Interfacial Engineering-Free Microfluidics: Toward a Mild and Cost-Effective Strategy for Surfactant- and Demulsifier-Free Hydrogel Microsphere Fabrication

This study proposes a simple yet versatile microfluidic strategy for fabricating monodisperse alginate hydrogel microspheres using a symmetric flow-focusing device. The system integrates three key innovations: (1) Cost-effective mold fabrication: A paper-based positive master replaces conventional SU-8 photoresist, significantly simplifying device prototyping. (2) Surfactant-free droplet generation: Alginate hydrogel droplets are formed at the first flow-focusing junction without requiring interfacial stabilizers. (3) In situ solidification with coalescence suppression: Acetic acid-infused corn oil is introduced at the adjacent junction, simultaneously triggering ionic crosslinking of alginate via pH reduction while preventing droplet aggregation. Notably, the hydrogel microspheres can be efficiently harvested through oscillatory aqueous phase separation, removing post-fabrication washing steps (typically 6-8 cycles for surfactant and oil removal). This integrated approach demonstrates exceptional advantages in fabrication simplicity, process scalability, and operational robustness for high-throughput hydrogel microsphere production.