Detection of oligonucleotide sequences with quartz crystal oscillators

20 mer phosphodiester oligonucleotides modified at their 5′-termini with disulfide or thiol groups were synthesized and immobilized on a gold surface. Hybridization studies with complementary, partially complementary and non-complementary oligonucleotides were carried out using a thickness shear mode resonator (TSMR) in a continuos flow apparatus. Monitoring the hybridization processes, a concentration-dependent frequency shift was observed. Moreover, even a single mismatch in the complementary strand could be detected. In addition, the formation of duplexes was confirmed by capillary gel electrophoresis (CGE) and electrospray mass spectrometry (ESI-MS).