Nanopore Field-Effect Transistors for Single-Protein Detection: Design and Operation Optimization via Compact Modeling

Nanopore-based direct detection of single proteins represents a highly promising, yet complex, area of research, primarily due to the rapid translocation of proteins, which significantly exceeds the speed of typical DNA-based analytes. In this study, we introduce a compact model for nanopore field-effect transistors (NP-FETs) that predictively allows to examine the intrinsic capabilities of nanopore-based systems in detecting free-moving proteins of different sizes and charges. We evaluate the signal-tonoise ratio (SNR) at the output of the first amplifier stage. Our framework includes a calculation of the translocation velocity through the nanopore, accounting for both electrophoretic (EP) and typically strong electro-osmotic (EO) components. In addition, we identify configurations where increasing the Cis–Trans voltage across the nanopore is advantageous. This setup demonstrates the potential for detecting small analytes, even at low molar concentrations, relative to the nanopore size, paving the way for simultaneous charge and volume detection.