A Step toward Amino Acid-Labeled DNA Sequencing: Boosting Transmission Sensitivity of Graphene Nanogap

Abstract

Existing obstacles in next-generation DNA sequencing techniques, for instance, high noise, high translocation speed, and configurational fluctuations, call for approaches capable of reaching the goal and accelerating the process of personalized medicine development. The labeling nucleotide approach has the potential to overcome these barriers and boost the recognition sensitivity of a solid-state nanodevice. In this theoretical report, the first-principles density functional theory calculations have been employed to study the role of three different labels, tyrosine (Tyr), aspartic acid (Asp), and arginine (Arg), for labeling DNA nucleotides and study their effect in rapid and controlled DNA sequencing at atomic resolution. Remarkable differences in interaction energy values are noticed in all three cases of differently labeled nucleotides. The zero-bias transmission spectra confirm that proposed labels have the ability to detect the individual nucleotide, amplifying the tunneling current sensitivity by several orders of magnitude. The current-voltage characteristics of Arg-labeled nucleotides are found to be promising for single nucleotide recognition even at a very low bias voltage of 0.1 V. © 2022 American Chemical Society.