High Field Electrospray/MALDI Fourier Transform Mass Spectrometer

描述（由申请人提供）：该研究者联盟集中在布法罗大学化学系，旨在获得具有电喷雾电离和成像基质辅助激光解吸电离（MALDI）源的12特斯拉傅里叶变换离子回旋共振质谱仪（FT-ICR-MS），以增强对人类健康具有重要意义的几个项目。所包括的项目在生物医学可植入设备、基础生物医学科学和个体疾病（包括自闭症、癌症、糖尿病、关节炎和动脉粥样硬化）两个层面都有广泛的应用。一些研究人员计划使用所提出的仪器来获得关于蛋白质内的一级氨基酸序列和共价修饰位点的信息。为了获得这样的关键结构信息，需要电子转移解离（ETD）模块。其他用途包括高质量准确度测量结合串联质谱法用于代谢物鉴定和非共价核酸-配体和蛋白质-配体相互作用的检查。此外，成像MALDI源被要求执行表面的分子询问，例如正在开发的用于植入式生物医学装置的电极材料和已经吸收化疗药物的肿瘤细胞。高磁场在通过质谱法进行分子鉴定和结构测定中提供了许多优点，包括：改进的质量分辨能力和准确度、更大的光谱采集速度、更高的质量上限、更长的离子捕获时间、更高的离子动能、更大数量的捕获离子（因此更低的检测限）和降低的峰聚结。现代外部离子注入系统（使用多极离子导向器和离子漏斗）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。纳入12特斯拉FT-ICR-MS将填补蛋白质鉴定和表面的分子询问目前缺乏在西纽约的空白，并将提高已经多样化的生物信息学能力（NMR，X射线晶体学，和分子建模）在这个地区。 公共卫生相关性：本申请要求为布法罗大学化学系仪器中心提供最先进的傅里叶变换离子回旋共振质谱仪，以协助那里的研究人员及其合作者。拟议的仪器将有利于现有的和悬而未决的NIH支持的研究计划，这些计划需要拟议仪器的不同元素（例如，高分辨率和串联质谱的结构说明，高灵敏度，分子成像），并将大大增加的可能性，这些研究计划实现和超过他们的个人努力的目标。还预计，通过大幅升级该部的质谱仪仪器基础设施，化学，这些项目的新方向将出现，一直难以与现有的仪器在布法罗大学追求。

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.