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Innovative Instruments and Softwares for Cytopathology Digital Imaging Françoise Soussaline, Jerome Sallette, Michel Soussaline IMSTAR, Paris France [email protected] Success in microarray technology requires new approaches to microarray analysis methodology. A new microarray reader system, the Optical Scanning Array (OSA) reader, based on high-content, automated, light microscopy, was developed. The reader allows fast capture of high resolution (down to 0.35 µm) microarray images using a large range of fluorescent dyes in the 380 – 700 nm range, also allowing up to 4 simultaneous labels. Controlled by high performance software, the system is adapted to scanning and quantitative analysis and interpretation of any dry microarrays, such as DNA and protein microarrays, cell arrays, rolling-circle amplification associated microarray. An innovative feature of the OSA reader allowing a wide range of on-chip chemical and enzymatic reactions including PCR amplification is a microarray-holder with a temperature-controlled hybridization chamber. Examples can be shown in the field of biomedical research. The system was used for the development of oligonucleotide microarrays for cystic fibrosis (CFTR) gene mutation detection. On-chip registration of hybridization kinetics and analysis of duplex stabilities for all spots of the microarray allowed the optimization the hybridization conditions for maximum match/mismatch discrimination. Registration of on-chip kinetics and melting curves were used to improve the accurate detection and quantification within gene expression microarray. Finally, both capability of capture of high resolution images and advanced algorithms for spots or cell clusters morphology analysis give access to massive parallel functional studies of sub-cellular markers in cell-arrays.