Photonic wire biosensor microarray chip and instrumentation with application to serotyping of Escherichia coli isolates.

A complete photonic wire molecular biosensor microarray chip architecture and supporting instrumentation is described. Chip layouts with 16 and 128 independent sensors have been fabricated and tested, where each sensor can provide an independent molecular binding curve. Each sensor is 50 µm in diameter, and consists of a millimeter long silicon photonic wire waveguide folded into a spiral ring resonator. An array of 128 sensors occupies a 2 × 2 mm2 area on a 6 × 9 mm2 chip. Microfluidic sample delivery channels are fabricated monolithically on the chip. The size and layout of the sensor array is fully compatible with commercial spotting tools designed to independently functionalize fluorescence based biochips. The sensor chips are interrogated using an instrument that delivers sample fluid to the chip and is capable of acquiring up to 128 optical sensor outputs simultaneously and in real time. Coupling light from the sensor chip is accomplished through arrays of sub-wavelength surface grating couplers, and the signals are collected by a fixed two-dimensional detector array. The chip and instrument are designed so that connection of the fluid delivery system and optical alignment are automated, and can be completed in a few seconds with no active user input. This microarray system is used to demonstrate a multiplexed assay for serotyping E. coli bacteria using serospecific polyclonal antibody probe molecules.

Bronchoscopic treatments for emphysema.

In late stage chronic obstructive pulmonary disease, emphysema can worsen respiratory symptoms, not only via the loss of surface for gas exchange, but also via alterations in mechanical properties of the respiratory system (dynamic and static hyperinflation). Emphysematous lung volume reduction aims at improving respiratory mechanics and symptomatology in patients with advanced emphysema. Lung volume reduction surgery (LVRS) has been shown to be effective in selected patient populations, but its morbidity and costs are quite elevated. Alternatives to LVRS do not remove emphysematous lung tissue per se, but rather consist of devices aiming to: 1) reduce the volume that affected lung parenchyma occupies (unidirectional endobronchial valves or plugs, parenchymal injection of bioactive scarring agents); 2) redistribute ventilatory flow (airway bypass systems). Preliminary studies of these devices have shown that they are relatively safe. These also show modest benefits in exercise capacity, although individual subjects can experience spectacular improvement. Current objective is to identify predictors of response to therapy with such devices.

Real-time cancellation of temperature induced resonance shifts in SOI wire waveguide ring resonator label-free biosensor arrays.

A comprehensive investigation of real-time temperature-induced resonance shift cancellation for silicon wire based biosensor arrays is reported for the first time. A reference resonator, protected by either a SU8 or SiO(2) cladding layer, is used to track temperature changes. The temperature dependence of resonators in aqueous solutions, pertinent to biosensing applications, is measured under steady-state conditions and the operating parameters influencing these properties are discussed. Real-time measurements show that the reference resonator resonances reflect the temperature changes without noticeable time delay, enabling effective cancellation of temperature-induced shifts. Binding between complementary IgG protein pairs is monitored over 4 orders of magnitude dynamic range down to a concentration of 20 pM, demonstrating a resolvable mass of 40 attograms. Reactions are measured over time periods as long as 3 hours with high stability, showing a scatter corresponding to a fluid refractive index fluctuation of ± 4 × 10(-6) in the baseline data. Sensor arrays with a SU8 protective cladding are easy to fabricate, while oxide cladding is found to provide superior stability for measurements involving long time scales.

Label-free biosensor array based on silicon-on-insulator ring resonators addressed using a WDM approach.

We report a silicon-on-insulator ring resonator biosensor array with one output port, using wavelength division multiplexing as the addressing scheme. With the use of on-chip referencing for environmental drift cancellation, simultaneous monitoring of multiplexed molecular bindings is demonstrated, with a resolution of 0.3 pg/mm(2) (40 ag of total mass) for protein concentrations over 4 orders of magnitude down to 20 pM. Reactions are measured over time periods as long as 3 h with high stability.

