High Field Electrospray/MALDI Fourier Transform Mass Spectrometer

描述（由申请人提供）：该研究联盟集中在布法罗大学化学系，旨在获得一台带有电喷雾电离和成像基质辅助激光解吸电离（MALDI）源的12特斯拉傅立叶变换离子回旋共振质谱仪（FT-ICR-MS），以增加对人类健康有重要影响的几个项目。所纳入的项目在生物医学植入装置、基础生物医学科学以及个体疾病（包括自闭症、癌症、糖尿病、关节炎和动脉粥样硬化）层面都有广泛的应用。一些研究人员计划使用该仪器来获取蛋白质内初级氨基酸序列和共价修饰位点的信息。为了获得这些关键的结构信息，需要一个电子转移解离（ETD）模块。其他用途包括高质量精度测量结合串联质谱鉴定代谢物和检查非共价核酸-配体和蛋白质-配体相互作用。此外，需要成像MALDI源对表面进行分子询问，例如为植入式生物医学设备开发的电极材料和已经接受化疗药物的肿瘤细胞。高磁场为质谱法分子鉴定和结构测定提供了许多优势，包括：提高质量分辨率和精度，提高光谱采集速度，更高的质量上限，更长的离子捕获时间，更高的离子动能，更多的被捕获离子（因此更低的检测限）和减少峰聚结。现代外部离子注入系统（使用多极离子波导和离子漏斗）与改进的FT-ICR检测电子设备相结合，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的加入将填补目前纽约西部缺乏的蛋白质鉴定和表面分子调查的空白，并将增强该地区已经多样化的生物信息学能力（核磁共振、x射线晶体学和分子建模）。

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.