Novel Mass Spectrometer for Comprhensive No-Loss MS/MS of All Stored Ions

用于所有存储离子的全面无损 MS/MS 的新型质谱仪

• 批准号: 7806394
• 负责人: SUNNIE MYUNG
• 金额: $ 2.61万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7806394
• 关键词: Argon; Beds; Biological; Canis familiaris; Cells; Complex; Cyclin-Dependent Kinases; Detection; Development; Devices; Diabetes Mellitus; Disease; Dissociation; Electronics; Future; Gases; Gene Expression; Genomics; Goals; Helium; Human Genome Project; Injection of therapeutic agent; Ions; Laboratories; Malignant Neoplasms; Mass Fragmentography; Mass Spectrum Analysis; Measurement; Messenger RNA; Methods; Microscope; Modification; Monitor; Nature; Optics; Peptides; Performance; Phase; Phosphoproteins; Phosphorylated Peptide; Phosphorylation; Physiologic pulse; Process; Property; Proteins; Proteome; Proteomics; Research; Resolution; Rheumatoid Arthritis; Ribosomes; Sampling; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Speed; Structure; System; Techniques; Testing; Time; Universities; Yeasts; data acquisition; detector; high throughput technology; instrument; instrumentation; interest; ion source; mass analyzer; mass spectrometer; novel; pressure; professor; protein profiling; prototype; research study; retinal rods; tool

DESCRIPTION (provided by applicant): The human genome project has inspired significant advancements in high-throughput technologies for the study of function and activation in gene expression. However, in order to truly tackle disease, the changes associated with gene expression at the mRNA and proteome levels has to be understood. Since the post-genomic era, the field of proteomics-the systematic profiling of proteins under a given set of conditions such as diseased versus healthy state- has grown tremendously. One of the major problems of proteomics is the low abundance of post-trans la tiona I ly modified proteins in complex biological mixtures such as phosphoproteins. This mandates a need for robust and highly sensitive detection system in which mass spectrometry (MS) has evolved as the method of choice for these analyses due to its fast experimental timescales and sensitivity. The long term goal of this proposal is to develop an ultra-sensitive ion trap mass spectrometry technique to routinely carry out comprehensive MS/MS analysis of complex biological mixtures. The key to this development is the ability to monitor all ions that are stored in an ion trap without discarding any, which is typically done in a standard proteomics experiment. The specific aims of this proposal are to: (1) Optimize the recently constructed high-capacity ion trap instrument by isolating the pressure within the ion trap to allow us to use optimal gases in the various regions of the instrument: helium in the high-capacity ion trap, N2 in the ion source cooling region, and N2 or argon in the collision cell. In addition, we will modify the geometry of the high-capacity ion trap to increase the resolution of the instrument. These straightforward improvements are expected to further enhance the performance of the high-capacity ion trap instrument. (2) The next phase of the research will couple an orthogonal injection reflectron TOP mass analyzer to the high-capacity ion trap. (3) Finally, future experiments will be geared towards the comprehensve sample analysis using this new high-capacity ion trap TOP MS instrument. Abnormal levels of protein phosphorylation are known to be associated with major diseases such as cancer, diabetes, and rheumatoid arthritis. The ability to identify and study these phosphorylation processes will ultimately bring us a step closer to finding a cure.

描述（由申请人提供）：人类基因组项目激发了高通量技术的显着进步，用于研究基因表达中的功能和激活。但是，为了真正解决疾病，必须了解与mRNA和蛋白质组水平上基因表达相关的变化。自后期时代以来，蛋白质组学领域 - 蛋白质的系统分析在给定的一组疾病（例如患病状态与健康状态）的领域已经大大增长。蛋白质组学的主要问题之一是，在复杂的生物混合物（例如磷蛋白）中，经衰变后的经历较低。这要求需要强大且高度敏感的检测系统，其中质谱（MS）由于其快速的实验时间表和灵敏度而进化为这些分析的选择方法。该提案的长期目标是开发一种超敏感的离子陷阱质谱技术，以常规对复杂生物混合物进行全面的MS/MS分析。这种开发的关键是能够监测所有存储在离子陷阱中的离子而不丢弃任何离子，这通常是在标准蛋白质组学实验中进行的。该提案的具体目的是：（1）通过隔离离子陷阱内的压力，使我们能够在仪器的各个区域中使用最佳气体来优化最近构建的高容量离子陷阱仪器：在离子源冷却区域中的N2中的N2中的N2中的氦气以及碰撞单元格中的N2中的N2中的氦气。此外，我们将修改高容量离子陷阱的几何形状，以增加仪器的分辨率。这些直接的改进有望进一步增强高容量离子陷阱仪器的性能。 （2）研究的下一阶段将将正交注射反射量顶质量分析仪与高容量离子陷阱相结合。 （3）最后，使用这种新的大容量离子陷阱顶部MS仪器将未来的实验用于综合样品分析。已知蛋白质磷酸化的异常水平与癌症，糖尿病和类风湿关节炎等主要疾病有关。识别和研究这些磷酸化过程的能力最终将使我们更接近找到治愈方法。