The aim of this study was to develop a rapid method to measure IgE in human serum by use of a direct aptamer-based biosensor based on a quartz crystal microbalance (QCM). An avidin monolayer was applied to immobilize aptamers specific for IgE on the gold surface of a quartz crystal. The frequency shifts (FS) of the QCM were measured and related to IgE concentrations. We could demonstrate that aptamers were able to detect IgE with high specificity and sensitivity in 15 min. A linear relationship existed between the FS (Hz) and the IgE concentrations from 2.5 to 200 microg/L in buffer and human serum. The regression equation was y = 1.03x - 0.06 for this QCM method and chemiluminescence in 50 clinical human serum samples. In addition, the aptamer receptors tolerated repeated affine layer regeneration after ligand binding and recycling of the biosensor with little loss of sensitivity. When stored for 3 weeks, the FS were all greater than 90% of those on the response at the first day. The QCM biosensor can measure IgE and offer advantages of high specificity, reusability, low detection limit, no label or sample pretreatment, and low sample requirement. The aptamer QCM biosensor was suitable for sensitive and specific protein detection, representing an innovative tool for future proteomics.