ISFET-Based Sensing and Electric Field Actuation of DNA for On-Chip Detection: A Review

The advent of complementary metal-oxide-semiconductor (CMOS) based lab-on-chip (LoC) technology, which combines on-chip sample handling with integrated sensing, heralds the production of revolutionary biomedical devices capable of detecting pathogenic DNA at the point-of-care (PoC) and diagnosing infectious diseases. The ion-sensitive field effect transistor's (ISFET) inherent sensitivity to hydrogen ions makes them ideal for pairing with DNA amplification reactions to form adept LoC diagnostic devices. This paper reviews the state-of-the-art of CMOS-based LoC devices for DNA detection and discusses electric field actuation as an opportunity for enhanced sensing capabilities. Following our previous review centred on instrumentation, we provide an overview of reported architectures in recent years which have led to portable ISFET-based devices for PoC diagnostics. We then discuss the use of dielectrophoresis (DEP) for electric field manipulation of DNA using low-power, CMOS-compatible microelectrodes. The technique enables positioning of DNA close to ISFET sensing regions to localise hydrogen ion production. This provides a signal boost to the ISFETs that lowers the limit-of-detection and time-to-result of the device, as well as providing a means of on-chip sample preparation. Major challenges include electrode spoiling reactions, hindering electrokinetic effects, and the strong dependence of trapping efficiency on applied voltage. The combination of an ISFET LoC platform with a DEP actuation system is expected to represent a landmark step for the next generation of PoC diagnostics devices.