Whispering gallery mode bio-sensor  for label-free detection of single molecules: thermo-optic vs reactive mechanism

Arnold, Stephen; Shopova, Siyka I.; Holler, Stephen

doi:10.1364/oe.18.000281

Cited by 87 publications

(73 citation statements)

References 12 publications

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“…This microcavity Raman laser sensing method holds several advantages. On the one hand, the beat frequency of the Raman lasers, which corresponds to the mode splitting (18), is inherently immune to many noise sources, such as laser frequency noise and thermal noise (including that induced both by the environmental temperature fluctuations and by probe laser heating), which are the main noise sources in sensing systems using the mode shift mechanism (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Over the last few years, significant effort has been made to suppress the laser frequency noise in the mode-shift detection method, such as by using a reference interferometer (27) and by performing backscattering detection with frequency locking techniques (28,29), but both approaches involve a substantial increase in the complexity of the sensing systems.…”

mentioning

confidence: 99%

Single nanoparticle detection using split-mode microcavity Raman lasers

Clements

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

256

137

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Ultrasensitive nanoparticle detection holds great potential for early-stage diagnosis of human diseases and for environmental monitoring. In this work, we report for the first time, to our knowledge, single nanoparticle detection by monitoring the beat frequency of split-mode Raman lasers in high-Q optical microcavities. We first demonstrate this method by controllably transferring single 50-nm-radius nanoparticles to and from the cavity surface using a fiber taper. We then realize real-time detection of single nanoparticles in an aqueous environment, with a record low detection limit of 20 nm in radius, without using additional techniques for laser noise suppression. Because Raman scattering occurs in most materials under practically any pump wavelength, this Raman laser-based sensing method not only removes the need for doping the microcavity with a gain medium but also loosens the requirement of specific wavelength bands for the pump lasers, thus representing a significant step toward practical microlaser sensors.stimulated Raman scattering | optical microcavity | mode splitting | optical sensor | label free S timulated Raman scattering holds great potential for various photonic applications, such as label-free high-sensitivity biomedical imaging (1) and for extending the wavelength range of existing lasers (2), as well as for generating ultra-short light pulses (3). In high Q microcavities (4), stimulated Raman scattering, also called Raman lasing, has been experimentally demonstrated to possess ultra-low thresholds (5-12), due to the greatly increased light density in microcavities (13). Such microcavity Raman lasers hold great potential for sensing applications. In principle, Raman lasing initially occurs in the two initially degenerate counter propagating traveling cavity modes. These two modes couple to each other due to backscattering when a nanoscale object binds to the cavity surface. For a sufficiently strong coupling, in which the photon exchange rate between the two initial modes becomes larger than the rates of all of the loss mechanisms in the system, two new split cavity modes form (14-18) and lase simultaneously. Thus, by monitoring the beat frequency of the split-mode Raman lasers, ultrasensitive nanoparticle detection can be realized.In this work, we report, to our knowledge, the first experimental demonstration of single nanoparticle detection using split-mode microcavity Raman lasers. The sensing principle is first demonstrated in air, by controllably binding or removing single 50-nm-radius polystyrene (PS) nanoparticles to and from the cavity surface using a fiber taper (19) and measuring the changes in the beat frequency of the two split Raman lasers. Real-time single nanoparticle detection is then performed in an aqueous environment by monitoring the discrete changes in beat frequency of the Raman lasers, and a detection limit of 20 nm in particle radius is realized. This microcavity Raman laser sensing method holds several advantages. On the one hand, the beat frequency of the Raman las...

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mentioning

confidence: 99%

Single nanoparticle detection using split-mode microcavity Raman lasers

Clements

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

256

137

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“…This thermo-optic effect is distinct from the reactive effect described in [80], which is power-independent. However, attempts to increase the sensitivity with the thermo-optic effect have produced no reliable results, and a recent theoretical comparison between the two mechanisms, thermo-optics and reactive, concluded that no significant enhancement could be obtained from the thermo-optic effect [83]. Measuring the resonance shift was also applied to detect other types of single objects, such as the influenza A virus [84] and nanospheres [85].…”

Section: Qδν Fsr 2πνmentioning

confidence: 99%

Nonlinear optics in spheres: from second harmonic scattering to quasi‐phase matched generation in whispering gallery modes

Kozyreff

Domínguez-Juárez

Martorell

2011

Laser & Photonics Reviews

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Over the last fifteen years, a series of theoretical and experimental investigations have demonstrated the usefulness of circular geometries to tailor second-order nonlinear optical effects. However, until recently, such effects have remained rather weak, calling for their enhancement. In parallel, developments in the field of high quality factor spherical or ring resonators have shown that many different types of light-matter interactions can be dramatically amplified when light is coupled in the whispering gallery modes of such resonators. In high-quality spherical micro-resonators, close to one million interactions can occur between a nonlinear molecule and a circulating light pulse. Recent research on nonlinear optics in spherical geometry is reviewed, from micrometer-size spheres to whispering gallery mode resonators.

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“…quick aspect, handiness, precision and inspection cost, to satisfy such demands. Recently, for the label-free optical detection of viruses and pathogens, [1][2][3][4][5][6][7] whispering gallery mode (WGM) resonators with a high Q factor have attracted attention. Because the WGM of a microsphere is sensitive to the change of the refractive index of the microsphere environment, the WGM microsphere resonator may work as an optical biosensor with high sensitivity and a short measurement time.…”

Section: Introductionmentioning

confidence: 99%

Optical Characterization of the Antigen-Antibody Thin Layer Using the Whispering Gallery Mode

et al. 2014

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We immobilized an antibody (anti-β-Galactosidase) on a polystyrene microsphere by using a covalent bond, and observed the resonance peaks in the scattered light intensity spectra related to the whispering gallery mode (WGM) excitation of the microsphere. The amount and the optical parameters, i.e., thickness and refractive index, of anti-β-Galactosidase on the sphere surface were evaluated based on an absorbance measurement and a resonance peak shift measurement, respectively. Moreover, we measured the variation of the WGM spectra depending on the concentration of the enzyme solution (β-Galactosidase), which allowed us to optically evaluate the thickness and the refractive index of the antigen-antibody layer from the shift of the WGM spectra peak.

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Whispering gallery mode bio-sensor  for label-free detection of single molecules: thermo-optic vs reactive mechanism

Cited by 87 publications

References 12 publications

Single nanoparticle detection using split-mode microcavity Raman lasers

Single nanoparticle detection using split-mode microcavity Raman lasers

Nonlinear optics in spheres: from second harmonic scattering to quasi‐phase matched generation in whispering gallery modes

Optical Characterization of the Antigen-Antibody Thin Layer Using the Whispering Gallery Mode

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Whispering gallery mode bio-sensor for label-free detection of single molecules: thermo-optic vs reactive mechanism

Cited by 87 publications

References 12 publications

Single nanoparticle detection using split-mode microcavity Raman lasers

Single nanoparticle detection using split-mode microcavity Raman lasers

Nonlinear optics in spheres: from second harmonic scattering to quasi‐phase matched generation in whispering gallery modes

Optical Characterization of the Antigen-Antibody Thin Layer Using the Whispering Gallery Mode

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Whispering gallery mode bio-sensor  for label-free detection of single molecules: thermo-optic vs reactive mechanism