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Optics Express

Optics Express

  • Editor: C. Martijn de Sterke
  • Vol. 18, Iss. 24 — Nov. 22, 2010
  • pp: 25081–25088
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Analysis of single nanoparticle detection by using 3-dimensionally confined optofluidic ring resonators

Hao Li, Yunbo Guo, Yuze Sun, Karthik Reddy, and Xudong Fan  »View Author Affiliations


Optics Express, Vol. 18, Issue 24, pp. 25081-25088 (2010)
http://dx.doi.org/10.1364/OE.18.025081


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Abstract

We theoretically analyze the ability of 3-dimensionally confined optofluidic ring resonators (OFRRs) for detection of a single nanoparticle in water and in air. The OFRR is based on a glass capillary, on which bottle-shaped and bubble-shaped ring resonators can form. The spectral position of the whispering gallery mode in the OFRR shifts when a nanoparticle is attached to the OFRR inner surface. For both ring resonator structures, the electric field at the inner surface can be optimized by choosing the right wall thickness. Meanwhile, different electric field confinement along the capillary longitudinal axis can be achieved with different curvatures. Both effects significantly increase the sensitivity of the ring resonator for single nanoparticle detection. It is found that the sensitivity is enhanced about 10 times, as compared to that of a solid microsphere biosensor recently reported, and that the smallest detectable nanoparticle is estimated to be less than 20 nm in radius for a Δλ/λ resolution of 10−8. The high sensitivity and the naturally integrated capillary based microfluidics make the OFRR a very promising sensing platform for detection of various nano-sized bio/chemical species in liquid as well as in air.

© 2010 OSA

1. Introduction

In this work, we investigate the ability of the optofluidic ring resonator (OFRR) for single nanoparticle detection [5

5. X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008). [CrossRef] [PubMed]

]. The OFRR is based on a glass capillary, whose cross section forms the ring resonator. In contrast to the solid microsphere and microtoroid where the outer surface is used for detection, the OFRR utilizes its interior surface to capture the analyte. Its naturally integrated capillary microfluidics enables efficient and rapid delivery of analytes in liquid and in air. Furthermore, by changing the wall thickness of the OFRR, the electric field of the WGM in the radial direction can be optimized for detection of different sizes of molecules near the OFRR inner surface [6

6. H. Li and X. Fan, “Characterization of sensing capability of optofluidic ring resonator biosensors,” Appl. Phys. Lett. 97(1), 011105 (2010). [CrossRef]

]. In addition, bottle-shaped and bubble-shaped OFRRs can be created along the capillary, which strongly confine the WGM in the axial direction and significantly reduces the mode volume [7

7. M. Sumetsky, Y. Dulashko, and R. S. Windeler, “Optical microbubble resonator,” Opt. Lett. 35(7), 898–900 (2010). [CrossRef] [PubMed]

, 8

8. M. Sumetsky, Y. Dulashko, and R. S. Windeler, “Super free spectral range tunable optical microbubble resonator,” Opt. Lett. 35(11), 1866–1868 (2010). [CrossRef] [PubMed]

]. Both radial and axial effects tremendously enhance the sensitivity of the OFRR in detecting a single nanoparticle. In this paper, we will theoretically analyze the sensing capability of the microbottle and microbubble ring resonators under different conditions (wall thickness, poloidal curvature, and nanoparticle size, etc.). It is shown that about 10-fold sensitivity enhancement over a microsphere biosensor could be achieved and that the smallest detectable nanoparticle is estimated to be less than 20 nm in radius. The high sensitivity in combination of the naturally integrated microfluidics makes the OFRR a very promising sensing platform for detection of various sizes of bio/chemical species in liquid and in air.

