Purchase of a Liquid Chromatograph-Orbitrap VELOS mass spectrometer

描述（由申请人提供）：我们请求资助新的 Orbitrap Velos ETD (Thermo)，并计划将其整合到加州理工学院 (Caltech) 贝克曼研究所的蛋白质组探索实验室 (PEL)。 PEL 成立于 2007 年，是加州理工学院唯一可以进行基于质谱的蛋白质组分析的资源中心。 PEL 与加州理工学院的学生和博士后研究员合作，开展蛋白质组学相关的研究。 PEL 的主要长期目标是深入阐明和量化蛋白质组和亚蛋白质组，以获得对生物调控机制的基本见解。常见的实验范式是监测用药物或天然配体处理细胞或使细胞受到环境或遗传扰动后发生的整体蛋白质变化。为了实现这一目标，人们不断开发新的方法。我们请求资金有两个主要原因。首先，加州理工学院社区的需求已经超出了我们当前的仪器套件。其次，更重要的是，我们现有仪器的技术限制正在阻碍我们合作者实验室中 NIH 资助的项目的进展。 Orbitrap Velos ETD 能够比第一代仪器以更高的效率传输离子，扫描速度更快，从而提高整体灵敏度。此外，高能 C 陷阱解离 (HCD) 和电子转移解离 (ETD) 提供了我们无法使用的互补碎片技术，但对于拟议项目的进展至关重要。此外，我们在购买 Orbitrap Velos 时购买了配备 nanoESI 源的 Proxeon Easy nanoHPLC，可以在一维和二维 LC 分离之间快速切换，考虑到在 PEL 中分析的样品复杂性范围很大，这一点至关重要。为了表明我们对这一应用的承诺，PEL 已经为 Orbitrap Velos 购买了必要的辅助设备，并将使用从私人来源获得的资金来弥补该拨款机制下允许的最大资金与 Orbitrap Velos 购买价格之间的差额。 Orbitrap Velos 质谱仪与 Proxeon LC 系统和信号源相结合，与我们现有的生物信息学管道协同工作，将在推进涵盖广泛基础和应用研究的项目中发挥至关重要的作用，这些研究包括癌症、神经系统疾病（如阿尔茨海默病、帕金森病）、自身免疫性疾病、血管疾病和感染。这些领域的基本见解将有助于预防和/或治愈以前被认为无法治愈的疾病。

DESCRIPTION (provided by applicant): We request funding for a new Orbitrap Velos ETD (Thermo) and plan to integrate this in the Proteome Exploration Laboratory (PEL) of the Beckman Institute at the California Institute of Technology (Caltech). The PEL was established in 2007 and is the only resource center at Caltech where mass spectrometry-based proteome analyses can be performed. The PEL collaborates with students and postdoctoral fellows of the Caltech community to enable their proteomics-related research. The main long-term objective of the PEL is to enable the in-depth elucidation and quantification of proteomes and subproteomes to gain fundamental insights into biological regulatory mechanisms. A common experimental paradigm is to monitor global protein changes that occur after either treating cells with drugs or natural ligands or subjecting them to an environmental or genetic perturbation. Novel methods are constantly being developed to achieve this goal. We request funding for two main reasons. First, demand in the Caltech community has overwhelmed our current suite of instruments. Second and more importantly, technological limitations of our current instruments are hampering the progress of NIH-funded projects in the laboratories of our collaborators. The Orbitrap Velos ETD has the ability to transmit ions with higher efficiency and scan faster than the first generation instruments, thus increasing overall sensitivity. In addition, higher energy C-trap dissociation (HCD) and electron transfer dissociation (ETD) offer complementary fragmentation techniques not available to us, but essential for the progress of the proposed projects. Moreover, the Proxeon Easy nanoHPLC with nanoESI source that we acquired in anticipation of purchasing an Orbitrap Velos allows for rapid switching between 1D and 2D LC separations, which is critical given the great range in complexity of samples that are analyzed at the PEL. To demonstrate our commitment to this application, the PEL has already purchased essential auxiliary equipment for the Orbitrap Velos and will use money obtained from private sources to cover the difference between the maximum allowable funding under this grant mechanism and the purchase price of the Orbitrap Velos. An Orbitrap Velos mass spectrometer coupled with the Proxeon LC system and source, working in concert with our existing bioinformatics pipeline, will play a vital role in advancing projects that span a broad range of fundamental and applied studies that include cancer, neurological disorders (such as Alzheimer's disease, Parkinson), autoimmune diseases, vascular diseases and infections. Fundamental insights in any of these areas will help to prevent and/or cure diseases that have previously been considered incurable.