Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction

Danny Bavli, Sebastian Prill, Elishai Ezra, Gahl Levy, Merav Cohen, Mathieu Vinken, Jan Vanfleteren, Magnus Jaeger, Yaakov Nahmias

Research output: Contribution to journalArticlepeer-review


Microfluidic organ-on-a-chip technology aims to replace animal toxicity testing, but thus far has demonstrated few advantages over traditional methods. Mitochondrial dysfunction plays a critical role in the development of chemical and pharmaceutical toxicity, as well as pluripotency and disease processes. However, current methods to evaluate mitochondrial activity still rely on end-point assays, resulting in limited kinetic and prognostic information. Here, we present a liver-on-chip device capable of maintaining human tissue for over a month in vitro under physiological conditions. Mitochondrial respiration was monitored in real time using two-frequency phase modulation of tissue-embedded phosphorescent microprobes. A computer-controlled microfluidic switchboard allowed contiguous electrochemical measurements of glucose and lactate, providing real-time analysis of minute shifts from oxidative phosphorylation to anaerobic glycolysis, an early indication of mitochondrial stress. We quantify the dynamics of cellular adaptation to mitochondrial damage and the resulting redistribution of ATP production during rotenone-induced mitochondrial dysfunction and troglitazone (Rezulin)-induced mitochondrial stress. We show troglitazone shifts metabolic fluxes at concentrations previously regarded as safe, suggesting a mechanism for its observed idiosyncratic effect. Our microfluidic platform reveals the dynamics and strategies of cellular adaptation to mitochondrial damage, a unique advantage of organ-on-chip technology.

Original languageEnglish
Pages (from-to)E2231-40
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - 19 Apr 2016


  • Chromans/adverse effects
  • Hep G2 Cells
  • Humans
  • Lab-On-A-Chip Devices
  • Liver/metabolism
  • Mitochondria, Liver/metabolism
  • Mitochondrial Diseases/chemically induced
  • Oxygen Consumption/drug effects
  • Thiazolidinediones/adverse effects
  • Troglitazone


Dive into the research topics of 'Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction'. Together they form a unique fingerprint.

Cite this