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）：该阶段II STTR项目的总体目标是基于大气压力放电的流动余辉的环境质谱的新电离源的商业化。该技术有望在药品，临床和生物医学研究中产生重大影响。最终，我们设想可以在几种大气压力电离技术中轻松切换的商业离子源，并且可以重新安装到几种不同类型的质谱器或离子迁移率光谱仪中。 该项目的第一阶段非常成功。 α原型已开发，测试和可行性证明。光谱测量结果揭示了与电离机理有关的新型物种（HE2+）。 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空间分辨率。电源，排放气温控制器和排放气流控制器。最后，将开发软件以控制这些元素并自动化样本收集。印第安纳大学和普罗索里亚同时，至少有两个用于测试和验证的Beta原型。 2。在大气压下对采样过程的表征和优化：我们将使用Schlieren摄影与质谱和计算机模拟结合使用Schlieren摄影，以在试剂离子气盘与真空入口之间的界面上提供理想的采样环境，并提供质谱仪。 3。源表征和应用开发：我们的方法是三倍：1）测试和表征AIM 1中通过检查整齐样品而开发的beta beta原型FAPA源，同时改变气体流量，加热器温度和设备影响角度，并评估普通的功绩，检测限制，准确性，准确性，准确性，随身携带，携带和遍及； 2）检查修饰气相化学的影响以实现大气压力碎片反应以产生可搜索的光谱； 3）将最佳装置参数，气相化学和采样条件应用于对各种特性的一百个“类似药物样”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，向客户展示一系列大小和疏水性的分子很重要，以使他们更容易评估他们提议的应用程序的可能性将成功。 成功完成拟议的目标后，Prosolia将继续进行第三阶段的商业化，其中FAPA离子源产品（硬件和软件）和服务将被商业化。此外，将确保战略许可和合作伙伴关系将技术商业化为激光消融腔，气相色谱和/或液态色谱仪的附加配件。 公共卫生相关性：Prosolia的质谱法新的和多功能的环境电离源有望实现高吞吐性化学筛查，这将显着影响药物，临床和生物医学研究。