Single-cell microfluidics: opportunity for bioprocess development.

Cell-to-cell heterogeneity in microbial biotechnological processes caused by biological (intrinsic) and environmental (extrinsic) fluctuations can have a severe impact on productivity. However, as yet little is known about the complex interplay between environmental reactor dynamics and cellular activity. A few years ago, innovative microfluidic systems were introduced facilitating the spatiotemporal analysis of single cells under well-defined environmental conditions allowing so far unachievable insights into population heterogeneity and bioreactor inhomogeneity. Examples of microfabricated systems include microfluidic cavities harbouring micropopulations of several thousand cells down to femtolitre-size structures entrapping individual bacteria. In well-defined perfusion experiments, central questions in biotechnology regarding, for example, growth, productivity, and heterogeneity on the single-cell level have been addressed for the first time. Microfluidics will take its place as a single-cell analytical technique in biotechnological process and strain characterization.