Ions Sensitive Field Effect Transistors (ISFETs) are becoming the platform sensors for important chemical and biomedical applications. However, the accuracy of ISFET output measurement is greatly affected by the presences of low-frequency noise, drift and slow response of the device. This requires more safety in measured results and the tools of analysis. In this paper, we present fundamental limits on the sensitivity of ISFETs micro-sensors, arising from intrinsic and extrinsic noise sources. We developed an algorithm in MATLAB in order to model the frequency analysis of the 1/f noise in ISFET sensor using Hooge theory. We have shown that the 1/f noise of the ISFETs sensors is due to both the electrochemical system (pH solution) and the MOS component (canal size, insulator thickness). The temperature effect on the ISFET noise and the signal conditioning are also performed.