High Resolution MALDI-TOF Mass Spectrometer

高分辨率 MALDI-TOF 质谱仪

• 批准号: 7611102
• 负责人: MARVIN L VESTAL
• 金额: $ 10万
• 依托单位: VIRGIN INSTRUMENTS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611102
• 关键词: Area; Biological; Calibration; Chromatography; Collaborations; Complex; Computer software; Detection; Drug Formulations; Electrospray Ionization; Elements; Engineering; Evaluation; Family; Fourier transform ion cyclotron resonance; Future; Gel; Goals; Human Genome Project; Intervention; MALDI-TOF Mass Spectrometry; Maintenance; Marketing; Measurement; Medicine; Methods; Operative Surgical Procedures; Peptides; Performance; Phase; Preparation; Procedures; Production; Protein Analysis; Proteins; Proteomics; Protocols documentation; Relative (related person); Reliability of Results; Research Design; Resolution; Sampling; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Speed; Spottings; System; Technology; Time; TimeLine; Work; base; clinical practice; commercialization; cost; design; drug discovery; engineering design; fibrinopeptide; improved; instrument; instrumentation; mass spectrometer; member; metabolomics; performance tests; price lists; prototype; public health relevance; small molecule; software development; tool

DESCRIPTION (provided by applicant): High-performance MALDI-TOF MS for Peptides and Small Molecules Summary. This project will build on recent advances in MALDI-TOF mass spectrometry to develop new instruments and software that provide resolving power and mass accuracy competitive with electrospray ionization on FTICR and Orbitrap instruments, but with speed, throughput, sensitivity and dynamic range orders of magnitude greater than are possible with any electrospray system. In preliminary work a prototype instrument has been developed that provides greater than 30,000 resolving power at a selected mass, and ppm mass accuracy over a broad mass range on known protein digests. Based on preliminary results and theoretical calculations the ultimate resolving power is expected to be at least 100,000 in a small, inexpensive benchtop instrument with better than 1ppm RMS mass accuracy for all spots on a large format MALDI plate using automated internal calibration with no operator intervention and sensitivity to detect and accurately determine masses at the 1 attomole level. The long-range goal of this project is to provide practical commercial instruments that make the full power of high-performance MALDI-TOF mass spectrometry routinely available for difficult biological applications that are not satisfactorily served by the tools presently available. This effort will include technical advances in TOF MS and will also focus on the needs of specific applications and on developing reliable and cost-effective means for satisfying these needs. PUBLIC HEALTH RELEVANCE: The proposed instrument is a vital component of new integrated analytical systems based on MALDI that will make large-scale proteomics and metabolomics practical. Completion of the human genome project and improved methods for analyzing proteins and small molecules in complex biological samples have been widely predicted to dramatically change drug discovery and clinical practice of medicine in the near future, but this has not yet been realized. Current technology is clearly not up to the task.

描述（由申请人提供）：肽和小分子摘要的高性能MALDI-TOF MS。该项目将基于MALDI-TOF质谱的最新进展，以开发新的仪器和软件，这些仪器和软件可在FTICR和Orbitrap仪器上提供解决能力和质量精确度，但具有速度，吞吐量，灵敏度和动态范围，更大与任何电喷雾系统相比可能。在初步工作中，已经开发了一种原型仪器，可在选定的质量下提供超过30,000个分辨能力，并且在已知蛋白质消化方面的广泛质量范围内PPM质量精度。基于初步结果和理论计算，预计最终的解决能力将在一种廉价的小型台式仪器中至少为100,000，该仪器的尺寸高于1ppm RMS的质量精确度，用于使用自动化的内部校准，没有操作员干预和操作员干预和操作员干预，并且敏感性检测并准确确定1 attomole水平的质量。该项目的远距离目标是提供实用的商业仪器，以使高性能MALDI-TOF质谱法的全部功能通常用于难以在目前可用的工具满意的困难生物应用中使用。这项工作将包括TOF MS的技术进步，还将重点关注特定应用程序的需求以及为满足这些需求而开发可靠且具有成本效益的手段。 公共卫生相关性：拟议的工具是基于MALDI的新综合分析系统的重要组成部分，该系统将使大规模蛋白质组学和代谢组学实用。在不久的将来，已广泛预测，人类基因组项目的完成和改进的分析复杂生物样品中蛋白质和小分子的方法已被广泛预测，可以极大地改变药物发现和临床医学实践，但尚未实现。当前的技术显然不符合任务。