Electrically switching transverse modes in high power THz quantum cascade lasers.

The design and fabrication of a high power THz quantum cascade laser (QCL), with electrically controllable transverse mode is presented. The switching of the beam pattern results in dynamic beam switching using a symmetric side current injection scheme. The angular-resolved L-I curves measurements, near-field and far-field patterns and angular-resolved lasing spectra are presented. The measurement results confirm that the quasi-TM(01) transverse mode lases first and dominates the lasing operation at lower current injection, while the quasi-TM(00) mode lases at a higher threshold current density and becomes dominant at high current injection. The near-field and far-field measurements confirm that the lasing THz beam is maneuvered by 25 degrees in emission angle, when the current density changes from 1.9 kA/cm(2) to 2.3 kA/cm(2). A two-dimension (2D) current and mode calculation provides a simple model to explain the behavior of each mode under different bias conditions.

[Bronchoscopic treatment of emphysema]. / Traitement instrumental non chirurgical de l'emphysème.

In late stage chronic obstructive pulmonary disease, emphysema can worsen respiratory symptoms not only via the loss of surface for gas exchange but also via alterations in mechanical properties of the respiratory system (dynamic and static hyper-inflation). Emphysematous lung volume reduction aims at improving respiratory mechanics and symptomatology in patients with advanced emphysema. Lung volume reduction surgery (LVRS) has been shown to be effective in selected patient populations but its morbidity and costs are quite elevated. Alternatives to LVRS do not remove emphysematous lung tissue per say but rather consist of devices aiming to: 1) reduce the volume that affected lung parenchyma occupies (unidirectional endobronchial valves or plugs, parenchymal injection of bioactive scarring agents); 2) redistribute ventilatory flow (airway bypass systems). Preliminary studies of these devices have shown that they are relatively safe. These also show modest benefit in exercise capacity, although individual subjects can experience spectacular improvement. Current objective is to identify predictors of response to therapy with such devices.

Silicon photonic wire biosensor array for multiplexed real-time and label-free molecular detection.

We demonstrate a silicon photonic wire waveguide biosensor array chip for the simultaneous monitoring of different molecular binding reactions. The chip is compatible with automated commercial spotting tools and contains a monolithically integrated microfluidic channel for sample delivery. Each array sensor element is a 1.8-mm-long spiral waveguide folded within a 130 microm diameter spot and is incorporated in a balanced Mach-Zehnder interferometer with a near temperature independent response. The sensors are arranged in a 400 microm spacing grid pattern and are addressed through cascaded 1x2 optical power splitters using light from a single input fiber. We demonstrate the real-time monitoring of antibody-antigen reactions using complementary and mismatched immunoglobulin G receptor-analyte pairs and bovine serum albumin. The measured level of detection for each sensor element corresponds to a surface coverage of less than 0.3 pg/mm(2).

Silicon-on-insulator guided mode resonant grating for evanescent field molecular sensing.

We present experimental and theoretical results of label-free molecular sensing using the transverse magnetic mode of a 0.22 mum thick silicon slab waveguide with a surface grating implemented in a guided mode resonance configuration. Due to the strong overlap of the evanescent field of the waveguide mode with a molecular layer attached to the surface, these sensors exhibit high sensitivity, while their fabrication and packaging requirements are modest. Experimentally, we demonstrate a resonance wavelength shift of approximately 1 nm when a monolayer of the protein streptavidin is attached to the surface, in good agreement with calculations based on rigorous coupled wave analysis. In our current optical setup this shift corresponds to an estimated limit of detection of 0.2% of a monolayer of streptavidin.

Extracting coupling and loss coefficients from a ring resonator.

A method is developed for extracting the coupling and loss coefficients of ring resonators from the peak widths, depths, and spacings of the resonances of a single resonator. Although the formulas used do not distinguish which coefficient is coupling and which is loss, it is shown how these coefficients can be disentangled based on how they vary with wavelength or device parameters.

