Various embodiments of the present application are directed towards an ion-sensitive field-effect transistor for enhanced sensitivity. In some embodiments, a substrate comprises a pair of first source/drain regions and a pair of second source/drain regions. Further, a first gate electrode and a second gate electrode underlie the substrate. The first gate electrode is laterally between the first source/drain regions, and the second gate electrode is laterally between the second source/drain regions. An interconnect structure underlies the substrate and defines conductive paths electrically shorting the second source/drain regions and the second gate electrode together. A passivation layer is over the substrate and defines a first well and a second well. The first and second wells respectively overlie the first and second gate electrodes, and a sensing layer lines the substrate in the first and second wells. In some embodiments, sensing probes are in the first well, but not the second well.