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Development of an IR/UV Laser Desorption Electrospray Ionization Source for Mass

红外/紫外激光解吸电喷雾电离源的开发

基本信息

批准号：
7746643
负责人：
Eli Margalith
金额：
$ 10万
依托单位：
OPOTEK, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2010-07-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7746643
关键词：
Agreement Applications Grants Area Atmospheric Pressure Back Biochemistry Biological Markers Caliber Cells Characteristics Charge Chemistry Collaborations Computer software Detection Development Devices Diagnostic Disadvantaged Disease Drops Drug Residues Electrospray Ionization Engineering Environment Evaluation Event Fiber Food Forensic Medicine Gel General Population Goals Guidelines Health Image Ions Knowledge Lasers Lead Learning Life Light Lighting Mass Spectrum Analysis Measurement Medical Medical Research Medicine Methodology Methods Microscope Molecular Molecular Weight Monitor One-Step dentin bonding system Operative Surgical Procedures Optics Organism Performance Personal Satisfaction Pharmaceutical Preparations Pharmacologic Substance Phase Physiologic pulse Plasma Positioning Attribute Post-Translational Protein Processing Process Proteins Proteomics Reaction Reproducibility Research Research Personnel Research Project Grants Resolution Sampling Scientist Side Signal Transduction Site Solutions Solvents Source Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Staging Surface System Tablets Techniques Technology Temperature Testing Time Tissues Vacuum Variant aqueous base commercial application commercialization consumer product data acquisition hazard improved instrument ion source ionization ionization technique irradiation laser capture microdissection mass analyzer mass spectrometer millimeter novel particle performance tests programs protein structure prototype public health relevance research and development research study small molecule tool virtual voltage

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this research project is the development of a laser desorption electrospray ionization (LDESI) mass spectrometer source. The desorption laser is a tunable mid-IR laser system based on optical parametric oscillator (OPO) technology. The source will be available in front and back-side laser illumination modes depending on the application and have the option of UV laser light for matrix-assisted samples. To our knowledge, no commercially available source is available using both laser desorption and electrospray ionization. We envision a mass analysis of a variety of samples at room temperature and atmospheric pressure. Therefore, the sample would remain in its native environment and real time mass identification of sample constituents would be obtained with little to no sample pretreatment. Mass spectrometers using this technique will offer a useful tool to obtain mass identification for a variety of compounds important to fields such as proteomics, medical diagnostics, consumer products, pharmaceutical research and forensics. In an LDESI analysis, the sample is desorbed with the laser and the resultant plume of predominately neutral particles are captured and ionized by an electrospray source directed towards the mass spectrometer inlet millimeters above the sample surface. The key principle here is that desorption is separated from ionization. Analyzing samples in this way has many advantages over techniques that desorb and ionize in one step. One advantage is an increase in sensitivity since a larger portion of laser desorbed neutral particles are ionized by the electrospray. Also, high mass molecules in excess of 100 kDa can be analyzed at atmospheric pressure because of the "soft" mid-IR desorption and the multiple charging effect of ESI. We envision two types of laser desorption geometries in one source: front-side illumination for direct analysis of high mass proteins, gel separated proteins and bulk materials such as drug tablets and food products and back-side illumination for high spatial resolution tissue imaging and laser capture microdissection. Switching between the two sampling modes will simply involve changing fiber delivery position. When not using laser desorption, the electrospray remains in place for ESI MS. No switching of the LDESI source for the original electrospray source is necessary. The source will be constructed by OPOTEK, based on our past research with mid-IR OPO tunable lasers and MALDI MS sources. MS performance tests will be carried out on commercial mass spectrometers at the UCLA Department of Chemistry and Biochemistry through collaboration with Dr. Joseph Loo, an expert in the field of bioanalytical methods for the structural characterization of proteins. PUBLIC HEALTH RELEVANCE: The analytical device proposed in this grant application will provide a simple tool for researchers to analyze one of the most important groups of molecules necessary for the functioning of all living organisms: proteins. Learning about the characteristics of proteins will give our scientists the knowledge to develop better medical and forensic tools, medicines, food products, and other important fields relevant to the health and well-being of the general public. The proposed device will add capabilities to an existing analytical methodology called mass spectrometry where information about the structure of proteins can be obtained.

描述（由申请人提供）：该研究项目的长期目标是开发激光解吸电喷雾电离（LDESI）质谱仪源。解吸激光器是一种基于光学参量振荡器（OPO）技术的可调谐中红外激光系统。根据应用，该光源将提供正面和背面激光照明模式，并且可以选择用于基质辅助样品的紫外激光。据我们所知，目前还没有同时使用激光解吸和电喷雾电离的商用源。我们设想在室温和大气压下对各种样品进行质量分析。因此，样品将保留在其天然环境中，并且无需进行任何样品预处理即可获得样品成分的实时质量鉴定。使用该技术的质谱仪将提供一种有用的工具，以获得对蛋白质组学、医学诊断、消费品、药物研究和法医学等领域重要的各种化合物的质量鉴定。在 LDESI 分析中，用激光解吸样品，产生的主要为中性粒子的羽流被指向样品表面上方几毫米处的质谱仪入口的电喷雾源捕获并电离。这里的关键原则是解吸与电离分开。与一步解吸和电离的技术相比，以这种方式分析样品具有许多优点。一个优点是灵敏度提高，因为大部分激光解吸的中性粒子被电喷雾电离。此外，由于“软”中红外解吸和 ESI 的多重充电效应，超过 100 kDa 的高质量分子可以在大气压下进行分析。我们设想在一个光源中实现两种类型的激光解吸几何形状：用于直接分析高质量蛋白质、凝胶分离蛋白质和散装材料（例如药片和食品）的正面照明，以及用于高空间分辨率组织成像和激光捕获显微切割的背面照明。两种采样模式之间的切换仅涉及改变光纤传输位置。当不使用激光解吸时，电喷雾保留在 ESI MS 的位置。无需将 LDESI 源切换为原始电喷雾源。该光源将由 OPOTEK 基于我们过去对中红外 OPO 可调谐激光器和 MALDI MS 光源的研究而构建。 MS性能测试将通过与蛋白质结构表征生物分析方法领域专家Joseph Loo博士的合作，在加州大学洛杉矶分校化学与生物化学系的商用质谱仪上进行。公共健康相关性：本次拨款申请中提出的分析装置将为研究人员提供一个简单的工具，用于分析所有生物体功能所必需的最重要的分子组之一：蛋白质。了解蛋白质的特性将为我们的科学家提供知识，以开发更好的医疗和法医工具、药品、食品以及与公众健康和福祉相关的其他重要领域。拟议的设备将为现有的质谱分析方法增加功能，可以获得有关蛋白质结构的信息。