Single Molecule Detection of Metal-Biomolecule Binding Conformations Using Conductance Signatures

Developing a fundamental understanding of the interactions between biogenic molecules and noble metal surfaces is important for guiding and advancing the development of biotic-abiotic interfaces, conductance measurements of biomolecule conductivity, and biosensing. Here, we use the Scanning Tunneling Microscope-based Break Junction (STMBJ) technique to measure the conductance and binding orientation of a single nucleobase, Adenine (Ade), and its derivatives on gold. We systematically study the conductance features of Ade and other structurally similar molecules that lack one or more of the candidate binding sites of Ade to assign individual molecular conductance features to specific metal-Ade binding configurations. Our results allow us to determine the binding orientations of Ade on gold unambiguously. To demonstrate the biosensing potential of these measurements, we show that we can sense and distinguish Ade from its biologically relevant variants, 6-methyladenine and 2'-deoxyadenosine. Finally, we apply these methods to determine the molecular conductance and binding configurations of other biologically functional molecules on gold, such as histidine and histamine. Our work establishes STMBJ as a powerful tool for characterizing the atomic structure of metal-organic interfaces and lays the foundation for biosensing on gold using single molecule conductance readout.