Ion-sensitive field-effect transistors (ISFETs) are used as elementary devices to build many types of chemical sensors and biosensors. Organic thin-film transistor (OTFT) ISFETs use either small molecules or polymers as semiconductors together with an additive manufacturing process of much lower cost than standard silicon sensors and have the additional advantage of being environmentally friendly. OTFT ISFETs’ drawbacks include limited sensitivity and higher variability. In this paper, we propose a novel design technique for integrating extended-gate OTFT ISFETs (OTFT EG-ISFETs) together with dual-gate OTFT multiplexers (MUXs) made in the same process. The achieved results show that our OTFT ISFET sensors are of the state of the art of the literature. Our microsystem architecture enables switching between the different ISFETs implemented in the chip. In the case of sensors with the same gain, we have a fault-tolerant architecture since we are able to replace the faulty sensor with a fault-free one on the chip. For a chip including sensors with different gains, an external processor can select the sensor with the required sensitivity.