Abstract

We, for the first time, report the detection and the size measurement of single nanoparticles (i.e. polystyrene) in aquatic environment using mode splitting in a whispering gallery mode (WGM) optical resonator, namely a microtoroid resonator. Using this method we achieved detecting and measuring individual synthetic hemozoin nanocrystals―a hemoglobin degradation by-product of malarial parasites―dispersed in a solution or in air. The results of size measurement in solution and in air agree with each other and with those obtained using scanning electron microscope and dynamic light scattering. Moreover, we compare the sensing capabilities of the degenerate (single resonance) and non-degenerate (split mode, doublet) operation regimes of the WGM resonator.

© 2012 OSA

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  6. C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
    [CrossRef] [PubMed]
  7. J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
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    [CrossRef] [PubMed]
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    [CrossRef]
  27. V. S. Ilchenko and M. L. Gorodetsky, “Thermal nonlinear effects in optical whispering gallery microresonators,” Laser Phys.2(6), 1004–1009 (1992).
  28. J. Zhu, S. K. Özdemir, L. He, D. R. Chen, and L. Yang, “Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities,” Opt. Express19(17), 16195–16206 (2011).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  33. S. Arnold, M. Khoshsima, I. Teraoka, S. Holler, and F. Vollmer, “Shift of whispering-gallery modes in microspheres by protein adsorption,” Opt. Lett.28(4), 272–274 (2003).
    [CrossRef] [PubMed]
  34. I. Teraoka and S. Arnold, “Theory of resonance shifts in TE and TM whispering gallery modes by nonradial perturbations for sensing applications,” J. Opt. Soc. Am. B23(7), 1381–1389 (2006).
    [CrossRef]
  35. I. Teraoka, S. Arnold, and F. Vollmer, “Perturbation approach to resonance shifts of whispering-gallery modes in a dielectric microsphere as a probe of a surrounding medium,” J. Opt. Soc. Am. B20(9), 1937–1946 (2003).
    [CrossRef]
  36. 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(12), 4466–4472 (2007).
    [CrossRef] [PubMed]
  37. X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
    [CrossRef]

2011

B. R. Wood, E. Bailo, M. A. Khiavi, L. Tilley, S. Deed, T. Deckert-Gaudig, D. McNaughton, and V. Deckert, “Tip-enhanced Raman scattering (TERS) from hemozoin crystals within a sectioned erythrocyte,” Nano Lett.11(5), 1868–1873 (2011).
[CrossRef] [PubMed]

W. Kim, S. K. Ozdemir, J. Zhu, and L. Yang, “Observation and characterization of mode splitting in microsphere resonators in aquatic environment,” Appl. Phys. Lett.98(14), 141106 (2011).
[CrossRef]

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
[CrossRef] [PubMed]

L. He, S. K. Ozdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol.6(7), 428–432 (2011).
[CrossRef] [PubMed]

S. K. Özdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A83(3), 033817 (2011).
[CrossRef]

J. Zhu, S. K. Özdemir, L. He, D. R. Chen, and L. Yang, “Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities,” Opt. Express19(17), 16195–16206 (2011).
[CrossRef] [PubMed]

2010

X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
[CrossRef]

S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultrasensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a periodically poled lithium-niobate frequency doubled distributed feedback laser,” Rev. Sci. Instrum.81(10), 103110 (2010).
[CrossRef] [PubMed]

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (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(7), 071111 (2010).
[CrossRef]

C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
[CrossRef] [PubMed]

2009

2008

Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
[CrossRef] [PubMed]

J. Homola, “Surface plasmon resonance sensors for detection of chemical and biological species,” Chem. Rev.108(2), 462–493 (2008).
[CrossRef] [PubMed]

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(52), 20701–20704 (2008).
[CrossRef] [PubMed]

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Methods5(7), 591–596 (2008).
[CrossRef] [PubMed]

2007

M. Li, H. X. Tang, and M. L. Roukes, “Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe and very high-frequency applications,” Nat. Nanotechnol.2(2), 114–120 (2007).
[CrossRef] [PubMed]

A. Mazzei, S. Götzinger, 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(17), 173603 (2007).
[CrossRef] [PubMed]

T. Hänscheid, T. J. Egan, and M. P. Grobusch, “Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator,” Lancet Infect. Dis.7(10), 675–685 (2007).
[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(12), 4466–4472 (2007).
[CrossRef] [PubMed]

