HIGH MASS RESOLUTION FOR MALDI TOF MASS SPECTROMETRY

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The use of ion formation methods such as matrix-assisted laser desorption/ionization (MALDI) in tandem with mass spectrometry (MS) has revolutionized the characterization of biologically significant molecules. MS has now become an indispensable technique for the analysis of large molecules such as lipids, peptides, proteins and nucleic acids. The ToF mass analyzer is widely used because of its simplicity, quasi-parallel detection and theoretically unlimited mass range. One historical drawback to the use of ToF is poor mass peak resolving power. The ability to resolve mass peaks is critical to the success of using accurate mass measurement to assign peak composition and structure. We feel the best approach to improving MALDI mass resolution is to decouple the ionization and extraction from acceleration and mass analysis by adding an interstitial collisional cooling stage. The proposed instrument design should markedly improve the resolution of MALDI mass spectra. To further improve resolution and timing accuracy and mass measurement accuracy, we will use the IOnwerks multi-channel time-to-digital converter (TDC). The combination of multi-pixel detector and multi-channel TDC will increase the dynamic range of the TDC data recorder to the point that it should compete with transient digitizers, but provide superior timing resolution. PROPOSED COMMERCIAL APPLICATION MALDI mass spectrometry is widely and effectively used in all aspects of biomolecule characterization. Should Phase I be successful, we will provide an instrument with mass resolution and mass accuracy superior to currently available instrumentation. We envision that the instrument will be immediately marketable to the biotechnology and pharmaceutical industries with applications as wide ranging as research scale protein scale protein assay to small scale clinical diagnosis.