An approach to enhance accuracy of the output signal obtained from ISFET interface electronics due to the body effect is proposed. Based on an MOS drawing the same drain current as the ISFET, the scheme allows reduction of influence of body effect. The presented readout interface improves the accuracy of pH measurements, while maintaining operation at constant drain-source voltage and current condition. Using only one ISFET with a differential output configuration, we obtained temperature-dependency and long-term drift as well as common noise compensation. The proposed technique is simple and has a universal use for different ISFETs. In addition, a voltage-controlled dc offset error compensation circuit modulates the extracted signal to the desired dc level for the A/D converter for each sensor. Simulation and experimental results show a great effect on monolithic ISFET integration in CMOS technology.