2006

2004

P. F. Scholl, D. Kongkasuriyachai, P. A. Demirev, A. B. Feldman, J. S. Lin, D. J. Sullivan, and N. Kumar, “Rapid detection of malaria infection in vivo by laser desorption mass spectrometry,” Am. J. Trop. Med. Hyg.71(5), 546–551 (2004).
[PubMed]

2003

F. Vollmer, S. Arnold, D. Braun, I. Teraoka, and A. Libchaber, “Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities,” Biophys. J.85(3), 1974–1979 (2003).
[CrossRef] [PubMed]

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultra-high-Q toroid microcavity on a chip,” Nature421(6926), 925–928 (2003).
[CrossRef] [PubMed]

S. Arnold, M. Khoshsima, I. Teraoka, S. Holler, and F. Vollmer, “Shift of whispering-gallery modes in microspheres by protein adsorption,” Opt. Lett.28(4), 272–274 (2003).
[CrossRef] [PubMed]

I. Teraoka, S. Arnold, and F. Vollmer, “Perturbation approach to resonance shifts of whispering-gallery modes in a dielectric microsphere as a probe of a surrounding medium,” J. Opt. Soc. Am. B20(9), 1937–1946 (2003).
[CrossRef]

2002

F. Vollmer, D. Braun, A. Libchaber, M. Khoshsima, I. Teraoka, and S. Arnold, “Protein detection by optical shift of a resonant microcavity,” Appl. Phys. Lett.80(21), 4057–4059 (2002).
[CrossRef]

2000

P. W. Stephens, S. Pagola, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment beta-haematin,” Nature404(6775), 307–310 (2000).
[CrossRef] [PubMed]

M. L. Gorodetsky, A. D. Pryamikov, and V. S. Ilchenko, “Rayleigh scattering in high-Q microspheres,” J. Opt. Soc. Am. B17(6), 1051–1057 (2000).
[CrossRef]

1992

V. S. Ilchenko and M. L. Gorodetsky, “Thermal nonlinear effects in optical whispering gallery microresonators,” Laser Phys.2(6), 1004–1009 (1992).

1975

E. O. Knutson and K. T. Whitby, “Aerosol classification by electric mobility: apparatus, theory, and applications,” J. Aerosol Sci.6(6), 443–451 (1975).
[CrossRef]

1974

B. Y. H. Liu and D. Y. H. Pui, “A submicron aerosol standard and the primary, absolute calibration of the condensation nucleicounter,” J. Colloid Interface Sci.47(1), 155–171 (1974).
[CrossRef]

Akira, S.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
[CrossRef] [PubMed]

Aoshi, T.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Armani, D. K.

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultra-high-Q toroid microcavity on a chip,” Nature421(6926), 925–928 (2003).
[CrossRef] [PubMed]

Arnold, S.

S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultrasensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a periodically poled lithium-niobate frequency doubled distributed feedback laser,” Rev. Sci. Instrum.81(10), 103110 (2010).
[CrossRef] [PubMed]

S. Arnold, D. Keng, S. I. Shopova, S. Holler, W. Zurawsky, and F. Vollmer, “Whispering Gallery Mode Carousel--a photonic mechanism for enhanced nanoparticle detection in biosensing,” Opt. Express17(8), 6230–6238 (2009).
[CrossRef] [PubMed]

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Methods5(7), 591–596 (2008).
[CrossRef] [PubMed]

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(52), 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(12), 4466–4472 (2007).
[CrossRef] [PubMed]

I. Teraoka and S. Arnold, “Theory of resonance shifts in TE and TM whispering gallery modes by nonradial perturbations for sensing applications,” J. Opt. Soc. Am. B23(7), 1381–1389 (2006).
[CrossRef]

F. Vollmer, S. Arnold, D. Braun, I. Teraoka, and A. Libchaber, “Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities,” Biophys. J.85(3), 1974–1979 (2003).
[CrossRef] [PubMed]

I. Teraoka, S. Arnold, and F. Vollmer, “Perturbation approach to resonance shifts of whispering-gallery modes in a dielectric microsphere as a probe of a surrounding medium,” J. Opt. Soc. Am. B20(9), 1937–1946 (2003).
[CrossRef]

S. Arnold, M. Khoshsima, I. Teraoka, S. Holler, and F. Vollmer, “Shift of whispering-gallery modes in microspheres by protein adsorption,” Opt. Lett.28(4), 272–274 (2003).
[CrossRef] [PubMed]

F. Vollmer, D. Braun, A. Libchaber, M. Khoshsima, I. Teraoka, and S. Arnold, “Protein detection by optical shift of a resonant microcavity,” Appl. Phys. Lett.80(21), 4057–4059 (2002).
[CrossRef]

Bailo, E.

