No 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.

In this work, a multistep microcontinuous flow-through synthesis procedure for the generation of homogeneous, high-quality silver nanoprisms is presented. The particle synthesis is based on the wet chemical reduction of silver nitrate in the presence of the polyanionic polymer poly(sodium styrenesulphonate). To obtain a high yield of homogeneous prism-shaped Ag nanoparticles with a triangular base, two main experimental steps are necessary. The first step is the synthesis of seed particles. To match the quality criteria for small, homogeneous seed particles, the synthesis was carried out in a microcontinuous flow-through system. Constant residence times and an effective mixing of the reactants were realized by the application of the microsegmented flow technique. The advantage of good reactant mixing was also adapted in the second experimental step. The growth of silver nanoprisms by reduction of silver nitrate on the noncapped surfaces of the seed particles was again carried out within microfluid segments during a continuous flow-through synthesis. The obtained colloidal solutions of both, Ag seeds and Ag nanoprisms, were analyzed using differential centrifugal sedimentation, UV–vis spectrophotometry, and scanning electron microscopy. The size distributions of the product particles of the individual process steps were extremely narrow. For the Ag seed particles, an average particle diameter of 3.8 nm with a distribution half-width of 2.3 nm was found. The edge length of the Ag nanoprisms could be varied between 35 and 180 nm, while the size distribution remained narrow and the yield of particles of the desired shape high. Because of the strong sensitivity of the optical properties of the nanoprisms from the geometrical aspects, Ag nanoprisms promise a high potential for sensor applications. Constraints on nanoparticles presented by these applications, such as uniformity and narrow size distributions, can be met by microreaction technology. In particular, by applying a microsegmented flow, an improvement of the product quality can be achieved because of the enhanced segment-internal mixing and the suppression of a residence time distribution.

A micro-continuous-flow process was applied for the preparation of swellable polyacrylamide particles incorporating silver nanoparticles. These sensor particles are formed from a mixture of a colloidal solution of silver nanoparticles and monomer by a droplet-based procedure with in situ photoinitiation of polymerization and a subsequent silver enforcement in batch. The obtained polymer composite particles show a strong SERS effect. Characteristic Raman signals of aqueous solutions of adenine could be detected down to 0.1 μM by the use of single sensor particles. The chosen example demonstrates that the composite particles are suitable for quantitative microanalytical procedures with a high dynamic range (3 orders of magnitude for adenine).

The particular advantages of micro segmented flow are discussed with respect to the specific requirements in the synthesis of nanoparticles. Compartimentation of a liquid, slug-flow transport behavior, decoupling between reaction solution and wall, and induction of a fast radial mass and heat transfer by flow-induced segment-internal convection are the most important aspects for realizing a focussed nucleation and homogeneous particle growth under micro continuousflow conditions. In addition, the micro fluid-segment technique allows the automated realization of large parameter studies and combinatorial investigations by a simple flow rate variation. Beside some concepts of process design, examples for the synthesis of ZnO micro-and nanoparticles as well as for plasmonic nanoparticles are given in order to demonstrate the power of micro segmented flow for generation of nanoparticles of high homogeneity and for tuning of particle properties.