Label-free biosensors, including conventional quartz-crystal-microbalance (QCM) biosensors, 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 when the quartz resonator is thinned, which also makes the resonance frequency higher, causing high-speed surface movement. Contaminants weakly (nonspecifically) interact with the quartz surface, but 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 have developed a MEMS QCM biosensor in which an AT-cut quartz resonator, 26 μm thick, is packaged without fixing, and we demonstrate this phenomenon by comparing the frequency changes of the 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 to the label-free and sandwich-free, direct detection of C-reactive protein (CRP) in serum and confirmed its applicability.
In this study, we developed an electromagnetically driven micropump with a magnetic fluid seal, which greatly contributes to the miniaturization of medical analytical sensor systems. The magnetic ...fluid seal applied to this micropump prevented the solution from entering the inside of the thrust bearing attached to the gap between the liquid feed rotor and the stator, and the abrasion powder generated from the bearing was prevented from being mixed into the solution. Furthermore, because the liquid feed rotor was rotated in a noncontact manner by the electromagnetic force from the coil attached to the external pump, continuous feeding of liquid with reduced pulsation was possible. When the rotational speed of the liquid feed rotor was 500 rotations per minute, the feed rate of pure water was 2 ml/min. At this rotational speed, there was no pure water intrusion into the thrust bearing nor separation of the magnetic fluid from the neodymium magnet. This result indicates that the magnetic fluid seal for the thrust bearing is effective. The micropump developed is a device that can be integrated with a biosensor chip, thereby contributing to the realization of a compact medical analysis sensor system that can be easily operated beside a patient.
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•Compact MEMS-QCM hydrogen-gas sensor is developed, which shows nearly the highest sensitivity at room temperature.•A large number of identical high-sensitive QCM sensors are ...simultaneously obtained through the MEMS process.•The fundamental QCM frequency is the highest among reported QCM gas sensors.•We discovered that a very conventional air plasma treatment can improve the sensitivity significantly.•We clarified the role of oxygen atom in lowering the hydrogen migration energy from surface to subsurface.
A highly sensitive hydrogen-gas sensor fabricated using MEMS technology is presented. The sensor chip consists of glass substrates, silicon substrate, and an AT-cut quartz crystal resonator, which is embedded in the microchannel constructed on the substrates. The quartz resonator has a fundamental resonant frequency of 165 MHz and a 200 nm palladium film deposited on its single surface as the hydrogen-gas sensing material. The MEMS hydrogen-gas sensor operates in a wireless manner by exciting and detecting the resonator vibration using the non-contacting antennas. The curvature induced resonant frequency change of the resonator plate caused by the expansion of the palladium film is used for the detection of the hydrogen gas. We succeeded in improving the hydrogen absorption rate and then the sensitivity for the hydrogen-gas detection by applying the air-plasma treatment method, and clarified the role of palladium oxide in lowering the energy barrier for the hydrogen-atom migration from surface to subsurface with the X-ray photoelectron spectroscopy. Thus sensitivity enhanced MEMS hydrogen-gas sensor exhibits a detection limit of 10 ppm or less at room temperature both in nitrogen and air.
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.
Unlike previous in vitro measurements where Amyloid β (Aβ) aggregation was studied in bulk solutions, we detect the structure change of the Aβ aggregate on the surface of a wireless ...quartz-crystal-microbalance biosensor, which resembles more closely the aggregation process on the cell membrane. Using a 58 MHz quartz crystal, we monitored changes in the viscoelastic properties of the aggregate formed on the quartz surface from monomers to oligomers and then to fibrils, involving up to the 7th overtone mode (406 MHz). With atomic-force microscopy observations, we found a significant stiffness increase as well as thinning of the protein layer during the structure change from oligomer to fibrils at 20 h, which indicates that the stiffness of the fibril is much higher. Viscoelasticity can provide a significant index of fibrillation and can be useful for evaluating inhibitory medicines in drug development.
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