The development of a high performance electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer (ESI/FTICR) will continue. The magnetic field used for mass analysis also will be used to simultaneously confine the radial trajectories of electrospray ions delivered to the trapped ion cell for detection. This type of focusing provides a superior quality ion beam including increased ion flux and a tunable distribution of near mono-energetic ions, to be delivered to the mass analyzer. Sub-attomole quantities of proteins will be detected in high yield under continuous flow conditions. A novel, shuttered, differentially pumped concentric tube vacuum chamber will allow ion detection below 10(-9) torr, consequently isotope resolution will be achieved within individual charge states for ions extending to 30 kDa. Careful control of the space charge environment will allow accurate mass assignment to be achieved at the sub-ppm level. In order to handle more realistic sampling environments, the present vacuum chamber will be modified to support probe mounted micro-LC and capillary electrophoresis interfaces that are inserted into the strong magnetic field ESI/FTICR. Injection limits in the sub-femtomole levels will be achieved for complex protein and peptide mixtures separated by LC/MS or CE/MS; exploiting the multiplex nature of FTICR detection, a broadband, high resolution mass spectrum will be obtained from these amounts of sample. A variety of analytical measurements specific to FTICR and ion trapping will be applied to electrosprayed biomolecules to obtain structural and physical-chemical information. Remeasurement techniques will be applied for signal enhancement purposes and to efficiently monitor the real-time progress of gas phase dissociation and reaction progresses. Careful manipulation of the injected ion kinetic energy will permit the selection of ions on the basis of both charge state and gas-phase conformation. Novel open trapped ion cell designs will permit the examination of ion-ion reactions between multiply charged electrospray ions and reagent ions. Quadrupolar excitation will be applied to provide for charge state selectivity and to massage the ion cloud to achieve improved mass resolution and sensitivity. Finally, collaborations established with protein chemists will provide a ready supply of challenging samples with which to carry out the electrospray experiments.
