LD FTMS OF HIGH MASS BIOMOLECULES

请求为继续调查以下申请提供支助 傅里叶变换质谱仪在非挥发性物质分析中的应用 质量在2,000到10,000道尔顿或 再高一点。研究的一个主要重点将是进一步发展 高分辨基质辅助激光解吸新技术的研究 (MALDI)允许将其应用于以前的生物分析问题 不可能通过质谱学进行研究。这项研究将利用 Extrel 7.2特斯拉FTMS双电池仪器和3特斯拉Nicolet FTMS- 最近改装的1000台单电池仪器用于激光解吸 手术。有待探索的工具和方法方面的发展 包括：研究一种新的五板门控捕集方法 在MALDI应用中。一种新的激光解吸几何结构的检验， 垂直于磁场而不是平行于磁场对材料进行解吸 轴；高质量离子四极轴化的进展 与MALDI相结合；增加了高性能快速切换 用于公理化和表面诱导的陷印模块 解离实验。样品制备与分析应用 研究将：进一步审查混合MALDI矩阵的使用和 基质组成对高质量分子MALDI的影响 用于产生多电荷离子的样品制备方法 MALDI，目标是实现一些质量范围和分辨率 允许的优势；探索MALDI-FTMS的应用 蛋白质以外的化合物类别，如核苷酸， 核苷和寡糖；以及改进离线MALDI方法 毛细管电泳液。 还将研究MALDI的基本原理，目的是了解 主导这一过程的因素。这些研究预计将包括 在设计有效的新技术方面提供大量帮助 生物分析应用。

Support is requested for continued investigations of applications of Fourier transform mass spectrometry to analysis of non-volatile biomolecules with masses in the range of 2,000 to 100,000 daltons or higher. A principle emphasis of the research will be further development of the new technique of high resolution matrix-assisted laser desorption (MALDI) to allow its application to bioanalytical problems previously impossible to investigate by mass spectrometry. The research will utilize an Extrel 7.2 Tesla FTMS dual cell instrument and a 3 Tesla Nicolet FTMS- 1000 single cell instrument recently converted for laser desorption operation. Instrumental and methodological developments to be explored include: investigation of a new 5-plate gated trapping procedure for use in MALDI applications; examination of a new laser desorption geometry, desorbing materials normal, rather than parallel, to the magnetic field axis; development of quadripolar axialization of high mass ions in conjunction with MALDI; addition of a high performance rapid switching trapping module for use in both axialization and surface-induced dissociation experiments. Sample-preparation and analytical application studies will: further examine the use of mixed MALDI matrices and the effects of matrix composition on MALDI of high mass molecules; investigate sample preparation methods intended to produce multiply-charged ions by MALDI, with the goal of achieving some of the mass range and resolution advantages that would allow; explore application of MALDI-FTMS to categories of compounds other than proteins, such as nucleotides, nucleosides, and oligosaccharides; and improve methods for off-line MALDI of capillary electrophoresis effluents. Fundamentals of MALDI also will be studied with the aim of understanding the factors governing the process. These studies are expected to be of substantial assistance in designing efficacious new techniques for bioanalytical applications.