Label-Free Detection of Specific RNA Sequences by a DNA-Based CMOS BioMEMS

In this work we propose a resonant mass sensor based on a CMOS-compatible MEMS bulk technology, targeted at the label-free, selective detection of biomolecules. Both the MEMS fabrication phase and the bioactivation protocol were designed to ensure functionality of on-chip test electronic circuitry. Specifically, the bioactivation steps were performed with single drops of the reagents on the active part of the chip to minimize impact on the electronics and package. The CMOS compatibility of the final device is demonstrated by simultaneous operation of the MEMS resonator and the test electronics. The resonator mass sensitivity, determined by resonator loading with gold nanoparticles, compares favorably with those of QCMs and other MEMS resonant mass sensors. To validate the device operation as a biosensor, synthetic oligonucleotide sequences designed to bind to a specific human mRNA (involved in the synthesis of human methylguanine-DNA methyltransferase, a DNA repair protein) were used as probes and covalently bound to the resonator surface. The resonance frequency shift of different sensors at the same concentration of the analyte confirms the inverse dependence of the sensitivity on the mass of the resonator.