Highly sensitive optical biosensing in whispering gallery microcavities

1. Highly sensitive optical biosensingin whispering gallery microcavities Yun-Feng Xiao (肖云峰) Peking University, Beijing 100871, P. R. China Email: yfxiao@pku.edu.cn Tel: (86)10-62765512 http://www.phy.pku.edu.cn/~yfxiao/

2. Bei-Bei Li Xu Yi Yong-Chun Liu Qiu-Shu Chen Collaborators Lan Yang, Jiangang Zhu, and Lina He @ WUSTL Microcavity Photonics and Quantum Optics Group @ PKU

3. Biomedical research • Healthcare • Environmental monitoring • Homeland security Optical biosensors Optical biosensors are a powerful detection and analysis tool that has vast applications in

4. Two general detection protocols of optical biosensors • Fluorescence-based detection Intensity of the fluorescence: the number of target molecules Extremely sensitive, down to a single molecule detection (1) Suffers from laborious labeling processes, that may also interfere with the function of a biomolecule; (2) Quantitative analysis is challenging due to the fluorescence signal bias, as the fluorophores number on each molecule cannot be precisely controlled • Label-free detection Molecules are not labeled/altered, detected in their natural forms. Relatively easy and cheap to perform • Allow for quantitative and kinetic measurement of molecular interaction; • Detection signal does not scale down with the sample volume, which is particularly attractive when ultrasmall (femtoliter to nanoliter) detection volume is involved. Fan et al., Analytica chimica acta 620, 8-26 (2008)

5. Label-free optical detections Surface plasmon resonance based biosensors Interferometer-based biosensors Optical waveguide based biosensors Optical fiber based biosensors Photonic crystal based sensors Optical resonator based biosensors

6. Increase interaction Increase sensitivity WHY resonator based biosensors? • Optical sensors fundamentally require interaction • between light and the target molecules. • In a waveguide or optical fiber sensor, light interacts with target molecule • only once. • In a resonator, light circulates in the resonator multiple times. Number of round trip  Finesse (F), Q

7. WHY ultra-high-Q whispering gallery resonator? Advantages of microcavities Cavity power build-up factor: Experimental data in our group Cavity photon lifetime: Q ~1×108, D ~ 50m, Vm ~ 600 m3 B ~ 105 Pin = 1 mW  Pcav ~ 100 W, Icav ~ 2.5 GW/cm2,  ~ 100 ns, # of round trip ~ 2105. > 100 W 1 mW

8. Detection mechanism of WGM resonator-based biosensor Li et al., unpublished

9. 1, Resonant wavelength shift detection 2, Intensity detection at a single wavelength Detection methods of resonator-based sensor High concentration detection Limited by the wavelength resolution! Low concentration detection Limited by the detector noise!

10. Silica microtoroid Polymer ring resonator SOI ring resonator Capillary-based ring resonator Glass ring resonator array Silica microsphere Optical biosensing with whispering gallery microcavities For a review, e.g., See Fan et al., Analytica chimica acta 620, 8-26 (2008)

11. Optical biosensing with whispering gallery microcavities The sensing is dependent on monitoring the resonance shift Though the high sensitivity, the detection limit is strongly degraded • Temperature drift: including thermal expansion, thermal refraction • Nonlinear optical effect; • Surround stress; • Optical pressure induced by the probe field. • Dominantly confined in the high-refraction-index dielectric material, i.e., the inside of the cavity. • The few energy is stored in the form of weak exterior evanescent field with a characteristic length of ~ 100 nm. Detection sensitivity is limited.

12. Outline • Coupled resonators --- sensitivity enhancement • Compensating thermal-refraction noise with a cavity surface function --- detection limit improved • Biosensing with mode splitting --- new detection mechanism • Summary

13. From symmetric to asymmetric lineshape Resonance of a single cavity: symmetric Lorenzian lineshape Coupled-cavity configuration: asymmetric lineshape, a larger transmission slope  improved sensitivity in sensing Fano Resonance S. Fan, Appl. Phys. Lett. 80, 908-910 (2002). C.-Y. Chao and L. J. Guo, Appl. Phys. Lett. 83, 1527-1529 (2003). W. M. N. Passaro and F. D. Leonardis, IEEE J. Sel. Top. Quantum Electron. 12, 124-133 (2006).

14. Sensitivity-enhanced method: coupled resonators EIT-like two microresonators are coupled through a waveguide. Sensitivity one order of magnitude enhancement in detection sensitivity. Propagting phase, k*L

15. EIT/Fano resonance in a single microcavity Probe Control Both: over coupled High-Q: over coupled Low-Q: under coupled Fano Coupling decreasing EIT Li, Xiao* et al., Appl. Phys. Lett. 96, 251109 (2010) Xiao et al, Appl. Phy. Lett. 94, 231115 (2009)

16. Fano resonance in two controllable coupled microcavities transmission of individual microdisk transmission of individual microtoroid transmission of coupled disk/toroid A microdisk free from its silicon pillar is indirectly coupled with a microtoroid through a fiber taper. Fano resonance Fano resonance takes place only when the cavity surface roughness can strongly scatter light to the counter-propagating mode (high-Q) Li, Xiao* et al., APL (2012)

17. Compensating thermal refraction noise Han and Wang, Opt. Lett., 2007 Silica: positive thermal-optic effect Polymer: negative thermal-optic effect

