Microfluidic Chamber Design for Controlled Droplet Expansion and Coalescence

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.

Highly flexible and accurate serial picoinjection in droplets by combined pressure and flow rate control

“…With respect to concentration gradient formation in droplets, several other microfluidic techniques have been described. These methods for example rely on passive co-flow of reagents 42 or controlled coalescence 43 in smart channel geometries, on controlled dosing of reagents by syringe pumps prior to chip loading, 41 on droplet-on-demand systems followed by electro-coalescence 40 or passive droplet fusion, 44 or on plug generation by valve-based systems 45 or aspiration from 96-well plates 46 followed by plug splitting into small droplets. Typically, the previously reported methods are based on generating combinations of reagents or concentration gradients prior to droplet production.…”

Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications

“…In addition to analyzing droplets contents, the precise injection of fluid volumes is essential for applications like viability assays, long-term cultivation, or high throughput drug screenings. Different strategies for merging existing droplet sequences have been developed in recent years, encompassing active and passive approaches [60][61][62]. One example is a strategy based on electrical fields.…”

“…One example is a strategy based on electrical fields. Kielpinski et al presented a microfluidic device featuring variable merging strategies with an applied electrical field, demonstrating the capability to merge droplets, even those stabilized with surfactants [62]. Another approach involves the use of magnetic particles and the application of a magnetic field to the microfluidic channel [63].…”

Microfluidics for Peptidomics, Proteomics, and Cell Analysis

“…High throughput methods MF included “controlled incremental filtration”, “continuous particle separation in a spiral microchannel,” and “shear modulated inertial migration”. Data analysis was performed using MATLAB software [ 186 , 187 ]. In the study, three different passive MF methods were demonstrated for stepwise filtering of fluid from the main channel into the side channels to achieve single-cell isolation.…”