Abstract: It was reported in this paper that a highly sensitive piezo-immunosensor for using in the determination of medium or low contents of HDL in human sera was fabricated.In the fabrication,a monolayer of mercaptopropionic acid (MPA) was assembled on the surface of gold electrode of piezo-electric crystal by the self-assembled monlayer membrane (SAM) technique,during which 1-ethyl-3-(3-dimethylaminopropyl)-carbon diimine and N-hydroxy succinimide were used as coupling reagents and the HDL antibody was bound onto it by covalency.By the initial rate method,the linearity obtained by using this sensor in the determination of HDL was in the range of 1.63-18.8 mg·L-1 with a detection limit of 0.82 mg·L-1.Based on the real-time inspection function of the piezoelectric installation,the process and mechanism of the course of SAM of MPA on the surface of the gold electrode was investigated and immobilization of antibody by crystal oscillation,the behavior of liquid phase oscillation of the reaction of binding with antigens and the sensor characteristics were also studied.