TSQ Vantage Bundle with Acquity UltraPerformance LC

描述（申请人提供）：阿肯色州医学科学大学（UAMS）临床研究科学家的4个主要用户组，持有7个目前的NIH同行评审赠款，申请化学分离和分析系统，其包括（a）Applied Biosystems（AB）/Sciex QTRAP（R）5500 AM三重四极杆/线性离子TRAP质谱仪和（B）沃茨Acquity UPLC（R）Ultra-高效液相色谱仪。UAMS医学和药学学院提供基础设施支持，以完全覆盖保修后服务合同，直至保修后第三年，1名全职技术员/操作员为期两年，并对现有LC-MS实验室进行微小修改（溶剂排气管，泵噪音消除）。用户组在其NIH赠款中记录了一个明确的需求，即在现有UAMS设备上提高色谱分辨率和光谱灵敏度。他们通过对现有系统的审查得出结论，Acquity UPLC（R）- QTRAP（R）5500 AM系统可以最好地满足这一需求，并估计由七个NIH奖项资助的实验将占用80%的仪器时间。值得注意的是，NIH资助的项目都依赖于两种核心方法中的一种或两种：利用（i）L-瓜氨酸和相关精氨酸途径底物作为肠道健康和活动的指标;以及（ii）L-苯丙氨酸、3-甲基-L-组氨酸和其他选定常量营养素的稳定（重）同位素异构体作为蛋白质合成和周转的指标。自从沃尔夫和道依茨博士，衰老和长寿转化研究中心（CTRAL，唐纳德W。Reynolds Department of Geriatrics，UAMS）共同拥有超过50年的专业知识来解释这些和相关代谢物测量的结果，用户组将在CTRAL在其现有的LC-MS/GC-MS核心中安装所需的UPLC-QTRAP系统。该中心的主任Thaden博士拥有超过10年的生物有机分离化学家经验，5包括AB/Sciex三重四极杆质谱仪和AB/Sciex Analyst（R）软件的日常操作。瓜氨酸和氨基酸稳定同位素是强大的代谢示踪剂，能够报告健康状况，因为它适用于许多公共卫生问题。所请求的系统将进一步理解和治疗或减轻败血症、辐射诱导的肠道损伤、慢性阻塞性肺病以及与癌症、重大手术事件、晚期衰老、饥饿等相关的脂肪酸相关底物循环异常。 公共卫生相关性：我们在理解和治疗4个看似不同的公共卫生问题方面的进展都严重依赖于能够测量血液、尿液和组织中某些研究分子（瓜氨酸和一系列稳定、安全的同位素）痕量的仪器。这些健康问题是阿肯色州大学医学科学院资助的7个项目的主题，它们是辐射暴露后肠道的严重损伤;败血症（血液感染）来自主要感染;伴随慢性阻塞性肺疾病（COPD）的肌肉萎缩;以及与一系列病症相关的脂肪酸和蛋白质代谢紊乱，例如癌症、晚期衰老、强迫性不活动，和重大手术事件。所要求的QTRAP（r）5500 AM质谱仪和Acquity UPLC（r）色谱系统将明显加快阿肯色州中部关于脓毒症、辐射防护剂、COPD和代谢底物循环的研究工作的进展。

DESCRIPTION (provided by applicant): A major user group of 4 University of Arkansas for Medical Sciences (UAMS) clinical research scientists, holding 7 current NIH peer-reviewed grants, request a chemical separation and analysis system comprising (a) an Applied Biosystems (AB)/Sciex QTRAP(R) 5500 AM triple Quadrupole/linear ion TRAP mass spectrometer and (b) a Waters Acquity UPLC(R) Ultra-High Performance Liquid Chromatograph. There is infrastructural support from the UAMS Colleges of Medicine and Pharmacy to fully cover post-warranty service contracts through the 3rd post-warranty year, 1 full-time technician/operator for two years, and minor modifications (solvent vent line, pump noise abatement) to an existing LC-MS laboratory. The user group documents a clear need in their NIH grants for improved chromatographic resolution and increased spectrometric sensitivity over that possible on existing UAMS equipment. They conclude from their review of available systems that the Acquity UPLC(R)- QTRAP(R) 5500 AM system can address this need best, and estimate that experiments funded by seven refereed NIH awards will occupy 80% of instrument time. Notably, the NIH-funded projects all rely on one or both of two core methodologies: utilization of (i) L-citrulline and related arginine pathway substrates as metrics of intestinal health and activity; and (ii) stable (heavy) isotopomers of L-phenylalanine, 3-methyl-L-histidine, and other select macronutrients as metrics of protein synthesis and turnover. Since Drs. Wolfe and Deutz, founders of the Center for Translational Research in Aging and Longevity (CTRAL, Donald W. Reynolds Department of Geriatrics, UAMS), jointly have >50 years expertise interpreting the results of these and related metabolite measurements, the user group would situate the requested UPLC-QTRAP system at CTRAL in its existing LC-MS/GC-MS core. That core's director Dr. Thaden has >10 years experience as a bioorganic separations chemist, 5 including day-to-day operation of AB/Sciex triple-quadrupole mass spectrometers and AB/Sciex Analyst(R) software. Citrulline and the amino-acid stable isotopes are powerful metabolic tracers, able to report on health status as it applies to a number of public health issues. The requested system would further understanding and the treatment or palliation of sepsis, radiation-induced gut damage, chronic obstructive lung disease, and fatty acid related substrate-cycling aberrancies associated with cancer, major surgical events, advanced aging, starvation, etc. PUBLIC HEALTH RELEVANCE: Advances in our understanding and treatment of 4 seemingly disparate public health problems share a heavy dependence on instruments able to measure traces of certain research molecules - citrulline, and a family of stable, safe isotopes - in blood, urine and tissue. The health problems, topics of 7 NIH-funded projects at the University of Arkansas for Medical Science (UAMS), are severe damage to the intestines after radiation exposure; sepsis (blood infection) coming from major infection; muscle wasting accompanying chronic obstructive pulmonary disease (COPD); and disturbed fatty acid and protein metabolism associated with a spectrum of conditions, for instance, cancer, advanced aging, enforced inactivity, and major surgical events. The requested QTRAP(r) 5500 AM Mass Spectrometer and Acquity UPLC(r) chromatograph system would appreciably speed progress in these research efforts on sepsis, radioprotective agents, COPD and metabolic substrate cycling here in Central Arkansas.