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，这些领域的操作简单性和快速结果至关重要。造成这些限制的原因在于质谱的时间尺度有限，需要进行复杂的样品预处理，以及仪器操作和数据分析所需的特殊技能，以及现有仪器的尺寸、成本和复杂性。普渡大学的这个研究小组的长期目标是开发用于临床现场各种护理点测试的微型质谱设备，并最终用于个人医疗保健。在本项目中，我们建议开发一种质谱采样和电离系统，该系统使用简单的一次性装置，无需样品制备。该方法和设备将基于纸喷雾作为直接采样/电离过程，可以连接到微型离子阱质谱仪进行化学质量分析。目标应用是生物流体样品的分析，特别是干燥的血斑。具体目标包括：1)开发纸喷雾取样/电离方法；2)开发用于生物流体测试的微型质谱系统；3)开发用于治疗药物监测和相关代谢物和偶联物测量的定量方法和改进设备性能。拟议的研究预计将建立和验证一种新的范例，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直接取样/电离方法在临床应用中的潜力。开发适用于复杂混合物定量分析的微型质谱装置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，这是一个对药物开发和个性化医疗有直接影响的项目。本研究将使用一组具有代表性的治疗药物，包括化疗药物伊马替尼、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。

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.