DIRECT SAMPLE ANALYSIS WITH AN ATMOSPHERIC PRESSURE GLOW DISCHARGE

描述(由申请人提供)：这个第一阶段STTR项目的总体目标是基于大气压辉光放电(APGD)流动的余辉，将一种新的用于环境质谱分析的电离源商业化。这项技术有望对制药、临床和生物医学研究产生重大影响，它与现有技术相结合实现体内质谱学检测的潜力是真实存在的。迫切需要开发新的技术，使快速测量能够在最少的样品预处理的情况下进行。通过减少从原料到结果所需的时间，最大限度地减少前期样品制备增加了样品产量。最近环境质谱学方法的发展已经导致了这些颠覆性技术中的少数几项成功商业化。该项目涉及由Gary Heiftje教授在印第安纳大学开发的基于大气压辉光放电流动余辉的质谱学直接采样新技术的基本表征、优化和开发。大气压辉光放电已被广泛研究，但直到最近才尝试使用大气压辉光放电在开放环境空气中直接采样表面。我们设想的商用离子源可以很容易地在几种大气压电离技术之间转换，并可以改装成几种不同类型的质谱仪或离子迁移率光谱仪。第一阶段STTR方案的具体目标是：目标1：利用光谱技术研究APGD和流动余辉化学环境。目标2：确定阳极和阴极的电极结构和材料，试图利用完成目标1所获得的信息来优化大气辉光放电特性。优化的电池将使试剂离子密度最大化并控制其空间分布。目标3：将APGD电池与质谱学结合使用，并确定目标2中所研究的电池几何形状的操作条件。目标4：评估将APGD与商用激光消融质谱仪系统耦合的可行性。该项目的第二阶段将包括根据第一阶段确定的标准开发APGD离子源的商业原型，进一步优化其性能和稳定性，与其他环境电离方法进行比较，以及在制药和生物医学研究领域开发应用程序。具体地说，第二阶段将部分集中于APGD细胞的开发，结合商业上可用的激光消融质谱仪系统，这将使生物组织的直接3D分子成像成为可能。将利用相同仪器探索的其他应用领域包括组合文库的高通量筛选和体外细胞色素P450检测。与公众健康相关：Prosolia用于质谱学的新型多功能环境电离源有望实现高通量化学筛选，这将对制药、临床和生物医学研究产生重大影响。

DESCRIPTION (provided by applicant): The overall objective of this Phase I STTR project is the commercialization of a new ionization source for ambient mass spectrometry based on the flowing afterglow of an atmospheric pressure glow discharge (APGD). This technology promises to have significant impact in pharmaceutical, clinical and biomedical research and its potential for enabling in vivo mass spectrometry detection in combination with existing technology is real. There is an acute need for the development of new technologies which enable rapid measurements with minimal sample pretreatment. Minimizing up-front sample preparation increases sample through-put by reducing the time required to go from raw material to a result. The recent development of ambient mass spectrometry methods has already resulted in the successful commercialization of just a few of these disruptive technologies. This project involves the fundamental characterization, optimization and development of a new direct sampling technology for mass spectrometry based on the flowing afterglow of an atmospheric pressure glow discharge developed at Indiana University by Prof. Gary Heiftje. Atmospheric pressure glow discharges have been extensively studied but not until very recently has it been attempted to use an atmospheric pressure glow discharge for direct sampling of surfaces in the open ambient air. We envision commercial ion sources that can be easily converted among several atmospheric pressure ionization techniques and can be retro-fitted to several different types of mass spectrometers or ion mobility spectrometers. The specific aims of this Phase I STTR proposal are: Aim 1: Investigate the APGD and flowing afterglow chemical environment using spectroscopic techniques. Aim 2: Identify electrode structures and materials for the anode and cathode in an attempt to optimize the atmospheric glow discharge characteristics using the information gained through completion of Aim 1. An "optimized" cell will be one which maximizes reagent ion density and controls their spatial distribution. Aim 3: Operate the APGD cell in combination with mass spectrometry and identify operating conditions for the cell geometries investigated in Aim 2. Aim 4: Assess the feasibility for coupling APGD to a commercial laser ablation mass spectrometry system. Phase II of this project will include the development of a commercial prototype of the APGD ion source based on the criteria defined in Phase I, further optimization of its performance and robustness, comparisons to other ambient ionization methods and applications development in the areas of pharmaceutical and biomedical research. Specifically, Phase II will focus in part on the development of the APGD cell in combination with commercially available laser ablation mass spectrometry systems, which will enable direct, 3D molecular imaging of biological tissues. Other application areas that will be explored with the same instrumentation include high throughput screening of combinatorial libraries and in vitro cytochrome P450 assays. PUBLIC HEALTH RELEVANCE: Prosolia's new and versatile ambient ionization source for mass spectrometry promises to enable high throughput chemical screening that will significantly impact pharmaceutical, clinical and biomedical research.