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 i nclude: 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.
(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.
|Snyder, Dalton T; Pulliam, Christopher J; Ouyang, Zheng et al. (2016) Miniature and Fieldable Mass Spectrometers: Recent Advances. Anal Chem 88:2-29|
|Ma, Xiaoxiao; Ouyang, Zheng (2016) Ambient ionization and miniature mass spectrometry system for chemical and biological analysis. Trends Analyt Chem 85:10-19|
|Li, Linfan; Chen, Tsung-Chi; Ren, Yue et al. (2014) Mini 12, miniature mass spectrometer for clinical and other applications--introduction and characterization. Anal Chem 86:2909-16|
|Zhou, Xiaoyu; Liu, Jiangjiang; Cooks, Robert Graham et al. (2014) Development of miniature mass spectrometry systems for bioanalysis outside the conventional laboratories. Bioanalysis 6:1497-508|
|Liu, Jiangjiang; Cooks, R Graham; Ouyang, Zheng (2013) Enabling quantitative analysis in ambient ionization mass spectrometry: internal standard coated capillary samplers. Anal Chem 85:5632-6|
|Wang, He; Ren, Yue; McLuckey, Morgan N et al. (2013) Direct quantitative analysis of nicotine alkaloids from biofluid samples using paper spray mass spectrometry. Anal Chem 85:11540-4|
|Chen, Chien-Hsun; Lin, Ziqing; Garimella, Sandilya et al. (2013) Development of a mass spectrometry sampling probe for chemical analysis in surgical and endoscopic procedures. Anal Chem 85:11843-50|
|Ren, Yue; Wang, He; Liu, Jiangjiang et al. (2013) Analysis of Biological Samples Using Paper Spray Mass Spectrometry: An Investigation of Impacts by the Substrates, Solvents and Elution Methods. Chromatographia 76:1339-1346|
|Su, Yuan; Wang, He; Liu, Jiangjiang et al. (2013) Quantitative paper spray mass spectrometry analysis of drugs of abuse. Analyst 138:4443-7|
|Liu, Jiangjiang; Ouyang, Zheng (2013) Mass spectrometry imaging for biomedical applications. Anal Bioanal Chem 405:5645-53|
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