A Microfluidic Platform for the Culture & Analysis of Single Cells

Abstract

In modern biology, it is often assumed that populations of cells are composed primarily of average cells; cells that do not deviate significantly from an observational mean. This assumption is empirically convenient and until recently was necessary due to technological limitations. However, it is possible that ignorance of cellular individuality may lead one to draw incorrect conclusions, especially when the population under study is heterogeneous. Cells that exhibit significant deviation from the mean behavior can reveal important information which would be normally obscured by ensemble averaging techniques.We have developed an array of microfluidic analytical techniques capable of studying the biochemistry of single cells [1,2,3]. Our current effort focuses on the development of a microfluidic device capable of sustaining a cell culture of a unicellular microorganism, Synechococcus, which can be resolved at the single-cell level. In our microchip, cells are captured hydrodynamically via a pressure-driven cross-flow of nutrient media. With efficient manipulation of the cellular microenvironment, the individuality of the cells' adaptive responses to stress conditions such as nutrient deprivation can be studied quantitatively using fluorescence microscopy. The design of imaging system with controlled illumination source as well as the use of different pumping mechanisms is described.1. Wheeler, A.R., Throndset, W.R., Zare, R.N. et al. Anal Chem 75, 3581-3586 (2003).2. Wu, H., Wheeler, A. & Zare, R.N. Proc Natl Acad Sci U S A 101, 12809-12813 (2004).3. Huang, B., Wu, H., Zare, R.N. et al. Science 315, 81-84 (2007).