A microfluidic chip for adaption and selection of whole-cells

Adaptive laboratory evolution (ALE) is widely used in biotechnology and a key tool to study fundamental evolution processes. Conventional experimental setups for ALE lack some features that are common in nature such as spatial chemical gradients. Microfluidics can overcome these limitations as it can mimic naturally occurring microenvironments creating microbial population heterogeneities ranging from planktonic cells to biofilm states.
In this talk a microfluidic chip is presented, which contains compartments that can be used to adapt microbial cells to defined profiles of stressors such as antibiotics. The controlled change in the concentration of the antibiotic in the successive wells of the chip leads to an adaptation of the bacteria to the presence of the antibiotic and also enables the distinction between persistent and resistant cells. Importantly, previously unknown mutations in Escherichia coli conferring resistance to nalidixic acid were discovered via adaptation experiments employing the chip. Recently, using this microfluidic device, the thermophilic organism Thermus thermophilus was successfully adapted to kanamycin.
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The novel microfluidic chip presented in this talk thus enhances the occurrence of mutations employing cultivation under quasi-static conditions with tunable and spatially stable concentrations. This kind of miniaturized chip-based ALE can be applied to generate data to better understand the mechanism of antibiotic resistance and adapt virtually any microorganism to changes in environmental conditions.