A commercially available 27MHz quartz crystal microbalance (QCM) has been employed to investigate the in-situ binding of avidin to carbodiimide hydrochloride/N-hydroxysuccinimide activated carboxylic acid modified QCM electrodes, and the subsequent binding of single-stranded 21- and 30-mer biotinylated DNA [single-stranded (ss) biotin-DNA]. The interaction between surface-immobilized ss biotin-DNA and complementary 21-mer DNA in solution was also examined. Each step was followed by monitoring changes in the QCM frequency with time. Hybridization of immobilized ss biotin-DNA with complementary 21-mer DNA oligonucleotides revealed an immobilized DNA-probe (ss biotin-DNA) to hybridized-DNA target ratio of 1:1. The 27MHz QCM is shown to be approximately 10 times more sensitive than the 9MHz QCMs commonly used in sensing experiments.