DIRECT SAMPLE ANALYSIS WITH AN ATMOSPHERIC PRESSURE GLOW DISCHARGE

描述（由申请人提供）：该第I阶段STTR项目的总体目标是基于大气压辉光放电（APGD）的流动余辉将用于环境质谱的新型电离源商业化。该技术有望在制药、临床和生物医学研究中产生重大影响，并且其与现有技术相结合实现体内质谱检测的潜力是真实的。迫切需要开发新技术，使快速测量与最少的样品预处理。最大限度地减少前期样品制备，通过减少从原材料到结果所需的时间来提高样品吞吐量。环境质谱法的最新发展已经导致这些颠覆性技术中的一些成功商业化。该项目涉及一种新的直接进样质谱技术的基本表征、优化和开发，该技术基于印第安纳州大学加里·海弗捷教授开发的大气压辉光放电的流动余辉。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的环境空气中的表面的直接采样。我们设想商业离子源，可以很容易地在几个大气压电离技术之间转换，并可以改装到几个不同类型的质谱仪或离子迁移谱仪。第一阶段STTR提案的具体目标是：目标1：使用光谱技术调查APGD和流动余辉化学环境。目标二：确定阳极和阴极的电极结构和材料，尝试使用通过完成目标1获得的信息优化大气辉光放电特性。“优化的”池将是使试剂离子密度最大化并控制其空间分布的池。目的3：操作APGD池与质谱法的组合，并确定目标2中研究的池几何形状的操作条件。目的4：评估将APGD耦合到商业激光烧蚀质谱系统的可行性。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鲁棒性，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的应用开发。具体来说，第二阶段将部分集中在APGD细胞的开发与商业上可用的激光消融质谱系统相结合，这将使生物组织的直接，3D分子成像。其他应用领域，将探索与相同的仪器包括高通量筛选组合库和体外细胞色素P450测定。 公共卫生相关性：Prosolia的新型多功能常压电离质谱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.