High reflectivity gratings on silicon-on-insulator waveguide facets.

We demonstrate by numerical simulations and experiments that highly reflective (HR) facets can be formed on silicon waveguides with high reflectivity diffraction gratings. We use an HR grating with a plane wave reflectivity exceeding 99.99%, as calculated by rigorous coupled wave analysis. Experimentally, we demonstrate the HR effect for silicon-on-insulator waveguide facets patterned lithographically with grating structures. Due to a strong mode size dependence, the maximum facet reflectivity for 1.5 microm thick waveguide is 77%, but finite difference time-domain simulations show that modal reflectivies larger than 90% can be achieved for silicon waveguides with thicknesses of 4 microm or more.

Folded cavity SOI microring sensors for high sensitivity and real time measurement of biomolecular binding.

We demonstrate folded waveguide ring resonators for biomolecular sensing. We show that extending the ring cavity length increases the resonator quality factor, and thereby enhances the sensor resolution and minimum level of detection, while at the same time relaxing the tolerance on the coupling conditions to provide stable and large resonance contrast. The folded spiral path geometry allows a 1.2 mm long ring waveguide to be enclosed in a 150 microm diameter sensor area. The spiral cavity resonator is used to monitor the streptavidin protein binding with a detection limit of approximately 3 pg/mm(2), or a total mass of approximately 5 fg. The real time measurements are used to analyze the kinetics of biotin-streptavidin binding.

Interference effect in scattering loss of high-index-contrast planar waveguides caused by boundary reflections.

We present theoretical and experimental results on an interference effect caused by boundary reflections on the optical scattering loss in high-index-contrast planar waveguides. Analytical expressions for the polarization-dependent scattering loss are derived using a surface Green's function. For high-index-contrast waveguides of submicrometer dimensions a significant deviation from accepted theory arises, including scattering loss suppression owing to a thin-film interference effect. Our theoretical predictions are confirmed by loss measurements on silicon-on-insulator channel waveguides.

Spiral-path high-sensitivity silicon photonic wire molecular sensor with temperature-independent response.

We demonstrate a new silicon photonic wire waveguide evanescent field (PWEF) sensor that exploits the strong evanescent field of the transverse magnetic mode of this high-index-contrast, submicrometer-dimension waveguide. High sensitivity is achieved by using a 2 mm long double-spiral waveguide structure that fits within a compact circular area of 150 microm diameter, facilitating compatibility with commercial spotting apparatus and the fabrication of densely spaced sensor arrays. By incorporating the PWEF sensor element into a balanced waveguide Mach-Zehnder interferometer circuit, a minimum detectable mass of approximately 10 fg of streptavidin protein is demonstrated with near temperature-independent response.

A high-resolution silicon-on-insulator arrayed waveguide grating microspectrometer with sub-micrometer aperture waveguides.

We demonstrate a 50-channel high-resolution arrayed waveguide grating microspectrometer with a 0.2 nm channel spacing on a silicon-on-insulator (SOI) platform. The chip size is 8 mm x 8 mm. High channel density and spectral resolution are achieved using high aspect ratio 0.6 mum x 1.5 mum waveguide apertures to inject the light into the input combiner and to intercept different spectral channels at the output combiner focal region. The measured crosstalk is <-10 dB, the 3 dB channel bandwidth is 0.15 nm, and the insertion loss is -17 dB near the central wavelength of lambda = 1.545 mum.

Fresnel diffraction effects in Fourier-transform arrayed waveguide grating spectrometer.