B. R. Wood, E. Bailo, M. A. Khiavi, L. Tilley, S. Deed, T. Deckert-Gaudig, D. McNaughton, and V. Deckert, “Tip-enhanced Raman scattering (TERS) from hemozoin crystals within a sectioned erythrocyte,” Nano Lett.11(5), 1868–1873 (2011).
[CrossRef] [PubMed]

Bélisle, J. M.

J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
[CrossRef] [PubMed]

Bellemare, M.-J.

J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
[CrossRef] [PubMed]

Benson, O.

A. Mazzei, S. Götzinger, 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(17), 173603 (2007).
[CrossRef] [PubMed]

Bohle, D. S.

P. W. Stephens, S. Pagola, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment beta-haematin,” Nature404(6775), 307–310 (2000).
[CrossRef] [PubMed]

Braun, D.

F. Vollmer, S. Arnold, D. Braun, I. Teraoka, and A. Libchaber, “Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities,” Biophys. J.85(3), 1974–1979 (2003).
[CrossRef] [PubMed]

F. Vollmer, D. Braun, A. Libchaber, M. Khoshsima, I. Teraoka, and S. Arnold, “Protein detection by optical shift of a resonant microcavity,” Appl. Phys. Lett.80(21), 4057–4059 (2002).
[CrossRef]

Chen, D.

J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (2010).
[CrossRef]

Chen, D. R.

Chen, T.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
[CrossRef] [PubMed]

Choi, W.

Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Coban, C.

C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
[CrossRef] [PubMed]

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Costantino, S.

J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
[CrossRef] [PubMed]

de S. Menezes, L.

A. Mazzei, S. Götzinger, 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(17), 173603 (2007).
[CrossRef] [PubMed]

Deckert, V.

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T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
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T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
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S. K. Özdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A83(3), 033817 (2011).
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C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
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C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
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T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
[CrossRef] [PubMed]

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L. He, S. K. Ozdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol.6(7), 428–432 (2011).
[CrossRef] [PubMed]

W. Kim, S. K. Ozdemir, J. Zhu, and L. Yang, “Observation and characterization of mode splitting in microsphere resonators in aquatic environment,” Appl. Phys. Lett.98(14), 141106 (2011).
[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(7), 071111 (2010).
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P. W. Stephens, S. Pagola, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment beta-haematin,” Nature404(6775), 307–310 (2000).
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C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
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P. F. Scholl, D. Kongkasuriyachai, P. A. Demirev, A. B. Feldman, J. S. Lin, D. J. Sullivan, and N. Kumar, “Rapid detection of malaria infection in vivo by laser desorption mass spectrometry,” Am. J. Trop. Med. Hyg.71(5), 546–551 (2004).
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T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
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[CrossRef] [PubMed]

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X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
[CrossRef]

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J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (2010).
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M. Li, H. X. Tang, and M. L. Roukes, “Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe and very high-frequency applications,” Nat. Nanotechnol.2(2), 114–120 (2007).
[CrossRef] [PubMed]

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X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
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[CrossRef]

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P. F. Scholl, D. Kongkasuriyachai, P. A. Demirev, A. B. Feldman, J. S. Lin, D. J. Sullivan, and N. Kumar, “Rapid detection of malaria infection in vivo by laser desorption mass spectrometry,” Am. J. Trop. Med. Hyg.71(5), 546–551 (2004).
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B. Y. H. Liu and D. Y. H. Pui, “A submicron aerosol standard and the primary, absolute calibration of the condensation nucleicounter,” J. Colloid Interface Sci.47(1), 155–171 (1974).
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X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
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X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
[CrossRef]

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T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
[CrossRef] [PubMed]

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Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

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P. W. Stephens, S. Pagola, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment beta-haematin,” Nature404(6775), 307–310 (2000).
[CrossRef] [PubMed]

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A. Mazzei, S. Götzinger, 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(17), 173603 (2007).
[CrossRef] [PubMed]

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B. R. Wood, E. Bailo, M. A. Khiavi, L. Tilley, S. Deed, T. Deckert-Gaudig, D. McNaughton, and V. Deckert, “Tip-enhanced Raman scattering (TERS) from hemozoin crystals within a sectioned erythrocyte,” Nano Lett.11(5), 1868–1873 (2011).
[CrossRef] [PubMed]

Nakagawa, A.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

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S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultrasensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a periodically poled lithium-niobate frequency doubled distributed feedback laser,” Rev. Sci. Instrum.81(10), 103110 (2010).
[CrossRef] [PubMed]

Noto, M.

