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This paper describes an integrated ISFETs instrumentation system in a 0.18 µm 1-poly-6-metal CMOS process. The chip is able to compute the average of CMOS ISFETs' threshold voltages by using an averaging array employing global negative current feedback. In addition, neither reference voltage nor current is required to set up the sigma-delta modulator because the internal signal is converted and processed in the frequency domain. The chip operates at 3.3 V for the analog blocks and the digital input/output blocks, and at 1.8 V for the core digital logic. It achieves 8 bits accuracy under 80 µW static power consumption. The die area is 2.6 mm². [ABSTRACT FROM AUTHOR]