18. Compensating thermal refraction noise PDMS coating • Thermal expansion noise is still difficult to be compensated. • Monitoring the small mode shift is a challenging. Complete Compensation Stable cavity modes! The coated microtoroids can be used in bio-sensing to improve the measurement precision, and also hold potential applications in nonlinear optics. Lina He et al., APL 93, 201102 (2008)

19. Ultrastable single-nanoparticle detection - Physics 1, • scattering back (counter-propagating mode) • scattering to the vacuum modes Polarizability: 2, WGM: traveling mode CW CCW Zhu et al., Nature Photonics 4, 46 (2010)

20. Ultrastable single-nanoparticle detection - Physics • Superposition of CW and CCW modes: Standing Wave modes • (CW+CCW)/2 (symmetric) • (CW-CCW)/2 (anti-symmetric) symmetric anti-symmetric Shift and damping Not affected • It is independent of the particle position r; • It is independent of the temperature drift.

21. Ultrastable single-nanoparticle detection - Experiment Zhu et al., Nature Photonics 4, 46 (2010)

22. Ultrastable single-nanoparticle detection - Result Detection of R=100 nm PS nanospheres Zhu et al., Nature Photonics 4, 46 (2010)

23. Ultrastable single-nanoparticle detection with WGM 670 nm band 1450 nm band Zhu et al., Nature Photonics 4, 46 (2010)

24. TM TE Ultrastable single-particle detection – nonspherical particle Mode-splitting method in detecting non-spherical nanoparticle Case 1: a nanosphere in TE or TM mode field Case 2: a standing cylinder in TM mode field Case 3: a standing cylinder in TE mode field, or a lying cylinder in TM mode field S strongly depends on the orientation of particle on the cavity surface and the choice of the detection mode, TE or TM polarized mode. Yi, Xiao*et al., Appl. Phys. Lett., 97, 203705 (2010)

25. Ultrastable single-particle detection – nonspherical particle Combing TE and TM mode detection This polarization-dependent effect allows for studying the orientation of single biomolecule, molecule-molecule interaction on the microcavity surface, and possibly distinguishing inner configuration of similar biomolecules. Yi, Xiao*et al., Appl. Phys. Lett., 97, 203705 (2010)

26. Considering the random nature of scatterer adsorption, we use Monte Carlo simulation and obtain Linewidth broadings Mode shifts g =0.87 Linewidth difference Mode splitting Multiple-Rayleigh-scatterer-induced mode splitting In real optical biosensing, many molecules may interact with the cavity mode simultaneously. By involving the phase factors of propagating WGMs, we extend to the multi-nanoparticle-induced mode splitting situation. Resonance shifts and linewidth broadenings: increase linearly with N (N>>N1/2) Resonance splitting and linewidth difference: increase linearlywith N1/2. Yi, Xiao*et al., Phys. Rev. A 83, 023803 (2011)

27. Multiple-Rayleigh-scatterer-induced mode splitting Small nanoparticle, r = 20 nm Large nanoparticle, r = 100 nm The splitting tends to dissolve with larger number N The splitting tends to be more resolvable with larger number N Yi, Xiao*et al., Phys. Rev. A 83, 023803 (2011)

28. Detection ability with multiple-nanoparticle scattering Detection limit? Mode splitting can be resolved only if the frequency splitting is larger than the half of the resonant linewidth of new modes, composing of the original linewidth and the additional broadenings. • Nanoparticle sizing • merely relevant to the inherent property of the nanoparticle; • immune to thermal noises and particle positions. With various nanoparticles, the size of nanoparticles that can be detected is extended down to tennanometers (small biomolecules). Yi, Xiao*et al., Phys. Rev. A 83, 023803 (2011)

29. Detection ability with multiple-nanoparticle scattering Experimental realization

30. The impact of the biorecognition The label-free nature originates from that the biorecognitions are pre-covered on microresonators. For the mode shift mechanism, by resetting the zero point of the signal, the detection of the biological targets can be realized. However, for the mode-splitting mechanism, the pre-covering also produces Rayleigh scattering. Moreover, the magnitude of frequency splitting does not monotonously increase (in some cases, it may even decrease) with more and more nanoparticles binding on microcavity, and this cannot be removed by simply setting the zero point of the detection signal. 3nm 8nm IgG antibody

31. The impact of the biorecognition The impact of the biorecognition can be removed by resetting the zero point of the signal. Furthermore, the total linewidth broadeningis immune to the thermal fluctuation of the environment. Nevertheless, the linewidth broadening still depends on the binding positions of the targets. When N is large enough, Monte Carlo treatment can be utilized, f(theta)  f

32. Splitting in aquatic environment From air to aquatic environment Observable splitting: splitting > linewidth Li, Xiao*et al., unpublished

33. Splitting in aquatic environment Li, Xiao*et al., unpublished

34. Summary • To enhance the sensitivity of WGM-based biosensing, we studied Fano resonance linewidth in coupled resonators, and experimentally demonstrate Fano resonances in a single or coupled WG microcavities. • To suppress the thermal-noise, we coated the silica microcavity with a negative thermal-optic-coefficient PDMS. The thermal-optic noise can be nearly compensated. • We investigated the mode splitting mechanism in detail, and demonstrated single-nanoparticle response ability. We further found that the multi-nanoparticle-induced splitting help to improve the detection limit. By considering the presence of the biomarkers, we demonstrate the mode splitting mechanism is also feasible in truly biosensing. Thank you for your attention! For more information: www.phy.pku.edu.cn/~yfxiao/index.html