Capacitive morpholino diagnostics for analysis of nucleic acids

Abstract

Use of Morpholinos, a class of uncharged DNA analogues, for surface-hybridization applications. Monolayers of Morpholino probes on gold supports are fabricated with methods similar to those employed with DNA, and are used to hybridize efficiently and sequence-specifically with target strands. Hybridization-induced changes in the interfacial charge organization are analyzed with electrochemical methods and compared for Morpholino and DNA probe monolayers. Molecular mechanisms connecting surface hybridization state to the interfacial capacitance are identified and interpreted through comparison to numerical Poisson-Boltzmann calculations. Positive as well as negative capacitive responses (contrast inversion) to hybridization are possible, depending on surface populations of mobile ions as controlled by the applied potential. Quantitative comparison of surface capacitance with target coverage (targets/area) reveals a near-linear relationship, and demonstrates sensitivities (limits of quantification) in the pg mmrange.