Discerning biomolecular interactions using Kelvin probe technology

Biomolecular conformational differences of oligomeric nucleic acids were discerned using scanning Kelvin probe (SKP) analysis in an array format on gold-coated silicon substrates. Variations in work function, measured as contact potential difference, of single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), and dsDNA with internal mismatches were clearly distinguished under ambient conditions without the use of an external label. We propose that the effectiveness of SKP analysis is based upon subtle changes in biomolecular conformation resulting from variations in molecule polarizability and induced dipole properties. This sensing technique can be readily incorporated into microarray format for discrimination of specific biological and chemical molecular interactions.