Microfluidic Single-Cell Analytics.

What is the impact of cellular heterogeneity on process performance? How do individual cells contribute to averaged process productivity? Single-cell analysis is a key technology for answering such key questions of biotechnology, beyond bulky measurements with populations. The analysis of cellular individuality, its origins, and the dependency of process performance on cellular heterogeneity has tremendous potential for optimizing biotechnological processes in terms of metabolic, reaction, and process engineering. Microfluidics offer unmatched environmental control of the cellular environment and allow massively parallelized cultivation of single cells. However, the analytical accessibility to a cell's physiology is of crucial importance for obtaining the desired information on the single-cell production phenotype. Highly sensitive analytics are required to detect and quantify the minute amounts of target analytes and small physiological changes in a single cell. For their application to biotechnological questions, single-cell analytics must evolve toward the measurement of kinetics and specific rates of the smallest catalytic unit, the single cell. In this chapter, we focus on an introduction to the latest single-cell analytics and their application for obtaining physiological parameters in a biotechnological context from single cells. We present and discuss recent advancements in single-cell analytics that enable the analysis of cell-specific growth, uptake, and production kinetics, as well as the gene expression and regulatory mechanisms at a single-cell level.