IMPROVED DETECTION OF LARGE BIOMOLECULES IN TOF-MS

质谱学与生物医学研究正变得越来越相关 和临床应用主要是通过基质辅助激光解吸 电离(MALDI)和电喷雾电离方法。它的未来在 这些领域在于解决宏离子检测问题，其中非常重要的 对于高质量生物分子离子的探测器灵敏度和效率较低 变得很关键。提出的创新将大大改善 微通道板(MCP)作为宏离子的探测器。这将是 通过实施和集成多个检测器来实现 增强功能：(1)增强掠入射几何形状以应对撞击 离子，以及(2)降低MCP表面功函数，这两者都将 提高离子-电子和离子-离子的转化率，改善信号到离子的转换 噪声比；(3)提高MCP内部场强，以大大 增强轻二次离子的离子-电子转化 冲击宏离子；以及(4)显著改善MCP探测器的动态 射程，这一直是分析宏观离子的一个严重限制因素， 特别是在(MALDI)。这些增强功能将集成到 第三阶段商业化的原型探测器硬件。激进分子 探测器性能将出现偏差，MCP探测器假定 在进入丙二醛质量范围的宏离子检测中发挥主导作用-就像 它们现在被公认为低质量离子的主要探测器。 建议的商业应用：探测器的成功增强 高质量生物分子的灵敏度和动态范围 大大扩展商业飞行时间质量的能力 用于蛋白质分析、酶分析、DNA分析、 药物研究、液、气相色谱和表面 分析(SIMS)。

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).