Sensing Amino Acids with Nanopore

Primary structure identification of peptides and proteins is essential for the advancement of proteomics, as it determines how these biopolymers fold and perform their biological function. Previous works found that, very often, even subtle changes in the primary sequence of a protein can cause debilitating pathologies [1]. Currently, the most common method for protein sequencing and proteomic analysis is mass spectrometry (MS), a technique that involves fractionating a protein into many smaller peptides and then obtaining the mass-to-charge ratio of each new peptide from the mass spectrometer [2]. However, known limitations affecting this method are: 1) low abundance of precursor peptide and poor fractionation efficiency; 2) The sensitivity varies among different analytes and between instrument models. For example, matrixassisted laser desorption/ionization-time of flight MS suffers from significant loss of sensitivity on samples with high concentration of salts; 3) Accurate sequencing becomes challenging with mass spectrometry in certain instances as some amino acids have similar mass and charges; 4) MS instruments are too expensive and sophisticated for broad application [3].