation decreases as the splitting quality Q sp increases (Fig. 2(f)).

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Equations (11)

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Δ ω 1 −   =   ω 1 −   −   ω 0   =   2 g 1 ,   Δ ω 1 +   =   ω 1 +   −   ω 0   =   0
Δ γ 1 −   = γ 1 −   −   γ 0   =   2 Γ 1 ,   Δ γ 1 +   =   γ 1 +   −   γ 0   =   0 .
α 1   =   − Γ 1 g 1 3 λ 3 8 π 2   =   − Δ γ 1 − Δ ω 1 − 3 λ 3 8 π 2
Δ ω N −   =   ∑ i = 1 N 2 g i cos 2   ( ψ N i ) ,   Δ ω N +   =   ∑ i = 1 N 2 g i   sin 2   ( ψ N i )
Δ γ N −   =   ∑ i = 1 N 2 Γ i cos 2   ( ψ N i ) ,   Δ γ N +   =   ∑ i = 1 N 2 Γ i   sin 2   ( ψ N i )
tan ( 2 ϕ N )   =   Σ i = 1 N g i sin ( 2 β i ) Σ i = 1 N g i   cos ( 2 β i ) .
δ N −   =   2 ∑ i = 1 N g i cos ( 2 ψ N i ) ,   δ N +   =   2 ∑ i = 1 N g i
ρ N −   =   2 ∑ i = 1 N Γ i cos ( 2 ψ N i ) ,   ρ N +   =   2 ∑ i = 1 N Γ i
α N = − Γ N g N   3 λ 3 8 π 2   =   − 3 λ 3 8 π 2 ρ N +   −   ρ N − 1 + δ N +   −   δ N − 1 + = − 3 λ 3 8 π 2   ( γ N +   +   γ N − )   −   ( γ N − 1 +   +   γ N − 1 − ) ( ω N +   +   ω N − )   −   ( ω N − 1 +   +   ω N − 1 − )
R N   =   [ α N 4 π   ɛ p   +   2 ɛ p   −   1 ] 1 / 3 .
α eff   =   − 3 λ 3 8 π 2 ρ N − δ N −   =   − 3 λ 3 8 π 2   ( γ N +   −   γ N − ) ( ω N +   −   ω N − )

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