Design and performance of an ESI interface for selective external ion accumulation coupled to a Fourier transform ion cyclotron mass spectrometer

The coupling of Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) with electrospray ionization has advanced the analysis of large biopolymers and provided the basis for high-throughput protein characteriz ation (e.g,, for rapid "proteome" analyses). In this work, the combination of high-performance capillary liquid chromatography with FTICR mass spectro metry and external ion accumulation has been shown to increase both sensiti vity and analysis duty cycle. Instrument versatility is further improved by ion preselection followed by ion accumulation in an external linear quadru pole ion trap. The interface was tested with a 3.5-T FTICR mass spectromete r and evaluated with a number of peptides and proteins whose molecular weig hts ranged from 500 to 66 000. A significant increase in the sensitivity, d uty cycle, and dynamic range over that of the previously used accumulated t rapping was achieved, exhibiting a detection limit of similar to 10 zmol (s imilar to 6000 molecules) for smaller proteins such as cytochrome c. Capill ary LC external accumulation interface with FTICR was successfully applied for the study of whole-proteome mouse tryptic digests.