The characteristics of a waveguide-coupled bimetallic surface plasmon resonance (WcBiM SPR) sensor using (3-dimethylaminopropyl)-3-ethylcarbodiimide(EDC)-N-hydroxysuccinimide(NHS)-activated protein A was investigated, and the detection of IgG using the EDC-NHS-activated protein A was studied in comparison with protein A and a self-assembled monolayer (SAM). The WcBiM sensor, which has a narrower full width at half maximum (FWHM) and a steeper slope, was selected since it leads to a larger change in the reflectance in the intensity detection mode. A preparation of the EDC-NHS-activated protein A for site-directed immobilization of antibodies was relative easily compared to the engineered protein G and A. In antigen–antibody interactions, the response to IgG at the concentrations of 50, 100, and was investigated. The results showed that the sensitivity of the WcBiM sensor using the EDC-NHS-activated protein A, protein A, and SAM was 0.0185 , 0.0065 , and 0.0101 , respectively. The lowest detectable concentrations of IgG with the EDC-NHS-activated protein A, protein A, and SAM were 4.27, 12.83, and , respectively. Therefore, the increased sensitivity and lower detection capability of the WcBiM SPR chip with the EDC-NHS-activated protein A suggests that it could be used in early diagnosis where the trace level concentrations of biomolecules should be detected.