2. Model and theory

The geometries of the cylindrical OFRR, microbottle OFRR, microbubble OFRR, and solid microsphere, along with their respective parameters, are shown in Fig. 1
Fig. 1 Schematic of different ring resonators under study. (a) Cylindrical OFRR in cylindrical coordinates (r, θ and z with the origin at the arbitrary location on z axis). (b) Microbottle OFRR in cylindrical coordinates (r, θ and z with the origin at the bottle center). (c) Microbubble OFRR in spherical coordinates (r, θ and φ with the origin at the bubble center). (d) Solid microsphere in spherical coordinates (r, θ and φ with the origin at the sphere center).
. The cylindrical

OFRR is essentially a 2-dimentional ring resonator without any confinement along the axial direction where the other three structures provide 3-dimensional confinement. In this study, we focus on the microbottle OFRR and microbubble OFRR, whose WGMs are analyzed separately.

For the microbottle OFRR, we use the adiabatic invariants method [9

9. M. Sumetsky, “Whispering-gallery-bottle microcavities: the three-dimensional etalon,” Opt. Lett. 29(1), 8–10 (2004). [CrossRef] [PubMed]

, 10

10. Y. Louyer, D. Meschede, and A. Rauschenbeutel, “Tunable whispering-gallery-mode resonators for cavity quantum electrodynamics,” Phys. Rev. A 72(3), 031801 (2005). [CrossRef]

]. As shown in Fig. 1(b), we assume that the profile of the microbottle radius along the z direction, R(z), can be described as:
R(z)=R0/1+(Δkz)2,
(1)
where Δk is a parameter to describe the curvature of the profile. When (Δkz)2<0.05 (or Δk<0.22 assuming the field extension in the z direction is 1 μm) the adiabatic approximation is applicable and the field distribution E(r, φ, z) can be separated as E=Er(r, z)Eφ(φ)Ez(z). Eφ(φ) can be solved as Eφ(φ)=exp(imφ) and Er(r, z) can be written as [11

11. C. F. Bohren, and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1998).

, 12

12. X. Fan, I. M. White, H. Zhu, J. D. Suter, and H. Oveys, “Overview of novel integrated optical ring resonator bio/chemical sensors,” Proc. SPIE 6452, 64520M (2007). [CrossRef]

]:
Er={AJm(kφ(m,l)n1r),rR1(z)BJm(kφ(m,l)n2r)+CHm(1)(kφ(m,l)n2r),R1(z)<rR2(z)DHm(1)(kφ(m,l)n3r),r>R2(z)
(2)
where Jm and Hm (1) are the mth Bessel function and mth Hankel function of the first kind, respectively. kφ ( m,l ) is the amplitude of the resonant wave vector component in φ direction labeled by the azimuthal index m and the radial index l.

In the z direction, the equation for Ez is the same as the harmonic oscillator problem and the corresponding solution can be expressed as [10

10. Y. Louyer, D. Meschede, and A. Rauschenbeutel, “Tunable whispering-gallery-mode resonators for cavity quantum electrodynamics,” Phys. Rev. A 72(3), 031801 (2005). [CrossRef]

]:
Ez=E0Hq(mΔkR0z)exp(mΔk2R0z2),
(3)
where Hq is the qth Hermite polynomial. The relevant resonant wave vector component in the z direction is kz=[m 2/R 0 2+(2q+1)mΔk/R 0]1/2 and the total wave vector is k=(kφ 2+kz 2)1/2. Note that when Δk=0, the microbottle OFRR is the same as the cylindrical OFRR in Fig. 1(a), which can be described by Eq. (2).

The electric field distribution of the microbubble OFRR, E(r, θ, φ), can be separated into Er(r)Ylm(θ, φ), where Ylm is the spherical harmonics of the lth degree and the mth order. Er can be written as [11

11. C. F. Bohren, and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1998).

]:
Er={Ajm(k(m,l)n1r),rR1Bjm(k(m,l)n2r)+Chm(1)(kφ(m,l)n2r),R1<rR2Dhm(1)(k(m,l)n3r),r>R2,
(4)
where jm and hm are the mth order spherical Bessel function and the mth order spherical Hankel function of the first kind. Note that when n 1=n 2 in Fig. 1(c), the microbubble OFRR becomes a solid microsphere. Er can be simplified as:

Er={Ajm(k(m,l)n1r),rR1Bhm(1)(k(m,l)n2r),r>R1,
(5)

In order to compare the field distribution form different structures, we also introduce the normalization condition|Er|2dr=1 and|Ez|2dz=1 for all modes, where the unit of r and z is chosen to be μm.

