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

Abstract

Nano-scaling of metal-oxide-semiconductor (MOS) fieldeffect 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 nextgeneration 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.

(Invited) BioFETs and Nanopore FETs: Nanoscale Silicon Field-Effect Transistors for Single-Molecule Sensing

“…The resistive divider effect by itself results in a typical sigmoid curve shape as in the case of figure 6b for a neutral particle for which no Coulomb effect is present. In our recent simulation work making use of a dedicated nanofluidic nanodevice simulator (31) we have investigated the NPFET signal due to molecular structures as a function of separation to determine resolution (30). Moreover, based on this simulator we also reveal that sensitivity can be boosted exponentially by increasing cis-trans bias (31), see figure 7.…”

“…In our recent simulation work making use of a dedicated nanofluidic nanodevice simulator (31) we have investigated the NPFET signal due to molecular structures as a function of separation to determine resolution (30). Moreover, based on this simulator we also reveal that sensitivity can be boosted exponentially by increasing cis-trans bias (31), see figure 7. Fig.…”

“…Fig. 7 An exponential sensitivity (Smax) boost can be obtained with the NPFET by increasing cis-trans bias (31) for the NPFET structure shown in Fig. 6.…”

Design Principles of DNA-Barcodes for Nanopore-FET Readout, Based on Molecular Dynamics and TCAD Simulations

“…43 Predictions further show that operating the FET in the subthreshold regime boosts the sensitivity. 44 However, no dedicated studies exist that unravel the potential of barcodes in an NP-FET setup.…”

Sugar Molecules Detection via C2N Transistor-Based Sensor: First Principles Modeling

“…The sensing mechanism of transistor-based sensors depends on the change in the channel electrical resistance due to molecular addition and adsorption [ 31 , 32 , 33 ]. These devices have shown effective identification of molecules, ions, bacteria, and several biological entities [ 28 , 31 , 34 , 35 , 36 , 37 ].…”