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Linear quadrupole/linear ion trap LC/MS/MS mass spectrometer

线性四极杆/线性离子阱 LC/MS/MS 质谱仪

基本信息

批准号：
7794719
负责人：
RODNEY C. BAKER
金额：
$ 44.16万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-22 至 2011-04-21
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7794719
关键词：
10 year old Address Arachidonic Acids Biomedical Research Brain Buffers Cells Charge Clinical Research Commit Coupled Estrogens Funding Health Hypertension Insulin Investigation Ions Janus kinase Lasers Leptin Liquid Chromatography Mass Spectrum Analysis Measures Medical center Methodology Methods Mississippi Molecular Weight Noble Gases Phosphorylation Site Plasma Request for Applications Research Personnel Sampling Services Source Time Underserved Population United States National Institutes of Health Universities dalton diabetic rat flexibility glucose uptake improved instrument instrumentation interest ion source ionization liquid chromatography mass spectrometry macromolecule mass spectrometer microbial alkaline proteinase inhibitor molecular mass novel public health relevance research facility tandem mass spectrometry tool

项目摘要

DESCRIPTION (provided by applicant): Advances in mass spectrometry instrumentation and methods have pushed mass spectrometry to the forefront in modern biomedical research. Electrospray and matrix-assisted laser desorption have dramatically extended the range of molecular weights that can be analyzed by mass spectrometry. Electrospray instruments extend the range to well over 50,000 Daltons. Macromolecules introduced into the mass spectrometer using an electrospray source carry multiple charges such that the compounds are within the mass-to-charge ratio range of a quadrupole mass filter. Tandem mass spectrometry uses two analytical compartments, one to select ions and a second to measure the mass-to-charge ratio of fragments produced by collision of the preselected ion with an inert gas. Tandem mass spectrometers are typically triple quadrupole instruments. The ion of interest is generated in the ion source and selected in the first mass filter, fragmented in the second sector, and analyzed with the second resolving quadrupole. Combining liquid chromatography and mass spectrometry provides a very powerful tool to investigators addressing biomedical questions, and improves or extends the capabilities of both methodologies. Compounds separated by liquid chromatography can be identified by molecular mass, and since the compounds enter the mass spectrometer over time, the efficiency of ionization is improved. Coupled with the appropriate buffers, liquid chromatography desalts the sample, again increasing sensitivity. At this time liquid chromatography/mass spectrometry instrumentation is not available on the University of Mississippi Medical Center Campus. NIH funded investigators have expressed a need for convenient and more efficient access to a mass spectrometry facility for specific analysis including the following: Identification of phosphorylation sites on Janus Kinase molecules; Determine the residues responsible for the hyperphosphorylation of coilin, which is involved in Cajal body formation; Identification and quantification of arachidonic acid metabolites and estrogenic compounds which are proposed to contribute to hypertension; and identification of novel circulating plasma compound(s) produced by directly infusing leptin into the brains of diabetic rats that stimulate glucose uptake in isolated cells independent of insulin. The requested Applied Biosystems 4000 Q Trap LC/MS/MS will provide the instrumentation needed to carry out the analysis requested by our NIH funded investigators. PUBLIC HEALTH RELEVANCE: The University of Mississippi Medical Center, the major biomedical research facility for the state of Mississippi, is committed to basic and clinical research that addresses the prevalent health issues of the public at large, as well as those of Mississippi's disproportionately high medically under-served population. Modern analytical instrumentation is essential for effective biomedical research, and specifically the combination of liquid chromatography and mass spectrometry, a most powerful tool for biomedical investigation, is not available to UMMC investigators. The existing liquid chromatography instrumentation available to UMMC investigators is greater than ten (10) years old, service is not available and the instrument (API 365) lacks the necessary sensitivity and flexibility of operating modes for some of the applications requested by NIH funded investigators.

描述（申请人提供）：质谱仪器和方法的进步将质谱技术推向了现代生物医学研究的前沿。电喷雾和基质辅助激光解吸极大地扩展了可以通过质谱法分析的分子量范围。电喷雾仪器将范围扩展到远远超过50，000道尔顿。使用电喷雾源引入质谱仪的大分子携带多个电荷，使得化合物在四极质量过滤器的质荷比范围内。串联质谱法使用两个分析室，一个用于选择离子，第二个用于测量预选离子与惰性气体碰撞产生的碎片的质荷比。串联质谱仪通常是三重四极杆仪器。感兴趣的离子在离子源中产生，并在第一质量过滤器中选择，在第二扇区中碎裂，并用第二分辨四极杆分析。液相色谱和质谱的结合为研究人员解决生物医学问题提供了一个非常强大的工具，并提高或扩展了这两种方法的能力。通过液相色谱法分离的化合物可以通过分子质量来识别，并且由于化合物随着时间的推移而进入质谱仪，因此提高了电离效率。再加上适当的缓冲液，液相色谱法使样品脱盐，再次提高灵敏度。目前，密西西比大学医学中心校区还没有液相色谱/质谱仪器。NIH资助的研究人员表示需要方便和更有效地使用质谱设备进行特定分析，包括以下内容：鉴定Janus激酶分子上的磷酸化位点;确定导致卷曲蛋白过度磷酸化的残基，卷曲蛋白参与Cajal体形成;鉴定和定量花生四烯酸代谢物和拟引起高血压的雌激素化合物;以及鉴定通过将瘦素直接输注到糖尿病大鼠的脑中产生的新的循环血浆化合物，所述化合物刺激独立于胰岛素的分离细胞中的葡萄糖摄取。所要求的Applied Biosystems 4000 Q Trap LC/MS/MS将提供进行NIH资助研究者要求的分析所需的仪器。公共卫生关系：密西西比大学医学中心是密西西比州的主要生物医学研究机构，致力于基础和临床研究，解决广大公众普遍存在的健康问题，以及密西西比不成比例的高医疗服务不足的人口。现代分析仪器对于有效的生物医学研究是必不可少的，特别是液相色谱法和质谱法的结合，这是生物医学研究的最有力工具，UMMC研究人员无法使用。UMMC研究者可用的现有液相色谱仪使用时间超过十（10）年，无法使用，仪器（API 365）缺乏NIH资助研究者要求的某些应用所需的灵敏度和操作模式灵活性。