DRILL: Droplet Desolvation and Ion Transmission Interface for Mass Spectrometry

DRILL：用于质谱分析的液滴去溶剂化和离子传输接口

• 批准号: 8800094
• 负责人: ANDREI G FEDOROV
• 金额: $ 54.99万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8800094
• 关键词: Address; Atmospheric Pressure; Biochemical; Biological; Biological Markers; Biological Preservation; Biomedical Engineering; Cancer Model; Charge; Chickens; Cleaved cell; Clinical; Collection; Complex; Complex Mixtures; Coupled; Deposition; Detection; Development; Devices; Disease; Drug Design; Educational workshop; Effectiveness; Electrodes; Electrospray Ionization; Engineering; Evaluation; Gases; Generations; Geometry; Goals; Guidelines; Health; Health Sciences; Heating; Infusion procedures; Injection of therapeutic agent; Interdisciplinary Study; Ion Transport; Ions; Knowledge; Lasers; Link; Location; Locomotion; Malignant neoplasm of ovary; Maps; Mass Spectrum Analysis; Methodology; Methods; Metric; Microdissection; Modeling; Molecular; Noise; Ovarian Tissue; Paper; Performance; Physics; Plasma; Plasma Proteins; Polysaccharides; Production; Protein Analysis; Proteins; Proteomics; Reproducibility; Research; Research Infrastructure; Research Personnel; Resources; Sampling; Science; Scientist; Sensitivity and Specificity; Side; Signal Transduction; Site; Solvents; Special Event; Stream; System; Technology; Thermometers; Tissue Sample; Tissues; Training; Width; Work; Yeasts; base; design; drug development; engineering design; hydrophilicity; improved; innovation; insight; interdisciplinary collaboration; ion source; ionization; ionization technique; mass analyzer; meetings; member; metabolomics; model design; neoplastic cell; novel; operation; particle; public health relevance; research study; sensor; simulation; sound; tool; transmission process

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.

描述（由申请人提供）：该提案的总体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输送到质量分析器，这将显着提高质谱（MS）的灵敏度和动态范围）用于复杂的生化样品。这种接口是将 MS 能力提高到新水平的关键使能技术，并进一步推进这一关键工具在健康相关科学领域的应用，包括在蛋白质组学、代谢组学、生物标志物发现和药物开发中的应用。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、演示和优化新型接口系统 DRILL（干离子定位和运动），用于 ESI LC-MS 工作流程，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，并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支持，以应对挑战蛋白质组学问题。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去溶剂化不完全（包括信号抑制）和离子收集效率低下而导致的离子损失，并与当前的检测方法相比，显着提高检测的灵敏度和动态范围。最先进的。研究团队成员在离子源、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拥有成功研究记录，能够很好地应对与解决改进 MS 接口需求相关的科学和工程挑战。这项工作的结果是，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，旨在提高当前的 MS 性能，并为自上而下和自下而上的蛋白质组学。将通过多项活动实现广泛传播，以增进科学技术理解。特别是，研究成果将通过技术论文和科学论坛上的演示进行交流，开发在线资源，总结钻具操作的设计和操作指南，启用新的 LC-MS 工作流程，以及特别活动（实践培训）研究小组计划组织的临床实践者研讨会）。