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Whispering-gallery-mode sensors for biological and physical sensing

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Abstract

The term whispering gallery mode (WGM) was first introduced to describe the curvilinear propagation of sound waves under a cathedral dome. The physical concept has now been generalized to include light waves that are continuously reflected along the closed concave surface of an optical cavity such as a glass microsphere. The circular path of the internally reflected light results in constructive interference and optical resonance, a morphology-dependent resonance that is suitable for interferometric sensing. WGM resonators are miniature micro-interferometers that use the multiple-cavity passes of light for very sensitive measurements at the microscale and nanoscale, including single-molecule and ion measurements. This Primer introduces various WGM sensors based on glass microspheres, microtoroids, microcapillaries and silicon microrings. We describe the sensing mechanisms, including mode splitting and resonance shift, exceptional-point-enhanced sensing and optomechanical and optoplasmonic signal transductions. Applications and experimental results cover in vivo and single-molecule sensing, gyroscopes and microcavity quantum electrodynamics. We also discuss data analysis methods and the limitations of WGM techniques. Finally, we provide an outlook for molecule, in vivo and quantum sensing.

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Fig. 1: Whispering gallery modes in microspheres, microbubbles and microtoroids.
Fig. 2: Single-nanoparticle and single-molecule sensing.
Fig. 3: Exceptional point-enhanced sensing.
Fig. 4: Biological sensing using microring resonators.
Fig. 5: Whispering-gallery-mode microcavity-based optomechanics.
Fig. 6: Single-molecule detection of optoplasmonic sensors.
Fig. 7: Microcavity quantum electrodynamics.

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Acknowledgements

F.V. acknowledges funding from EPSRC (grant number EP/R031428/1) and from The Royal Society (WRMA). M.H. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement number 851143) and from the Slovenian Research Agency (ARRS) (grant numbers N1-0104, J1-1697 and P1-0099). R.C.B. acknowledges funding from the US National Institutes of Health and the National Institute of Allergy and Infectious Diseases (NIAID; grant number AI141591). S.N.C. acknowledges funding from the Okinawa Institute of Science and Technology Graduate University (OIST).

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Contributions

Introduction (D.Y., S.N.C. and F.V.); Experimentation (D.Y., M.H., K.M., R.C.B., S.N.C. and F.V.); Results (D.Y., M.H., K.M., R.C.B., S.N.C. and F.V.); Applications (D.Y., M.H., S.N.C. and F.V.); Reproducibility and data deposition (M.H., K.M. and R.C.B.); Limitations and optimizations (D.Y., M.H., K.M., R.C.B., S.N.C. and F.V.); Outlook (D.Y., M.H., S.N.C. and F.V.); Overview of Primer (F.V.). All authors discussed and edited the full manuscript.

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Correspondence to Matjaž Humar, Ryan C. Bailey, Síle Nic Chormaic or Frank Vollmer.

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Nature Reviews Methods Primers thanks Shuwen Zeng and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Total internal reflection

An optical phenomenon in which the light is completely reflected when it is incident from a more dense medium into a less dense medium.

Evanescent field

An oscillating electric field whose amplitude rapidly decays in a certain spatial direction, resulting in no power transport.

Effective mode volume

A volume that measures the spatial confinement of the electromagnetic energy of a cavity mode.

Purcell factor

The enhancement factor of the spontaneous emission rate of a photon emitter located inside an optical cavity.

Finesse

The number of round trips for a light ray travelling inside an optical resonator before escaping from the resonator in a dissipative manner.

Plasmonic hotspot

The region near sharp corners and tips of metal nanoparticles. Within this region, the electric field is strongly boosted, owing to the localized surface plasmon resonance.

Optical gain

A measure of a medium transferring part of its energy to a light field through stimulated emission.

Barcoding

The labelling of individual cells with a unique (optical or non-optical) barcode to enable tracking of cells and investigation of heterogeneous cell populations.

Exceptional points

The singularities in the spectrum of a nonconservative system. Around a singularity point, the system responds strongly to a small perturbation.

Quasi-droplet regime

A regime related to the shell thickness of a microbubble, where the shell starts to lose the ability to confine whispering gallery modes.

