Variations in concentrations of ions in biological systems can be important events in the onset of a physiological disorder. In an episode of myocardial ischemia, acidosis and elevation of potassium ion concentration has been observed in the extra-cellular matrix of the myocardium. As a spectrum of markers, they can help detect onset of ischemia as well as infarctions. In this study, Flexible Organic Ion-Sensitive Field-Effect Transistors (ISFETs) have been characterized to detect Ischemia-like variations in pH and potassium ion concentration. Detection capabilities, of the sensors, have been shown as pure chemical concentration to current signal transduction of the ISFET. Independent of peripheral amplifier-converter circuits, they are standalone sensors. The sensors have been evaluated for their sensitivity and signal resolution. Calibration expression, following a thermo-electric model for device operation, represents an explicit relations between transistor drain current and ion concentrations. Signal conditioning, by normalization, has been attempted to make the calibration expression explicit in ion-concentration. Finally a reliable detection strategy, in differential mode, is proposed for a reference electrode free device.