title: Cell-patterned glass spray for direct drug assay using mass spectrometry.
abstract: In this work, the establishment of a glass spray mass spectrometry (GS-MS) platform for direct cell-based drug assay was described. Cell co-culture, drug-induced cell apoptosis, proliferation analysis and intracellular drug absorption measurement were performed simultaneously on this specifically designed platform. Two groups of co-cultured cells (NIH-3T3/HepG2 and HepG2/MCF-7) were cultivated and they showed high viability within 3 days. The biocompatibility of the platform facilitated the subsequent bioassays, in which, cyclophosphamide (CPA) and genistein were used as the model drugs. The distinctions of cell apoptosis and proliferation between the mono-cultured and co-cultured cells were clearly observed and well explained by in situ GS-MS measurements. A satisfactory linearity of the calibration curve between the relative MS intensity and CPA concentrations was obtained using stable isotope labeling method (y = 0.16545 + 0.0985x, R(2) = 0.9937). The variations in the quantity of absorbed drug were detected and the results were consistent with the concentration-dependence of cell apoptosis. All the results demonstrated that direct cell-based drug assay could be performed on the stable isotope labeling assisted GS-MS platform in a facile and quantitative manner.
authors.affiliation: School of Science, China University of Geosciences (Beijing), Beijing 100083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing 100084, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing 100084, China.
authors.forename: Qiushui
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Science, China University of Geosciences (Beijing), Beijing 100083, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: School of Science, China University of Geosciences (Beijing), Beijing 100083, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing 100084, China. Electronic address: jmlin@mail.tsinghua.edu.cn.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003520:Cyclophosphamide / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008401:Gas Chromatography-Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D019833:Genistein / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D005898:Glass / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D007553:Isotope Labeling; D061986:MCF-7 Cells; D051379:Mice; D041681:NIH 3T3 Cells
chemical_list: D003520:Cyclophosphamide; D019833:Genistein
keywords: Cell co-culture; Drug assay; Glass spray mass spectrometry; Stable isotope labeling