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/

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Li et al., unpublished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.