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High-performance dual-gate (DG) ion-sensitive field-effect transistors (ISFETs) beyond the Nernstian limit of 59 mV/pH were realized using the fully depleted (FD) silicon-on-insulator (SOI) substrate. The FD SOI-based DG ISFET exhibited a significantly enhanced pH sensitivity of 379.2 mV/pH for DG operation amplified by capacitive coupling, while it exhibited a relatively poor sensitivity of 47.9 mV/pH for single-gate (SG) operation. Meanwhile, the non-ideal effects for long-term use slightly increased by the DG operation compared to the SG operation. Therefore, the FD SOI-based DG ISFETs compatible with the complementary metal-oxide-semiconductor process are considered to be very promising bio-chemical sensors.