Microtechnology meets systems biology: the small molecules of metabolome as next big targets.

One of the key objectives of systems biology is to study and control biological processes in terms of interactions of components at different molecular levels. Advances in genome sequencing, transcriptomics and proteomics have paved the way for a systemic analysis of cellular processes at gene and protein levels. However, tools are still missing for a reliable and systemic analysis of the small molecules inside cells, the so-called metabolome. Due to the generally very low concentration, high turn-over rate and chemical diversity of metabolites their quantification under physiological, in vivo and dynamic conditions presents major challenges and the missing link for a real systems biology approach on the way from genome to cellular function. To this end, microfluidics can play an important role owing to its unique characteristics such as highly spatial and temporal resolution of sample treatment and analysis. Despite impressive progresses in microtechnology in recent years, many of the microfluidic studies or devices remain at the level of proof-of-principle and have been seldom applied to the real world of metabolomic analysis. In this review article, we first present the major obstacles and challenges for determining in vivo metabolite dynamics in complex biological systems. The progresses in microfluidics, their characteristics and possible applications to solving some of the compelling problems in metabolomic analysis are then discussed. Emphases are put on pinpointing the deficits of the presently available devices and technologies and directions for further development to fulfill the special need of systems biology.