Detecting single viruses and nanoparticles using whispering gallery microlasers

Abstract

Detection and characterization of individual nano-scale particles, virions, and pathogens are of paramount importance to human health, homeland security, diagnostic and environmental monitoring 1 .There is a strong demand for high-resolution, portable, and cost-effective systems to make label-free detection and measurement of individual nanoparticles, molecules, and viruses 2-6 . Here, we report an easily accessible, real-time and label-free detection method with single nanoparticle resolution that surpasses detection limit of existing micro-and nano-photonic devices. This is achieved by using an ultra-narrow linewidth whispering gallery microlaser, whose lasing line undergoes frequency splitting upon the binding of individual nano-objects. We demonstrate detection of polystyrene and gold nanoparticles as small as 15 nm and 10 nm in radius, respectively, and Influenza A virions by monitoring changes in self-heterodyning beat note of the split lasing modes. Experiments are performed in both air and aqueous environment. The built-in self-heterodyne interferometric method achieved in a microlaser provides a self-reference scheme with extraordinary sensitivity 7,8 , and paves the way for detection and spectroscopy of nano-scale objects using micro-and nano-lasers.Most of the biological agents and synthetic particles of interest have low polarizability due to their small size and low refractive index contrast with the surrounding medium, leading to weak light-particle interactions which make their label-free optical detection at single particle resolution difficult. Micro-and nano-photonic resonant devices have emerged as highly sensitive platforms for detection of individual virions and nanoparticles due to the significantly enhanced light-matter interactions originating from the high ratio of their quality-factor (Q) to mode volume (V) 7,9-15 . For example, detection of single Influenza virions and polystyrene nanospheres as small as 30 nm in radius have been demonstrated in whispering gallery mode (WGM) microspheres using reactive shift 12 and in microtoroids using mode splitting technique 7 , respectively. In both techniques, wavelength of a tunable laser is scanned to obtain the transmission spectrum of a resonant mode from which specific information, either the resonance shift and/or the mode splitting, is extracted to detect and measure nanoparticles. The ultimate detection limit strongly relies on Q/V which not only determines the light-matter interaction strength but also sets the smallest resolvable changes in the WGM spectrum 16 . Higher Q, limited by material absorption, implies narrower resonance linewidth and better resolution.Here we report the first microlaser-based detection scheme with single particle resolution surpassing the detection capabilities of existing micro-and nano-photonic devices. The ultimate detection limit is set by the laser linewidth, which can be as narrow as a few Hertz for a WGM microlaser, and is certainly much narrower than the resonance linewidth of any passive resonators 17 ...

Cavity optomechanics on a microfluidic resonator with water and viscous liquids

“…We believe that in the future, a differential detection scheme could cancel out drifts using a split mechanical mode similar to what is currently done in optical detection. 4 The optical quality factor, Q O , is measured using the resonance linewidth to be near 7310 6 . Moreover, this value of Q O is not affected by introducing water inside the bubble resonator.…”

“…A major application of optical resonators is in the field of sensing where microresonators were used to sense biomarkers in serum 1 and to detect viruses and nanoparticles [2][3][4] in an aqueous environment. With similar motivation and in a parallel effort, mechanical resonators were used to weigh biomolecules and cells.…”

Microsphere Solid‐State Biolasers

“…[1] In the last decade, the passive whispering gallery mode (WGM) resonators have significantly improved the sensor sensitivity, reaching down to the single mole cule level. [2][3][4] In these WGM biosensors, a tapered fiber is an important component that serves to drive the resonance mode and to guide the analyte induced wavelength shift. However, the presence of the fiber makes the sensing system complex.…”

Cavity ring-up spectroscopy for dissipative and dispersive sensing in a whispering gallery mode resonator

“…dispersive) frequency shift of the whispering gallery modes [19] as a result of perturbations that may be present. Alternatively, a perturbation may increase the optical linewidth of the WGM by introducing more dissipation [21,22], or may change the back-scattering strength [23] and subsequent mode splitting if modal coupling is present [17,20]. The optomechanical properties of WGRs can also be used for force [24] or viscosity sensing [25].…”