Paper Spray Ionization Mass Spectrometry Device for Direct Analysis of Biofluid S

描述（由申请人提供）：质谱（MS）提供高度特异性的分子信息，可用作临床诊断的基础。然而，有限的使用已经取得了MS的现场临床诊断或个人健康护理，操作简单和快速的结果是必不可少的领域。这些限制的原因在于MS的时间尺度和复杂的样品预处理的需要，以及仪器操作和数据分析所需的特殊技能，以及当前仪器的尺寸、成本和复杂性。普渡大学这个研究团队的长期目标是开发微型MS设备，用于诊所的各种即时检测，并最终用于个人医疗保健。在这个项目中，我们建议开发一个质谱采样和电离系统，使用一个简单的一次性设备，不涉及样品制备。该方法和装置将基于纸喷雾作为直接采样/电离程序，可以连接到一个微型离子阱质谱仪进行化学质量分析。目标应用是分析生物流体样本，尤其是干血斑。具体目标包括：1）开发纸喷雾采样/电离方法，2）开发用于生物流体测试的微型MS系统，以及3）开发定量方法并改善用于治疗药物监测和测量相关代谢物和缀合物的装置性能。拟议的研究预计将建立和验证一个新的模式，用于执行基于MS的即时检测，涉及简单的操作，但具有高灵敏度和特异性。将充分探索纸喷雾作为临床应用的直接采样/电离方法的潜力。开发一个微型MS设备，适用于复杂混合物的定量分析的技术挑战将得到解决。集成仪器和实施的分析方法的能力将在治疗药物监测的情况下进行表征和演示，该项目对药物开发以及个性化医疗有直接影响。本研究将使用一组代表性治疗药物，包括化疗伊马替尼、免疫抑制药物西罗莫司和环孢素A、抗癫痫药物奥卡西平和抗生素庆大霉素。 公共卫生相关性（由申请人提供）：拟议的研究可能会导致开发各种基于质谱法的生物样本化学分析设备。 它通过为临床诊断或个人健康护理提供快速、简便、高灵敏度和选择性化学监测的工具，与公众健康密切相关。

DESCRIPTION (provided by applicant): Mass spectrometry (MS) provides highly specific molecular information and can be used as the basis for clinical diagnoses. However, limited use has been made of MS for on-site clinical diagnosis or personal health care, areas where simplicity of operation and rapid results are essential. The causes of these limitations lie in the in time scale of MS and the need for complex sample pretreatment, as well as the special skills required for instrument operation and data analysis, and the size, cost and complexity of the current instrumentation. The long term goal of this research team at Purdue is to develop miniature MS devices for a wide variety of point-of-care tests at clinic sites and ultimately also for personal health care. In this project, we propose to develop a mass spectrometry sampling and ionization system that uses a simple disposable device and involves no sample preparation. The methodology and device will be based on paper spray as a direct sampling/ionization procedure that can be interfaced to a miniature ion trap mass spectrometer for chemical mass analysis. The target application is the analysis of the biofluid samples, especially dried blood spots. The specific aims include: 1) to develop a paper spray sampling/ionization method, 2) to develop a miniature MS system for biofluid testing, and 3) to develop quantitative methods and to improve device performance for therapeutic drug monitoring and measurement of associated metabolites and conjugates. The proposed research is expected to establish and validate a new paradigm for performing MS-based point-of-care tests, involving simple operations but giving high sensitivity and specificity. The potential of paper spray as a direct sampling/ionization method for clinical applications will be fully explored. The technological challenges of developing a miniature MS device suitable for quantitative analysis of complex mixtures will be addressed. The capabilities of the integrated instrumentation and implemented analytical methods will be characterized and demonstrated in the case of therapeutic drug monitoring, a project that has a direct impact on the drug development as well as the personalized medicine. A representative set of therapeutic drugs including the chemotherapeutic imatinib, the immunosuppressive drugs sirolimus and cyclosporine A, the antiepileptic oxcarbazepine, and the antibiotic gentamicin will be used in this study. PUBLIC HEALTH RELEVANCE (provided by the applicant): The proposed research potentially will lead to the development of a variety of devices for chemical analysis of biological samples based on mass spectrometry. It has strong relevance to general public health by providing a tool for fast, easy, highly sensitive and selective chemical monitoring for clinical diagnosis or personal health care.