A microfluidic chip for adaption and selection of whole-cells

Introduction
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 physico-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.
Objectives
The ability to generate spatially defined gradients of stressors in microfluidic chip systems is still limited and the screening of adapted mutants in these systems is not well optimized. Therefore, the aim was to develop a miniaturized ALE chip design that employs adjustable stressor profiles creating an inflow-gradient which enables an efficient on chip screening of the complete cell population.
Materials & methods
In this poster presentation a microfluidic chip is presented which contains microcompartments and that can be used to perform long-term ALE experiments to adapt microbial cells to defined profiles of stressors such as antibiotics. [1]
Results
The controlled change in the concentration of the antibiotic in the successive compartments 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. ... mehrImportantly, 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.
Conclusion
The novel microfluidic chip presented on this poster 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.

References
[1] Zoheir, A. E., Späth, G. P., Niemeyer, C. M., Rabe, K. S., Microfluidic Evolution-On-A-Chip Reveals New Mutations that Cause Antibiotic Resistance. Small 2021, 17, 2007166.