Towards Single Molecule Protein Sequencing by Nanopore Mass Spectrometry

Here we describe an approach to sequencing single protein molecules that will combine the advantages of mass spectrometry with those of nanopores. The basic idea is to cleave the individual amino acids from a protein molecule as they transit a small hole in sequence, and then identify each one by determining its mass-to-charge ratio in a mass spectrometer. We present the results of studies of the transfer of single amino acid ions from liquid into vacuum from the nanoscale orifice of a charged needle. We also summarize the development of an instrument featuring a magnetic mass filter and an array of channeltron detectors, which will be able to photo-dissociate single proteins and then measure both the mass and the time of detection of the resulting fragments.