Double-sided silicon strip detectors: new applications within genomics and proteomics

The development of microarrays and other high-throughput molecular screening techniques has dramatically improved the possibilities for unravelling of the underlying molecular changes in disease states, both through minimization of necessary sample volumes and through access to multiparametric analysis of the large volume of available data. Here, we present a novel and sensitive addition to the microarray armamentarium. Critical factors affecting the detection of target hybridization on microarrays include the design of capture probes, the way they are attached to the support, incorporation efficiency of labeled nucleotides into target RNA, and the sensitivity of the detection method. Microarray analysis is commonly based on detection of fluorescence signals through a confocal laser scanner. However, with human or other tissues that may not be readily available, sensitive radioactive hybridization techniques offer attractive opportunities, reducing the need for target or signal amplification. We have developed a new instrument with a double-sided silicon strip detector, for reading microarray slides labeled with isotopes. In this current work, we present data demonstrating that the resolution, sensitivity levels, dynamic range and linearity of this isotope-based detection system makes it an attractive supplement to fluorescence-based scanners. In model experiments, we demonstrate the usefulness of isotopic detection for several high-throughput applications in biology. (C) 2004 Elsevier B.V. All rights reserved.