Precise Control of Sodium Alginate Microdroplets through pH-Sensitive Cross-Linkers and Geometric Factors

This study presents a novel approach to achieve internal and on-chip gelation of sodium alginate microdroplets using pH-sensitive water-insoluble cross-linkers. Gelation is initiated by precisely controlling the introduction of acetic acid, which decreases the pH, through the generation of microdroplets via step emulsification. Unlike current approaches in microfluidic droplet generation, where droplet size depends on various external factors such as flow rate ratio and fluid properties, our strategy utilizes the device’s geometry to regulate droplet size. Importantly, this approach ensures that there is no aggregation in the channels following microgel creation. The empirical investigation focuses on exploring the impact of geometrical factors on alginate droplet formation in our customized microfluidic device. To expedite the production of polydimethylsiloxane (PDMS) microfluidic devices, we utilized 3D-printed molds, which provide effective control over channel height. Using our method, we successfully generate microdroplets with a coefficient of variation (CV) below 3% and diameters ranging from 100 to 200 µm. It is worth noting that these microdroplets experience an average shrinkage of 16% following gelation, indicating the successful formation of stable gels. By combining pH-sensitive cross-linkers, precise control over acetic acid introduction, and the geometric regulation of droplet size, our approach demonstrates great potential for the development of microfluidic devices capable of producing uniform and stable microdroplets for various applications, including drug delivery, tissue engineering, and biotechnology.