The determination of temporal fluxes of cellular metabolic analytes promises to revolutionize the study of metabolomics and systems biology. A review Of Our work oil the multianalyte microphysiometer (MMP), an instrument capable of measuring extracellular changes in the flux rates of oxygen, glucose, lactate, and acid, is presented as a useful tool in extracting Cellular metabolic information. Applications are reviewed in three areas: biodefense agent discrimination by monitoring changes in metabolic fluxes in response to ricin, botulinum and cholera toxins, as well as anthrax protective antigen (PA); cancer cell studies in relation to hypoxia and cell proliferation, and the short term effects of environmental agents on cell Populations. Future directions include the incorporation of additional electrodes, improvements in temporal and spatial metabolic flux analysis, and miniaturization of the cell chamber and sensor technology for more cost effective and high-through put applications in drug screening and discovery. (c) 2005 Elsevier B.V. All rights reserved.