High Field Electrospray/MALDI Fourier Transform Mass Spectrometer

描述(由申请人提供)：这个由布法罗大学化学系集中的研究人员联盟寻求获得一台12特斯拉傅里叶变换离子回旋共振质谱仪(FT-ICR-MS)，该仪器具有电喷雾电离和成像基质辅助激光解吸电离(MALDI)源，以增强几个对人类健康具有重要影响的项目。所包括的项目在生物医学植入设备、基础生物医学科学以及包括自闭症、癌症、糖尿病、关节炎和动脉粥样硬化在内的个别疾病水平上都有广泛的应用。几名研究人员计划使用拟议的仪器来获得蛋白质中初级氨基酸序列和共价修饰位置的信息。为了获得这种关键的结构信息，需要一个电子转移解离(ETD)模块。其他用途包括与串联质谱仪相结合的高质量精确度测量，以鉴定代谢物，以及检查非共价核酸-配体和蛋白质-配体相互作用。此外，需要成像MALDI源来执行表面的分子询问，例如正在为可植入生物医学设备开发的电极材料和已经服用化疗药物的肿瘤细胞。强磁场在分子鉴定和质谱学结构测定中具有许多优点，包括：提高质量分辨率和准确度，更快的光谱获取速度，更高的质量上限，更长的离子捕获时间，更高的离子动能，更多的捕获离子(因此检测下限更低)，以及减少峰合并。现代外部离子注入系统(使用多极离子导轨和离子漏斗)，再加上FT-ICR检测电子设备的改进，大大提高了布法罗大学现有高分辨率质谱仪的灵敏度。12特斯拉FT-ICR-MS的加入将填补纽约西部目前缺乏的蛋白质鉴定和表面分子询问方面的空白，并将增强该地区本已多样化的生物信息学能力(核磁共振、X射线结晶学和分子建模)。 公共卫生相关性：该应用程序要求为布法罗大学化学系仪器中心配备最先进的傅里叶变换离子回旋共振质谱仪，以帮助那里的研究人员及其合作者。建议的仪器将有利于NIH支持的现有和即将进行的研究计划，这些计划需要建议仪器的不同元素(例如，用于结构鉴定的高分辨率和串联质谱仪、高灵敏度、分子成像)，并将极大地增加这些研究计划实现和超过其个人努力目标的可能性。还预计，通过大幅升级该部的质谱学仪器基础设施。在化学领域，这些项目的新方向将出现，而这些方向在布法罗大学现有的仪器设备下是难以实现的。

DESCRIPTION (provided by applicant): This consortium of investigators concentrated in the Department of Chemistry at the University at Buffalo seeks to obtain a 12 Tesla Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS) with electrospray ionization and imaging matrix-assisted laser desorption ionization (MALDI) sources to augment several projects which have important implications for human health. The projects included have broad application at both the level of biomedical implantable devices, basic biomedical science, and at the level of individual diseases, including autism, cancer, diabetes, arthritis, and atherosclerosis. Several of the investigators plan to use the proposed instrumentation to obtain information on primary amino acid sequence and sites of covalent modification within proteins. To obtain such critical structural information, an electron transfer dissociation (ETD) module is requested. Other uses include high mass accuracy measurements combined with tandem mass spectrometry for metabolite identification and the examination of non-covalent nucleic acid-ligand and protein-ligand interactions. In addition, an imaging MALDI source is requested to perform molecular interrogation of surfaces such as electrode materials being developed for implantable biomedical devices and tumor cells which have taken up chemotherapeutic drugs. The high magnetic field provides numerous advantages in molecular identification and structural determination by mass spectrometry, including: improved mass resolving power and accuracy, greater spectrum acquisition speed, a higher upper mass limit, longer ion trapping time, higher ion kinetic energy, greater number of trapped ions (hence lower detection limits) and decreased peak coalescence. The modern external ion injection system (using multipole ion guides and an ion funnel) coupled with improvements in FT-ICR detection electronics provide greatly improved sensitivity over existing high resolution mass spectrometers at the University at Buffalo. The inclusion of a 12 Tesla FT-ICR-MS will fill a gap in protein identification and molecular interrogation of surfaces currently lacking in Western New York, and will enhance the already diverse bioinformatics capabilities (NMR, x-ray crystallography, and molecular modeling) in this region. PUBLIC HEALTH RELEVANCE: This application requests a state-of-the-art Fourier transform ion cyclotron resonance mass spectrometer for the Instrumentation Center in the Department of Chemistry at the University at Buffalo to assist researchers there and their collaborators. The proposed instrumentation will benefit existing and pending NIH-supported research programs which require different elements of the proposed instrument (e.g., high resolution and tandem mass spectrometry for structural elucidation, high sensitivity, molecular imaging) and will greatly increase the likelihood that these research programs achieve and exceed the aims of their individual efforts. It is also expected that by substantially upgrading the mass spectrometry instrumentation infrastructure in the Dept. of Chemistry, new directions for these projects will emerge that have been difficult to pursue with existing instrumentation available at the University at Buffalo.