High-resolution mass spectrometer for metabolomics and lipidomics

这笔赠款将使我们能够购买一台高分辨率四极飞行时间(QTOF)质谱仪，这对于我的实验室在康科迪亚大学新成立的实验室继续改进代谢组学和脂质组学方法的研究至关重要。我的实验室致力于通过开发新的提取方法和材料来改进低丰度代谢物的检测，为了这项工作，绝对有必要在现场专门访问高灵敏度质谱仪，如本申请所要求的Agilent 6550 QTOF。质谱学生物应用中心拥有适合这项工作的LTQ Velos Orbitrap。Vuckovic集团每周可使用该仪器约1.5天，因为这是整个康科迪亚大学的共享仪器，按全年365天、每天24小时运行。该中心现有的其余仪器是两个10年前的QTOF，它们不能为这里描述的工作提供足够的灵敏度/质量分辨率。Vuckovic实验室目前培养7名研究生，因此每周1.5天的Orbitrap时间不足以及时推进我的学生的研究。我们的典型分析时间是每个样品30分钟，因此1.5天足以为一个学生运行一个分析批次。为了暂时解决这个问题，我们获得了为期一年的安捷伦QTOF仪器贷款，允许我们在我们的协议中测试仪器的灵敏度和分辨率，并决定该仪器是否适合我们的工作。这一为期一年的借款期现在已经到期，如果没有资金可供购买，仪器将被从Vuckovic实验室移走。然而，这种设备对Vuckovic的研究项目是绝对关键的，该项目包括研究(I)开发新的分析方法来表征人类生物样本(如血液和组织)中的低丰度代谢物，(Ii)系统地表征代谢物-蛋白质结合并研究代谢物浓度对昼夜节律的依赖，(Iii)使用大型跨加拿大尿样登记来评估二十烷类化合物作为过敏反应的可能生物标记物，(Iv)研究免疫系统对纳米颗粒和霉菌毒素暴露的反应，(V)比较不同的脑脂组学提取方法，以协助药物发现；及(Vi)进行大规模新陈代谢组学和类脂组学研究，以支持康科迪亚执行中心的预防性健康研究。该设备对于在分析和临床代谢组学/脂类组学和样品制备方面建立国际水平的Vuckovic实验室至关重要。所要求的购买还将作为学生设计/执行基于高分辨率质谱学的组学分析时的最先进的动手培训工具。

This grant will allow the purchase of a high-resolution quadrupole time-of-flight (QTOF) mass spectrometer which is essential for my laboratory to continue our research in improving metabolomics and lipidomics methods in our newly-established laboratory at Concordia University. My laboratory focuses on improving the detection of low abundance metabolome through the development of new extraction approaches and materials, and for this work it is absolutely necessary to have an on-site dedicated access to a highly sensitive mass spectrometer such as Agilent 6550 QTOF requested in this application. The Centre for Biological Applications of Mass Spectrometry houses LTQ Velos Orbitrap that is suitable for this work. This instrument is available to Vuckovic group ~1.5 days per week since this is shared instrument for entire Concordia University running on 24/7, 365 days/year schedule. The remaining instruments available in the centre are two >10-year old QTOFs which do not provide sufficient sensitivity/mass resolving power for the work described herein. Vuckovic lab currently trains 7 graduate students, so 1.5 day availability of Orbitrap time per week is insufficient for timely progress of my students’ research. Our typical analysis times are 30 min per sample, so 1.5 days is sufficient to run only one analytical batch for one student. To temporarily address this issue, we received 1-year loan of Agilent QTOF instrument to permit us to test the instrument’s sensitivity and resolution in our protocols and decide if this instrument is suitable for our work. This 1-year loan period has now expired, and if there are no funds available for purchase, the instrument will be removed from Vuckovic lab. However, this equipment is absolutely critical for Vuckovic's research program which includes studies (i) to develop new analytical methods to characterize the low abundance metabolites in human biological samples such as blood and tissues, (ii) to systematically characterize metabolite-protein binding and study the dependence of metabolite concentrations on circadian rhythm, (iii) to evaluate eicosanoids as possible biomarkers of anaphylaxis using a large cross-Canada registry of urine samples, (iv) to study the immune system response to nanoparticle and mycotoxin exposure, (v) to compare different extraction methods for lipidomics of brain to aid in drug discovery and (vi) to perform large-scale metabolomics and lipidomics studies to support preventative health studies in Concordia's PERFORM Centre. The equipment is critical to establish Vuckovic laboratory on an international level in analytical and clinical metabolomics/lipidomics and sample preparation. The requested purchase will also serve as a state-of-the-art hands-on training tool for students as they design/execute high-resolution mass spectrometry-based omics assays.