  Label-free biosensors, including conventional quartz-crystal-microbalance
(QCM) biosensor, are seriously affected by nonspecific adsorption of
contaminants involved in analyte solution, and it is exceptionally difficult to
extract the sensor responses caused only by the targets. In this study, we
reveal that this difficulty can be overcome with an ultrahigh-frequency
wireless QCM biosensor. The sensitivity of a QCM biosensor dramatically
improves by thinning the quartz resonator, which also makes the resonance
frequency higher, causing high-speed surface movement. Contaminants weakly
(nonspecifically) interact with the quartz surface, and they fail to follow the
fast surface movement and cannot be detected as the loaded mass. The targets
are, however, tightly captured by the receptor proteins immobilized on the
surface, and they can move with the surface, contributing to the loaded mass
and decreasing the resonant frequency. We develop a MEMS QCM biosensor, in
which an AT-cut quartz resonator of 26 {\mu}m thick is packaged without fixing,
and demonstrate this phenomenon by comparing the frequency changes of
fundamental (about 64 MHz) and ninth (about 576 MHz) modes. At
ultrahigh-frequency operation with the ninth mode, the sensor response is
independent of the amount of impurity proteins, and the binding affinity is
unchanged. We then applied this method for the label-free and sandwich-free
direct detection of C-reactive protein (CRP) in serum, and confirmed its
applicability.
