Measuring conductance switching in single proteins using quantum tunneling

Interpreting the electrical signatures of single-proteins in electronic junctions has facilitated a better understanding of the intrinsic properties of proteins that are fundamental to chemical- and biological processes. Often such information is not accessible using ensemble and even single-molecule approaches. However, the fabrication of nanoscale single-protein junctions remains challenging as they often require sophisticated methods to ensure only a single protein is detected. We report on the fabrication of tunneling probes, direct measurement, and active control (switching) of single-protein conductance with an external field in solution. The probes allowed us to bridge a single streptavidin molecule to two independently addressable, biotin terminated electrodes and measure single protein tunneling response over long periods (up to 2 hours). We show that charge transport through the protein has multiple conductive pathways that depend on the magnitude of the applied bias. These findings open the door for the reliable fabrication of protein-based junctions, a better understanding of electronic properties of single protein molecules, and can enable their use in future protein-embedded bioelectronics applications.