Development of a Novel Atmospheric Pressure Glow Discharge for Ambient Mass Spect

用于环境质谱的新型大气压辉光放电的开发

• 批准号: 8198467
• 负责人: Justin Michael Wiseman
• 金额: $ 38.59万
• 依托单位: PROSOLIA, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-09 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8198467
• 关键词: Ablation; Address; Area; Atmospheric Pressure; Biological; Biomedical Research; Blood; Businesses; Cells; Chemicals; Chemistry; Clinical; Clinical Research; Computer Simulation; Computer software; Computers; Coupled; Coupling; Data; Detection; Development; Devices; Diffuse; Electronics; Elements; Environment; Fee-for-Service Plans; Food Safety; Forensic Medicine; Gases; Grant; Hot Spot; Hydrocarbons; Hydrophobicity; In Situ; Indiana; Ions; Lasers; Licensing; Liquid substance; Marketing; Mass Spectrum Analysis; Measurement; Methodology; Methods; Molecular; Mycobacterium smegmatis; Nature; Optics; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Photography; Plasma; Positioning Attribute; Power Sources; Preparation; Process; Property; Reaction; Reagent; Resolution; Risk; Sampling; Screening procedure; Secure; Security; Services; Small Business Technology Transfer Research; Source; Spectrum Analysis; Speed; Spottings; Sterols; Stream; Surface; System; Techniques; Technology; Temperature; Testing; Time; Universities; Vacuum; Validation; Vendor; base; combinatorial; commercialization; design; improved; insight; interest; ion mobility; ion source; ionization; ionization technique; mass spectrometer; novel; operation; prototype; rapid technique; research and development; sample collection; software systems; tool; voltage

DESCRIPTION (provided by applicant): The overall objective of this Phase II 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. This technology promises to have significant impact in pharmaceutical, clinical and biomedical research. Ultimately, we envision commercial ion sources that can be easily switched among several atmospheric pressure ionization techniques and can be retro-fitted to several different types of mass spectrometers or ion mobility spectrometers. Phase I of this project was highly successful. Alpha prototypes were developed, tested and feasibility proven. Optical spectroscopy measurement revealed novel species (He2+), which are implicated in the ionization mechanism. Further, the plume temperature measurements revealed "hot spots' within the afterglow where thermal desorption is most efficient and results in higher sensitivity. We demonstrated that the ion source could directly desorb and ionize a variety of chemical species and further tested the method in the direct analysis of mycobacterium smegmatis cells. Finally, the coupling of the ion source to a laser ablation cavity proved to yield molecular information with high spatial resolution. The phase II specific aims are as follows: 1. Prototype Development. Beta prototypes of the FAPA ion source will be designed and built based on the criteria defined at the conclusion of the Phase I grant. The sources will include the development of an optimized FAPA discharge cell and a mass spectrometer mounting system with computer controlled sample positioning system. Additionally, prototype support electronics, including the constant current, high voltage DC power supply, a discharge gas temperature controller, and a discharge gas flow controller. Finally, software will be developed to control these elements and automate sample collection. There will be a minimum two beta prototypes built for testing and validation simultaneously at Indiana University and Prosolia. 2. Characterization and Optimization of the sampling process at atmospheric pressure: We will use schlieren photography in combination with mass spectrometry and computer simulations to provide the ideal sampling environment at the interface between the reagent ion gas plume and the vacuum inlet to the mass spectrometer. 3. Source Characterization and applications development: Our approach is three-fold: 1) to test and characterize the beta prototype FAPA source developed in Aim 1 by examining neat samples while varying the gas flow, heater temperature, and device impact angle and assessing the usual figures of merit, detection limits, precision, accuracy, carry-over, and throughput; 2) examining the effects of modifying gas phase chemistries to effect atmospheric pressure fragmentation reactions for generating NIST searchable spectra; and 3) to apply the optimal device parameters, gas-phase chemistry and sampling conditions to a combinatorial study of one hundred "drug-like" molecules of various properties and compare the results to the same study by DESI. We believe it is important to show our customers a range of molecules in size and hydrophobicity to make it easier for them to assess the likelihood their proposed application will be successful. Upon successful completion of the proposed aims, Prosolia will proceed into phase III commercialization where FAPA ion source products (hardware and software) and services will be commercialized. Further, strategic licensing and partnerships will be secured to commercialize the technology as an add-on accessory to laser ablation cavities, gas chromatographs and/or liquid chromatographs. 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.

描述（由申请人提供）：第二阶段 STTR 项目的总体目标是基于大气压辉光放电的流动余辉的环境质谱分析的新型电离源的商业化。该技术有望对制药、临床和生物医学研究产生重大影响。最终，我们设想商业离子源可以在几种大气压电离技术之间轻松切换，并且可以改装到几种不同类型的质谱仪或离子迁移谱仪。 该项目第一阶段非常成功。开发、测试了 Alpha 原型并验证了可行性。光谱测量揭示了与电离机制有关的新物种（He2+）。此外，羽流温度测量揭示了余辉内的“热点”，其中热解吸效率最高，灵敏度更高。我们证明了离子源可以直接解吸和电离多种化学物质，并进一步测试了该方法的直接最后，离子源与激光烧蚀腔的耦合被证明可以产生具有高空间分辨率的分子信息： 1. 原型开发。 FAPA 离子源将根据第一阶段拨款结束时定义的标准进行设计和建造，这些离子源将包括开发优化的 FAPA 放电室和带有计算机控制样品定位系统的质谱仪安装系统。支持电子设备，包括恒流、高压直流电源、放电气体温度控制器和放电气体流量控制器。最后，将开发软件来控制这些元素并自动收集样本。印第安纳大学和 Prosolia 将同时构建至少两个测试原型用于测试和验证。 2. 大气压下采样过程的表征和优化：我们将使用纹影摄影与质谱和计算机模拟相结合，在试剂离子气体羽流和质谱仪真空入口之间的界面处提供理想的采样环境。 3. 源表征和应用开发：我们的方法有三层：1) 通过检查纯样品，同时改变气流、加热器温度和设备冲击角度，并评估目标 1 中开发的 beta 原型 FAPA 源，并对其进行表征。通常的品质因数、检测限、精密度、准确度、残留和通量； 2) 检查改变气相化学物质以影响大气压碎裂反应以生成 NIST 可搜索光谱的效果； 3) 将最佳设备参数、气相化学和采样条件应用于一百种不同性质的“类药物”分子的组合研究，并将结果与​​ DESI 的同一研究进行比较。我们认为，向客户展示一系列分子的大小和疏水性非常重要，以便他们更容易评估其提议的应用成功的可能性。 成功完成拟议目标后，Prosolia 将进入第三阶段商业化，FAPA 离子源产品（硬件和软件）和服务将实现商业化。此外，还将获得战略许可和合作伙伴关系，以将该技术作为激光烧蚀腔、气相色谱仪和/或液相色谱仪的附加配件进行商业化。 公共健康相关性：Prosolia 用于质谱分析的新型多功能环境电离源有望实现高通量化学筛选，这将显着影响制药、临床和生物医学研究。