DRILL: Droplet Desolvation and Ion Transmission Interface for Mass Spectrometry

描述(由申请人提供)：这项建议的总体目标是开发一种新型的常压液滴去溶/离子收集接口，用于高效地将软电离生物分子输送到质谱仪，这将显著提高复杂生化样品的质谱分析(MS)的灵敏度和动态范围。这种接口是将MS能力提升到下一个水平的关键使能技术，并进一步推动这一关键工具在健康相关科学中的应用，包括应用于蛋白质组学、新陈代谢组学、生物标记物发现和药物开发。一个由生物工程师、分析化学家和蛋白质组科学家组成的跨学科研究团队将为ESI LC-MS工作流程开发、演示和优化新型界面系统Drill(Dry Ion Location And Locomotion)，该系统具有许多独特的功能，采用多方面的方法，结合创新的工程设计，由强大的电流体动力学分析、模拟和实验、先进的DOE(实验设计)分析表征方法和最先进的应用程序来挑战蛋白质组学问题。通过优化设计的钻头去溶和离子传输接口，我们的目标是消除由于不完全去溶(包括信号抑制)和低效离子收集而造成的离子损失，并使检测的灵敏度和动态范围与当前技术相比有显著提高。研究团队成员在离子源、生物分析设备和传感器、质谱学、蛋白质组学和跨学科合作方面有着成功的研究记录，能够很好地应对与解决改善MS界面的需求相关的科学和工程挑战。作为这项工作的结果，研究小组将完成所有必要的步骤，使拟议的钻探系统成为生物和临床研究人员广泛适用的工具，旨在改善目前的MS性能，并为自上而下和自下而上的蛋白质组学开发新的MS应用程序。将通过几项活动进行广泛传播，以增进对科学技术的了解。特别是，研究成果将通过技术论文和科学论坛上的演示文稿进行交流，开发一个在线资源，总结钻探设备操作的设计和操作指南，并启用新的LC-MS工作流程，以及研究团队计划组织的特别活动(针对临床从业者的动手培训研讨会)。

DESCRIPTION (provided by applicant): The overarching goal of this proposal is to develop a novel atmospheric pressure droplet desolvation/ ion collection interface for efficient delivery of softly ionized biomolecules to mass analyzers, which will dramatically improve sensitivity and dynamic range of mass spectrometry (MS) for complex biochemical samples. Such an interface is a critical enabling technology for raising MS capability to the next level, and to further advance this key tool in health related sciences, including applications to proteomics, metabolomics, biomarker discovery and drug development. An interdisciplinary research team comprised of a bioengineer, an analytical chemist, and a proteomics scientist will develop, demonstrate and optimize the novel interface system, DRILL (DRy Ion Localization and Locomotion), for ESI LC-MS workflows with a number of unique capabilities, using a multifaceted approach that combines innovative engineering design, supported by powerful electrohydrodynamics analysis, simulation and experiments, advanced DOE (design of experiment) analytical characterization methodology, and state-of-the-art applications to challenging proteomics problems. With an optimally-designed DRILL desolvation and ion transport interface, we aim to eliminate ion losses due to incomplete desolvation (including signal suppression) and inefficient ion collection, and to enable a dramatic improvement in sensitivity and dynamic range of detection as compared to the current state of the art. The research team members are well situated to meet the scientific and engineering challenges associated with addressing the need for an improved MS interface, with a track record of successful research on ion sources, bio-analytical devices and sensors, mass spectrometry, proteomics and interdisciplinary collaboration. As a result of this work, the research team will have completed all steps necessary to make the proposed DRILL system a widely applicable tool for biological and clinical researchers, aiming to improve current MS performance and to develop new MS applications for both top-down and bottom-up proteomics. Broad dissemination to enhance scientific and technological understanding will be achieved through several activities. In particular, the research results will be communicated through technical papers and presentations in scientific forums, developing an online resource summarizing the design and operation guidelines for DRILL device operation and enabled new LC-MS workflows, as well as special events (hands-on training workshops for clinical practitioners) that the research team plans to organize.