LD FTMS OF HIGH MASS BIOMOLECULES

请求支持继续调查应用程序 傅里叶变换质谱法分析非挥发性物质 质量在 2,000 至 100,000 道尔顿范围内的生物分子或 更高。研究的主要重点是进一步发展 高分辨率基质辅助激光解吸新技术的研究进展 （MALDI）允许其应用于以前的生物分析问题 无法通过质谱分析进行研究。该研究将利用 Extrel 7.2 Tesla FTMS 双池仪器和 3 Tesla Nicolet FTMS- 1000 个单细胞仪器最近改装为激光解吸 操作。有待探索的仪器和方法的发展 包括：对新的 5 板门控捕获程序的使用进行研究 在 MALDI 应用中；检查新的激光解吸几何结构， 解吸材料垂直于磁场，而不是平行于磁场 轴；高质量离子四极轴化的发展 与 MALDI 结合；添加高性能快速开关 捕获模块可用于轴向和表面诱导 解离实验。样品制备和分析应用 研究将： 进一步检验混合 MALDI 矩阵的使用以及 基质组成对高质量分子MALDI的影响；调查 旨在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 除蛋白质以外的化合物类别，例如核苷酸， 核苷和寡糖；并改进离线MALDI方法 毛细管电泳废水。 还将研究 MALDI 的基础知识，以便理解 控制过程的因素。这些研究预计将是 为设计有效的新技术提供了实质性帮助 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.