Abstract

The defined formation and expansion of droplets are essential operations for droplet-based screening assays. The volumetric expansion of droplets causes a dilution of the ingredients. Dilution is required for the generation of concentration graduation which is mandatory for many different assay protocols. Here, we describe the design of a microfluidic operation unit based on a bypassed chamber and its operation modes. The different operation modes enable the defined formation of sub-µL droplets on the one hand and the expansion of low nL to sub-µL droplets by controlled coalescence on the other. In this way the chamber acts as fluidic interface between two fluidic network parts dimensioned for different droplet volumes. Hence, channel confined droplets of about 30–40 nL from the first network part were expanded to cannel confined droplets of about 500 to about 2500 nL in the second network part. Four different operation modes were realized: (a) flow rate independent droplet formation in a self-controlled way caused by the bypassed chamber design, (b) single droplet expansion mode, (c) multiple droplet expansion mode, and (d) multiple droplet coalescence mode. The last mode was used for the automated coalescence of 12 droplets of about 40 nL volume to produce a highly ordered output sequence with individual droplet volumes of about 500 nL volume. The experimental investigation confirmed a high tolerance of the developed chamber against the variation of key parameters of the dispersed-phase like salt content, pH value and fluid viscosity. The presented fluidic chamber provides a solution for the problem of bridging different droplet volumes in a fluidic network.

Highlights

  • During the last decade, droplet-based microfluidics [1] has been established as a very powerful tool for parallelized chemical syntheses [2,3] as well as for biological and biomedical research [4] and various screening applications [4,5,6]

  • Four different operation modes were realized: (a) flow rate independent droplet formation in a self-controlled way caused by the bypassed chamber design, (b) single droplet expansion mode, (c) multiple droplet expansion mode, and (d) multiple droplet coalescence mode

  • Channel confined droplet- or micro segmented flow techniques in a sub-μL volume [11] were developed for the generation and manipulation of droplets in ordered sequences of individually composed droplets with well-defined process history

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Summary

Introduction

Droplet-based microfluidics [1] has been established as a very powerful tool for parallelized chemical syntheses [2,3] as well as for biological and biomedical research [4] and various screening applications [4,5,6]. Channel confined droplet- or micro segmented flow techniques in a sub-μL volume [11] were developed for the generation and manipulation of droplets in ordered sequences of individually composed droplets with well-defined process history Each droplet in such a serial sequence can be assigned to its fluidic history, and the composition can be decoded by determination its position within the sequence. The identification of individual droplets due to their formation and process history within a multi-droplet sequence is one of the main advantages of micro segmented-flow techniques compared to the emulsion-based technique, where the droplets arise as a mixed population without spatial confinement This technique is an important tool to realize experiments in the sub-microliter and nanoliter range that require complex concentration variations [12]. Camera images, fluidic- and electronic-parameters were recorded and analyzed offline

Results and Discussion
Self-Controlled Droplet Formation Mode
Conclusions and Outlook
Full Text
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