A Simple Vortex-Based Method for the Generation of High-Throughput Spherical Micro- and Nanohydrogels

Abstract

Hydrogel particles, renowned for their high water content and biocompatibility in drug delivery and tissue engineering, typically rely on complex, costly microfluidic systems to reach sub 5 µm dimensions. We present a vortex-based inverse-emulsion polymerization strategy in which UV crosslinking of polyethylene glycol diacrylate (PEGDA) dispersed in n-hexadecane and squalene yields tunable micro- and nanogels while delineating the parameters that govern particle size and uniformity. Systematic variation in surfactant concentration, vessel volume, continuous phase viscosity, vortex speed and duration, oil-to-polymer ratio, polymer molecular weight, and pulsed vortexing revealed that increases in surfactant level, vortex intensity/duration, vessel volume, and oil-to-polymer ratio each reduced mean diameter and PDI, whereas higher polymer molecular weight and continuous phase viscosity broadened the size distribution. We further investigated how these same parameters can be tuned to shift particle populations between nano- and microscale regimes. Under optimized conditions, microhydrogels achieved a coefficient of variation of 0.26 and a PDI of 0.07, with excellent reproducibility, and nanogels measured 161 nm (PDI = 0.05). This rapid, cost-effective method enables precise and scalable control over hydrogel dimensions using only standard laboratory equipment, without specialized training.