Droplet‐based microfluidics for microtoxicological studies

Abstract

The specific sensitivity of different organisms, cells, and tissues against chemicals, the huge number of produced and applied substances, and the combinatorial explosion of effects by the combination of substances demand new concepts for the efficient determination of toxicological dose/response relations. The generation, processing, and characterization of microdroplets of different chemical compositions enable microfluidic approaches to offer a very promising strategy for strongly miniaturized toxicological screenings. Over the last decade, several developments demonstrated the applicability of droplet-based microfluidic systems for toxicological studies. We review the current state of developments in microfluidics for toxicological applications. These have become powerful alternatives to microtiter plates and are very promising for replacing the standard methods in many fields. This article will focus on toxicological dose/response screenings with the variation of droplet composition, particularly on the possibility of generating "concentration spaces," as well as on the applied sensing principles of organisms and cells inside the microdroplets.

Microfluidics for Antibiotic Susceptibility and Toxicity Testing

“…Mohan et al [ 32 ] developed a multiplexed reactor array to investigate the combinatorial effect of two or four different antibiotics while significantly reducing AST time to 2~4 h. The network of microfluidic channels provides the capability of simultaneously generating a concentration gradient without tedious dilution steps, making it possible to assess the combinatorial effect of multiple antibiotics [ 57 ], anticancer drugs [ 58 ] and inhibitors [ 59 ]. Droplet-based microfluidic systems are capable of accommodating a large number of reactions in droplets and the composition of droplets can be programed by users with high reproducibility and homogeneity [ 60 ]. A series of T-junctions [ 61 ] or fluid manifolds [ 62 ] has been used to generate droplets containing multiple antibiotics in a concentration range, culture medium, and cells ( Figure 1 f).…”

Microfluidic Chamber Design for Controlled Droplet Expansion and Coalescence

“…This technique is an important tool to realize experiments in the sub-microliter and nanoliter range that require complex concentration variations [12]. The segmented flow technique has been successfully introduced for a wide spread field of applications such as: (a) concentration-dependent synthesis of different types of nanoparticles [13]; (b) cultivation and susceptibility studies of microorganisms [14,15], in particular, for highly-resolved dose/response functions in micro-toxicology [16,17]; (c) for the screening of two-or three-dimensional concentration spaces and for realizing the principle of stochastic confinement for the search of rare microorganisms [18,19]; and (d) the synthesis of polymeric micro-rods [20], to name some exemplary applications.…”

“…Hence, the motivation for the development of droplet dilution strategies is the generation of droplet series with concentration graduation. Various droplet dilution strategies have already been described to solve this problem, e.g., the adjustment of the effector concentration during the initial droplet formation [16,35,36], or the volume expansion of the initial droplets by adding a dilution media [11] and the serial dilution of trapped droplets [37].…”

Stochastically reduced communities—Microfluidic compartments as model and investigation tool for soil microorganism growth in structured spaces

“…The micro‐segmented flow technique was applied, in particular, for the determination of highly resolved dose/response functions of bacterial growth on various toxic substances. This technique is well suited for the evaluation of combinatorial effects of two or three toxic substances on microbial populations . The microfluidic technique was applied for the characterization of the responses of soil microorganisms on toxic substances .…”