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(12), 4466–4472 (2007).
[CrossRef] [PubMed]

Nuñez, G.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Ohata, K.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
[CrossRef] [PubMed]

Ozdemir, S. K.

L. He, S. K. Ozdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol.6(7), 428–432 (2011).
[CrossRef] [PubMed]

W. Kim, S. K. Ozdemir, J. Zhu, and L. Yang, “Observation and characterization of mode splitting in microsphere resonators in aquatic environment,” Appl. Phys. Lett.98(14), 141106 (2011).
[CrossRef]

J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (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(7), 071111 (2010).
[CrossRef]

Özdemir, S. K.

S. K. Özdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A83(3), 033817 (2011).
[CrossRef]

J. Zhu, S. K. Özdemir, L. He, D. R. Chen, and L. Yang, “Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities,” Opt. Express19(17), 16195–16206 (2011).
[CrossRef] [PubMed]

Pagola, S.

P. W. Stephens, S. Pagola, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment beta-haematin,” Nature404(6775), 307–310 (2000).
[CrossRef] [PubMed]

Park, Y.

Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Popescu, G.

Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Pryamikov, A. D.

Pui, D. Y. H.

B. Y. H. Liu and D. Y. H. Pui, “A submicron aerosol standard and the primary, absolute calibration of the condensation nucleicounter,” J. Colloid Interface Sci.47(1), 155–171 (1974).
[CrossRef]

Rajmangal, R.

S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultrasensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a periodically poled lithium-niobate frequency doubled distributed feedback laser,” Rev. Sci. Instrum.81(10), 103110 (2010).
[CrossRef] [PubMed]

Reimer, T.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Roukes, M. L.

M. Li, H. X. Tang, and M. L. Roukes, “Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe and very high-frequency applications,” Nat. Nanotechnol.2(2), 114–120 (2007).
[CrossRef] [PubMed]

Sakurai, K.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Sandoghdar, V.

A. Mazzei, S. Götzinger, 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(17), 173603 (2007).
[CrossRef] [PubMed]

Scholl, P. F.

P. F. Scholl, D. Kongkasuriyachai, P. A. Demirev, A. B. Feldman, J. S. Lin, D. J. Sullivan, and N. Kumar, “Rapid detection of malaria infection in vivo by laser desorption mass spectrometry,” Am. J. Trop. Med. Hyg.71(5), 546–551 (2004).
[PubMed]

Scott Bohle, D.

J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
[CrossRef] [PubMed]

Shopova, S. I.

S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultrasensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a periodically poled lithium-niobate frequency doubled distributed feedback laser,” Rev. Sci. Instrum.81(10), 103110 (2010).
[CrossRef] [PubMed]

S. Arnold, D. Keng, S. I. Shopova, S. Holler, W. Zurawsky, and F. Vollmer, “Whispering Gallery Mode Carousel--a photonic mechanism for enhanced nanoparticle detection in biosensing,” Opt. Express17(8), 6230–6238 (2009).
[CrossRef] [PubMed]

Spillane, S. M.

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultra-high-Q toroid microcavity on a chip,” Nature421(6926), 925–928 (2003).
[CrossRef] [PubMed]

Stephens, P. W.

P. W. Stephens, S. Pagola, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment beta-haematin,” Nature404(6775), 307–310 (2000).
[CrossRef] [PubMed]

Sullivan, D. J.

P. F. Scholl, D. Kongkasuriyachai, P. A. Demirev, A. B. Feldman, J. S. Lin, D. J. Sullivan, and N. Kumar, “Rapid detection of malaria infection in vivo by laser desorption mass spectrometry,” Am. J. Trop. Med. Hyg.71(5), 546–551 (2004).
[PubMed]

Suresh, S.

Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

Takeshita, F.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Tang, H. X.

M. Li, H. X. Tang, and M. L. Roukes, “Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe and very high-frequency applications,” Nat. Nanotechnol.2(2), 114–120 (2007).
[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(12), 4466–4472 (2007).
[CrossRef] [PubMed]

I. Teraoka and S. Arnold, “Theory of resonance shifts in TE and TM whispering gallery modes by nonradial perturbations for sensing applications,” J. Opt. Soc. Am. B23(7), 1381–1389 (2006).
[CrossRef]

F. Vollmer, S. Arnold, D. Braun, I. Teraoka, and A. Libchaber, “Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities,” Biophys. J.85(3), 1974–1979 (2003).
[CrossRef] [PubMed]

