Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling

Yanan Zhao, Brian Ashcroft, Peiming Zhang, Hao Liu, Suman Sen, Weisi Song, Jongone Im, Brett Gyarfas, Saikat Manna, Sovan Biswas, Chad Borges, Stuart Lindsay

Research output: Contribution to journalArticlepeer-review

178 Scopus citations


The human proteome has millions of protein variants due to alternative RNA splicing and post-translational modifications, and variants that are related to diseases are frequently present in minute concentrations. For DNA and RNA, low concentrations can be amplified using the polymerase chain reaction, but there is no such reaction for proteins. Therefore, the development of single-molecule protein sequencing is a critical step in the search for protein biomarkers. Here, we show that single amino acids can be identified by trapping the molecules between two electrodes that are coated with a layer of recognition molecules, then measuring the electron tunnelling current across the junction. A given molecule can bind in more than one way in the junction, and we therefore use a machine-learning algorithm to distinguish between the sets of electronic a €fingerprintsa € associated with each binding motif. With this recognition tunnelling technique, we are able to identify D and L enantiomers, a methylated amino acid, isobaric isomers and short peptides. The results suggest that direct electronic sequencing of single proteins could be possible by sequentially measuring the products of processive exopeptidase digestion, or by using a molecular motor to pull proteins through a tunnel junction integrated with a nanopore.

Original languageEnglish (US)
Pages (from-to)466-473
Number of pages8
JournalNature nanotechnology
Issue number6
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering


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