Highly sensitive optical biosensingin whispering gallery microcavities
Yun-Feng Xiao (肖云峰 )Peking University, Beijing 100871, P. R. China
Email: [email protected]
Tel: (86)10-62765512
http://www.phy.pku.edu.cn/~yfxiao/
Collaborators
Bei-Bei Li
Yong-Chun Liu
Xu Yi
Qiu-Shu Chen
Lan Yang, Jiangang Zhu, and Lina He @ WUSTL
Microcavity Photonics and Quantum Optics Group @ PKU
Optical biosensors are a powerful detection and analysis tool that has vast applications in
• Healthcare
• Homeland security
• Environmental monitoring
• Biomedical research
Optical biosensors
Fan et al., Analytica chimica acta 620, 8-26 (2008)
Two general detection protocols of optical biosensors1. Fluorescence-based detection
2. Label-free detection
Intensity of the fluorescence: the number of target moleculesExtremely 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
(1) Allow for quantitative and kinetic measurement of molecular interaction;(2) Detection signal does not scale down with the sample volume, which is
particularly attractive when ultrasmall (femtoliter to nanoliter) detection volume is involved.
Molecules are not labeled/altered, detected in their natural forms.Relatively easy and cheap to perform
Surface plasmon resonance based biosensors
Interferometer-based biosensors
Optical waveguide based biosensors
Optical resonator based biosensors
Optical fiber based biosensors
Photonic crystal based sensors
Label-free optical detections
• Optical sensors fundamentally require interaction
between light and the target molecules.
Increase interaction Increase sensitivity
• 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
WHY resonator based biosensors?
Advantages of microcavities
Q
22cav
in
P QB
P nD
Cavity power build-up factor:
Q ~1×108, D ~ 50m, Vm ~ 600 m3 B ~ 105
Cavity photon lifetime:
WHY ultra-high-Q whispering gallery resonator?
Pin = 1 mW
Pcav ~ 100 W, Icav ~ 2.5 GW/cm2,
~ 100 ns, # of round trip ~ 2105.
Experimental data in our group
1 mW> 100 W
Detection mechanism of WGM resonator-based biosensor
Li et al., unpublished
Detection methods of resonator-based sensor
1, Resonant wavelength shift detection
High concentration detectionLimited by the wavelength resolution!
Low concentration detectionLimited by the detector noise!
2, Intensity detection at a single wavelength
Optical biosensing with whispering gallery microcavities
SOI ring resonator Polymer ring resonator Silica microtoroid
Glass ringresonator array
Capillary-based ring resonatorSilica microsphere
For a review, e.g., See Fan et al., Analytica chimica acta 620, 8-26 (2008)
0• Temperature drift: including thermal expansion, thermal refraction• Nonlinear optical effect;• Surround stress;• Optical pressure induced by the probe field.
Though the high sensitivity, the
detection limit is strongly
degraded
Optical biosensing with whispering gallery microcavities
The sensing is dependent on monitoring the resonance shift
• 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.
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
From symmetric to asymmetric lineshape
Resonance of a single cavity: symmetric Lorenzian lineshape
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).
Coupled-cavity configuration: asymmetric lineshape, a larger
transmission slope improved sensitivity in sensing
FanoResonance
Sensitivity-enhanced method: coupled resonators
two microresonators are coupledthrough a waveguide. -4 -2 0 2 4
0.0
0.2
0.4
0.6
0.8
1.0
R, Single cavity R, coupled cavities
EIT-like
Sensitivity
one order of magnitude enhancement in detection sensitivity.
