Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, D-21073 Hamburg, Germany.
J Biotechnol. 2010 Aug 20;149(1-2):33-51. doi: 10.1016/j.jbiotec.2010.05.002. Epub 2010 Jun 30.
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.
系统生物学的主要目标之一是根据不同分子水平的组件相互作用来研究和控制生物过程。基因组测序、转录组学和蛋白质组学的进步为在基因和蛋白质水平上对细胞过程进行系统分析铺平了道路。然而，仍然缺乏可靠和系统的分析细胞内小分子（所谓的代谢组学）的工具。由于代谢物的浓度普遍非常低、周转率高、化学多样性高，因此在生理、体内和动态条件下对其进行定量分析是一个重大挑战，也是真正的系统生物学方法从基因组到细胞功能的缺失环节。为此，微流控技术由于其独特的特点，如样品处理和分析的高时空分辨率，可以发挥重要作用。尽管近年来微技术取得了令人印象深刻的进展，但许多微流控研究或设备仍处于原理验证阶段，很少应用于代谢组学分析的真实世界。在这篇综述文章中，我们首先介绍了在复杂生物系统中确定体内代谢物动态的主要障碍和挑战。然后讨论了微流控技术的进展、它们的特点以及它们在解决代谢组学分析中一些紧迫问题方面的可能应用。重点是指出目前可用的设备和技术的缺陷，以及为满足系统生物学的特殊需求而进一步发展的方向。