I. Teraoka, S. Arnold, and F. Vollmer, “Perturbation approach to resonance shifts of whispering-gallery modes in a dielectric microsphere as a probe of a surrounding medium,” J. Opt. Soc. Am. B20(9), 1937–1946 (2003).
[CrossRef]

S. Arnold, M. Khoshsima, I. Teraoka, S. Holler, and F. Vollmer, “Shift of whispering-gallery modes in microspheres by protein adsorption,” Opt. Lett.28(4), 272–274 (2003).
[CrossRef] [PubMed]

F. Vollmer, D. Braun, A. Libchaber, M. Khoshsima, I. Teraoka, and S. Arnold, “Protein detection by optical shift of a resonant microcavity,” Appl. Phys. Lett.80(21), 4057–4059 (2002).
[CrossRef]

Tilley, L.

B. R. Wood, E. Bailo, M. A. Khiavi, L. Tilley, S. Deed, T. Deckert-Gaudig, D. McNaughton, and V. Deckert, “Tip-enhanced Raman scattering (TERS) from hemozoin crystals within a sectioned erythrocyte,” Nano Lett.11(5), 1868–1873 (2011).
[CrossRef] [PubMed]

Tsukui, T.

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
[CrossRef] [PubMed]

Vahala, K.

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
[CrossRef] [PubMed]

Vahala, K. J.

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultra-high-Q toroid microcavity on a chip,” Nature421(6926), 925–928 (2003).
[CrossRef] [PubMed]

Vollmer, F.

S. Arnold, D. Keng, S. I. Shopova, S. Holler, W. Zurawsky, and F. Vollmer, “Whispering Gallery Mode Carousel--a photonic mechanism for enhanced nanoparticle detection in biosensing,” Opt. Express17(8), 6230–6238 (2009).
[CrossRef] [PubMed]

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(52), 20701–20704 (2008).
[CrossRef] [PubMed]

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Methods5(7), 591–596 (2008).
[CrossRef] [PubMed]

F. Vollmer, S. Arnold, D. Braun, I. Teraoka, and A. Libchaber, “Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities,” Biophys. J.85(3), 1974–1979 (2003).
[CrossRef] [PubMed]

I. Teraoka, S. Arnold, and F. Vollmer, “Perturbation approach to resonance shifts of whispering-gallery modes in a dielectric microsphere as a probe of a surrounding medium,” J. Opt. Soc. Am. B20(9), 1937–1946 (2003).
[CrossRef]

S. Arnold, M. Khoshsima, I. Teraoka, S. Holler, and F. Vollmer, “Shift of whispering-gallery modes in microspheres by protein adsorption,” Opt. Lett.28(4), 272–274 (2003).
[CrossRef] [PubMed]

F. Vollmer, D. Braun, A. Libchaber, M. Khoshsima, I. Teraoka, and S. Arnold, “Protein detection by optical shift of a resonant microcavity,” Appl. Phys. Lett.80(21), 4057–4059 (2002).
[CrossRef]

Whitby, K. T.

E. O. Knutson and K. T. Whitby, “Aerosol classification by electric mobility: apparatus, theory, and applications,” J. Aerosol Sci.6(6), 443–451 (1975).
[CrossRef]

Wiseman, P. W.

J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
[CrossRef] [PubMed]

Wood, B. R.

B. R. Wood, E. Bailo, M. A. Khiavi, L. Tilley, S. Deed, T. Deckert-Gaudig, D. McNaughton, and V. Deckert, “Tip-enhanced Raman scattering (TERS) from hemozoin crystals within a sectioned erythrocyte,” Nano Lett.11(5), 1868–1873 (2011).
[CrossRef] [PubMed]

Xiao, Y. F.

X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
[CrossRef]

J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (2010).
[CrossRef]

Yagi, M.

C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
[CrossRef] [PubMed]

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Yang, L.

S. K. Özdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A83(3), 033817 (2011).
[CrossRef]

J. Zhu, S. K. Özdemir, L. He, D. R. Chen, and L. Yang, “Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities,” Opt. Express19(17), 16195–16206 (2011).
[CrossRef] [PubMed]

L. He, S. K. Ozdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol.6(7), 428–432 (2011).
[CrossRef] [PubMed]

W. Kim, S. K. Ozdemir, J. Zhu, and L. Yang, “Observation and characterization of mode splitting in microsphere resonators in aquatic environment,” Appl. Phys. Lett.98(14), 141106 (2011).
[CrossRef]

J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (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(7), 071111 (2010).
[CrossRef]

Yi, X.

X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
[CrossRef]

Zhu, J.

