Usually most pH-ISFET readout circuits, with temperature compensation, were designed using transistors operating in strong regime. However, a classes of circuits elaborated with respect to MOS weak inversion are also very suitable for low-voltage and low-power applications. In this work, we discuss the problem of temperature variation at the sensor and circuit level. An analysis was made of the sensor operating in weak and moderate inversion regime. It has been shown that a simplified version of the EKV model combined with site-binding model can describe the behavior of ISFET toward the temperature and pH change. The experimental results agree very well with the analytical model for devices in large intervals of pH and temperature. Finally, the usage of model development is considered with an original concept of a readout circuit. The result of the simulation shows that the output signal is linear with pH, the design technique permits improving temperature insensitivity. The proposed circuit can be integrated with an ISFET by standard CMOS technology.