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We report a systematic theoretical investigation on magnetoelastic (ME) micro-resonator sensing system. The system, composed of ME micro-resonator immersed in target liquid and excitation/test coil with network analyzer, features as a wireless sensing mode, which enables the real-time high-sensitivity pathogen detection. A detailed four-step modeling methodology and a new equivalent circuit model for the sensing system are developed, with the system design, simulation, optimization, and experimental validation. Influences of various magnetostrictive materials, resonating structures, and excitation/test coils design on system sensing performance are discussed, revealing systematic design guidelines on real ME micro-resonator system for ultrasensitive mass-sensing applications.