A High-Repetition-Rate IR Laser for Mass Spectrometry

用于质谱分析的高重复率红外激光器

• 批准号: 7157517
• 负责人: Eli Margalith
• 金额: $ 47.83万
• 依托单位: OPOTEK, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157517
• 关键词: gel; ions; lasers; mass spectrometry; sectioning; tissues

DESCRIPTION (provided by applicant): The goal of this Phase II SBIR research program is to continue development of a high-repetition-rate tunable IR laser system for high-throughput and high-sensitivity IR MALDI applications. The program goals are to generate a compact prototype laser system and to demonstrate novel high repetition-rate IR-MALDI applications. The specific program tasks of the project are: Develop and test the second-generation compact high repetition-rate OPO based on a commercially available pump laser system; Demonstrate the second-generation OPO on a MALDI time-of-flight (TOF) mass spectrometer; Interface and demonstrate the second-generation OPO with an orthogonal extraction MALDI ion source hybrid quadrupole-time-of-flight mass spectrometer; and develop scanning IR MALDI and LDI mass spectrometry for spatially resolved gel and tissue analysis. Traditional MALDI has utilized low-repetition-rate laser systems, which can yield lengthy measurement times when large numbers of samples must be analyzed, or in cutting-edge scanning/mapping applications such as blot, direct gel or tissue analysis. Reducing analysis times is important for commercial high-volume laboratories in several areas including functional proteomics and drug discovery. Recent research has focused on utilizing high-repetition-rate (1 kHz) UV laser systems for both improved throughput and increased sensitivity in UV-MALDI and AP-MALDI experiments. However due to lack of suitable laser systems, there has been no research in the area of high repetition- rate IR MALDI, which has several advantages over UV MALDI including analysis of high-mass DNA and other high molecular weight biomolecules, analysis of biopolymers from gel blots or directly from cell or tissue samples, and the analysis of pharmaceuticals and other low molecular weight molecules (200 - 1500 Da). This program will address the need for a high-repetition rate mid-IR laser system for MALDI applications by developing and testing a prototype compact laser system, and demonstrating its capabilities in a number of key applications which will benefit from the increase in data collection rate and ion flux. Mass spectrometry of biological molecules is a key bioanalytical technology, and plays an important part in public health both directly as a component of clinical diagnostics and as a key tool in biochemical research, enhancing our understanding of the basic biochemical processes of proteins and genes and their interrelation among their environment. Key techniques such as MALDI mass spectrometry have provided a wealth of proteomics data which has greatly enhanced our knowledge of the various proteins and their distribution and function in living systems. The proposed work will further enhance MALDI performance by providing a high-repletion-rate IR laser capable of improving both the speed of data collection but also the quality of the data in a variety of applications.

描述（由申请人提供）：该II阶段SBIR研究计划的目标是继续开发用于高通量和高敏化IR MALDI应用的高重复速率可调IR激光系统。程序目标是生成紧凑的原型激光系统，并展示新颖的高重复率IR-MALDI应用。该项目的特定程序任务是：开发和测试基于市售泵激光系统的第二代紧凑型高重复率OPO；在MALDI飞行时间（TOF）质谱仪上演示第二代OPO；界面并用正交提取的MALDI离子源混合四极杆质谱仪演示第二代OPO；并开发扫描IR MALDI和LDI质谱法进行空间分辨的凝胶和组织分析。 传统的MALDI使用了低重复率的激光系统，在必须分析大量样品时，或在尖端的扫描/映射应用程序（例如污点，直接凝胶或组织分析）中，可以产生冗长的测量时间。减少分析时间对于包括功能性蛋白质组学和药物发现在内的多个领域的商业高量实验室很重要。最近的研究集中在利用高重复率（1 kHz）紫外线激光系统来改善吞吐量和提高紫外线和AP-MALDI实验的敏感性。然而，由于缺乏合适的激光系统，在高重复率的IR MALDI领域没有研究，该领域比紫外线MALDI具有多个优势，包括分析高质量DNA和其他高分子生物分子，分析来自凝胶或直接来自细胞或组织的凝胶和直接分析的生物分析的生物聚合物，以及15个dae dae dae dae dae dae dae dae dae dae dae dae dae dae dae da da。 该程序将通过开发和测试原型紧凑型激光系统，并在许多关键应用中证明其功能，从而使其对MALDI应用程序进行高重复速率MID-IR激光系统的需求，这些功能将受益于数据收集速率和ION FORM。 生物分子的质谱是一种关键的生物分析技术，在公共卫生中既是临床诊断的组成部分又是生物化学研究的关键工具，在公共卫生中起着重要作用，增强了我们对我们对蛋白质和基因的基本生物化学过程及其环境中的相互关系的理解。 MALDI质谱等关键技术提供了大量的蛋白质组学数据，这些数据极大地增强了我们对各种蛋白质及其在生活系统中的分布和功能的了解。拟议的工作将通过提供高复制率IR激光器来进一步提高MALDI的性能，该激光激光能够提高数据收集速度以及在各种应用中的数据质量。