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Detecting single viruses and nanoparticles using whispering gallery microlasers

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 Publication date 2011
  fields Physics
and research's language is English




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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.



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Whispering gallery mode biosensors allow selective unlabelled detection of single proteins and, combined with quantum limited sensitivity, the possibility for noninvasive realtime observation of motor molecule motion. However, to date technical noise sources, most particularly low frequency laser noise, have constrained such applications. Here we introduce a new technique for whispering gallery mode sensing based on direct detection of back-scattered light. This experimentally straightforward technique is immune to frequency noise in principle, and further, acts to suppress thermorefractive noise. We demonstrate 27 dB of frequency noise suppression, eliminating frequency noise as a source of sensitivity degradation and allowing an absolute frequency shift sensitivity of 76 kHz. Our results open a new pathway towards single molecule biophysics experiments and ultrasensitive biosensors.
Recently optical whispering-gallery-mode resonators (WGMRs) have emerged as promising platforms to achieve label-free detection of nanoscale objects and to reach single molecule sensitivity. The ultimate detection performance of WGMRs are limited by energy dissipation in the material they are fabricated from. Up to date, to improve detection limit, either rare-earth ions are doped into the WGMR to compensate losses or plasmonic resonances are exploited for their superior field confinement. Here, we demonstrate, for the first time, enhanced detection of single-nanoparticle induced mode-splitting in a silica WGMR via Raman-gain assisted loss-compensation and WGM Raman lasing. Notably, we detected and counted individual dielectric nanoparticles down to a record low radius of 10 nm by monitoring a beatnote signal generated when split Raman lasing lines are heterodyne-mixed at a photodetector. This dopant-free scheme retains the inherited biocompatibility of silica, and could find widespread use for sensing in biological media. It also opens the possibility of using intrinsic Raman or parametric gain in other systems, where dissipation hinders the progress of the field and limits applications.
We have demonstrated a 165 micron oblate spheroidal microcavity with free spectral range 383.7 GHz (3.06nm), resonance bandwidth 25 MHz (Q ~ 10^7) at 1550nm, and finesse F > 10^4. The highly oblate spheroidal dielectric microcavity combines very high Q-factor, typical of microspheres, with vastly reduced number of excited whispering-gallery (WG) modes (by two orders of magnitude). The very large free spectral range in the novel microcavity - few hundred instead of few GigaHertz in typical microspheres - is desirable for applications in spectral analysis, narrow-linewidth optical and RF oscillators, and cavity QED.
We investigate numerically and experimentally the statistics of the changes in the amount of frequency splitting upon the adsorption of particles one-by-one into the mode volume of whispering gallery mode (WGM) microresonator and microlasers. This multiple-particle induced frequency splitting (MPIFS) statistics carries information on the size and the number of adsorbed particles into the mode volume, and it is strongly affected by two experimental parameters, namely the WGM field distribution and the positions of the particles within the mode volume. We show that the standard deviation and maximum value of the MPIFS are proportional to the polarizability of the particles, and propose a method to estimate particle size from the MPIFS if the only available data from experiments is frequency splitting.
We review our recent work on tunable, ultrahigh quality factor whispering-gallery-mode bottle microresonators and highlight their applications in nonlinear optics and in quantum optics experiments. Our resonators combine ultra-high quality factors of up to Q = 3.6 times 10^8, a small mode volume, and near-lossless fiber coupling, with a simple and customizable mode structure enabling full tunability. We study, theoretically and experimentally, nonlinear all-optical switching via the Kerr effect when the resonator is operated in an add-drop configuration. This allows us to optically route a single-wavelength cw optical signal between two fiber ports with high efficiency. Finally, we report on progress towards strong coupling of single rubidium atoms to an ultra-high Q mode of an actively stabilized bottle microresonator.
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