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

描述(申请人提供)：质谱学(MS)提供高度特异的分子信息，可作为临床诊断的基础。然而，MS在现场临床诊断或个人保健方面的应用有限，在这些领域，操作简单和快速见效是必不可少的。造成这些限制的原因在于质谱仪的时间尺度和复杂样品前处理的需要，以及仪器操作和数据分析所需的特殊技能，以及当前仪器的规模、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，用于临床现场的各种护理点测试，最终也用于个人健康护理。在这个项目中，我们建议开发一种使用简单的一次性设备的质谱学采样和电离系统，并且不涉及样品制备。该方法和装置将以纸张喷雾为基础，作为直接采样/电离程序，可与微型离子陷阱质谱仪接口，用于化学质量分析。目标应用是生物流体样本的分析，特别是干血斑的分析。具体目标包括：1)开发纸质喷雾采样/电离方法，2)开发用于生物流体测试的微型MS系统，3)开发用于治疗药物监测和相关代谢物和结合物测量的定量方法和改进设备性能。这项拟议的研究有望建立和验证一种执行基于MS的护理点测试的新范例，它涉及简单的操作，但具有高度的敏感性和特异性。我们将充分发掘纸质喷雾作为一种直接采样/电离方法在临床应用中的潜力。开发一种适用于复杂混合物定量分析的微型MS设备的技术挑战将被解决。综合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展示，这是一个对药物开发以及个性化药物具有直接影响的项目。具有代表性的治疗药物包括化疗药物伊马替尼、免疫抑制剂西罗莫司和环孢素A、抗癫痫药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基于质谱学的生物样品化学分析的各种设备。它为临床诊断或个人保健提供了一种快速、简单、高度敏感和选择性的化学监测工具，与一般公共卫生具有很强的相关性。

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.