We present an analysis of Fourier-transform arrayed waveguide gratings in the Fresnel diffraction regime. We report a distinct spatial modulation of the interference pattern referred to as the Moiré-Talbot effect. The effect and its influence in a FT AWG device is explained by deriving an original analytical expression for the modulated field, and is also confirmed by numerical simulations using the angular spectrum method to solve the Fresnel diffraction integral. We illustrate the retrieval of spectral information in a waveguide Fourier-transform spectrometer in the presence of the Moiré-Talbot effect. The simulated device comprises two interleaved waveguide arrays each with 180 waveguides and the interference order of 40. It is designed with a Rayleigh spectral resolution of 0.1 nm and 8 nm bandwidth at wavelength lambda approximately 1.5 mum. We also demonstrate by numerical simulations that the spectrometer crosstalk is reduced from -20 dB to -40 dB by Gaussian apodization.

Monolithically integrated asymmetric graded and step-index couplers for microphotonic waveguides.

A monolithically integrated asymmetric graded index (GRIN) or step-index (GRIN) mode converters for microphotonic waveguides are proposed and described. The design parameters and tolerances are calculated for amorphous silicon (a-Si) couplers integrated with silicon-on-insulator waveguides. The GRIN and step-index couplers operate over a wide wavelength range with low polarization dependence, and the lithographic resolution needed is only +/-1 microm. Finally, experimental results are presented for a single layer 3 microm thick step-index a-Si coupler integrated on a 0.8 microm thick SOI waveguide. The measured variation of coupling efficiency with coupler length is in agreement with theory, with an optimal coupling length of 15 microm for this device.

Eliminating the birefringence in silicon-on-insulator ridge waveguides by use of cladding stress.

We propose and demonstrate the use of the cladding stress-induced photoelastic effect to eliminate modal birefringence in silicon-on-insulator (SOI) ridge waveguides. Birefringence-free operation was achieved for waveguides with otherwise large birefringence by use of properly chosen thickness and stress of the upper cladding layer. With the stress levels typically found in cladding materials such as SiO2, the birefringence modification range can be as large as 10(-3). In arrayed waveguide grating demultiplexers that were fabricated in a SOI platform, we demonstrated the reduction of the birefringence from 1.2 x 10(-3) (without the upper cladding) to 4.5 x 10(-5) when a 0.8-microm oxide upper cladding with a stress of -320 MPa (compressive) was used. Because the index changes induced by the stress are orders of magnitude smaller than the waveguide core-cladding index contrast, the associated mode mismatch loss is negligible.

Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a double-blind study versus placebo.

Omega-3 polyunsaturated fatty acids (OPFA) have beneficial effects on inflammatory reactions and production of cytokines. They decrease the release of 5HT by platelets and possess vasorelaxant activity. This led them to be tried in the prophylactic treatment of migraine. After 4 weeks of a single-blind placebo run-in period, patients were randomized and treated in double-blind condition by placebo or OPFA 6 g a day for 16 weeks, followed by a 4-week placebo run-out period. The intention to treat population included 196 patients. Those who received all four treatment periods included 96 patients taking OPFA and 87 taking placebo. The primary efficacy analysis was the number of migraine attacks during the last 4 weeks of treatment. During this period, the mean number of attacks was 1.20 +/- 1.40 in the OPFA group and 1.26 +/- 1.11 in the placebo group (NS). The total number of attacks during the 4-month period of the study was significantly different between groups: 7.05 in the placebo group, 5.95 in the OPFA group (P = 0.036). Mean intensity, mean duration of the attacks and rescue medication use, were not significantly different between the two groups. Except for a significant difference against OPFA for eructations, the tolerance was satisfying. Despite a run-in placebo period of 1 month, a very strong placebo effect was observed in this trial: 45% reduction of the attacks between run-in and 4-month treatment period (55% in the OPFA group, P = 0.058). Finally, this large study did not confirm two previous studies based on a small number of patients.

[Treatment of migraine attacks]. / Traitement de la crise migraineuse.

The authors have presented a review of the main controlled studies on drug treatment for the management of migraine attacks: non-steroidal anti-inflammatory drugs (NSAIDs), rye ergot derivatives, and the recently commercialized triptan group of drugs. An overview is provided of their specific properties, indications and contraindications, and their respective use in the treatment of migraine headaches.