Enhanced Biosensing Resolution with Foundry Fabricated Individually Addressable Dual-Gated ISFETs

The adaptation of semiconductor technologies for biological applications may lead to a new era of inexpensive, sensitive, and portable diagnostics. At the core of these developing technologies is the ion-sensitive field-effect transistor (ISFET), a biochemical to electrical transducer with seamless integration to electronic systems. We present a novel structure for a true dual-gated ISFET that is fabricated with a silicon-on-insulator (SOI) complementary metal-oxide-semiconductor process by Taiwan Semiconductor Manufacturing Company (TSMC). In contrast to conventional SOI ISFETs, each transistor has an individually addressable back-gate and a gate oxide that is directly exposed to the solution. The elimination of the commonly used floating gate architecture reduces the chance of electrostatic discharge and increases the potential achievable transistor density. We show that when operated in a “dual-gate” mode, the transistor response can exhibit sensitivities to pH changes beyond the Nernst limit. This enhancement in sensitivity was shown to increase the sensor’s signal-to-noise ratio, allowing the device to resolve smaller pH changes. An improved resolution can be used to enhance small signals and increase the sensor accuracy when monitoring small pH dynamics in biological reactions. As a proof of concept, we demonstrate that the amplified sensitivity and improved resolution result in a shorter detection time and a larger output signal of a loop-mediated isothermal DNA amplification reaction (LAMP) targeting a pathogenic bacteria gene, showing benefits of the new structure for biosensing applications.