Detectability limits of single proteins with nanopore-based voltage and ionic-current sensing

Nanopore-based direct detection of single proteins is a promising yet challenging research topic due to the fast translocation of proteins, especially when compared to DNA-based analytes. We explore the inherent capabilities of nanopore-based setups by predictively determining the detectability of free-moving proteins dependent on their size and charge. Included in our framework is a calculation of the translocation velocity through the nanopore, which consists of an electrophoretic and typically a strong electroosmotic component. Both conventional ionic-current-based measurement setups and nanopore field-effect transistor (NP-FET) voltage-based measurement setups are considered, and the signal-to-noise ratio (SNR) at the output of the first amplifier stage of these detectors is determined. We also document when it is beneficial to increase the Cis-Trans voltage applied across the nanopore. The NP-FET voltage-based setup shows potential to detect smaller analytes at lower molarities, opening up the possibility of charge detection on top of volume detection.