A novel amperometric immunosensor based on the micro electromechanical systems (MEMS) technology, using protein A and self-assembled monolayers (SAMs) for the orientation-controlled immobilization of antibodies, has been developed. Using MEMS technology, an “Au, Pt, Pt” three-microelectrode system enclosed in a SU-8 micro pool was fabricated. Employing SAMs, a monolayer of protein A was immobilized on the cys- teamine modified Au electrode to achieve the orientation-controlled immobilization of the human immunoglobulin (HIgG) antibody. The immunosensor aimed at low unit cost, small dimension, high level of integration and the prospect of a biosensor system-on-a-chip. Cyclic voltammetry and chronoamperometry were conducted to characterize the im- munosensor. Compared with the traditional immunosensor using bulky gold electrode or screen-printed electrode and the procedure directly binding protein A to electrode for im- mobilization of antibodies, it had attractive advantages, such as miniaturization, compati- bility with CMOS technology, fast response (30 s), broad linear range (50―400 μg/L) and low detection limit (10 μg/L) for HIgG. In addition, this immunosensor was easy to be de- signed into micro array and to realize the simultaneously multi-parameter detection. A novel amperometric immunosensor based on the micro electromechanical systems (MEMS) technology, using protein A and self-assembled monolayers (SAMs) for the orientation-controlled immobilization of antibodies, has been developed. Using MEMS technology, an “Au, Pt, Pt ”Three-microelectrode system enclosed in a SU-8 micro pool was fabricated. Employing SAMs, a monolayer of protein A was immobilized on the cys-teamine modified Au electrode to achieve the orientation-controlled immobilization of the human immunoglobulin (HIgG) antibody. Compared with the traditional immunosensor using bulky gold electrode or screen-printed electrode and the procedure directly binding protein A to electrode for im- mobilization of antibodies, it had attractive advantages, such as a s miniaturization, compatibility with CMOS technology, fast response (30 s), broad linear range (50-400 μg / L) and low detection limit (10 μg / L) for HIgG. de-signed into micro array and to realize the simultaneously multi-parameter detection.