The resonant wave vectors for all three structures (microbottle, microbubble, and solid microsphere) are numerically solved by home-made programs based on the Mie scattering theory [11

11. C. F. Bohren, and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1998).

].

In the presence of a nanoparticle on the ring resonator surface, the resonant wavelength shifts, which can be numerically calculated by [13

13. 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]

, 14

14. S. Arnold, R. Ramjit, D. Keng, V. Kolchenko, and I. Teraoka, “MicroParticle photophysics illuminates viral bio-sensing,” Faraday Discuss. 137, 65–83 (2007). [CrossRef]

]:
Δλλ=particle(np2n2)|E|2dV2n2|E|2dV
(6)
where np and n are the refractive indices of the nanoparticle and the medium and n is usually a function of space coordinates. The integration in numerator is taken within the nanoparticle and the integration in denominator is calculated in the whole space. For simplicity, in this work only the modes with the electric field parallel to the surface are studied. The other modes with the magnetic field parallel to the surface will generate slightly better improvement in the sensitivity (approximately 25% increase in Δλ/λ) due to the electric field discontinuity at the interfaces.

3. Results and discussion

In Fig. 2(a) and (d), the wall thickness is 2.5 μm and the most part of the electric field resides inside the wall. According to Eq. (6), the sensitivity for surface mass detection is proportional to the field strength near the surface. Therefore, when the field at the water-glass interface is only a tail of an exponential decay, the sensitivity is low. In Fig. 2(b) and (e), the wall thickness is reduced to 1.6 μm and the first electric field peak emerges near the water-glass interface, which increases the sensitivity for surface mass or surface adsorption detection. When the wall thickness further decreases to 1.3 μm, as shown in Fig. 2(c) and (f), the first peak of the field is pushed into the core and the surface mass sensitivity deteriorates. For comparison, the electric field of a microsphere with a radius of 36 μm surrounded with water is also drawn in Fig. 2(g). Due to the light confinement of the mode, the field peak never reaches the water-glass interface.

The electric field distribution along the capillary axis (i.e., the z direction for the microbottle and the θ direction for the microbubble and microsphere) are also investigated. In Fig. 3(a)
Fig. 3 (a) The normalized 0th order mode field distribution of the microbottle and microsphere along the capillary with different Δk. For the microbottle, m=288, R 0=36 μm. For the microsphere, l=288, R 1=36 μm. Inset is their actual geometries. (b) The relation between |Ez 0|2 and Δk. z=0.
, the field distributions of the 0th order mode in Eq. (3) for the microbottle with different Δk is shown and compared with that of the microbubble. The inset shows the actual geometries for those structures. It is clear that the large curvature can efficiently decrease the field extension and confine the light in the central region of the microbottle. We define Ez 0 as the field amplitude at z=0 (in the subsequent studies, we assume that the nanoparticle is always attached to the equator). |Ez 0|2 as a function of Δk is plotted in Fig. 3(b) and is compared with that for the microbubble. Note that at the point that (R 0Δk)=1, the microbottle becomes the microbubble and has the same field intensity, suggesting that our original adiabatic approximation to describe the microbottle is applicable and compatible with the accurate solution. When (R 0Δk)>1, |Ez 0 |2 for the microbottle is larger than that for spherical structures. Therefore, in this region, the microbottle has the better sensing performance.

