Issue 3, 2012

Uncovering toxicological complexity by multi-dimensional screenings in microsegmented flow: modulation of antibiotic interference by nanoparticles

Abstract

The technique of microsegmented flow was applied for the generation of two- and higher dimensional concentration spaces for the screening of toxic effects of selected substances on the bacterium Escherichia coli at the nanolitre scale. Up to about 5000 distinct experiments with different combinations of effector-concentrations could be realized in a single experimental run. This was done with the help of a computer program controlling the flow rates of effector-containing syringe pumps and resulted in the formation of multi-dimensional concentration spaces in segment sequences. Prior to the application of this technique for toxicological studies on E. coli the accuracy of this method was tested by simulation experiments with up to five dissolved dyes with different spectral properties. Photometric microflow-through measurement of dye distribution inside the concentration spaces allowed the monitoring of microfluid segment compositions. Finally, we used this technique for the investigation of interferences of the antibiotics ampicillin and chloramphenicol towards E. coli cultures and their modulation by silver nanoparticles by measuring bacterial autofluorescence. Each concentration point in this three-dimensional concentration space was represented by 4 or 5 single segments. Thus, a high reliability of the measured dose/response relations was achieved. As a result, a complex response pattern was discovered including synergistic and compensatory effects as well as the modulation of the range of stimulation of bacterial growth by a sublethal dose of chloramphenicol by silver nanoparticles.

Graphical abstract: Uncovering toxicological complexity by multi-dimensional screenings in microsegmented flow: modulation of antibiotic interference by nanoparticles

Article information

Article type
Paper
Submitted
30 Jun 2011
Accepted
21 Oct 2011
First published
14 Nov 2011

Lab Chip, 2012,12, 474-484

Uncovering toxicological complexity by multi-dimensional screenings in microsegmented flow: modulation of antibiotic interference by nanoparticles

J. Cao, D. Kürsten, S. Schneider, A. Knauer, P. M. Günther and J. M. Köhler, Lab Chip, 2012, 12, 474 DOI: 10.1039/C1LC20584F

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