Highly sensitive optical biosensing
in 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/
Collaborators
Lan Yang, Jiangang Zhu, and Lina He @ WUSTL
Microcavity Photonics and Quantum Optics Group @ PKU
Bei-Bei Li
Xu Yi
Yong-Chun Liu
Qiu-Shu Chen
Optical biosensors
Optical biosensors are a powerful detection and analysis tool
that has vast applications in
• Biomedical research
• Healthcare
• Environmental monitoring
• Homeland security
Two general detection protocols of optical biosensors
1. 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
2. Label-free detection
Molecules are not labeled/altered, detected in their natural forms.
Relatively easy and cheap to perform
(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.
Fan et al., Analytica chimica acta 620, 8-26 (2008)
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
WHY resonator based biosensors?
• 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 ultra-high-Q whispering gallery resonator?
Advantages of microcavities
Cavity power build-up factor:
B
Pcav
Q
 2
Pin 2 nD
Cavity photon lifetime:

Q

Experimental
data in our
group
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
Detection mechanism of WGM resonator-based biosensor
Li et al., unpublished
Detection methods of resonator-based sensor
1, Resonant wavelength shift detection
2, Intensity detection at a single wavelength
High concentration detection
Limited by the wavelength resolution!
Low concentration detection
Limited by the detector noise!
Optical biosensing with whispering gallery microcavities
SOI ring resonator
Glass ring
resonator array
Polymer ring resonator
Silica microsphere
Silica microtoroid
Capillary-based
ring resonator
For a review, e.g., See Fan et al., Analytica chimica acta 620, 8-26 (2008)
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
0
• 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.
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
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).
Sensitivity-enhanced method: coupled resonators
1.0
R, Single cavity
R, coupled cavities
0.8
EIT-like
0.6
0.4
0.2
two microresonators are coupled
through a waveguide.
0.0
Sensitivity
-4
-2
0

2
4
one order of magnitude
enhancement in detection
sensitivity.
Propagting phase, k*L
EIT/Fano resonance in a single microcavity
Probe
Control
High-Q: over coupled
Low-Q: under coupled
Fano
EIT
Xiao et al, Appl. Phy. Lett. 94, 231115 (2009)
Coupling decreasing
Both: over coupled
Li, Xiao* et al., Appl. Phys. Lett. 96, 251109 (2010)
Fano resonance in two controllable coupled microcavities
A microdisk free from its silicon pillar is
indirectly coupled with a microtoroid
through a fiber taper.
transmission of individual
microdisk
transmission of
individual microtoroid
Fano resonance
transmission of coupled
disk/toroid
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)
Compensating thermal refraction noise
Han and Wang, Opt. Lett., 2007
Silica: positive thermal-optic effect
Polymer: negative thermal-optic effect
Compensating thermal refraction noise
PDMS
coating
1. Thermal expansion noise is still difficult to be compensated.
2. Monitoring the small mode shift is a challenging.
Complete
Compensation
Stable cavity modes! The coated microtoroids can be used in biosensing to improve the measurement precision, and also hold
potential applications in nonlinear optics.
Lina He et al., APL 93, 201102 (2008)
Ultrastable single-nanoparticle detection - Physics
1,
• scattering back (counter-propagating mode)
• scattering to the vacuum modes
Polarizability:   4 R3 (n p 2  nm 2 ) /(n p 2  2nm 2 )
2, WGM: traveling mode
CW
CCW
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
Shift and damping
anti-symmetric
Not affected
3 3  1   2
S 2
   4 R3 (np 2  nm2 ) / (np 2  2nm2 )

8
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)
Ultrastable single-nanoparticle detection - Result
 Detection of R=100 nm PS nanospheres
Zhu et al., Nature Photonics 4, 46 (2010)
Ultrastable single-nanoparticle detection with WGM
670 nm band
23
1450 nm band
Zhu et al., Nature Photonics 4, 46 (2010)
Ultrastable single-particle detection – nonspherical particle
Mode-splitting method
in detecting nonspherical nanoparticle
TM
TE
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)
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)
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.
Considering the random nature of scatterer
adsorption, we use Monte Carlo simulation and obtain
g  Ng0   g0 N ,   N 0  0 N
Mode shifts
Linewidth broadings
g  2 g0 N ,   20 N
Mode splitting
 =0.87
Linewidth difference
Resonance shifts and linewidth broadenings: increase linearly with N (N>>N1/2)
Resonance splitting and linewidth difference: increase linearly with N1/2.
Yi, Xiao* et al., Phys. Rev. A 83, 023803 (2011)
Multiple-Rayleigh-scatterer-induced mode splitting
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
Yi, Xiao* et al., Phys. Rev. A 83, 023803 (2011)
Detection ability with multiple-nanoparticle scattering
g  2 g
N
 f 2 (n )e2ikxn
n 1
N
  2  f 2 (n )e2ikxn
n 1
   c3
S
 
g  g 3 v3
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 ten nanometers (small biomolecules).
Yi, Xiao* et al., Phys. Rev. A 83, 023803 (2011)
Detection ability with multiple-nanoparticle scattering
Experimental realization
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.
IgG antibody
The impact of the biorecognition
       n =1 2 n f ( n )+ n =1 2 n f 2 ( n )
Nb
2
Nt
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 aquatic environment
From air to aquatic environment
Observable splitting: splitting > linewidth
Li, Xiao* et al., unpublished
Splitting in aquatic environment
Li, Xiao* et al., unpublished
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