After the 3-dimensional electric field distribution is computed, the fractional resonant wavelength shift Δλ/λ caused by a single nanoparticle in water is numerically calculated using Eq. (6) and the results are shown in Fig. 4
Fig. 4 Results of single nanoparticle detection in water. The modes with the 3rd order in the r direction and the 0th order in the z direction are used. For the microbottle and microbubble, R 2=36 μm, m=288, l=288, n 1=1.33, n 2=1.45, n 3=1. For the microsphere, R 1=36 μm, m=288, l=288, n 1=1.45, n 2=1.33. The nanoparticle is located at the equator and at the inner surface of the OFRR based structures or at the outer surface of the microsphere. np=1.59. (a) Normalized wavelength shift caused by a single nanoparticle as a function of R 1. Wavelength shift from the microsphere is also shown for comparison. Nanoparticle radius is 50 nm. (b) The maximum wavelength shift vs. the nanoparticle radius for the microbottle with different Δk, microbubble, and microsphere. (c) The wavelength shift from the microbottle as a function of Δk. (d) The best wall thickness that gives the largest spectral shift as a function of the nanoparticle radius.
. In order to obtain the maximum shift, the location of the nanoparticle is assumed to be at the equator and is at the inner surface of the OFRR based structures (or at the outer surface of the microsphere). Note that when the nanoparticle location is off the equator, the corresponding shift can be deduced by comparing the local field intensity to the peak value in Fig. 3(a).

The dependence of the sensitivity on Δk is studied by calculating the maximum shift caused by a single nanoparticle with 50 nm in radius for different Δk. As shown in Fig. 4(c), the wavelength (Δλ/λ)maxk curve exceeds the microsphere value when Δk is about 0.003 and intersects with the microbubble value at Δk=0.028 where the shape of the microbottle is equivalent to microbubble. Note that in the simulation, there is no boundary for the curvature of the microbottle profile, which can increase indefinitely by continuously increasing Δk. But considering the adaptive range of adiabatic invariant assumption and fabrication limitations, we predict approximately 10 times enhancement by comparing a large Δk microbottle (Δk=0.2) with a microsphere.

In Fig. 5(c), Δλ/λ is plotted as a function of R 1 and compared with that of the microsphere. Δλ/λ increases when the fraction of light in the air core increases. Considering Fig. 5(b) and (c) in which the sensitivity is increased at the expense of the Q factor, a trade-off wall thickness is chosen to be around 1 μm where the Q factor is still about 1010 and the shift is more than 10 times larger than that of the microsphere. In Fig. 5(d), Δλ/λ for different nanoparticle radii is plotted for a microbubble with a 1-μm thick wall. The smallest detectable nanoparticle radius is also about 20 nm and the Δλ/λ is 10 times larger than that of a microsphere across a wide range of nanoparticle radii.

4. Conclusion

In the summary, the single nanoparticle detection capability of 3-dimensional confined OFRRs is studied analytically and is compared with microsphere biosensors. In the radial direction, the electric field at the inner surface can be optimized by choosing the right wall thickness. Along the long axis, the electric field can be efficiently confined by the curvature. Both effects significantly increase the sensitivity of the OFRR for single nanoparticle detection. It is found that the sensitivity is enhanced about 10 times, as compared to that of a solid microsphere biosensor in Ref [3

3. 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]

], and that the smallest detectable nanoparticle is estimated to be less than 20 nm in radius (assuming Δλ/λ of 10−8 spectral resolution). The extension of the detection capability to smaller nanoparticle sizes enables the detection of more types of important and lethal viruses (such as SARS virus and dengue virus with radii below 50 nm) [16

16. C. M. Rice, “Flaviviridae: the viruses and their replication,” in Fields virology, D. M. Knipe, and P. M. Howley, eds. (Philadelphia: Lippincott-Raven, 1996), pp. 931–959.

, 17

17. W. K. Leung, K. F. To, P. K. S. Chan, H. L. Y. Chan, A. K. L. Wu, N. Lee, K. Y. Yuen, and J. J. Y. Sung, “Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection,” Gastroenterology 125(4), 1011–1017 (2003). [CrossRef] [PubMed]

]. Very recently, Δλ/λ of 10−9 is achieved on a solid microsphere using the frequency-doubling technology via a PPLN [18

18. S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultra-sensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a PPLN doubled DFB laser,” Rev. Sci. Instrum. 81(10), 103110 (2010). [CrossRef] [PubMed]

