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In recent years, detection of DNA and proteins at very low concentration using silicon nanowire (SiNW) field-effect transistor (FET) biosensors have been experimentally demonstrated. Among these experiments, the detection of Biotin/Streptavidin binding is of special interest since the biotin/ Streptavidin system exhibits the strongest noncovalent biological interaction known and is widely demonstrated as a model system to study biorecognition between proteins and other biomolecules. In this paper, a comprehensive modeling theory and simulation approach is presented to account for the underlying detection mechanism of biotin/Streptavidin binding using SiNW FET biosensor. The preliminary simulation result shows it is feasible to detect binding of single streptavidin molecule when proper parameters are chosen.