S. K. Özdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A83(3), 033817 (2011).
[CrossRef]

W. Kim, S. K. Ozdemir, J. Zhu, and L. Yang, “Observation and characterization of mode splitting in microsphere resonators in aquatic environment,” Appl. Phys. Lett.98(14), 141106 (2011).
[CrossRef]

J. Zhu, S. K. Özdemir, L. He, D. R. Chen, and L. Yang, “Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities,” Opt. Express19(17), 16195–16206 (2011).
[CrossRef] [PubMed]

L. He, S. K. Ozdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol.6(7), 428–432 (2011).
[CrossRef] [PubMed]

J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (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(7), 071111 (2010).
[CrossRef]

Zumofen, G.

A. Mazzei, S. Götzinger, 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(17), 173603 (2007).
[CrossRef] [PubMed]

Zurawsky, W.

Allergol. Int.

C. Coban, M. Yagi, K. Ohata, Y. Igari, T. Tsukui, T. Horii, K. J. Ishii, and S. Akira, “The malarial metabolite hemozoin and its potential use as a vaccine adjuvant,” Allergol. Int.59(2), 115–124 (2010).
[CrossRef] [PubMed]

Am. J. Trop. Med. Hyg.

P. F. Scholl, D. Kongkasuriyachai, P. A. Demirev, A. B. Feldman, J. S. Lin, D. J. Sullivan, and N. Kumar, “Rapid detection of malaria infection in vivo by laser desorption mass spectrometry,” Am. J. Trop. Med. Hyg.71(5), 546–551 (2004).
[PubMed]

Appl. Phys. Lett.

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(7), 071111 (2010).
[CrossRef]

W. Kim, S. K. Ozdemir, J. Zhu, and L. Yang, “Observation and characterization of mode splitting in microsphere resonators in aquatic environment,” Appl. Phys. Lett.98(14), 141106 (2011).
[CrossRef]

F. Vollmer, D. Braun, A. Libchaber, M. Khoshsima, I. Teraoka, and S. Arnold, “Protein detection by optical shift of a resonant microcavity,” Appl. Phys. Lett.80(21), 4057–4059 (2002).
[CrossRef]

X. Yi, Y. F. Xiao, Y. Li, Y. C. Liu, B. B. Li, Z. P. Liu, and Q. H. Gong, “Polarization-dependent detection of cylinder nanoparticles with mode splitting in a high-Q whispering-gallery microresonator,” Appl. Phys. Lett.97(20), 203705 (2010).
[CrossRef]

Biophys. J.

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(12), 4466–4472 (2007).
[CrossRef] [PubMed]

J. M. Bélisle, S. Costantino, M. L. Leimanis, M.-J. Bellemare, D. Scott Bohle, E. Georges, and P. W. Wiseman, “Sensitive detection of malaria infection by third harmonic generation imaging,” Biophys. J.94(4), L26–L28 (2008).
[CrossRef] [PubMed]

F. Vollmer, S. Arnold, D. Braun, I. Teraoka, and A. Libchaber, “Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities,” Biophys. J.85(3), 1974–1979 (2003).
[CrossRef] [PubMed]

Cell Host Microbe

C. Coban, Y. Igari, M. Yagi, T. Reimer, S. Koyama, T. Aoshi, K. Ohata, T. Tsukui, F. Takeshita, K. Sakurai, T. Ikegami, A. Nakagawa, T. Horii, G. Nuñez, K. J. Ishii, and S. Akira, “Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9,” Cell Host Microbe7(1), 50–61 (2010).
[CrossRef] [PubMed]

Chem. Rev.

J. Homola, “Surface plasmon resonance sensors for detection of chemical and biological species,” Chem. Rev.108(2), 462–493 (2008).
[CrossRef] [PubMed]

J. Aerosol Sci.

E. O. Knutson and K. T. Whitby, “Aerosol classification by electric mobility: apparatus, theory, and applications,” J. Aerosol Sci.6(6), 443–451 (1975).
[CrossRef]

J. Colloid Interface Sci.

B. Y. H. Liu and D. Y. H. Pui, “A submicron aerosol standard and the primary, absolute calibration of the condensation nucleicounter,” J. Colloid Interface Sci.47(1), 155–171 (1974).
[CrossRef]

J. Opt. Soc. Am. B

Lancet Infect. Dis.

T. Hänscheid, T. J. Egan, and M. P. Grobusch, “Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator,” Lancet Infect. Dis.7(10), 675–685 (2007).
[CrossRef] [PubMed]

Laser Phys.

