Boosting the Sensitivity of the Nanopore Field-Effect Transistor to Translocating Single Molecules

Nano-scaling of metal-oxide-semiconductor (MOS) field-effect transistors (FETs) is exploited to benefit the interdisciplinary field of single-molecule biosensing. While single-molecule DNA sequencing is done successfully by ionic current sensing through nanopores, the unambiguous characterization of more complex single biomolecules, such as fast translocating proteins, remains challenging with existing techniques. However, the nanopore-FET (NP-FET), a device with a nanopore embedded within the channel of the FET, is a promising new device detecting the motion of a molecule through the nanopore based on the transistor’s electronic current. This nano-scale FET-based approach enables next-generation single-molecule sensing by offering larger signals and hence higher bandwidth, responding to a key challenge of detecting fast translocating molecules, and by offering denser electronic system packing and therefore more parallel sensing. However, the sensitivity of the nanopore-FET reported so far was limited to about 30%. In this paper, we show that the inherent potential of this hybrid nanofluidic-nanoelectronic device significantly exceeds the initial reportings by demonstrating sensitivity predictions up to 1000%. Our findings are supported with 3D nanofluidic-nanoelectronic open-source device simulations. Insight in the versatility of the device is provided through geometrical device optimization and demonstration that the device is sensitive to both positively and negatively charged molecules in both n- and p-channel FET configurations. These promising features, together with the immense expertise in MOS fabrication and scaling, offer a path to a highly parallelized and scalable sensor platform for genomics and proteomics.