Microfluidic synthesis of highly spherical calcium alginate hydrogels based on external gelation using an emulsion reactant

Alginate-based hydrogels are widely used in the biomedical and chemical fields, and their size and shape are significant to their applications like drug delivery and cell encapsulation. Here, we report a microfluidic external gelation process using an on-chip calcium chloride (CaCl₂) emulsion reactant for producing highly spherical calcium alginate (Ca-alginate) hydrogel particles. The microfluidic channels were two serial cross-junctions fabricated on quartz glass. Monodisperse sodium alginate (Na-alginate) droplets with diameters greater or smaller than the opening (ranging from 176 μm to 225 μm) with a coefficient of variation (CV) less than 3% were successfully generated at the upstream cross-junction; they then reacted with the CaCl₂ emulsion at the downstream cross-junction, forming Ca-alginate hydrogels. The effects of the fraction of the aqueous phase in the reactant CaCl₂ emulsion and the flow rates of continuous and emulsion phases on the roundness of the obtained hydrogels were studied. By optimizing the parameters above, monodisperse spherical hydrogel particles were obtained with diameters ranging from 147 μm to 176 μm with CVs around 5%. The synthesis of magneto-responsive hydrogels with asymmetric Fe₃O₄ coatings was also demonstrated.