V. S. Ilchenko and M. L. Gorodetsky, “Thermal nonlinear effects in optical whispering gallery microresonators,” Laser Phys.2(6), 1004–1009 (1992).

Nano Lett.

B. R. Wood, E. Bailo, M. A. Khiavi, L. Tilley, S. Deed, T. Deckert-Gaudig, D. McNaughton, and V. Deckert, “Tip-enhanced Raman scattering (TERS) from hemozoin crystals within a sectioned erythrocyte,” Nano Lett.11(5), 1868–1873 (2011).
[CrossRef] [PubMed]

Nat. Methods

F. Vollmer and S. Arnold, “Whispering-gallery-mode biosensing: label-free detection down to single molecules,” Nat. Methods5(7), 591–596 (2008).
[CrossRef] [PubMed]

Nat. Nanotechnol.

L. He, S. K. Ozdemir, J. Zhu, W. Kim, and L. Yang, “Detecting single viruses and nanoparticles using whispering gallery microlasers,” Nat. Nanotechnol.6(7), 428–432 (2011).
[CrossRef] [PubMed]

M. Li, H. X. Tang, and M. L. Roukes, “Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe and very high-frequency applications,” Nat. Nanotechnol.2(2), 114–120 (2007).
[CrossRef] [PubMed]

Nat. Photonics

J. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. He, D. Chen, and L. Yang, “On-chip single nanoparticle detection and sizing by mode splitting in an ultrahigh-Q microresonator,” Nat. Photonics4(1), 46–49 (2010).
[CrossRef]

Nature

D. K. Armani, T. J. Kippenberg, S. M. Spillane, and K. J. Vahala, “Ultra-high-Q toroid microcavity on a chip,” Nature421(6926), 925–928 (2003).
[CrossRef] [PubMed]

P. W. Stephens, S. Pagola, D. S. Bohle, A. D. Kosar, and S. K. Madsen, “The structure of malaria pigment beta-haematin,” Nature404(6775), 307–310 (2000).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Phys. Rev. A

S. K. Özdemir, J. Zhu, L. He, and L. Yang, “Estimation of Purcell factor from mode-splitting spectra in an optical microcavity,” Phys. Rev. A83(3), 033817 (2011).
[CrossRef]

Phys. Rev. Lett.

A. Mazzei, S. Götzinger, 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(17), 173603 (2007).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

Y. Park, M. Diez-Silva, G. Popescu, G. Lykotrafitis, W. Choi, M. S. Feld, and S. Suresh, “Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum,” Proc. Natl. Acad. Sci. U.S.A.105(37), 13730–13735 (2008).
[CrossRef] [PubMed]

T. Lu, H. Lee, T. Chen, S. Herchak, J. H. Kim, S. E. Fraser, R. C. Flagan, and K. Vahala, “High sensitivity nanoparticle detection using optical microcavities,” Proc. Natl. Acad. Sci. U.S.A.108(15), 5976–5979 (2011).
[CrossRef] [PubMed]

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(52), 20701–20704 (2008).
[CrossRef] [PubMed]

Rev. Sci. Instrum.

S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultrasensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a periodically poled lithium-niobate frequency doubled distributed feedback laser,” Rev. Sci. Instrum.81(10), 103110 (2010).
[CrossRef] [PubMed]

Other

J. Zhu, Ultra-high-Q microresonator with applications towards single nanoparticle sensing (Washington University in St. Louis, Ph.D dissertation, 2011).

J. Schurr and K. Schmitz, “Dynamic light scattering studies of biopolymers: effects of charge, shape, and flexibility,” Ann. Rev. Phys. Chem. 37(271), (1986).

C. William, Hinds, Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles (John Wiley & Sons, 1999).

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Figures (9)

Fig. 1
Fig. 1

(a) Hemozoin is continuously produced by Plasmodium parasites inside the erythrocytes. Plasmodium parasites have a repetitive life cycle within the erythrocytes of the mammalian host (erythrocytic blood-stage). Hemozoin is produced primarily within trophozoite-stage parasites and is almost continuously released into the blood stream during malaria infection. Released hemozoin is readily captured by immune system cells such as macrophages. Figure shows the life cycle of rodent parasite P. yoelii. (b) SEM pictures of synthetic hemozoin purified from hemin chloride.

Fig. 2
Fig. 2

Schematics of the setup used in mode-splitting based single particle detection and measurement experiments in aquatic environment. A high-Q whispering gallery mode microtoroid resonator is placed in an aquatic chamber (dimension: 3.2cm × 1cm × 0.5cm). The solution including hemozoin crystals or nanoparticles is pumped into and out of the chamber at a rate of 1ml/min using a micropump.

