Programmable Control of Multiscale Droplets using V‐Valves

Abstract

effect in numerous applications, including single-cell sequencing, [4,5] digital diagnostics, [6,7] nanoparticle synthesis, [8,9] drug screening, [10] directed evolution [11] and enzyme kinetic analysis. [12] Droplets can be generated in either a passive or active manner. Passive methods, that leverage geometric variations in microchannel structures have proved to be exceptionally effective in allowing the robust generation of pL-volume droplets at high speeds. The most common passive methods, include the use of T-junctions, [13,14] flow focusing geometries, [15] and coflow structures. [16] Under certain circumstances, these geometries can be used to generate femtoliter (fL)-volume droplets via tip-streaming. [17] Although, fL-volume droplets can be formed in a robust manner, it is exceptionally difficult to control both droplet volumes and generation frequencies at the same time. [18] In this regard, step-emulsification strategies provide some advantage, since droplet size is primarily controlled by the geometry and size of the microchannel itself, with only a weak dependence on the flow conditions. [19] Although, step-emulsification has been shown to be effective in generating fL-volume droplets at high speed, [20] it should be noted that the strategy is poorly suited for controlling droplet payloads.Active droplet generation methods are based on the principle of introducing additional energy into the fluidic system via mechanical, thermal, electrical, or optical means. [21][22][23][24] When compared to passive methods, active methods offer improved flexibility in regard to controlling droplet size and payloads, and in some cases enable on-demand droplet generation. [18] Amongst active strategies, pneumatic valving has been shown to be effective in generating, [25] splitting, [26] sorting, [27] and merging [25] droplets. Large numbers of pneumatic valves can be integrated within microfluidic devices, and typically comprise a control channel layer and flow channel layer, separated by a thin membrane. [28] The flow and control channels are aligned vertically, with the shared membrane between them acting as the valve. When pressure is applied to the control channel, the membrane is deformed and the flow is interrupted. Multiple valves can be integrated into a single device at high densities owing to the small size of each unit. [29] Microscale valves have proved to be exceptionally useful when performing complex experimental workflows. They can be used to isolate functional components and perform a range of droplet manipulations, including sorting, isolation, immobilization, and coalescence. [30] Through careful design, the operation of each individual functional unit can occur in isolation Contemporary droplet-based microfluidic platforms generate large numbers of sub-nanoliter (<10 −9 L) volume droplets on short timescales. The controllable generation of femtoliter (10 −15 L) volume droplets is however a far more challenging task. Herein, the design, fabrication, and testing of a valve-based droplet-on-demand ge...

Droplet-Based Microfluidics: Applications in Pharmaceuticals

“…The instrument served as an automated droplet generator, allowing the execution of droplet reactions without the need for microfluidic expertise. Xue et al developed and tested a novel active droplet generator based on a V-valve construct for femtoliter (fL)-volume droplet generation using pneumatic valve generation [ 86 ]. This device can produce a single droplet as small as 125 fL and subsequently merge it with an nL-volume sample droplet to generate a sequence of output droplets.…”