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In this paper, a novel chemical sensor system utilizing an Ion-Sensitive Field Effect Transistor (ISFET) for pH measurement is presented. Compared to other interface circuits, this system uses auto-zero amplifiers with a pingpong control scheme and array of Programmable-Gate Ion-Sensitive Field Effect Transistor (PG-ISFET). By feedback controlling the programable gates of ISFETs, the intrinsic sensor offset can be compensated for uniformly. Furthermore the chemical signal sensitivity can be enhanced due to the feedback system on the sensing node. A pingpong structure and operation protocol has been developed to realize the circuit, reducing the error and achieve continuous measurement. This system has been designed and fabricated in AMS 0.35μm, to compensate for a threshold voltage variation of ±5V and enhance the pH sensitivity to 100mV/pH.