Ultra-broadband high-resolution microdroplet spectrometers for the near infrared.

By stabilizing the evaporation dynamics of a microliter fluorocarbon droplet, we demonstrate a fast-scan optofluidic Fourier transform (FT) spectrometer on the tip of an optical fiber operating in the 1000-2000 nm window with a resolution of 3.5 cm-1 (i.e., <1 nm at 1560 nm). Compared with other FT near-infrared (NIR) small-scale spectrometers reported in the literature, the fluorocarbon droplet spectrometer shows the largest wavelength span and span/resolution ratio, allowing spectral analysis of broadband or narrowband radiation to be easily performed. Our results open the way for the practical application of droplet spectrometers as advanced optofluidic NIR analyzers with small size and low cost that are capable of operating in harsh environments, even in the absence of electrical power sources.

Light pressure in droplet micro-resonators excited by free-space scattering.

A droplet optical resonator is a unique environment to investigate light-matter interaction and optomechanics in liquids. Here, we report on light pressure effects derived from whispering gallery modes excited in a liquid-polymer droplet micro-resonator by free-space laser scattering. From the nonlinear resonance spectrum observed in the visible, we provide evidence of photon pressure exerted at the liquid-air boundary and quantify it with a coherent physical model. Our findings pave the way to studies on micro-rheology and nonlinear optofluidics, where droplets serve as miniature liquid laboratories.

Opto-mechanical oscillator in a nanoliter droplet.

Droplets are very simple physical systems, whereby surface tension shapes liquids into ideal opto-mechanical devices. This has recently enabled low-viscosity liquid samples to serve as miniature acoustic resonators harnessing optical generation of bulk vibrations, capillaries, or surface waves. Uniquely, a simple room-temperature pendant droplet can be activated as a hypersound-laser emitter when illuminated by a free-space, low-power visible laser thanks to stimulated Brillouin scattering of optical and acoustic whispering-gallery modes. Here, we demonstrate continuous operation of a liquid polymer opto-mechanical resonator and characterize its quality factor and long-term frequency stability. Our results point to the feasibility of all-liquid micro-mechanical oscillators working in the 50-100 MHz range. The stimulated generation of high-quality surface waves on nanoliter droplets gives momentum to new optical schemes for characterization of material viscous-elastic properties, laboratory investigation of atmospheric phenomena, and mass sensing for direct analysis of biological fluids based on ultrasound-hypersound coherent generation and detection.

Stimulated Brillouin Cavity Optomechanics in Liquid Droplets.

Liquid droplets are ubiquitous in nature wherein surface tension shapes them into perfect spheres with atomic-scale smooth surfaces. Here, we use stable droplets that cohost equatorial acoustical and optical resonances phase matched to enable the exchange of energy and momentum between sound and light. Relying on free-space laser excitation of multiple whispering-gallery modes, we harness a triple-resonant forward Brillouin scattering to stimulate optomechanical surface waves. Nonlinear amplification of droplet vibrations in the 60-70 MHz range is realized with spectral narrowing beyond the limit of material loss, thereby activating the droplet as hypersound-laser emitter.

Laser-frequency locking to a whispering-gallery-mode cavity by spatial interference of scattered light.

We present a simple and effective method for frequency locking a laser source to a free-space-coupled whispering-gallery-mode cavity. The scheme relies on the interference of spatial modes contained in the light scattered by the cavity, where low- and high-order modes are simultaneously excited. A dispersion-shaped signal proportional to the imaginary component of the resonant optical field is simply generated by spatial filtering of the scattered light. Locking of a diode laser to the equatorial modes of a liquid droplet resonator is demonstrated using this scheme, and its performance is compared to the Pound-Drever-Hall technique. This new approach makes laser-frequency locking straightforward and shows a number of advantages, including robustness, low cost, and no need for sophisticated optical and electronic components.

Fiber Bragg grating laser sensor with direct radio-frequency readout.

A fiber Bragg grating (FBG)-coupled ring laser sensor is demonstrated. In the proposed configuration the interrogating source, the sensing head and the readout instrument are integrated in a single fiber-optic device. An FBG inserted within a bidirectional fiber ring couples the two counterpropagating modes of the cavity, generating a splitting of the resonant wavelengths proportional to the FBG reflectivity. When the cavity gain is brought beyond threshold, the two peaks of the split resonances simultaneously lase, leading to a beat note in the emission spectrum whose frequency tracks any small shift of the FBG reflectivity spectrum. Such a beat note can be simply monitored by a frequency counter, without the need for an optical spectrometer, allowing to significantly reduce size and costs of the sensor setup. The sensing performance compares well to the state-of-the-art thermo-mechanical fiber sensors.

Enhanced spectral response of π-phase shifted fiber Bragg gratings in closed-loop configuration.

