(346b) Single-Molecule Conductance Measurements with Conformational Smear Characterization for Nucleotide Recognition
Our quantum point contact single-nucleotide conductance sequencing (QPICS) method enables reproducible conductance measurements of conformationally constrained single nucleotides within electrostatically bound DNA molecules on a self-assembled cysteamine monolayer . From these measurements, we quantify conformational variation, or smear, from the distance over which molecular junctions are maintained during each conductance measurement . Advanced algorithmic approaches rooted in machine learning were designed for accurate nucleotide identification from single-molecule conductance measurements and the unique conductance signatures for each nucleotide. We observed 93.9% accuracy for recognition of DNA nucleotides at 20× coverage (repeat measurements).
These results represent a significant improvement over contemporary sequencing methods and demonstrate the potential for using simple surface modifications and existing biochemical moieties in nucleobases for reliable single-molecule, nanoelectronic nucleotide identification.
 Afsari, Korshoj, Abel, Jr., Khan, Chatterjee, Nagpal, ACS Nano 11 (11), 11169-11181 (2017).
 Korshoj, Afsari, Chatterjee, Nagpal, J. Am. Chem. Soc. 139 (43), 15420-15428 (2017).