FEA-Guided Design and Experimental Validation of ZnO-Based Surface Acoustic Wave Biosensor with Au Sensing Layer for Label-Free EGFR L858R Mutation Detection

This study investigates the acoustic response of ZnO-based SAW devices fabricated on ZnO/Si and ZnO/SiO2/Si substrates through a combined finite element analysis and experimental approach. Two-dimensional FEA was used to analyze scattering parameters, three-dimensional FEA was used to determine eigenfrequencies and mode shapes, and ZnO thin films were deposited by RF magnetron sputtering with interdigital transducers defined by UV lithography. The ZnO/SiO2/Si device exhibited Rayleigh and Sezawa-type mode resonances at 145 MHz (4350 m/s) and 234 MHz (7020 m/s), respectively, in close agreement with simulation, while the ZnO/Si device resonated at 166 MHz with a phase velocity of 4980 m/s. Incorporation of the Au sensing layer improved signal transmission by approximately 2 dB, consistent with modeling predictions. For biosensing evaluation, the device was functionalized with a thiolated ssDNA probe targeting the EGFR L858R point mutation, a clinically relevant lung cancer biomarker. Probe immobilization and target hybridization were confirmed by contact angle measurements and resonance frequency shifts, with the sensor demonstrating a linear detection range of 0.1 to 0.6 µM and LOD of 0.09 µM. These findings establish an integrated framework of acoustic modeling, microfabrication, and biofunctionalization for ZnO-based SAW biosensors toward label-free nucleic acid detection.