Vadim Stepaniuk

Micro-optical force sensor concept based on whispering gallery mode resonators

A micro-optical force sensor concept based on the morphology-dependent shifts of optical modes of dielectric microspheres is investigated. The optical resonances, commonly referred to as the whispering gallery modes (WGM), were excited by evanescently coupling light from a tunable diode laser using a tapered single-mode fiber. A compressive force applied to the sphere induces a change in both the shape and the index of refraction of the sphere leading to a shift in WGM. By tracking the shifts, the force magnitude is determined using solid silica as well as solid and hollow Polymethyl-methacrylate (PMMA) microsphere resonators. A measurement sensitivity as high as dlambda/dF=7.664 nm/N was demonstrated with a 960 mum hollow PMMA sphere.

Real-Time Assessment of Granule Densification in High Shear Wet Granulation and Application to Scale-up of a Placebo and a Brivanib Alaninate Formulation

Real-time monitoring and control of high shear wet granulation (HSWG) using process analytical technologies is crucial to process design, scale-up, and reproducible manufacture. Although significant progress has been made in real-time measurement of granule size distribution using focused beam reflectance measurement (FBRM), real-time in-line assessment of granule densification remains challenging. In this study, a drag force flow (DFF) sensor was developed and used to probe wet mass consistency in real-time. In addition, responses from FBRM and DFF sensors were compared to assess complementarity of information on granulation progress from the two probes. A placebo and a brivanib alaninate formulation were granulated with different concentrations of binder or water, respectively, while measuring granule size growth, densification, and DFF sensor response. The DFF sensor was able to quantitatively characterize with high resolution a response of wet mass consistency distinct from granule size distribution. The wet mass consistency parameter correlated well with granule densification, which was shown as a critical material attribute that correlated with tablet dissolution. In addition, application of DFF sensor to scale-up of granulation was demonstrated. These results showed the value of wet mass consistency measurement using DFF for WG monitoring and control.

Measurement of gas temperature and convection velocity profiles in a dc atmospheric glow discharge

Gas temperature and convective velocity distributions are presented for an unconfined glow discharge in air at atmospheric pressure, with electric currents ranging between 30 and 92 mA. The vertically oriented discharge was formed between a pin anode (top) and an extended cathode. The temperature and velocity profiles were measured using laser-induced Rayleigh scattering and laser Doppler anemometry techniques, respectively. The temperature field exhibited a conical shape with the radius of hot temperature zone increasing toward the anode. A maximum temperature of 2470 K was observed on the discharge axis with the discharge current of 92 mA. Air velocity measurements around the discharge demonstrated that the shape and magnitude of the temperature field are strongly affected by natural convection. Estimates indicate that convective losses may account for more than 50% of the power input into the positive column of the discharge. The measured temperature fields and convective velocity profiles provide a se...

Optical Force Sensor Based on Whispering Gallery Mode Resonators

This paper discusses a novel micro-optical force sensor based on dielectric microspheres that are excited by coupling light from optical fibers. The technique exploits the morphology-dependent shifts in resonant frequencies that are commonly referred to as the whispering gallery modes (WGM). A small change in the size, shape or optical constants of the microsphere causes a shift in the resonant frequency (or the WGM). For example, a compression force applied to the microsphere will lead to a change in both its shape and its index of refraction distribution. These changes will result in a shift of the WGM. By monitoring this shift, the magnitude of the applied force can be determined. The WGM shifts are observed by scanning a tunable diode laser that is coupled into the optical fiber on one end and monitoring the transmission spectrum by a photo diode on the other end. When the microsphere is in contact with a bare section of the fiber, the optical modes are observed as dips (due to destructive interference) in the intensity of the light transmitted through the fiber. Current results demonstrate the WGM shifts due to compression force applied to micro-spheres along the polar direction. The measurements also indicate a force measurement resolution of ~ 10 N with the current sensor design.

Process Analytical Technology for High Shear Wet Granulation: Wet Mass Consistency Reported by In-Line Drag Flow Force Sensor Is Consistent With Powder Rheology Measured by At-Line FT4 Powder Rheometer®

Drag flow force (DFF) sensor that measures the force exerted by wet mass in a granulator on a thin cylindrical probe was shown as a promising process analytical technology for real-time in-line high-resolution monitoring of wet mass consistency during high shear wet granulation. Our previous studies indicated that this process analytical technology tool could be correlated to granulation end point established independently through drug product critical quality attributes. In this study, the measurements of flow force by a DFF sensor, taken during wet granulation of 3 placebo formulations with different binder content, are compared with concurrent at line FT4 Powder Rheometer characterization of wet granules collected at different time points of the processing. The wet mass consistency measured by the DFF sensor correlated well with the granulations resistance to flow and interparticulate interactions as measured by FT4 Powder Rheometer. This indicated that the force pulse magnitude measured by the DFF sensor was indicative of fundamental material properties (e.g., shear viscosity and granule size/density), as they were changing during the granulation process. These studies indicate that DFF sensor can be a valuable tool for wet granulation formulation and process development and scale up, as well as for routine monitoring and control during manufacturing.

Attenuation of single-tone ultrasound by an atmospheric glow discharge plasma barrier

Propagation of 143 kHz ultrasound through an atmospheric pressure glow discharge in air was studied experimentally. The plasma was a continuous dc discharge formed by a multipin electrode system. Distributions of the gas temperature were also obtained in and around the plasma using laser-induced Rayleigh scattering technique. Results show significant attenuation of the ultrasound by the glow discharge plasma barrier (up to −24 dB). The results indicate that sound attenuation does not depend on the thickness of the plasma and attenuation is caused primarily by reflection of the sound waves from the plasma due to the sharp gas temperatures gradients that form at the plasma boundary. These gradients can be as high as 80 K/mm.

Use of Penning ionization electron spectroscopy in plasma for measurements of environmental gas constituents.

A breadboard GC detector based on Penning ionization electron spectroscopy in plasma (PIES) was investigated. The PIES detector was set up in series with a gas chromatograph and a thermal conductivity detector. Two-dimensional PIES chromatograms were recorded for carbon monoxide, carbon dioxide, and methane. The analytes were identified independently of the GC retention time, and their concentrations were measured in a range between 1 and 100 ppm. PIES spectra for methane were observed for the first time and displayed two characteristic peaks with electron energies of 7.1 and 5.4 eV. Rate coefficients for Penning ionization due to collisions between 2(3)S helium metastable atoms and analyte molecules under study were found to be k*(CO) = (0.7 +/- 0.2) x 10(-10), k*(CO2) = (1.8 +/- 0.7) x 10(-10), k*(7.1 CH4) = (4.7 +/- 0.6) x 10(-10), and k*(5.4 CH4) = (8 +/- 2) x 10(-10) cm(3)/s. The work provides the basis for the development of a portable and robust analytical platform capable of in situ real-time monitoring of greenhouse gases, with a perspective toward laboratory-on-chip realization.