(292e) Morpholino Materials for Diagnostic Applications

Biosensing applications rely on careful tuning of molecular properties to optimize the specificity, sensitivity, and speed of an assay. Since biomolecules are typically charged, such optimization often involves consideration of charge effects. We have been examining the impact of charge in the context of nucleic acid assays by comparing the performance of DNA and morpholino monolayers for detection of complementary nucleic acid sequences. Morpholinos are synthetic DNA analogs based on an uncharged backbone. This talk will describe prospective benefits of morpholinos' nonionic character for diagnostic applications, with emphasis on electrostatic control of the underlying hybridization reactions. For example, in contrast to DNA probes, morpholinos enable facile cycling between hybridized and dehybridized states. The impact of ionic strength and temperature on effectiveness of electrostatic control is evaluated, as is the impact of mismatches. Optimal control is found when stability of probe-analyte duplexes is tuned so that electrostatics can efficiently switch between the forward (hybridization) and reverse (dehybridization) directions.