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  

作　　者：Samuel H.Kann Erin M.Shaughnessey Jonathan R.Coppeta Hesham Azizgolshani Brett CIsenberg Else M.Vedula Xin Zhang Joseph L.Charest 

机构地区：[1]Draper Scholar,555 Technology Square,Cambridge,MA 02139,USA [2]Department of Mechanical Engineering,Boston University,110 Cummington Mall,Boston,MA 02215,USA [3]Department of Biomedical Engineering,Tufts University,4 Colby Street,Medford,MA 02155,USA [4]Draper,555 Technology Square,Cambridge,MA 02139,USA [5]Present address:Biogen,225 Binney Street,Cambridge,MA 02142,USA

出　　处：《Microsystems & Nanoengineering》2022年第5期149-160,共12页微系统与纳米工程（英文）

基　　金：This material is based uponwork supported by the National Science Foundation under Grant nos.1804845 and 1804787.

摘　　要：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 models.However,current measurement approaches rely on fluorescent imaging or colorimetric assays that are focused on endpoints,require labels or added substrates,and lack real-time data.Here,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 devices.Each 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 days.For 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 systems.Finally,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 consumption.The 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 

分 类 号：R95[医药卫生—药学]