In this study, we have developed a new detection method using Si field effect transistor (FET)-type biosensors, which enables the direct monitoring of antigen-antibody binding within very high-ionic-strength solutions such as 1×PBS and human serum. In the new method, as no additional dilution or desalting processes are required, the FET-type biosensors can be more suitable for ultrasensitive and real-time analysis of raw sample solutions. The new detection scheme is based on the observation that the strength of antigen-antibody-specific binding is significantly influenced by the ionic strength of the reaction solutions. For a prostate specific antigen (PSA), in some conditions, the binding reaction between PSA and anti-PSA in a low-ionic strength reaction solution such as 10 µM phosphate buffer is weak (reversible), while that in high-ionic strength reaction solutions such as 1×PBS or human serum is strong.Key Words: Electronic detection, PSA, Si field effect transistor (FET), Ionic strength, Real-timeStep 1 (G1 measurement)Step 2 (reaction)Step 3