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.

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.

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.

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.

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.

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.

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).

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.

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.

Correlation between the nature and amount of carbohydrate in meal intake and insulin delivery by the artificial pancreas in 24 insulin-dependent diabetics.

We have studied the effects of mixed meals and dextrose intake on blood glucose and insulin delivery by the artificial pancreas in 24 insulin-dependent diabetics. A group of 12 patients had 3 mixed meals containing at random 20, 40, and 60 g of complex carbohydrate along with protein and fat; another group of 12 diabetics, comparable in weight, age, and duration of diabetes, received at random 20, 40, and 60 g of dextrose. Dextrose ingestion led to a higher initial blood glucose increase than did the mixed meal, but the duration of blood glucose increase lasted significantly longer after the mixed meal than after the dextrose load. The areas under the curves of hyperglycemia were not significantly different. There was a high (but not linear) correlation between the total amount of insulin delivered in order to restore initial blood glucose values and the amount of CHO consumed. There was no correlation with age, body weight, duration of diabetes, nor with the nature and order of administration of the CHO load; 5.1 +/- 1.6 to 13.7 +/- 2.1 units of insulin were needed for a period of 94 +/- 11 to 132 +/- 11 min. It is suggested that some of the data obtained in this study might be useful in the programming of an open-loop insulin infusion system.

Pneumocystis carinii infection of bone marrow in patients with malignant lymphoma and acquired immunodeficiency syndrome. Original report of three cases.

Pneumocystis carinii (PC) pneumonia was reported with increased frequency in patients presenting with acquired immunodeficiency syndrome (AIDS) or in patients receiving immunosuppressive chemotherapy for hemopathies. Extrapulmonary dissemination of PC is rare. In this study, three patients had PC infection of the bone marrow. Two of them presented with malignant lymphoma that had apparent immunosuppression, and the third patient presented with AIDS. In all three cases, such an infection was observed before or concomittantly with PC pneumonia. A bone marrow biopsy, bone marrow aspirate, or both can be useful, readily available tools for the diagnosis of a PC infection and especially its dissemination in patients with malignant lymphoma after intensive treatment or in patients with AIDS. The appreciation of such a dissemination may have some implications in the treatment of PC infection.

Plasma insulin and C-peptide levels during continuous subcutaneous insulin infusion.

A study was performed to estimate the absorption kinetics of insulin infused subcutaneously. Four insulin-dependent diabetic subjects had their insulin pumped through a subcutaneously implanted fine polyethylene catheter at a constant rate of 5.0 +/- 0.3 ml/h but at two different insulin concentrations: 218 mU/ml between meals, and 2400 mU/ml at the start of breakfast, lunch, and dinner (lasting 20, 30, and 30 min, respectively). The amount (40 U/day) and distribution of insulin delivered was identical in the four patients in order to facilitate comparison between the subjects. No attempt was made to normalize their blood glucose during the study period. A study of the kinetics of insulin absorption was made by assaying plasma insulin levels; lack of plasma anti-insulin antibodies was verified; plasma C-peptide levels were measured and were far below values observed in the fed state in nondiabetic patients. The mean maximum insulin level reached after switching from low to high concentration insulin was observed 87 +/- 2 min after breakfast, 117 +/- 22 min after lunch, and 125 +/- 20 min after dinner. Differences observed are not significant. These values are similar to those observed after subcutaneous injection of 40 U/ml Regular insulin as a single bolus. After switching from high to low concentration, plasma insulin levels did not return to their basal values before the third or fourth hour. Subcutaneous insulin infusion could be a safe and easy way of insulin administration in an open-loop system; however, this method does not seem to be suitable for a closed-loop system.

[Longitudinal study of radiologic anomalies in subjects working in asbestos-insulated buildings]. / Etude longitudinale des anomalies radiologiques chez des sujets travaillant dans des locaux floqués à l'amiante.

The respiratory effects of environmental pollution by asbestos was examined in a cohort of subjects working inside university buildings partly insulated with asbestos containing materials (University of Jussieu in Paris). The present study concerned 727 subjects having undergone two standard radiographic examinations (postero-anterior and oblique chest x-ray) in the period 1981-1992. The first examination was realized between 01/01/81 and 31/12/85 and the second examination took place between 01/01/86 and 31/12/92. The subjects were classified into three groups according to their exposure status: the group G1 consisted of 161 workers occupationally exposed to asbestos; the group G2 comprised 416 subjects working for at least 15 yr in asbestos-insulated buildings without known occupational exposure to asbestos; the group G3 consisted of 150 workers working for at least 15 yr in the university with no known exposure to asbestos. Whatever the radiological abnormalities considered, no significant difference was observed between G2 and G3 in cross-sectional analyses of the two phases. The group G1 exhibited a significantly higher prevalence of pleural thickening compared to the other exposure groups after adjustment for confounding variables. Detailed examination of oblique x-ray allowed to confirm that pleural thickening were largely due to extrapleural fat. Concerning the changes in pleural abnormalities between the two phases of the study, no difference was observed between G2 and G3. This study was unable to show any excess of radiographic chest abnormalities among subjects working in asbestos-insulated buildings compared to non-exposed subjects. However, the participation in the second phase of examination was 51.2%. The study is still on-going. Therefore, it would be necessary to continue to follow-up the subjects because respiratory disorders could occur after a long latent period.

[A case of disseminated Encephalitozoon intestinalis microsporidiosis in an AIDS patient in Nîmes]. / Un cas de microsporidiose disséminée à Encephalitozoon intestinalis au cours d'un SIDA à Nîmes.

The pathogene's role importance of the microsporidia in nature is considerable. The human being, easily in contact, presents clinical manifestations only with some of them and in a very occasional manner. The increased frequency of the immunodepression has permitted to describe recently a new protozoon, Encephalitozoon intestinalis (alias Septata intestinalis) of the family of the Glugeidae and the human illness of which it is the agent. This parasitose is interesting to be presented because of its rarity and its circulation to organs far from one another. The diagnostic has been done thanks to the only optic microscope and confirmed from its visible efficacity of one cure of albendazole. The pyrimethamine could present a relative efficiency on a relapse of the sinusitis.

[Is human Dirofilaria (Nochtiella) repens parasitosis mor frequent than it appears on the Mediterranean coast?]. / La parasitose humaine par Dirofilaria (Nochtiella) repens est-elle plus fréquente qu'il ne paraît sur les rivages méditerranéens?

Some observations of human parasitism by Dirofilaria (Nochtiella) repens are frequently enough reported but they are also individually reported by different authors. Nïmes's geographical situation makes of it a privileged observatory for this helminthiasis. The worm's maturity varies depending on the subjects: the sensitivity of those and the clinical reactions are of a large variety. The ones that seem to be constant are the parasit's migrations in the different territories during a lot of months. It is the case in the observation reported here; in another article, we have shown the possibility of an intraperitoneal migration which discovery can be only of an extreme fate. Next to some noisy manifestations, other cases stayed quiet advise the adaptation of some autochtones submissed to iteratif infestations.

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.