Optofluidic resonators

Optical microcavities whose materials are partially or completely fluid.

Degenerate

A group of cavity modes having the same resonance frequency.

Polarizability

A measure of the ability of a dielectric particle (such as an atom or molecule) to acquire an electric dipole moment when subjected to an electric field.

Rayleigh scattering

Elastic scattering of electromagnetic radiation by tiny particles whose size is much smaller than the radiation wavelength.

Dielectric nanoparticles

Small objects that are made of electrical insulators and have a size of 1 nm to 102 nm.

Beat frequency

The difference in frequency of two electromagnetic waves with close oscillation frequencies and a stable phase difference.

Localized surface plasmon resonance

An optical phenomenon occurring when light interacts with metal nanoparticles whose sizes are much smaller than the light wavelength. The incident light drives the collective oscillation of surface electrons in the conduction band of metal nanoparticles.

Ohmic losses

The energy losses due to heat generation when electrons pass through a conductor.

Lasing threshold

The minimum pump intensity at which stimulated emission dominates over spontaneous emission. Above the threshold, the emission intensity as a function of the pump intensity increases much more rapidly.

Waveguides

Geometrical structures capable of confining and directing the propagation of electromagnetic or sound waves.

Noise spectral density

The energy distribution of a noise time series in the frequency domain.

Quantum shot noise

A type of noise that arises from the discrete nature of particles such as electrons and photons. The arrivals of particles at a counter satisfy a Poisson process.

Susceptibility

A dimensionless proportionality constant of a material in response to an applied electric/magnetic field.

Heisenberg uncertainty

The fundamental limit imposed by quantum mechanics. The standard deviations \(\Delta A=\sqrt{{\hat{A}}^{2}-{\hat{A}}^{2}}\) and \(\Delta B=\sqrt{{\hat{B}}^{2}-{\hat{B}}^{2}}\) of two operators \(\hat{A}\) and \(\hat{B}\) satisfy \(\Delta A\Delta B\ge |\hat{C}|/2\) with \(\hat{C}=-\,i(\hat{A}\hat{B}-\hat{B}\hat{A})\).

Balanced homodyne detection

An approach for measuring the phase-dependent quadrature of a signal, where the signal and local oscillator have the same oscillation frequency and two photodetectors are applied to eliminate the excess noise of the local oscillator.

Quality factor

2π times the ratio of the optical energy stored in an interferometer to the energy dissipated per electromagnetic oscillation of the light wave.

Receptor–ligand binding

An attractive interaction, such as ionic bonds, hydrogen bonds and Van der Waals forces, between signalling (ligand) and receiving (receptor) molecules.

Förster resonance

A distance-dependent nonradiative energy transfer between a fluorescent molecule in its electronic excited state and a ground-state fluorescent molecule.

Sagnac interference

The change of the interference between a pair of laser beams, which counterpropagate along a closed loop, under the rotation of the optical path loop.

Sagnac loop

A closed optical path loop for the interference between two counterpropagating laser beams.

Angle random walk

The angular error that originates from the white noise in angular rate and measures the short-term stability of a gyroscope.

Bias drift

The zero-rate output (that is, the output of a gyroscope in the absence of rotation), which measures the long-term stability of the gyroscope.

Hermicity

The quality that a complex square matrix or an operator in quantum mechanics is equal to its own conjugate transpose.

Parity–time-symmetrical optical system

Optical systems composed of photonic components (such as waveguides and microcavities) that ensure the balance of optical gain and loss in space-reflection-related regions.

Nonreciprocity

An optical property that the light beam cannot follow its original forward path in a backward fashion.

Vacuum Rabi splitting

Mode splitting resulting from the strong coupling between a quantum emitter and a quantized cavity mode in the vacuum state, where the total energy is only one quantum.

Microspotting

A direct-contact-based technique that deposits biomolecules on a solid surface.

Thermorefractive noise floor

The fluctuations of the cavity resonance frequency resulting from the fluctuations of temperature acting on the refractive index of the optical cavity material.

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Yu, D., Humar, M., Meserve, K. et al. Whispering-gallery-mode sensors for biological and physical sensing. Nat Rev Methods Primers 1, 83 (2021). https://doi.org/10.1038/s43586-021-00079-2

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