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

描述(由申请人提供)：该二期STTR项目的总体目标是基于大气压辉光放电的流动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。最终，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切换，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。该项目的第一阶段非常成功。阿尔法原型被开发、测试和可行性验证。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中的“热点”，在那里热解吸最有效，并导致更高的灵敏度。我们证明了该离子源可以直接解吸和电离多种化学物种，并在污垢分枝杆菌细胞的直接分析中进一步测试了该方法。最后，离子源与激光烧蚀腔的耦合被证明能够产生高空间分辨率的分子信息。第二阶段的具体目标如下：1.原型开发。FAPA离子源的测试版原型将根据第一阶段拨款结束时确定的标准进行设计和建造。这些资源将包括开发优化的FAPA放电池和带有计算机控制的样品定位系统的质谱仪安装系统。此外，样机还支持电子学，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使样本收集自动化。印第安纳大学和普罗索利亚大学将至少建造两个测试版原型，用于同时进行测试和验证。2.大气压下采样过程的表征和优化：我们将使用纹影照相法，结合质谱仪和计算机模拟，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β原型FAPA源，方法是检查整齐的样品，同时改变气体流量、加热器温度和设备冲击角，并评估通常的优值系数、检测下限、精密度、准确度、结转和吞吐量；2)检查修改气相化学反应以影响大气压力裂解反应的效果，以生成NIST可搜索光谱；3)将优化的装置参数、气相化学和采样条件应用于100个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，向我们的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议的应用成功的可能性。在成功完成拟议的AIMS后，Prosolia将进入第三阶段商业化，FAPA离子源产品(硬件和软件)和服务将商业化。此外，将获得战略许可和合作伙伴关系，将该技术商业化，将其作为激光消融腔、气相色谱仪和/或液体色谱仪的附加附件。 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 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.