Imitation of drug metabolism in cell co-culture microcapsule model using a microfluidic chip platform coupled to mass spectrometry |
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Authors: | Yajing Zheng Zengnan Wu Jin-Ming Lin Ling Lin |
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Institution: | Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China; State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China |
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Abstract: | In this work, a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry (MS) detector was described. We constructed a three-dimensional tumor-endothelial co-culture model for simulating drug resistance during tumor treatment. On this specially designed integrated platform, the first step was to prepare heterogeneous cell-encapsulated alginate microcapsules for threedimensional co-culture, and the second step was to achieve on-line perfusion culture and continuous drug stimulation on chip. It facilitates cell proliferation analysis and the collection of metabolism medium. After micro solid phase extraction column (SPE) pretreatment, subsequent mass spectrometry could detect drug metabolism. The high activity of two kinds of cells (A549 and HUVEC) shows the biocompatibility of the platform. Paclitaxel was used as a model drug, the distinctions of drug absorption between the mono-culture group and co-culture group were clearly observed by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF MS). Therefore, the integrated platform has shown promise as a high throughput, low cost for cell metabolism research and drug screening processes. |
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Keywords: | Microfluidic chip ESI-Q-TOF MS Co-culture Drug metabolism Droplet technique Hydrogel microcapsule |
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