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We present a real-time monitoring, double-channel dynamic range chromosomal microarray platform (DDR-CGH) consisting of a heterogeneous array of pattern recognition receptors that significantly improves dynamic range, signal-to-noise ratio and spatial resolution over earlier CGH microarray designs. The DDR-CGH platform is based on a two-channel array of capture molecules in conjunction with two independent lasers that excite two fluorophores that are detected on the same photosensor and provide improved signal-to-noise ratio. Each capture molecule hybridizes to complementary DNA and RNA, forming localized fluorescent hybridization signals, which in turn give unique microarray patterns when imaged by a fluorescence microscope. The two-channel arrays can be used to perform simultaneous analysis of complementary DNA and RNA strands that, when captured on the same hybridization surface, compete for local probe sites with resulting fluorescence intensity ratio changes that can be monitored and used to determine relative quantities of the two types of target DNA or RNA in a duplex mixture. Comparisons of DDR-CGH performance with single- and dual-channel fluorescence-based methods on a dilution series of human genomic DNA demonstrated signal-to-noise ratio gains of 2.5- to 11-fold, dynamic range gains of 1.7- to 2.9-fold and spatial resolution gains of 1.5- to 2.4-fold when using DDR-CGH. DDR-CGH technology was used to detect a rare submicroscopic deletion in the 3125841983

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