A pHI sensor system, Integrated Circuit (IC) chip, and a method are provided. Embodiments of the pH sensor may a first p-channel ion-sensitive transistor (IST)-operational-transconductance-amplifier (PIOTA) and a second PIOTA. Each PIOTA may further include a p-channel IST, an n-channel load transistor having a source and drain, wherein each PIOTA may have a drain-to-source resistance different from each other. Each PIOTA may further include an operational-transconductance-amplifier (OTA). A differential sensor may be connected to the outputs of both PIOTAs, and an output from the differential sensor may indicate a change in pH. Each PIOTA may further have an n-type substrate, a potential of which may be varied to control sensitivity of pH change detection. The NMOS load transistors of one or both of the PIOTAs may be selected from a plurality of NMOS load transistors to enhance sensitivity.