CaSTL Seminar with Sepideh Afsari

Single-molecule DNA identification/sequencing can be accomplished using nanoscale electronics. However, individual nucleotide conformations and sample noise lead to overlapping electronic signatures, making it difficult to identify single nucleobases. We have investigated charge transport through individual nucleotides within the DNA macromolecule (perpendicular to the phosphate backbone) with a scanning tunneling microscopy-break junction (STM-BJ) technique. Fabricating well-defined single molecule junctions with individual nucleotides in a DNA strand allowed for measuring single-nucleotide conductivity independent from neighboring nucleotides, and therefore improved resolution between electronic signatures and reduced sample noise. While the ensemble measurements show some overlap between single nucleotide conductance signatures, using characteristic features of quantized molecular conductance: discrete nature of conductance peaks and reversible chemical modifications of anchoring groups forming the molecular junctions, we developed an algorithm to enhance identification of the nucleobases (base calling) by using multiple biases and pH conditions to turn conductance peaks “ON” and “OFF”. We utilize appearance and disappearance of signature conductance peaks to improve base calling accuracy and precision. These results highlight the potential for utilizing simple surface modifications and the biochemical moieties in individual DNA nucleobases for a reliable single-molecule nanoelectronic DNA sequencing method.