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

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, 1 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 µm thick is packaged without fixing, and demonstrate this phenomenon by comparing the frequency changes of fundamental (∼64 MHz) and ninth (∼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.

Mechanism of affinity-enhanced protein adsorption on bio-nanocapsules studied by viscoelasticity measurement with wireless QCM biosensor

“…Because the target-solution concentration, C IgG , remains unchanged during its flow in a flow-injection analysis system, the binding reaction can be treated as a pseudo-first-order reaction. The resonance frequency changes exponentially in this case (∆ f ∝ exp(−αt)), 25) and its exponential coefficient α is expressed by α = −k a C IgG + k d with reaction velocity constants for adsorption k a and that for dissociation 26) These velocity constants are determined from the relationship between α and 18) and the dissociation constant K D is then given by K D = k a /k d . The resultant values are shown in Table I.…”

Quartz Crystal Microbalance with Dissipation Monitoring of Dynamic Viscoelastic Changes of Tobacco BY-2 Cells under Different Osmotic Conditions

“…Poly-L-lysine (PLL)-3-hydroxyphenyl-boronic acid (3-PBA) composite was prepared via cyclic voltammetry Synergistic effect of 3-PBA's interactions with glycosyl compounds on the cell wall and PLL's electrostatic interactions with the negatively charged cell wall promoted the adhesion of plant cells [21] Direct, label-free detection of biomarkers in a large amount of contaminants Ultrahigh-frequency, wireless MEMS QCM biosensor Nonspecific adsorption of contaminants in analyte solution was avoided at ultrahigh-frequency (∼576 MHz) [22] Selecting highly dissipative probes for ultrasensitive DNA detection…”

Critical assessment of relevant methods in the field of biosensors with direct optical detection based on fibers and waveguides using plasmonic, resonance, and interference effects

“…Interfacial properties of solid-liquid interface have to be considered [79]. Nevertheless, QCMs are used for biosensing [80,81] and even cell behavior is examined [82]. Picomolar specific biomarker target detection was achieved for miss-matches of non-coding RNA [83] or using micro-cantilever arrays for early liver cancer diagnosis [84].…”