pH-change sensors and related methods are disclosed. One such sensor may have a first ion-sensitive transistor-operational-transconductance-amplifier (the “first IOTA”) and a second ion-sensitive transistor-operational-transconductance-amplifier (the “second IOTA”). Each IOTA may have an ion-sensitive transistor, a load transistor, and an output. In each IOTA, the drain region of the ion-sensitive transistor may be connected to the drain region of the load transistor. A differential sensor may be connected to the IOTAs, and an output from the differential sensor may indicate a voltage difference between the IOTA outputs. The output from the differential sensor may be used to provide an indication of a change in pH.