Resonant Acoustic Microbalance with Naked Quartz (RAMNE-Q) biosensor is developed by the Micro Electromechanical (MEMS) system process. It is a mass-detection based sensor, which detects the adsorbed mass through the change in the shear resonance frequency the AT-cut quartz resonator. It is different from general QCM biosensors, because the quartz resonator is electrodeless and operated wirelessly with the electromagnetic wave for the excitation and detection of the shear vibration. Furthermore, it is semi-permanent reusable. Both the thin naked quartz resonator is installed in the microchannel composed of three substrates (glass-silicon-glass), and it is lightly supported by the micropillars and semicircular walls without fixing. Thus, the vibration deterioration of the quartz resonator due to the structural damping is remarkably decreased, leading to higher quality factor (up to 1500) even during solution flow. The RAMNE-Q biosensor enables high speed analysis of the biomolecular reaction, because of high affinity between the blank quartz surface and protein molecules; the nonspecific adsorption is applied to immobilize the protein molecules on the quartz surfaces. We intend to develop the RAMNE-Q biosensor with fundamental resonance frequency higher than 170 MHz (approximately up to 700 MHz), which becomes possible by the wafer-level-package through the precision polishing process of the quartz substrate, and the development of the small evaluation system using a commercial network-analyzer.
As a demonstration of the RAMNE-Q biosensor, C-reactive protein (CRP) molecules were detected using the specific adsorption between the CRP molecules and the anti-CRP molecules oriented methodically via Fc region with the streptococcal protein G (SPG) molecules adsorbed on the quartz surfaces nonspecifically. The frequency change by the specific adsorption of CRP molecules via the anti-CRP molecules immobilized orientationally on SPG molecules was found to be 305 Hz (corresponding to 0.19 ng of CRP molecule). This result indicates that the RAMNE-Q biosensor allows high-sensitive detection to the concentration of the analyte at which the commercial QCMs would have never realized.