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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 liveron-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.microfluidics | liver tissue engineering | toxicology | organ-on-a-chip

For biomedical and textile applications, the comfort of the user will be enhanced if the electronic circuits are not only flexible but also elastic. This letter reveals a simple mouldedinterconnect-device technology for the construction of elastic point-to-point interconnections, based on 2-D spring-shaped metallic tracks, which are embedded in a highly elastic silicone film. Metal interconnections of 3-cm long were constructed with an initial resistance of about 3 Ω, which did not significantly increase (< 5%) when stretched. A stretchability above 100% in one direction has been demonstrated.