Time-resolved monitoring of metabolic activities in vitro (microphysiometry) is necessary to study the dynamic regulations of core biochemical pathways in cellular disease models. Following a brief review of recent developments in the field, this contribution presents the most important branches of current sensor-based methods of microphysiometry. The primary parameters assessed by microphysiometry are extracellular pH changes and the concentration of dissolved oxygen to conclude on extracellular acidification (EAR) and oxygen uptake rates (OUR) as quantitative measures for cell metabolism. Direct sensing of selected small molecule metabolites or metabolic heat are alternative assay strategies. The major physical transduction principles encompass electrochemical and optochemical sensing complemented by less popular approaches for highly specific applications. All microphysiometric devices include tissue culture maintenance systems that have to guarantee physiological conditions and that must be functionally aligned with the sensing component. The interplay of cell metabolic activity and sensors in microscaled reaction volumes can be simulated with appropriate numerical models describing the physical processes of reaction and diffusion. While aspects of automation and throughput belong more to the engineering side of microphysiometry, both form the basis for the inevitable statistical data acquisition and analysis. This paper concludes with a description of two selected applications of microphysiometry, one in toxicology and the other one in clinical cancer research.
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