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

描述（由申请人提供）：第二阶段STTR项目的总体目标是将基于大气压力辉光放电流动余辉的环境质谱新电离源商业化。这项技术有望对制药、临床和生物医学研究产生重大影响。最终，我们设想商业离子源可以很容易地在几种大气压电离技术之间切换，并且可以改装到几种不同类型的质谱仪或离子迁移谱仪上。该项目的第一期非常成功。Alpha原型开发，测试和可行性证明。光谱学测量发现了新物质（He2+），这与电离机制有关。此外，羽流温度测量揭示了余辉中的“热点”，在那里热解吸效率最高，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，并在耻垢分枝杆菌细胞的直接分析中进一步验证了该方法。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。第二阶段的具体目标如下：原型开发。FAPA离子源的Beta原型将根据第一阶段拨款结束时确定的标准进行设计和制造。这些资源将包括开发一个优化的FAPA放电电池和一个带有计算机控制的样品定位系统的质谱仪安装系统。此外，原型支持电子设备，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采集样本。至少有两个测试原型将同时在印第安纳大学和Prosolia进行测试和验证。常压下采样过程的表征和优化：我们将使用纹影摄影结合质谱和计算机模拟，在试剂离子气体羽流和质谱仪真空入口之间的界面提供理想的采样环境。3. 源表征和应用开发：我们的方法有三个方面：1)测试和表征在目标1中开发的beta原型FAPA源，通过检查整洁的样品，同时改变气体流量、加热器温度和设备冲击角度，并评估通常的优点、检测限、精度、准确度、结转和吞吐量；2)研究修改气相化学物质对大气压破碎反应的影响，以产生NIST可搜索的光谱；3)将最佳装置参数、气相化学和取样条件应用于100种不同性质的“类药物”分子的组合研究，并将结果与DESI的相同研究结果进行比较。我们认为，向客户展示一系列分子的大小和疏水性是很重要的，这样他们就可以更容易地评估他们提出的应用成功的可能性。在成功完成拟议目标后，Prosolia将进入第三阶段商业化，其中FAPA离子源产品（硬件和软件）和服务将商业化。此外，将确保战略许可和合作伙伴关系，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。

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.