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

描述（由申请人提供）：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质谱分析的分子量范围。电喷雾仪器将范围扩展到50,000道尔顿以上。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量电荷比范围内。串联质谱法使用两个分析室，一个用于选择离子，另一个用于测量由预先选择的离子与惰性气体碰撞产生的碎片的质量电荷比。串联质谱仪是典型的三重四极杆仪器。感兴趣的离子在离子源中产生并在第一个质量过滤器中选择，在第二个扇区中破碎，并使用第二个解析四极杆进行分析。结合液相色谱法和质谱法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，并改进或扩展了这两种方法的能力。通过液相色谱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进入质谱仪，电离效率得到了提高。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。在这个时候，液相色谱/质谱仪器是不可用的密西西比大学医学中心校园。美国国立卫生研究院资助的研究人员表示，需要方便和更有效地使用质谱分析设备进行具体分析，包括：鉴定Janus激酶分子上的磷酸化位点；确定参与Cajal小体形成的coilin过度磷酸化的残基；花生四烯酸代谢物及与高血压有关的雌激素化合物的鉴定和定量通过将瘦素直接注入糖尿病大鼠的大脑，可以刺激独立于胰岛素的分离细胞中的葡萄糖摄取，从而鉴定出新的循环血浆化合物。申请的Applied Biosystems 4000 Q Trap LC/MS/MS将提供执行NIH资助的研究人员所要求的分析所需的仪器。

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.