The transmission spectrum of a ring resonator enclosing a π-phase shifted fiber Bragg grating (π-FBG) shows a spectral feature at the Bragg wavelength that is much sharper than resonance of the π-FBG alone, and that can be detected with a simple integrated cavity output technique. Hence, the resolution of any sensor based on the fitting of the π-FBG spectral profile can be largely improved by the proposed configuration at no additional fabrication costs and without altering the sensor robustness. A theoretical model shows that the resolution enhancement attainable in the proposed closed-loop geometry depends on the quality factor of the ring resonator. With a commercial grating in a medium-finesse ring, a spectral feature 12 times sharper than the π-FBG resonance is experimentally demonstrated. A larger enhancement is expected in a low-loss, polarization maintaining setup.

High-sensitivity ring-down evanescent-wave sensing in fiber resonators.

We report on optical-fiber cavity ring-down spectroscopy (CRDS) in the liquid phase using a laser emitting at telecommunication wavelengths. A fiber-ring cavity, comprising a short evanescent-wave coupler for radiation-matter interaction, is used as a sensor while its resonance modes are frequency locked to the laser. Exploiting the intrinsic sensitivity and noise immunity of the CRDS technique, we show that liquid absorption can be detected down to a level that is nearly a factor of 20 above the shot noise limit. We provide a thorough comparison between the experimental results and various noise contributions and address different expressions that can be used to calculate the shot noise equivalent absorbance. As a proof of principle, polyamine detection in aqueous solutions is carried out demonstrating a minimum detectable absorbance of 1.8×10(-7) Hz(-1/2), which, to our knowledge, is the best sensitivity limit reported to date for evanescent-wave sensors.

Split-mode fiber Bragg grating sensor for high-resolution static strain measurements.

We demonstrate a strain sensor with very high sensitivity in the static and low frequency regime based on a fiber ring cavity that includes a π phase-shifted fiber Bragg grating. The grating acts as a partial reflector that couples the two counter-propagating cavity modes, generating a splitting of the resonant frequencies. The presence of a sharp transition within the π phase-shifted fiber Bragg grating's spectral transmittance makes this frequency splitting extremely sensitive to length, temperature, and the refractive index of the fiber in the region where the grating is written. The splitting variations caused by small mechanical deformations of the grating are tracked in real time by interrogating a cavity resonance with a locked-carrier scanning-sideband technique. The measurable strain range and bandwidth are characterized, and a resolution of 320 pϵ/Hz(1/2) at 0 Hz is experimentally demonstrated, the highest achieved to date with a fiber Bragg grating sensor.

The endogenous oxytocin after manipulative osteopathic treatment in full-term pregnant women.

OBJECTIVE: The aim of this study is to assess whether the touch of osteopathic manipulative treatment (OMT) can affect the endogenous production of oxytocin in full-term pregnant women and the assessment of well-being following the treatment. PATIENTS AND METHODS: In this study have been enrolled 57 pregnant women at full-term pregnancy (37th-41st week) for evaluation of the concentration of salivary oxytocin 2 minutes before and 2 minutes after a single session of OMT by an osteopath lasting for 30 minutes. Pre-OMT and post-OMT saliva samples were collected with the use of Salivette® salivary swabs. 7 salivary swabs were excluded from the analysis. 50 samples were analyzed with an appropriate ELISA kit. RESULTS: The mean OT salivary concentration pre-OMT was 89.98±16.39, and post-OMT was 100.60±19.13 tends to increase with p=0.0000051. In multivariate analysis, two subgroups show interesting data in the mean difference in OT salivary concentration post-OMT: women with painful contractions (p=0.06) and women under 35 years (p=0.09). CONCLUSIONS: The results of this study demonstrate that the effectiveness of OMT-increasing endogenous oxytocin is statistically significant in full-term pregnant women. The sensation of well-being found in most women indicates that there has been a predominantly central rather than peripheral oxytocin release after OMT.

Investigating the resonance spectrum of optical frequency combs in fiber-optic cavities.

We report a detailed theoretical and experimental study of fiber-optic cavities under broadband excitation by mode-locked laser combs. We calculate the effects of fiber dispersion on the cavity transmission. For any integer ratio between the comb repetition rate and cavity free spectral range, the theoretical resonant output spectrum exhibits a narrow group of resonant teeth, surrounded by minor, unevenly spaced resonances. Also, the central resonance can be rapidly and precisely tuned over the entire comb span by only acting on its repetition rate. Experimental observations are provided by a single-mode fiber ring and a telecom-wavelength comb laser. The resulting spectral pattern agrees very well with our theoretical prediction, allowing a thorough characterization of the cavity dispersion and opening new perspectives for comb spectroscopy in dielectric resonators.

Localized strain sensing with fiber Bragg-grating ring cavities.

