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

描述（由申请人提供）：该第II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将用于环境质谱的新型电离源商业化。这项技术有望在制药、临床和生物医学研究中产生重大影响。最终，我们设想商业离子源，可以很容易地在几个大气压电离技术之间切换，并可以改装到几个不同类型的质谱仪或离子迁移谱仪。 该项目的第一阶段非常成功。开发、测试了Alpha原型，并证明了其可行性。光谱测量揭示了新的物种（He 2+），这是牵连的电离机制。此外，羽流温度测量揭示了余辉内的“热点”，其中热解吸是最有效的，并导致更高的灵敏度。我们证明了离子源可以直接解吸和吸附各种化学物质，并进一步测试了直接分析耻垢分枝杆菌细胞的方法。最后，离子源耦合到激光烧蚀腔被证明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：1.原型开发。FAPA离子源的Beta原型将根据第一阶段赠款结束时定义的标准进行设计和建造。这些资源将包括开发一个优化的FAPA放电室和一个带有计算机控制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和自动化样本收集。将在印第安纳州大学和Prosolia同时建造至少两个测试原型进行测试和验证。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：我们的方法有三个方面：1）通过在改变气体流量、加热器温度和设备冲击角度的同时检查纯样品，并评估通常的品质因数、检测限、精密度、准确度、携带和吞吐量，来测试和表征目标1中开发的β原型FAPA源; 2）检查修改气相化学以实现大气压碎裂反应以产生NIST可搜索光谱的效果;以及3）为了应用最佳器件参数，气相化学和采样条件的组合研究的100个“药物样”分子的各种属性，并比较结果相同的研究DESI。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，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，届时FAPA离子源产品（硬件和软件）和服务将商业化。此外，还将获得战略许可和合作伙伴关系，以将该技术商业化，作为激光消融腔、气相色谱仪和/或液相色谱仪的附加配件。 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 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.