Screening of biochemical interactions becomes simpler, less expensive, and more accurate when labels, such as fluorescent dyes, radioactive markers, and colorimetric reactions, are not required to quantify detected material. SRU Biosystems has developed a biosensor technology that is manufactured on continuous sheets of plastic film and incorporated into standard microplates and microarray slides to enable label-free assays to be performed with high throughput, high sensitivity, and low cost per assay. The biosensor incorporates a narrowband guided-mode resonance reflectance filter, in which the reflected color is modulated by the attachment/detachment of biochemical material to the surface. The technology offers 4 orders of linear dynamic range and uniformity within a plate, with a coefficient of variation of 2.5%. Using conventional biochemical immobilization surface chemistries, a wide range of assay applications are enabled. Small molecule screening, cell proliferation/ cytotoxicity, enzyme activity screening, protein-protein interaction, and cell membrane receptor expression are among the applications demonstrated. (Journal of Biomolecular Screening 2004:481-490)

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This review describes a new type of label-free optical biosensor that is inexpensively manufactured from continuous sheets of plastic film and incorporated into standard format microplates to enable highly sensitive, high-throughput detection of small molecules, proteins and cells. The biosensor and associated detection instrumentation are applied to review two fundamental limiting issues for assays in proteomics research and drug discovery: requirement for quantitative measurement of protein concentration and specific activity, and measurements made with complex systems in highly parallel measurements. SRU BIosystems, Inc.'s BIND label-free detection will address these issues using data examples for hybridoma screening, epitope binning and mapping, small-molecule screening, and cell-based functional assays. The review describes several additional applications that are under development for the system, and the key issues that will drive adoption of the technology over the next 5 years.

The iron responsive element (IRE) is a conserved RNA structure that is found in the 5' UTR of ferritin mRNA and in the 3' UTR of transferrin receptor mRNA. It is the binding site of the iron responsive protein (IRP), and the interaction is part of the regulation of cellular iron metabolism. The IRE six-nucleotide hairpin loop, 5'C1A2G3U4G5N6, is conserved in sequence, and mutations have shown that it is required for IRP binding. On the basis of the thermodynamic and NMR experiments utilized here, the IRE loop structure 5'C1A2G3U4G5C6, is described in detail. Measurements of loop stability show that it has 2.9 kcal/mol more free energy than predicted. NMR data suggest that there is hydrogen bonding between C1 and G5 in a tertiary interaction across the loop. A model structure, produced by MC-SYM/energy minimization, illustrates the conformational flexibility of U4 and C6, which appear to exhibit considerable local motion in solution. NMR data indicate that the position of G3 is not well defined, leading to two families of loop structures.