"We propose to develop an analytical platform for single-cell metabolomics and apply it in fundamental studies carried out on a model eukaryotic organism, Saccharomyces cerevisiae. Due to the minute amounts of metabolites present in each cell, almost all current methods used in biochemistry and molecular biology provide data that are averaged over an entire cell population while even cells in monoclonal cultures display profound variations on all physiological levels. This approach to molecular biology is dramatically altering our view of the key questions in cellular function and interplay. The ultimate quest for a quantitative and mechanistic model comprising cellular processes requires a new methodology. The proposed single-cell metabolome studies will be achieved through microfluidic cell processing for sample preparation, on-line microscale separation of metabolites and detection by a high sensitivity mass spectrometric method. Our single-cell approach to metabolomics research will permit us to collect data on the cellular metabolome, which can then be utilized for the modelling of cellular metabolism. This new platform for systems biology can find numerous applications ranging from fundamental cell science to personalized medication."