Optimizing the Production of Hydrogel Microspheres Using Microfluidic Chips: The Influence of Surface Treatment on Droplet Formation Mechanism

Microfluidic chips have been widely applied in biology and medical research for stably generating uniform droplets that can be solidified into hydrogel microspheres. However, issues such as low microsphere yield, lengthy experimental processes, and susceptibility to environmental interference need to be addressed. In this work, a simple and effective method was developed to modify microfluidic chips at room temperature to improve the production performance of hydrogel microspheres. Numerical simulation-assisted experiments were conducted to comprehensively understand the effect of solution viscosity, hydrophilicity, and flow rate ratio on droplet formation during microsphere production. Chitosan was selected as the main component and combined with poly(ethylene glycol) diacrylate to prepare photocurable hydrogel microspheres as a demonstration. As a result, grafting fluoro-silane (FOTS) increased the contact angle of the channel from 90 to approximately 110°, which led to a 12.2% increase in droplet yield. Additionally, FOTS-modification attenuated the impact of the flow rate ratio on droplet yield by 19.1%. Alternatively, depositing dopamine decreased the channel's contact angle from 90 to 60°, resulting in a 21.4% increase in particle size and enabling the chip to adjust droplet size over a wider range. Further study demonstrates that the obtained hydrogel microspheres can be modified with layers of aldehyde, which can potentially be used for controlled drug release. Overall, this study proposed a facile method for adjusting the yield and droplet size through surface treatment of microfluidic chips while also enhancing the understanding of the synergistic effects of multiple factors in microfluidics-based microsphere production.