Continuous production and extraction of monodisperse alginate microgels via 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 in vitro 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.