]. The corresponding smallest detectable nanoparticle is reduced to 20 nm in radius [18

18. S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultra-sensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a PPLN doubled DFB laser,” Rev. Sci. Instrum. 81(10), 103110 (2010). [CrossRef] [PubMed]

]. Applying such a high spectral resolution technology to the OFRR should enable the detection of a nanoparticle of only approximately 7 nm in radius (see Fig. 4(b) and 5(d)). Similarly, detection of a single molecule (such as proteins whose size is around 5 nm in radius), which is the “holy grail” in label-free sensing, may even become possible. The high sensitivity for nanoparticle detection presented in this paper and for the detection of smaller molecules studied earlier [6

6. H. Li and X. Fan, “Characterization of sensing capability of optofluidic ring resonator biosensors,” Appl. Phys. Lett. 97(1), 011105 (2010). [CrossRef]

], and the naturally integrated microfluidics make the OFRR a very promising sensing platform for detection of various sizes of bio/chemical species in liquid and in air.

Acknowledgments

This work is supported by the Wallace H. Coulter Foundation Early Career Award. H.L. is supported by China Scholarship Council (No. 2009610120) and by the University of Michigan.

References and links

1.

T. C. Mettenleiter, and F. Sobrino, Animal viruses: molecular biology (Caister Academic Press, Norfolk, UK, 2008). [PubMed]

2.

P. W. Ewald, The next fifty years, J. Brockman, ed.c (Vintage Books, New York, 2002), pp. 289–301.

3.

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]

4.

J. G. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. N. 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(1), 46–49 (2010). [CrossRef]

5.

X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008). [CrossRef] [PubMed]

6.

H. Li and X. Fan, “Characterization of sensing capability of optofluidic ring resonator biosensors,” Appl. Phys. Lett. 97(1), 011105 (2010). [CrossRef]

7.

M. Sumetsky, Y. Dulashko, and R. S. Windeler, “Optical microbubble resonator,” Opt. Lett. 35(7), 898–900 (2010). [CrossRef] [PubMed]

8.

M. Sumetsky, Y. Dulashko, and R. S. Windeler, “Super free spectral range tunable optical microbubble resonator,” Opt. Lett. 35(11), 1866–1868 (2010). [CrossRef] [PubMed]

9.

M. Sumetsky, “Whispering-gallery-bottle microcavities: the three-dimensional etalon,” Opt. Lett. 29(1), 8–10 (2004). [CrossRef] [PubMed]

10.

Y. Louyer, D. Meschede, and A. Rauschenbeutel, “Tunable whispering-gallery-mode resonators for cavity quantum electrodynamics,” Phys. Rev. A 72(3), 031801 (2005). [CrossRef]

11.

C. F. Bohren, and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1998).

12.

X. Fan, I. M. White, H. Zhu, J. D. Suter, and H. Oveys, “Overview of novel integrated optical ring resonator bio/chemical sensors,” Proc. SPIE 6452, 64520M (2007). [CrossRef]

13.

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]

14.

S. Arnold, R. Ramjit, D. Keng, V. Kolchenko, and I. Teraoka, “MicroParticle photophysics illuminates viral bio-sensing,” Faraday Discuss. 137, 65–83 (2007). [CrossRef]

15.

I. M. White, N. M. Hanumegowda, H. Oveys, and X. Fan, “Tuning whispering gallery modes in optical microspheres with chemical etching,” Opt. Express 13(26), 10754–10759 (2005). [CrossRef] [PubMed]

16.

C. M. Rice, “Flaviviridae: the viruses and their replication,” in Fields virology, D. M. Knipe, and P. M. Howley, eds. (Philadelphia: Lippincott-Raven, 1996), pp. 931–959.

17.

W. K. Leung, K. F. To, P. K. S. Chan, H. L. Y. Chan, A. K. L. Wu, N. Lee, K. Y. Yuen, and J. J. Y. Sung, “Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection,” Gastroenterology 125(4), 1011–1017 (2003). [CrossRef] [PubMed]

18.

