Bond-rupture scanning for biomedical diagnostics is examined using quartz crystal microbalance (QCM) experiments and microparticle mechanics modeling calculations. Specific and nonspecific interactions between a microparticle and its binding QCM surface can be distinguished by gradually increasing the amplitude of driving voltage applied to QCM and monitoring its frequency changes. This research proposes a mechanical model of interactions between biological molecules and a QCM substrate surface. The mechanical force required to break a biotin-streptavidin bond was calculated through a one-pivot-point bottom-up vibration model. The bond-rupture force increases with an increase of the microparticle radius, the QCM resonant frequency, and the amplitude of driving voltage applied to the QCM. The significance of the research on biological molecular bond rupture is extremely important in characterizing microbial (such as cells and virus) specificity, due to the force magnitude needed to break bonds using a transducer.