Fig. 3
Fig. 3

Reactive shift (resonance shift) and mode splitting spectra. As a response to a binding particle, a single WGM resonance (a) shifts to a lower frequency and experiences linewidth broadening or (b) undergoes mode splitting where two spectrally shifted resonances of different linewidths are obtained in the transmission spectra. Upper spectra are obtained before particle binding.

Fig. 4
Fig. 4

(a) Resolvability of the split modes in the transmission spectra and its relation with the splitting quality, Qsp. The higher the Qsp, the better the resolvability of the doublets. (b) Standard deviation, σ, of the linewidth measurements obtained for three WGM resonances of different quality factors (linewidths) in the same microtoroid resonator in water. Standard deviation is higher for resonances of lower quality factors (larger linewidths). (c) Dependence of the standard deviations of the estimated linewidths as a function of the average linewidth µ. (d) Relation between the quality factor of a WGM resonance and coefficient of variation σ/µ.

Fig. 5
Fig. 5

A WGM resonator will experience either reactive shift or mode splitting depending on the size of the binding PS particle, quality factor of the resonance, and the noise level in the system. There are four possible regions: (1) mode splitting with highly accurate size measurement, (2) mode splitting but with erroneous size measurement, (3) reactive shift (mode splitting cannot be resolved or does not take place) with accurate size measurement, and (4) reactive shift with erroneous size measurement. The areas of these regions depend on the diameter (D) of the resonator, (a) D = 80µm, and (b) D = 53µm. Dotted line shows the noise level measured in our experiments.

Fig. 6
Fig. 6

Mode splitting based detection and single-shot size measurement of individual polystyrene (PS) particles of nominal size R = 75 ± 2.2nm binding to a microtoroid placed in aquatic environment. (a) Change in the amount of mode splitting as the particles enter the mode volume of a microtoroid one by one. Inset depicts typical particle induced transitions from single resonance to doublets (split resonances) in the transmission spectra. (b) Distribution of the estimated size of detected particles. (c) Size distribution obtained from dynamic light scattering measurements (DLS) for the same particles.

Fig. 7
Fig. 7

Detection and measurement of hemozoin crystals. (a) SEM image of hemozoin crystals deposited on a microtoroid resonator. (b) The amount of mode splitting induced by consecutively deposited hemozoin crystals on a microtoroid. Experiments were done in air. (c) Typical size distribution obtained from DLS measurements for the hemozoin crystals. (d) Result of mode splitting experiment performed in aquatic environment for hemozoin crystals. Discrete jumps in (b) and (d) signals that a hemozoin is within the mode volume of the resonator.

Fig. 8
Fig. 8

The ratio αTETM of the polarizabilities αTE and αTM of a rod-like particle with fixed volume making an angle θ with the resonator surface and orientation φ when the field is TE and TM, respectively, as a function of the refractive index of the particle.

Fig. 9
Fig. 9

Numerical simulation results showing the dependence of the amounts of mode splitting and the linewidth broadening induced by a single rod-like particle as a function of its volume for different polarizations of the resonator field and the orientation of the particle on the resonator.

Equations (19)

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

Z p = q c + q m 4πΛV
Λ= L ln( r 2 / r 1 )
Z p = e  C d 3πηd
d= e  C d 3πη 4πΛV ( q c + q m )
G 2 (τ)= 1 T 0 T I( t )I(t+τ)dτ
G 1 (τ)= 1 T 0 T E( t )E(t+τ)dτ
G 2 (τ)=B[ 1+β | G 1 (τ) | 2 ]
G 1 (τ)= e Γτ
Γ=D q 2
q= 4πn λ sin θ 2
D= kT 6πηr
2| g |= α f 2 ( r )ω V
2Γ= 2α| g | ω 3 3π υ 3
α=4π R 3 n e 2 n p 2 n e 2 n p 2 +2 n e 2
α= 3 8 π 2 ( λ n e ) 3 | γ N γ N1 δ N δ N1 |
α = 4 π R 3 n e 2 n p 2 n e 2 n p 2 + 2 n e 2 = 3 V p n e 2 n p 2 n e 2 n p 2 + 2 n e 2  
α T E = ξ 1 ( 1 sin 2 θ cos 2 φ ) + ξ 2 sin 2 θ cos 2 φ
α T M = ξ 2 sin 2 θ + ξ 2 cos 2 θ
α T E α T M = ( λ T E λ T M ) 3 Γ T E Γ T M | g T M | | g T E | ~ Γ T E Γ T M | g T M | | g T E |

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