Theoretical and experimental limits of monodisperse droplet generation

Droplet microfluidic systems are becoming routine in advanced biochemical studies such as single cell gene expression, immuno profiling, precise nucleic acid quantification (dPCR) and particle synthesis. For all these applications, ensuring droplet monodispersity is critical to minimize the uncertainty due to droplet volume variation. Despite the wide usage of droplet-based microfluidic systems, the limit of monodispersity for droplet generation systems is still unknown. Here, we present an analytical approach that takes into account all the system dynamics and internal/external factors that disturb monodisper-sity. Interestingly, we are able to model the dynamics of a segmented two-phase flow system using a single-phase flow analogy, electron flow, in electrical circuits. We offer a unique solution and design guidelines to ensure ultra-monodisperse droplet generation. Our analytical conclusions are experimentally verified using a T-junction droplet generator. Equally importantly, we show the limiting experimental factors for reaching the theoretical maximum of monodispersity. (C) 2020 Elsevier Ltd. All rights reserved.