Multiparametric microsensor chips for screening applications

The identification of drug targets for pharmaceutical screening can be greatly accelerated by gene databases and expression studies. The identification of leading compounds from growing libraries is realized by high throughput screening platforms. Subsequently, for optimization and validation of identified leading compounds studies of their functionality have to be carried out, and just these functionality tests are a limiting factor. A rigorous preselection of identified compounds by in vitro cellular screening is necessary prior to using the drug candidates for the further time consuming and expensive stage, e.g. in animal models. Our efforts are focused to the parallel development, adaptation and integration of different microelectronic sensors into miniaturized biochips for a multiparametric, functional on-line analysis of living cells in physiologically environments. Parallel and on-line acquisition of data related to different cellular targets is required for advanced stages of drug screening and for economizing animal tests.     

Synthesis of CoFe2O4 nanowire in carbon nanotubes. A new use of the confinement effect

Cobalt ferrite nanowires with an average diameter of 50 nm and lengths up to several micrometers were synthesized inside carbon nanotubes under mild reaction conditions using the confinement effect provided by the carbon tubular template.     

Development and validation of a glass-silicon microdroplet-based system to measure sulfite concentrations in beverages

Sulfite is often added to beverages as an antioxidant and antimicrobial agent. In fermented beverages, sulfite is also naturally produced by yeast cells. However, sulfite causes adverse health effects in asthmatic patients and accurate measurement of the sulfite concentration is therefore very important. Current sulfite analysis methods are time- and reagent-consuming and often require costly equipment. Here, we present a system allowing sensitive, ultralow-volume sulfite measurements based on a reusable glass-silicon microdroplet platform on which microdroplet generation, addition of enzymes through chemical-induced emulsion destabilization and pillar-induced droplet merging, emulsion restabilization, droplet incubation, and fluorescence measurements are integrated. In a first step, we developed and verified a fluorescence-based enzymatic assay for sulfite by measuring its analytical performance (LOD, LOQ, the dynamic working range, and the influence of salts, colorant, and sugars) and comparing fluorescent microplate readouts of fermentation samples with standard colorimetric measurements using the 5,5′-dithiobis-(2-nitrobenzoic acid) assay of the standard Gallery Plus Beermaster analysis platform. Next, samples were analyzed on the microdroplet platform, which also showed good correlation with the standard colorimetric analysis. Although the presented platform does not allow stable reinjection of droplets due to the presence of a tight array of micropillars at the fluidics entrances to prevent channel clogging by dust, removing the pillars, and integrating miniaturized pumps and optics in a future design would allow to use this platform for high-throughput, automated, and portable screening of microbes, plant, or mammalian cells.

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Simultaneous quantification of levofloxacin,pefloxacin, ciprofloxacin and moxifloxacin in microvolumes of human plasma using high‐performance liquid chromatography with ultraviolet detection

Levofloxacin, pefloxacin, ciprofloxacin and moxifloxacin are four fluoroquinolones used in the treatment of serious bacterial infections. The antibacterial activity of fluoroquinolones is concentration dependent. Therefore, therapeutic drug monitoring in daily clinical practice is warranted to ensure the therapy's efficacy and prevent bacterial resistance. The purpose of the present study was to develop a method using high‐pressure liquid chromatography with an ultraviolet detector for simultaneous quantification of these four fluoroquinolones in human plasma. A 50 μL aliquot of plasma was precipitated by 200 μL of methanol using gatifloxacin as internal standard. The chromatographic separation was performed on a Kinetex XB‐C₁₈ column using a mobile phase composed of a mixture of orthophosphoric acid 0.4% (v/v), acetonitrile and methanol at a flow rate of 1.2 mL/min. Dual UV wavelength mode was used, with levofloxacin and moxifloxacin monitored at 293 nm, and pefloxacin and ciprofloxacin monitored at 280 nm. The calibration was linear over the ranges of 0.125–25 mg/L for levofloxacin, 0.1–20mg/L for moxifloxacin and 0.05‐10 mg/L for both pefloxacin and ciprofloxacin. Inter‐ and intra‐day trueness and precision were <13% for all the compounds under study. The proposed method was simple, reliable, cost‐effective and suitable for therapeutic drug monitoring or pharmacokinetics studies.     