We report the theoretical description and the experimental demonstration of an optical resonator formed by inserting a Fiber Bragg Grating (FBG) in a closed fiber loop. The spectral characteristics of such a resonator strongly depend on the reflectivity of the FBG. In the wavelength region where the FBG reflectivity R is negligible, the system behaves like a conventional ring resonator. On the other hand, when R is not vanishing, a split-mode structure can be observed, associated to the degeneracy removal of two counterpropagating resonant modes. The magnitude of the mode splitting can be used to sense small variations of the FBG physical parameters, such as length, temperature or group index. An example of strain sensing with this setup is reported, showing that the mode splitting is sensitive to a mechanical strain applied to the FBG, while it is almost insensitive to a strain applied to any other point of the resonator. This peculiar feature allows to perform cavity-enhanced, local strain measurements with a reduced sensitivity to environmental perturbations, which represents an important improvement in the framework of the fiber-optic sensors.

Surface plasmon resonance optical cavity enhanced refractive index sensing.

We report on a method for surface plasmon resonance (SPR) refractive index sensing based on direct time-domain measurements. An optical resonator is built around an SPR sensor, and its photon lifetime is measured as a function of loss induced by refractive index variations. The method does not rely on any spectroscopic analysis or direct intensity measurement. Time-domain measurements are practically immune to light intensity fluctuations and thus lead to high resolution. A proof of concept experiment is carried out in which a sensor response to liquid samples of different refractive indices is measured. A refractive index resolution of the current system, extrapolated from the reproducibility of cavity-decay time determinations over 133 s, is found to be about 10(-5) RIU. The possibility of long-term averaging suggests that measurements with a resolution better than 10(-7) RIU/√Hz are within reach.

A self-operating broadband spectrometer on a droplet.

Small-scale Fourier transform spectrometers are rapidly revolutionizing infrared spectro-chemical analysis, enabling on-site and remote sensing applications that were hardly imaginable just few years ago. While most devices reported to date rely on advanced photonic integration technologies, here we demonstrate a miniaturization strategy which harnesses unforced mechanisms, such as the evaporation of a liquid droplet on a partially reflective substrate. Based on this principle, we describe a self-operating optofluidic spectrometer and the analysis method to retrieve consistent spectral information in spite of the intrinsically non-reproducible droplet formation and evaporation dynamics. We experimentally realize the device on the tip of an optical fiber and demonstrate quantitative measurements of gas absorption with a 2.6 nm resolution, in a 100 s acquisition time, over the 250 nm span allowed by our setup's components. A direct comparison with a commercial optical analyzer clearly points out that a simple evaporating droplet can be an efficient small-scale, inexpensive spectrometer, competitive with the most advanced integrated photonic devices.

Fundamental limits in high-Q droplet microresonators.

Liquid droplet whispering-gallery-mode microresonators open a new research frontier for sensing, optomechanics and photonic devices. At visible wavelengths, where most liquids are transparent, a major contribution to a droplet optical quality factor is expected theoretically from thermal surface distortions and capillary waves. Here, we investigate experimentally these predictions using transient cavity ring-down spectroscopy. With our scheme, the optical out-coupling and intrinsic loss are measured independently while any perturbation induced by thermal, acoustic and laser-frequency noise is avoided thanks to the ultra-short light-cavity interaction time. The measurements reveal a photon lifetime at least ten times longer than the thermal limit and indicate that capillary fluctuations activate surface scattering effects responsible for light coupling. This suggests that droplet microresonators are an ideal optical platform for ultra-sensitive spectroscopy of highly transparent liquid compounds in nano-liter volumes.

Super-Resonant Intracavity Coherent Absorption.

The capability of optical resonators to extend the effective radiation-matter interaction length originates from a multipass effect, hence is intrinsically limited by the resonator's quality factor. Here, we show that this constraint can be overcome by combining the concepts of resonant interaction and coherent perfect absorption (CPA). We demonstrate and investigate super-resonant coherent absorption in a coupled Fabry-Perot (FP)/ring cavity structure. At the FP resonant wavelengths, the described phenomenon gives rise to split modes with a nearly-transparent peak and a peak whose transmission is exceptionally sensitive to the intracavity loss. For small losses, the effective interaction pathlength of these modes is proportional respectively to the ratio and the product of the individual finesse coefficients of the two resonators. The results presented extend the conventional definition of resonant absorption and point to a way of circumventing the technological limitations of ultrahigh-quality resonators in spectroscopy and optical sensing schemes.

Inactivating mutations in GNA13 and RHOA in Burkitt's lymphoma and diffuse large B-cell lymphoma: a tumor suppressor function for the Gα13/RhoA axis in B cells.

