BACKGROUND: A new electrochemical immunosensor for human chorionic gonadotropin (HCG) assay was developed based on Pt hollow nanospheres and silver/titanium dioxide nanocomposites. Silver nanoparticles were initially doped into TiO2 and chitosan (Cs) colloids to form silver/titanium dioxide nanocomposites (Ag-TiO2-Cs), which had good redox electrochemical activity and excellent film-forming ability. Then, the free amino groups of chitosan were used to attach Pt hollow nanospheres for immobilization of human chorionic gonadotropin antibody (anti-HCG) to construct an immunosensor. RESULTS: Cyclic voltammetry and electrochemical impedance spectroscopy (EIS) confirmed consecutive growth of the multilayer films, and transmission electron microscopy (TEM) was used to describe the microstructure of nanoparticles. Optimal response of the immunosensor was obtained at pH 6.5 and 25 degrees C with an incubation time of 40 min. The immunosensor exhibited a linear range from 0.5 to 250 mIU mL(-1) HCG with a detection limit of 0.26 mIU mL(-1) at three times background noise. The selectivity, stability and repeatability of the immunosensor were satisfactory. CONCLUSION: The strategy showed low-cost, high sensitivity, broad linear range and fast analytical time. It is expected that the immobilized technique and the detection methodology could be further developed for other proteins. (C) 2010 Society of Chemical Industry