A priori bounds and multiplicity for fully nonlinear equations with quadratic growth in the gradient

We consider fully nonlinear uniformly elliptic equations with quadratic growth in the gradient, such as

$?F(x,u,Du,D^{2}u)=\lambda c(x)u+〈M(x)Du,Du〉+h(x)$

in a bounded domain with a Dirichlet boundary condition; here $\lambda \in \mathbb{R}$, $c,h\in L^p(\mathrm{\Omega })$, $p>n\ge 1$, $c?0$ and the matrix M satisfies $0<{\mu }_{1}I\le M\le {\mu }_{2}I$. Recently this problem was studied in the “coercive” case $\lambda c\le 0$, where uniqueness of solutions can be expected; and it was conjectured that the solution set is more complex for noncoercive equations. This conjecture was verified in 2015 by Arcoya, de Coster, Jeanjean and Tanaka for equations in divergence form, by exploiting the integral formulation of the problem. Here we show that similar phenomena occur for general, even fully nonlinear, equations in nondivergence form. We use different techniques based on the maximum principle.We develop a new method to obtain the crucial uniform a priori bounds, which permit to us to use degree theory. This method is based on basic regularity estimates such as half-Harnack inequalities, and on a Vázquez type strong maximum principle for our kind of equations.     

Facility Update: APS Operations and New Beamlines

Twenty years is a long time, but it seems to me as if it were yesterday when the three of us—Michel Belakhovsky, Christian Riekel and I—first scientists of the Experiments Division (except the directors) at the not yet created European Synchrotron Radiation Facility, living in a temporary and not very solid building, made the last corrections to the text of the famous “Red Book,” the ESRF Foundation Phase Report published in February 1987. The floor was shaking in our office when Ruprecht Haensel, the first Director General, walked along the corridor…. We had convened workshops of experts in the various fields to define the first set of beamlines to be built at the ESRF. The program was quite complete, comprising inelastic scattering, imaging (topography), microfocusing, small angle scattering, nuclear resonance, high energy, etc. Costs were particularly difficult to estimate, but finally we were not so far from the real figures.     

A statistical model of horizontal auditory localization performance data

Horizontal localization experiments are used to evaluate the listener's ability to locate the position of a sound source, and determine how signal characteristics affect this ability. These experiments generate circular, bimodal, and repeated data that are challenging to statistically analyze. A two-part mixture of wrapped Cauchys is proposed for these data, with the effects of signal type and position on localization bias, precision, and front-back confusion modeled using regression. The model is illustrated using mid- (1.0-2.0 kHz) and high- (3.0-6.0 kHz) frequency narrow band noises localization collected among ten normal hearing listeners.     

Diode-pumped single-frequency-Nd:YGG-MOPA for water–vapor DIAL measurements: design, setup and performance

A diode-pumped Q-switched and injection-seeded single-frequency laser, generating tunable laser radiation at 935 nm, is presented. Using Nd:YGG (Y₃Ga₅O₁₂) as the active medium, the laser that was developed to serve as a transmitter for water–vapor lidar measurements. The configuration consists of a stable resonator in rod geometry that is injection seeded by a narrowband diode laser and stabilized by the ramp-and-fire technique. Energy scaling was done in a power amplifier in slab geometry. Both oscillator and amplifier crystal were diode pumped at 806 nm. More than 30 mJ pulse energy at 100 Hz repetition rate with a beam propagation factor of M²<1.4 and pulse duration of 52 ns in single-frequency mode were generated. To our knowledge this is the first direct generation of 935 nm Q-switched pulses from Nd:YGG suitable for water–vapor measurements. The reported results show great promise of this laser in applications where high efficiency and reduced complexity is indispensable, such as for spaceborne or airborne water–vapor lidar instruments.