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Recent studies have demonstrated that acoustic wave devices are capable of quantitatively probing the behaviors of cells on the sensor surface, which has potential applications in biomedical research, environmental contaminant monitoring, drug screening and efficacy testing, and detecting bacteria and viruses in food safety and for anti-bioterrorism. Guided surface acoustic wave (or Love mode) sensor has many advantages among the acoustic wave devices. However, up to now, studies on the use of love-mode SAW devices as cell-based sensors are very limited, including theoretical and experimental studies. In this study, we developed a theoretical model to determine the attenuation and phase shift due to cells attaching on the device surface. According to the theoretical models, it has been found that the sensitivity of the love mode acoustic wave sensors can be optimized by appropriate selection of shear modulus and thickness of the wave-guiding layer and the piezoelectric substrate. The phase and attenuation shifts of the device are also sensitive to the properties and thickness of the interfacial layer between the cell layer and the substrate. This study indicates that love mode acoustic wave sensor system provides a powerful tool to study cell biological events, such as ECM production and cell adhesion, in a real-time, quick, easy, quantitative, and high- throughput fashion.