The ability to sense proteins and protein-related interactions at the singlemolecule level is becoming of increasing importance to understand biological processes and diseases better. Single-molecule sensors, such as nanopores have shown substantial promise for the label-free detection of proteins; however, challenges remain due to the lack of selectivity and the need for relatively high analyte concentrations. An aptamer-functionalized nanopore extended field-effect transistor (nexFET) sensor is reported here, where protein transport can be controlled via the gate voltage that in turn improves single-molecule sensitivity and analyte capture rates. Importantly, these sensors allow for selective detection, based on the choice of aptamer chemistry, and can provide a valuable addition to the existing methods for the analysis of proteins and biomarkers in biological fluids.