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

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

Polymorphism of turnip yellow mosaic virus empty shells and evidence for conformational changes occurring after release of the viral RNA. A differential scanning calorimetric study.

Turnip yellow mosaic virus (TYMV) is a small isometric plant virus which decapsidates by releasing its RNA through a hole in the capsid, leaving behind an empty shell [R. E. F. Matthews and J. Witz, (1985) Virology 144, 318-327]. Similar empty shells (artificial top component, ATC) can be obtained by submitting the virions to various treatments in vitro. We have used differential scanning calorimetry, analytical sedimentation, and electron microscopy to investigate the thermodenaturation of natural empty shells (NTC, natural top component) present in purified virus suspensions, and of several types of ATCs. ATCs divided in two major classes. Those obtained by alkaline titration, by the action of urea or butanol behaved as NTC: their thermograms contained only one peak corresponding to the irreversible dissociation of the shells and the denaturation of the coat protein. The temperature of this unique transition varied significantly with pH, from 71 degrees C at pH 4.5 to 84 degrees C at pH 8.5. The thermograms of ATCs obtained by freezing and thawing, or by the action of high pressure, contained two peaks: shells dissociated first into smaller protein aggregates at 57 degrees C (at pH 5.0) to 61 degrees C (at pH 8.5), which denatured at the temperature of the unique transition of NTC. Shells obtained by heating virions to 55 degrees C at pH 7.6, changed conformation after the release of the viral RNA, as upon continuous heating to 95 degrees C, their thermograms were similar to those of the shells obtained by freezing and thawing, whereas after purification they behaved like NTC. Structural implications of these observations are discussed