We have developed a field effect transistor (FET) sensor to sensitively detect copper ions (Cu2+) in a human serum (HS) sample for promising health-care diagnosis. By utilizing a Cu2+-binding prion protein that was immobilized on the FET gate surface, such an FET sensor can provide a simple, label free and highly selective performance, even in HS samples. We demonstrated the sensitivity of the sensor at the nanomolar level, 0-100 nM, which is very useful for the detection range of Cu2+ deficiency in practical applications.