Continuous production and extraction of monodisperse alginate microgels <i>via</i> deterministic lateral displacement.

Abstract

Over the past two decades, microfluidic approaches have been extensively explored for the production of monodisperse alginate hydrogel microparticles, particularly for applications such as 3D <i>in vitro</i> cell culture in tissue engineering. However, conventional methods often suffer from satellite droplet contamination and inefficient oil-to-water phase transfer, limiting purity and scalability. Here, we present an integrated microfluidic platform for the continuous, on-chip production, gelation, extraction, and purification of monodisperse alginate hydrogel microparticles. The device combines a flow-focusing droplet generator with a deterministic lateral displacement (DLD) array, which guides alginate precursor droplets (mean diameter ∼73 µm; CV ∼2.7%) through a water-in-oil emulsion containing calcium ions to induce in-flow ionic crosslinking. The DLD array effectively separates gelled particles from satellite droplets (<37 µm) and transfers them across the oil-water interface into an aqueous stream, eliminating the need for off-chip centrifugation. We demonstrate the platform's applicability to cell encapsulation using MCF-7 cells, achieving a post-processing viability of ∼80%. This work highlights the potential of integrating DLD-based trajectory control with in-flow chemical reactions to enable scalable, high-purity microparticle fabrication for biomedical applications.