This award supports development of a novel high sensitivity, atmospheric pressure, matrix-assisted laser desorption/ionization (AP-MALDI) Fourier transform Ion Cyclotron Resonance mass spectrometer (FTICR-MS) to advance proteomics research capabilities. Specific areas of ion source development targeted in this proposal will include matrix effects and reactivity, and improved ion capture and transmission. Atmospheric pressure operation presents the opportunity to investigate the functional requirements of MALDI matrix materials and carefully characterize each component individually. The resultant development of a high sensitivity AP-MALDI ion source, combined with the accurate mass, tandem MS/MS capabilities of FTICR-MS will provide an ideal platform for proteomics research and protein identification. These efforts will result in an instrument that is capable of both APMALDI and ElectroSpray Injection, giving accurate mass measurements for optimal peptide mass fingerprinting and allowing coupling with on-line chromatography for analysis of protein mixture digests. The intellectual merit of the following proposal centers on three aspects 1) the development of improved sensitivity of AP-MALDI sources through implementation of multiple ionization sources and matrix optimization combined with advances in ion optics, 2) a new design for an FTICR instrument compatible with lower cost wide-bore NMR magnets, and 3) new methods to exploit accurate mass, tandem MS capabilities with APMALDI- FTICR-MS technology for proteomics research. Such an instrument, when coupled with automation and on-line chromatography will result in much higher throughput protein identification capabilities than is currently achieved. As planned, the instrument can make use of relatively inexpensive wide bore magnets currently used for NMR, leading to significantly lower cost FTICR-MS instruments. This will lead to increased training of graduate student researchers in the skills involved in FTICR-MS, increased dissemination and adaptation of next-generation proteomics research and increased collaboration with, and involvement of graduate student education in industry, national laboratory and academic research programs.
