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Programmed Population Control by Cell-Cell Communication in a Microfluidic Chemostat

F.K. Balagadde, L. You, C. Hansen, F.H. Arnold and S.R. Quake
California Institute of Technology, US

Keywords:
microfluidics, chemostat

Abstract:
A microfluidic chemostat is a chip-based bioreactor that allows continuous culture and monitoring of bacteria for weeks at a time. Using a novel technique for active control of biofilm formation, the (chip) allows well-controlled planktonic growth in six independent 16-nanoliter reactors with no observable wall adhesion. Populations of a few thousand bacteria could be studied continuously for weeks at a time with single-cell resolution. The microfluidic chemostat enabled long-term, non-invasive measurement of the population dynamics of Escherichia coli containing a synthetic ‘population control’ circuit that controls cell density via a quorum-sensing based feedback system and a ‘killer’ gene. A key feature of the microfluidic system is the ability to monitor extremely small populations, which greatly reduces the probability that mutants, which escape this artificial control, will appear. This enabled us to observe sustained oscillations in population dynamics, which evaded detection in “macro-” cultures, over hundreds of hours.

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