DRILL: Droplet Desolvation and Ion Transmission Interface for Mass Spectrometry

描述（由申请人提供）：本提案的首要目标是开发一种新型大气压液滴去溶剂化/离子收集接口，用于将软电离生物分子有效递送至质量分析仪，这将显著提高复杂生化样品的质谱（MS）灵敏度和动态范围。这样的接口是将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，包括蛋白质组学，代谢组学，生物标志物发现和药物开发。由生物工程师、分析化学家和蛋白质组学科学家组成的跨学科研究团队将开发、演示和优化新型界面系统DRILL（DRY离子定位和运动），用于具有许多独特功能的ESI LC-MS工作流程，使用多方面的方法，结合创新的工程设计，并得到强大的电流体力学分析，模拟和实验的支持，先进的DOE（实验设计）分析表征方法，以及最先进的应用程序，具有挑战性的蛋白质组学问题。通过优化设计的DRILL去溶剂化和离子传输接口，我们的目标是消除由于不完全去溶剂化造成的离子损失（包括信号抑制）和低效的离子收集，与现有技术相比，能够显著提高检测的灵敏度和动态范围。研究小组成员能够很好地满足与解决以下需求相关的科学和工程挑战：改进的MS接口，在离子源、生物分析设备和传感器、质谱、蛋白质组学和跨学科合作方面的成功研究记录。作为这项工作的结果，研究团队将完成所有必要的步骤，使拟议的DRILL系统成为生物和临床研究人员广泛适用的工具，旨在改善当前的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。将通过若干活动进行广泛传播，以提高对科学和技术的了解。特别是，研究结果将通过技术论文和科学论坛上的演讲进行交流，开发一个在线资源，总结DRILL设备操作的设计和操作指南，启用新的LC-MS工作流程，以及研究团队计划组织的特殊活动（临床从业人员的实践培训研讨会）。

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.