Single-Molecule Classification of Aspartic Acid and Leucine by Molecular Recognition through Hydrogen Bonding and Time-Series Analysis.

Amino acid detection/identification methods are important for understanding biological systems. In this study, we developed single-molecule measurements for investigating quantum tunneling enhancement by chemical modification and carried out machine learning-based time series analysis for developing accurate amino acid discrimination. We performed single-molecule measurement of L-aspartic acid (Asp) and L-leucine (Leu) with a mercaptoacetic acid (MAA) chemical modified nano-gap. The measured current was investigated by a machine learning-based time series analysis method for accurate amino acid discrimination. Compared to measurements using a bare nano-gap, it is found that MAA modification improves the difference in the conductance-time profiles between Asp and Leu through the hydrogen bonding facilitated tunneling phenomena. It is also found that this method enables determination of relative concentration. even in the mixture of Asp and Leu. It improves selective analysis for amino acids and therefore would be applicable in medicine, diagnosis, and single-molecule peptide sequencing.