Ultrahigh-Frequency Wireless MEMS QCM Biosensor for Direct Label-Free Detection of Biomarkers in a Large Amount of Contaminants

TL;DR

This study introduces an ultrahigh-frequency wireless MEMS QCM biosensor that effectively distinguishes target biomarkers from contaminants by leveraging high-frequency surface movement, enabling direct label-free detection in complex samples.

Contribution

The paper presents a novel ultrahigh-frequency wireless MEMS QCM biosensor that improves sensitivity and contaminant discrimination by operating at high modes, especially the ninth mode around 576 MHz.

Findings

High-frequency operation reduces nonspecific contaminant detection.

The sensor accurately detects CRP in serum without labels.

Resonance frequency shifts are unaffected by impurities at ultrahigh frequencies.

Abstract

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.