Analytical techniques for biomass-restricted metabolomics: An overview of the state-of-the-art

Biomedical and clinical questions increasingly deal with biomass-restricted samples. To address these questions with a metabolomics approach, the development of new microscale analytical techniques and workflows is needed. Over the past few years, significant efforts have been made to improve the overall sensitivity of MSbased metabolomics workflows to enable the analysis of biological samples that are low in metabolite concentration or biomass. In this paper, factors that are crucial for the performance of biomass-restricted metabolomics studies are discussed, including sampling and sample preparation methods, separation techniques and ionization sources. Overviews of MS-based miniaturized metabolomics studies reported over the past five years are given in tables, with information provided on sample type, sample preparation volume, injection volume, separation techniques and MS analyzers. Finally, some general conclusions and perspectives are given.