G proteins and their cognate G protein-coupled receptors (GPCRs) function as critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression and/or function of these molecules have been linked to the growth, progression and metastasis of various cancers. As such, the analysis of mutations in the genes encoding GPCRs, G proteins and their downstream targets provides important clues regarding how these signaling cascades contribute to malignancy. Recent genome-wide sequencing efforts have unveiled the presence of frequent mutations in GNA13, the gene encoding the G protein Gα13, in Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL). We found that mutations in the downstream target of Gα13, RhoA, are also present in Burkitt's lymphoma and DLBCL. By multiple complementary approaches, we now show that that these cancer-specific GNA13 and RHOA mutations are inhibitory in nature, and that the expression of wild-type Gα13 in B-cell lymphoma cells with mutant GNA13 has limited impact in vitro but results in a remarkable growth inhibition in vivo. Thus, although Gα13 and RhoA activity has previously been linked to cellular transformation and metastatic potential of epithelial cancers, our findings support a tumor suppressive role for Gα13 and RhoA in Burkitt's lymphoma and DLBCL.

SIRT1 is involved in oncogenic signaling mediated by GPER in breast cancer.

A number of tumors exhibit an altered expression of sirtuins, including NAD+-dependent histone deacetylase silent information regulator 1 (SIRT1) that may act as a tumor suppressor or tumor promoter mainly depending on the tumor types. For instance, in breast cancer cells SIRT1 was shown to exert an essential role toward the oncogenic signaling mediated by the estrogen receptor-α (ERα). In accordance with these findings, the suppression of SIRT1 led to the inhibition of the transduction pathway triggered by ERα. As the regulation of SIRT1 has not been investigated in cancer cells lacking ER, in the present study we ascertained the expression and function of SIRT1 by estrogens in ER-negative breast cancer cells and cancer-associated fibroblasts obtained from breast cancer patients. Our results show that 17ß-estradiol (E2) and the selective ligand of GPER, namely G-1, induce the expression of SIRT1 through GPER and the subsequent activation of the EGFR/ERK/c-fos/AP-1 transduction pathway. Moreover, we demonstrate that SIRT1 is involved in the pro-survival effects elicited by E2 through GPER, like the prevention of cell cycle arrest and cell death induced by the DNA damaging agent etoposide. Interestingly, the aforementioned actions of estrogens were abolished silencing GPER or SIRT1, as well as using the SIRT1 inhibitor Sirtinol. In addition, we provide evidence regarding the involvement of SIRT1 in tumor growth stimulated by GPER ligands in breast cancer cells and xenograft models. Altogether, our data suggest that SIRT1 may be included in the transduction network activated by estrogens through GPER toward the breast cancer progression.

Smoking reduction in smokers compliant to a smoking cessation trial with nicotine patch.

The aim of this retrospective analysis was to assess the extent of smoking reduction in smokers who were compliant to a smoking cessation trial with nicotine patch, and failed to completely quit smoking. Out of 297 smokers in total, 237 participants received active treatment (60 received placebo). Eighty treated subjects attended all the scheduled visits and were classified as either abstainers (nonsmokers), regular smokers or occasional smokers. Compared to the remaining 157 participants, these 80 subjects had significantly lower mean baseline daily cigarette consumption (24 versus 30; p < 0.001), expired carbon monoxide levels (25 versus 33 ppm; p < 0.001), plasma nicotine and cotinine levels, and Fagerström Tolerance Questionnaire score (5.7 versus 7.0; p < 0.001). All subjects received active treatment for up to 18 weeks (full dose for 12 weeks plus tapering dose for 6 weeks), with follow-up visits scheduled up to 1 yr. A statistically significant reduction in cigarette consumption (versus baseline) was observed among both the occasional (-99%) and regular (-77%) smokers between week 1 and week 52 (p < 0.001). Concomitant smoking and patch use was well tolerated since adverse events were infrequent, mild and transient. Thus, in addition to those subjects who successfully quit smoking, a further group of subjects who attended all the follow-up visits during the smoking cessation trial significantly reduced their mean daily cigarette consumption.

Probing the ultimate limit of fiber-optic strain sensing.

The measurement of relative displacements and deformations is important in many fields such as structural engineering, aerospace, geophysics, and nanotechnology. Optical-fiber sensors have become key tools for strain measurements, with sensitivity limits ranging between 10(-9) and 10(-6)ε hertz (Hz)(-1/2) (where ε is the fractional length change). We report on strain measurements at the 10(-13)ε-Hz(-1/2) level using a fiber Bragg-grating resonator with a diode-laser source that is stabilized against a quartz-disciplined optical frequency comb, thus approaching detection limits set by thermodynamic phase fluctuations in the fiber. This scheme may provide a route to a new generation of strain sensors that is entirely based on fiber-optic systems, which are aimed at measuring fundamental physical quantities; for example, in gyroscopes, accelerometers, and gravity experiments.