HIGH PERFORMANCE MALDI/ITMS FOR PEPTIDE & DNA SEQUENCING

主要目标是开发一种基质辅助激光器 解吸/电离（MALDI）四极离子阱（QIT）作为高 高性能串联质谱仪，用于 从复杂的生物混合物中提取肽。 高性能特性 包括高灵敏度、高质量精度、单位质量分辨率 MS和MS/MS模式，串联实验中的单位质量选择，高效 碰撞激活，以及记录宽质量范围的能力 （多渠道优势）在每个周期。 在过去的三年里，一部小说 已经开发了一种有效捕获MALDI离子的方法， 当离子进入阱时，用于调制基本RF电压的方法 在质量扫描期间提供高线性度的辅助RF电压 和质量准确性，宽带和时间延伸SWIFT技术， 单一同位素质量选择和分离，以及脉冲重气体引入 在激励期间，使人们能够降低低质量截止值， 记录更宽范围的产物离子质量。 现在有人建议增加一个反射器来扩大这一努力 飞行时间（reTOF）质量分析仪。 当前QIT/TOF配置 （主要）提供一种用于连接连续电离方法的方法 (e.g.电喷雾）到TOF分析仪，但不利用高的 QIT的性能特点。 在拟议的文书中， reTOF将首先作为离子的快速多通道记录设备 在陷阱中被碰撞激活 此外，它还将提供 进行高能碰撞的能力， 陷阱，与多通道记录实现使用弯曲场反射器。 最后，研究者还将开发高质量MALDI QIT/reTOF 在5，000质量范围内对DNA寡聚体进行快速测序的仪器 到20，000道尔顿，使用连续的基本RF电源 相对于频率和振幅都可变。

DESCRIPTION: The major goal has been to develop a matrix-assisted laser desorption/ionization (MALDI) quadrupole ion trap (QIT) as a high performance tandem mass spectrometer for the amino acid sequencing of peptides from complex biological mixtures. High performance characteristics include high sensitivity, high mass accuracy, unit mass resolution in both MS and MS/MS modes, unit mass selection in tandem experiments, efficient collisional activation, and the ability to record wide mass ranges (multichannel advantage) in each cycle. During the past three years a novel method has been developed for efficiently trapping MALDI ions that ramps the fundamental RF voltage as the ions enter the trap, a method for modulating the supplementary RF voltage during mass scans that provides high linearity and mass accuracy, broadband and stretched in time SWIFT techniques for monoisotopic mass selection and isolation, and pulsed heavy gas introduction during excitation that enables one to lower the low mass cutoff for recording a wider range of product ion masses. It is now proposed to expand this effort by the addition of a reflectron time-of-flight (reTOF) mass analyzer. Current QIT/TOF configurations provide (primarily) a means for interfacing continuous ionization methods (e.g. electrospray) to the TOF analyzer, but do not exploit the high performance characteristics of the QIT. In the proposed instrument, the reTOF would serve first as a rapid, multichannel recording device for ions collisionally activated in the trap. Additionally, it would provide the ability to carry out high-energycollisions for ions mass-selected in the trap, with multichannel recording achieved using a curved -field reflectron. Finally, the investigator will also develop a high mass MALDI QIT/reTOF instrument from rapid sequencing of DNA oligomers in the mass range of 5,000 to 20,000 daltons, using a fundamental RF supply that is continuously variable with respect to both frequency and amplitude.