Microarrays offer the potential to profile genetic alterations in a highly multiplexed format, but have suffered from sub-optimal specificity of target capture. Array technologies which improve the specificity of target capture will be of commercial value by allowing the manufacture of arrays with superior performance characteristics. We propose to develop a novel Snap-To-It array technology that consists of arrayed PNA and DNA probes that are conformationally constrained by an intra-molecular chelate. Binding to target results in the chelate dissociation and the probe snapping to the target nucleic acid in what is an all-or-none mechanism. Consistent with previous, solution phase, thermodynamic studies using Snap-To-It probes, we hypothesize that constrained probes immobilized on an array will exhibit superior target specificity compared to unconstrained probes. The proposed chelate motifs are easily introduced into arrays using existing standard array synthesis methods with only a few additional process steps. Further, chelate binding is orthogonal to Watson-Crick pairing, and thus will not interfere with target hybridization. Phase I demonstrated feasibility of Snap-To-It probes and set the stage to move into an intensive Phase II program involving the development and testing of prototype Snap-To-It arrays for cancer analysis. DNA probes in solution and in high-throughput microarrays are invaluable tools used in areas from clinical diagnostics to fundamental research. The Snap-To-It probe technology we propose will produce microarrays with superior performance characteristics.
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