Microfluidic Device for Droplet Pairing by Combining Droplet Railing and Floating Trap Arrays

Abstract

Droplet microfluidics are characterized by the generation and manipulation of discrete volumes of solutions, generated with the use of immiscible phases. Those droplets can then be controlled, transported, analyzed or their content modified. In this wide droplet microfluidic toolbox, no means are available to generate, in a controlled manner, droplets co-encapsulating to aqueous phases. Indeed, current methods rely on random co-encapsulation of two aqueous phases during droplet generation or the merging of two random droplets containing different aqueous phases. In this study, we present a novel droplet microfluidic device to reliably and efficiently co-encapsulate two different aqueous phases in micro-droplets. In order to achieve this, we combined existing droplet microfluidic modules in a novel way. The different aqueous phases are individually encapsulated in droplets of different sizes. Those droplet populations are then filtered in order to position each droplet type towards its adequate trapping compartment in traps of a floating trap array. Single droplets, each containing a different aqueous phase, are thus paired and then merged. This pairing at high efficiency is achieved thanks to a unique combination of floating trap arrays, a droplet railing system and a droplet size-based filtering mechanism. The microfluidic chip design presented here provides a filtering threshold with droplets larger than 35 μm (big droplets) being deviated to the lower rail while droplets smaller than 20 μm (small droplets) remain on the upper rail. The effects of the rail height and the distance between the two (upper and lower) rails were investigated. The optimal trap dimensions provide a trapping efficiency of 100% for small and big droplets with a limited double trapping (both compartments of the traps filled with the same droplet type) of 5%. The use of electrocoalescence enables the generation of a droplet while co-encapsulating two aqueous phases. Using the presented microfluidic device libraries of 300 droplets, dual aqueous content can be generated in less than 30 min.

High precision, high throughput generation of droplets containing single cells

“…One merging strategy uses wells of different sizes to sequentially trap distinct types of droplets in a close vicinity prior to their electrocoalescence. [42][43][44] This technique is efficient and has the potential to pair and merge more than two types of droplets by carefully designing the wells. Another example is based on the alternating re-injection of two sizes (types) of droplets.…”

High precision, high throughput generation of droplets containing single cells

“…Currently, different merging strategies exist for the deterministic construction of new droplets from pre-defined droplets. One example uses wells of different sizes to trap sequentially distinct types of droplets in the same place, forming the correct droplet pairs prior to their electrocoalescence [41][42][43]. This technique is efficient and has the potential to pair and merge more than two types of droplets by carefully designing the wells.…”

Hydrogels for Single-Cell Microgel Production: Recent Advances and Applications

“…Both will result in ordering in an equally spaced train of particles, and when spacing is matched with frequency of droplet production, this can double the efficiency of single particle encapsulation compared to random Poisson encapsulation (Lagus and Edd, 2012;Lagus and Edd, 2013). When ordering is performed on particles in two different inlets, the encapsulation efficiency of two unique particles can be increased to around five times the efficiency of random Poisson encapsulation (Yaghoobi et al, 20202020;Duchamp et al, 2021). Performing such inertial ordering requires relatively simple device designs while maintaining the highthroughput nature characteristic to droplet microfluidics.…”