Quartz-crystal-microbalance (QCM)
biosensor is a typical label-free
biosensor, and its sensitivity can be greatly improved by removing
electrodes and wires that would be otherwise attached to the surfaces
of the quartz resonator. The wireless-electrodeless QCM biosensor
was then developed using a microelectro-mechanical systems (MEMS)
process, although challenges remain in the sensitivity, the coupling
efficiency, and the miniaturization (or mass production). In this
study, we establish a MEMS process to obtain a large number of identical
ultrasensitive and highly efficient sensor chips with dimensions of
6 mm square. The fundamental shear resonance frequency of the thinned
AT-cut quartz resonator packaged in the microchannel exceeds 160 MHz,
which is excited by antennas deposited on inner walls of the microchannel,
significantly improving the electro-mechanical coupling efficiency
in the wireless operation. The high sensitivity of the developed MEMS
QCM biosensors is confirmed by the immunoglobulin G (IgG) detection
using protein A and ZZ-tag displaying a bionanocapsule (ZZ-BNC), where
we find that the ZZ-BNC can provide more effective binding sites and
higher affinity to the target molecules, indicating a further enhancement
in the sensitivity of the MEMS QCM biosensor. We then perform the
label-free C-reactive protein (CRP) detection using the ZZ-BNC-functionalized
MEMS QCM biosensor, which achieves a detection limit of 1 ng mL–1 or less even with direct detection.