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Measurement of oxygen consumption rates of human renal proximal tubule cells in an array of organ-on-chip devices to monitor drug-induced metabolic shifts

引用

Microsystems & Nanoengineering 2022年第5期8卷 149-160页

作者： Samuel H.Kann Erin M.Shaughnessey Jonathan R.Coppeta hesham azizgolshani Brett CIsenberg Else M.Vedula Xin Zhang Joseph L.Charest Draper Scholar 555 Technology SquareCambridgeMA 02139USA Department of Mechanical Engineering Boston University110 Cummington MallBostonMA 02215USA Department of Biomedical Engineering Tufts University4 Colby StreetMedfordMA 02155USA Draper 555 Technology SquareCambridgeMA 02139USA Present address:Biogen 225 Binney StreetCambridgeMA 02142USA

Measurement of cell metabolism in moderate-throughput to high-throughput organ-on-chip(OOC)systems would expand the range of data collected for studying drug effects or disease in physiologically relevant tissue ***,current measurement approaches rely on fluorescent imaging or colorimetric assays that are focused on endpoints,require labels or added substrates,and lack real-time ***,we integrated optical-based oxygen sensors in a high-throughput OOC platform and developed an approach for monitoring cell metabolic activity in an array of membrane bilayer *** membrane bilayer device supported a culture of human renal proximal tubule epithelial cells on a porous membrane suspended between two microchannels and exposed to controlled,unidirectional perfusion and physiologically relevant shear stress for several *** the first time,we measured changes in oxygen in a membrane bilayer format and used a finite element analysis model to estimate cell oxygen consumption rates(OCRs),allowing comparison with OCRs from other cell culture ***,we demonstrated label-free detection of metabolic shifts in human renal proximal tubule cells following exposure to FCCP,a drug known for increasing cell oxygen consumption,as well as oligomycin and antimycin A,drugs known for decreasing cell oxygen *** capability to measure cell OCRs and detect metabolic shifts in an array of membrane bilayer devices contained within an industry standard microtiter plate format will be valuable for analyzing flowresponsive and physiologically complex tissues during drug development and disease research.

关键词： metabolism culture OCR

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