This paper presents the concept and experimental results of a mixed-signal instrumentation system featuring a high-voltage CMOS ASIC. This system is dedicated to operate an OFET-based gas sensor. It is composed of high-voltage amplifiers, used to bias the OFET, a low-voltage analog signal processing chain, a 12-bit. ADC, a 5-bit DAC and a digital SoC. This FPGA-implemented SoC controls the whole system. In particular, it generates specific control signals of the OFET's gate voltage. The high voltage supply is generated on-chip by means of dedicated charge pumps.