IMPROVED DETECTION OF LARGE BIOMOLECULES IN TOF-MS

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Mass spectrometry is becoming increasingly relevant to biomedical research and clinical applications largely through matrix-assisted laser desorption ionization (MALDI) and electrospray ionization methods. Its future in these areas lies in solving the macroion detection problem, where the very low detector sensitivity and efficiency for high mass biomolecular ions is becoming critical. The innovations proposed will substantially improve microchannel plates (MCPs) as detectors of macroions. This will be accomplished through implementation and integration of several detector enhancements: (1) enhancing the grazing incidence geometry for impacting ions, and (2) reducing the MCP surface work function, both of which will increase ion-electron and ion-ion conversion yields and improve signal-to- noise ratios; (3) increasing the MCP internal field strength, to greatly enhance ion-electron conversion of light secondary ions resulting from impacting macroions; and (4) substantially improving MCP detector dynamic range, which has been a serious limiting factor in analyzing macroions, particularly in (MALDI). These enhancements will be integrated into prototype detector hardware for Phase III commercialization. A radical departure in detector performance will result, with MCP detectors assuming the leading role in macroion detection into the MDa mass range - just as they are now well-established as the leading detectors for low mass ions. PROPOSED COMMERCIAL APPLICATION: The successful enhancement of detector sensitivity and dynamic range for high mass biomolecules will substantially extend the power of commercial time-of-flight mass spectrometry for protein analysis, enzyme analysis, DNA analysis, pharmaceutical research, liquid and gas chromatography, and surface analysis (SIMS).