The interaction of solid particles with various surfaces has been experiencing growing interest in many areas of nanotechnology, colloidal science, and biology. In this paper the interactions of solid particles with the surface of piezoelectric thickness shear mode (TSM) sensors have been studied. A mechanical model has been presented to evaluate the effect of particle loading on the behavior of a TSM sensor. The main sources contributing to the interaction, such as Van der Waals force, friction force, and electrostatic force, are discussed. Experiments have been designed for 10-100 microm particles on the 5-MHz and 10-MHz TSM sensors. It has been shown that the resonant frequencies of the TSM sensors might increase or decrease depending on the interaction conditions. The results have shown that the TSM sensor technique could provide the information on the mass/size of a particle and the binding energy between a particle and the sensor surface. This technique may find its applications in characterizing the properties of an interaction between particles and various surfaces.