Propagting phase, k*L
EIT/Fano resonance in a single microcavity
Control
Probe
Li, Xiao* et al., Appl. Phys. Lett. 96, 251109 (2010)
Coupling decreasing
Fano
EIT
Xiao et al, Appl. Phy. Lett. 94, 231115 (2009)
Both: over coupled
High-Q: over coupledLow-Q: under coupled
Fano resonance in two controllable coupled microcavities
transmission of individual microdisk
transmission of individual microtoroid
transmission of coupled disk/toroidFano resonance
Fano resonance takes place only when the cavity surface roughness can strongly scatter light to the counter-propagating mode (high-Q)
A microdisk free from its silicon pillar is indirectly coupled with a microtoroid through a fiber taper.
Li, Xiao* et al., APL (2012)
Compensating thermal refraction noise
Han and Wang, Opt. Lett., 2007
Silica: positive thermal-optic effect
Polymer: negative thermal-optic effect
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.
PDMS
coating
Lina He et al., APL 93, 201102 (2008)
Compensating thermal refraction noise
1. Thermal expansion noise is still difficult to be compensated.
2. Monitoring the small mode shift is a challenging.
Ultrastable single-nanoparticle detection - Physics
3 2 2 2 24 ( ) /( 2 )p m p mR n n n n Polarizability:
CW
CCW
1,
2, WGM: traveling mode
• scattering back (counter-propagating mode)• scattering to the vacuum modes
Zhu et al., Nature Photonics 4, 46 (2010)
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
33 2 2 2 21 2
2
34 ( ) / ( 2 )
8 p m p mS R n n n n
1. It is independent of the particle position r;
2. It is independent of the temperature drift.
Ultrastable single-nanoparticle detection - Experiment
Zhu et al., Nature Photonics 4, 46 (2010)
Detection of R=100 nm PS nanospheres
Ultrastable single-nanoparticle detection - Result
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)
Ultrastable single-particle detection – nonspherical particle
TE
TM
Case 1: a nanosphere in TE or TM mode fieldCase 2: a standing cylinder in TM mode fieldCase 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.
Mode-splitting method in detecting non-spherical nanoparticle
Yi, Xiao* et al., Appl. Phys. Lett., 97, 203705 (2010)
Ultrastable single-particle detection – nonspherical particle
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.
Combing TE and TM mode detection
Yi, Xiao* et al., Appl. Phys. Lett., 97, 203705 (2010)
Multiple-Rayleigh-scatterer-induced mode splitting
Yi, Xiao* et al., Phys. Rev. A 83, 023803 (2011)
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 linearly with N1/2.
Mode shifts Linewidth broadings
Considering the random nature of scatterer adsorption, we use Monte Carlo simulation and obtain
0 0 0 0,g Ng g N N N
0 02 2,g g N N =0.87
Mode splitting Linewidth difference
Multiple-Rayleigh-scatterer-induced mode splitting
Yi, Xiao* et al., Phys. Rev. A 83, 023803 (2011)
Small nanoparticle, r = 20 nm Large nanoparticle, r = 100 nm
The splitting tends to be more resolvable with larger number N
The splitting tends to dissolve with larger number N
Detection ability with multiple-nanoparticle scattering
With various nanoparticles, the size of nanoparticles that can be detected is extended down to ten nanometers (small biomolecules).
Yi, Xiao* et al., Phys. Rev. A 83, 023803 (2011)
1
222 ( ) nN
n
ikxng g f e
1
222 ( ) nN
n
ikxnf e
3
33cS
g g v
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.
Detection ability with multiple-nanoparticle scattering Experimental realization
The impact of the biorecognition
IgG antibody
8nm
3nm
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.
The impact of the biorecognition
2 2
=1 =12 ( )+ 2 ( ) b tN N
n n n nn nf f
The impact of the biorecognition can be removed by resetting the zero point of the signal. Furthermore, the total linewidth broadening is 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
Splitting in aquaticaquatic environment
Li, Xiao* et al., unpublished
From air to aquatic environment
Observable splitting: splitting > linewidth
Splitting in aquatic environment
Li, Xiao* et al., unpublished
Thank you for your attention!
For more information: www.phy.pku.edu.cn/~yfxiao/index.html
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.
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