Constraints of cell growth in narrow microchannels

Cell growth is fundamental to many processes in basic and applied biology. Growth rates afford a window into how cells respond to differing environmental and nutritional cues. Typically measured at the population level at scales of culture tubes, culture flasks and shake flasks, growth rates at the single cell level has emerged to be of keen scientific interest with the advent of techniques for handling and interrogating single cells. Writing in Nature Biotechnology, Manalis and coworkers outline a microfluidics approach for measuring growth rates of different types of cells at the single cell level. Specifically, the approach entails flowing single cells through micrometer-sized microfluidic channels, where passage through surface resonators afford precise measurement of cell mass. This then constitutes the basis for determining cell growth rate. Cell growth occurs in “recovery” channels where time is provided for cell growth, which is the key innovation in the authors’ device. However, the approach suffers from a number of deficiencies whose provenance lies in how cells respond to narrow channels as well as whether cells tested require adherent-dependent growth. Firstly, cells’ growth in microchannels may be fundamentally different from that experienced during cultivation in shake flasks, and thus, data obtained could not be translated to larger volume cultivation common in biotechnology experimentations. Second, stress experienced by cells during movement in microchannel may retard cell growth. Next, the authors’ device could not cater to cells that require adhesion to surfaces for growth. Finally, while “recovery” channels are provided for cell growth after mass measurement, actual duration of growth phase may be shorter than time spent in “recovery” channels, and thus, this translates to underestimation of cell growth rates. Overall, an innovative solution has been found for determining cell growth rates at the single cell level. But, the approach used could introduce serious artefacts into the conceptualization of cell growth measurement. Chief amongst which is the stress experienced by cells in microchannels that could retard cell growth. While expanding the size of the channels for flowing cells may be an option, it could not resolve the above challenge, and the deficiency remains a serious one for microfluidic-based surface resonator measurement of cell growth rates.