S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultra-sensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a PPLN doubled DFB laser,” Rev. Sci. Instrum. 81(10), 103110 (2010). [CrossRef] [PubMed]

OCIS Codes
(230.5750) Optical devices : Resonators
(280.1415) Remote sensing and sensors : Biological sensing and sensors

ToC Category:
Sensors

History
Original Manuscript: September 1, 2010
Revised Manuscript: October 16, 2010
Manuscript Accepted: October 22, 2010
Published: November 16, 2010

Citation
Hao Li, Yunbo Guo, Yuze Sun, Karthik Reddy, and Xudong Fan, "Analysis of single nanoparticle detection by using 3-dimensionally confined optofluidic ring resonators," Opt. Express 18, 25081-25088 (2010)
http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-18-24-25081


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References

  1. T. C. Mettenleiter, and F. Sobrino, Animal viruses: molecular biology (Caister Academic Press, Norfolk, UK, 2008). [PubMed]
  2. P. W. Ewald, The next fifty years, J. Brockman, ed.c (Vintage Books, New York, 2002), pp. 289–301.
  3. 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]
  4. J. G. Zhu, S. K. Ozdemir, Y. F. Xiao, L. Li, L. N. 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(1), 46–49 (2010). [CrossRef]
  5. X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun, “Sensitive optical biosensors for unlabeled targets: a review,” Anal. Chim. Acta 620(1-2), 8–26 (2008). [CrossRef] [PubMed]
  6. H. Li and X. Fan, “Characterization of sensing capability of optofluidic ring resonator biosensors,” Appl. Phys. Lett. 97(1), 011105 (2010). [CrossRef]
  7. M. Sumetsky, Y. Dulashko, and R. S. Windeler, “Optical microbubble resonator,” Opt. Lett. 35(7), 898–900 (2010). [CrossRef] [PubMed]
  8. M. Sumetsky, Y. Dulashko, and R. S. Windeler, “Super free spectral range tunable optical microbubble resonator,” Opt. Lett. 35(11), 1866–1868 (2010). [CrossRef] [PubMed]
  9. M. Sumetsky, “Whispering-gallery-bottle microcavities: the three-dimensional etalon,” Opt. Lett. 29(1), 8–10 (2004). [CrossRef] [PubMed]
  10. Y. Louyer, D. Meschede, and A. Rauschenbeutel, “Tunable whispering-gallery-mode resonators for cavity quantum electrodynamics,” Phys. Rev. A 72(3), 031801 (2005). [CrossRef]
  11. C. F. Bohren, and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1998).
  12. X. Fan, I. M. White, H. Zhu, J. D. Suter, and H. Oveys, “Overview of novel integrated optical ring resonator bio/chemical sensors,” Proc. SPIE 6452, 64520M (2007). [CrossRef]
  13. 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]
  14. S. Arnold, R. Ramjit, D. Keng, V. Kolchenko, and I. Teraoka, “MicroParticle photophysics illuminates viral bio-sensing,” Faraday Discuss. 137, 65–83 (2007). [CrossRef]
  15. I. M. White, N. M. Hanumegowda, H. Oveys, and X. Fan, “Tuning whispering gallery modes in optical microspheres with chemical etching,” Opt. Express 13(26), 10754–10759 (2005). [CrossRef] [PubMed]
  16. C. M. Rice, “Flaviviridae: the viruses and their replication,” in Fields virology, D. M. Knipe, and P. M. Howley, eds. (Philadelphia: Lippincott-Raven, 1996), pp. 931–959.
  17. W. K. Leung, K. F. To, P. K. S. Chan, H. L. Y. Chan, A. K. L. Wu, N. Lee, K. Y. Yuen, and J. J. Y. Sung, “Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection,” Gastroenterology 125(4), 1011–1017 (2003). [CrossRef] [PubMed]
  18. S. I. Shopova, R. Rajmangal, Y. Nishida, and S. Arnold, “Ultra-sensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a PPLN doubled DFB laser,” Rev. Sci. Instrum. 81(10), 103110 (2010). [CrossRef] [PubMed]

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