Purchase of a Liquid Chromatograph-Orbitrap VELOS mass spectrometer

描述（由申请人提供）：我们请求为新的Orbitrap Velos ETD（Thermo）提供资金，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的资源中心，可以进行基于质谱的蛋白质组分析。PEL与加州理工学院社区的学生和博士后研究员合作，使他们能够进行蛋白质组学相关的研究。PEL的主要长期目标是能够深入阐明和定量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。一个常见的实验范例是监测用药物或天然配体处理细胞或使它们受到环境或遗传干扰后发生的全局蛋白质变化。为了实现这一目标，不断开发新的方法。我们申请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过了我们目前的仪器套件。其次，更重要的是，我们现有仪器的技术限制阻碍了我们合作者实验室NIH资助项目的进展。与第一代仪器相比，Orbitrap Velos ETD能够以更高的效率传输离子，扫描速度更快，从而提高了整体灵敏度。此外，更高能量的C-陷阱解离（HCD）和电子转移解离（ETD）提供了我们无法获得的互补碎片化技术，但对拟议项目的进展至关重要。此外，我们在购买Orbitrap Velos时购买的Proxeon Easy nanoESI源可以在1D和2D LC分离之间快速切换，这对于在PEL分析的样品的复杂性范围很大至关重要。为了证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支付该赠款机制下最高允许资金与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，将在推进涵盖广泛的基础和应用研究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。对这些领域的基本认识将有助于预防和/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.