MISMATCH SENSITIVE HYBRIDIZATION DETECTION BY PEPTIDE NUCLEIC-ACIDS IMMOBILIZED ON A QUARTZ-CRYSTAL MICROBALANCE

A quartz crystal microbalance DNA hybridization biosensor, based on th iol-derivatized peptide nucleic acid (PNA) probes, offers unusual in s itu differentiation of single-base mismatches. A large excess of a sin gle-base mismatch oligonucleotide has no effect on the frequency respo nse of the target. Such remarkable distinction between perfect matches and mismatches is illustrated by the detection of a common mutation i n the p53 gene. The greater specificity of the new mass-sensitive indi catorless hybridization device over those of analogous PNA-based carbo n electrodes is attributed to the formation of a PNA monolayer and the use of a hydrophilic ethylene glycol linker. The improved specificity is coupled to very fast (3-5 min) hybridization in a low-ionic-streng th medium.