Reinhold Wimberger-Friedl

Packaging of silicon sensors for microfluidic bio-analytical applications

A new industrial concept is presented for packaging biosensor chips in disposable microfluidic cartridges to enable medical diagnostic applications. The inorganic electronic substrates, such as silicon or glass, are integrated in a polymer package which provides the electrical and fluidic interconnections to the world and provides mechanical strength and protection for out-of-lab use. The demonstrated prototype consists of a molded interconnection device (MID), a silicon-based giant magneto-resistive (GMR) biosensor chip, a flex and a polymer fluidic part with integrated tubing. The various processes are compatible with mass manufacturing and run at a high yield. The devices show a reliable electrical interconnection between the sensor chip and readout electronics during extended wet operation. Sandwich immunoassays were carried out in the cartridges with surface functionalized sensor chips. Biological response curves were determined for different concentrations of parathyroid hormone (PTH) on the packaged biosensor, which demonstrates the functionality and biocompatibility of the devices. The new packaging concept provides a platform for easy further integration of electrical and fluidic functions, as for instance required for integrated molecular diagnostic devices in cost-effective mass manufacturing.

The time-dependent stress-optical behavior of polycarbonate in the glass transition region

The mechanical and stress-optical behavior of Bisphenol-A polycarbonate was investigated in the glass-transition region. For this purpose, optical creep experiments were carried out in shear and elongation on a tensile tester specially designed for use on a microscope state. A Kohlrausch Williams Watts equation (KWW) with a temperature-independent parameter β could successfully be applied to the curves describing the time-dependent values of the stress-optical coefficient for several temperatures. The temperature dependence of the corresponding retardation time could be established and described by the WLF equation. For variable stresses the time-dependent birefringence is obtained from a generalized linear stress-optical rule as modeled according to linear superposition. The time-temperature superposition principle was applied to all measurements. With the dynamic moduli some deviations were observed at the transition from the rubbery plateau to the α relaxation. The strain-optical coefficient was found to decrease with increasing time and strain. The strain dependence was found to be independent of temperature at constant stress.

The peculiar rheo-optical behavior of bisphenol A-polycarbonate and polymethylmethacrylate

The rheological and stress-optical behavior of the melts of several grades ob bisphenol-A-polycarbonate (PC) and polymethylmethacrylate (PMMA) is investigated. Pertinent flow birefringence measurements are carried out in a remodelled cone-plate apparatus [1]. The shear stress in the polymer melt is calculated from the dynamic moduli, which are determined separately. It is shown that the linear stress optical rule is obeyed. In this way, the stress-optical coefficient C of the melt can be determined. The low-Mw polycarbonates all behave as Maxwellian fluids. The main stress direction does not deviate significantly from 45°. In the temperature range from 160° to 260°C the stress-optical coefficients of the different grades lie between 3 and 4×10−9 Pa−1 and show a weak temperature dependence. The stress-optical coefficient of PMMA is about a factor of 100 lower and shows a peculiar temperature-dependence, changing its sign at 144°C. The results are discussed in terms of the anisotropy of the polarizability of the polymer chain.

Real time quantitative amplification detection on a microarray : towards high multiplex quantitative PCR

Quantitative real-time polymerase chain reaction (qrtPCR) is widely used as a research and diagnostic tool. Notwithstanding its many powerful features, the method is limited in the degree of multiplexing to about 6 due to spectral overlap of the available fluorophores. A new method is presented that allows quantitative amplification detection at higher multiplexing by the integration of amplification in solution and monitoring via hybridization to a microarray in real-time. This method does not require any manipulation of the PCR product and runs in a single closed chamber. Employing labeled primers, one of the main challenges is to measure surface signals against a high fluorescence background from solution. A compact, confocal scanner is employed, based on miniaturized optics from DVD technology and combined with a flat thermocycler for simultaneous scanning and heating. The feasibility of this method is demonstrated in singleplex with an analytical sensitivity comparable to routine qrtPCR.