Microfluidic production of single micrometer-sized hydrogel beads utilizing droplet dissolution in a polar solvent

Abstract

In this study, a microfluidic process is proposed for preparing monodisperse micrometer-sized hydrogel beads. This process utilizes non-equilibrium aqueous droplets formed in a polar organic solvent. The water-in-oil droplets of the hydrogel precursor rapidly shrunk owing to the dissolution of water molecules into the continuous phase. The shrunken and condensed droplets were then gelled, resulting in the formation of hydrogel microbeads with sizes significantly smaller than the initial droplet size. This study employed methyl acetate as the polar organic solvent, which can dissolve water at 8%. Two types of monodisperse hydrogel beads-Caalginate and chitosan-with sizes of 6-10 lm (coefficient of variation < 6%) were successfully produced. In addition, we obtained hydrogel beads with non-spherical morphologies by controlling the degree of droplet shrinkage at the time of gelation and by adjusting the concentration of the gelation agent. Furthermore, the encapsulation and concentration of DNA molecules within the hydrogel beads were demonstrated. The process presented in this study has great potential to produce small and highly concentrated hydrogel beads that are difficult to obtain by using conventional microfluidic processes. V C 2013 AIP Publishing LLC.

Cell-sized condensed collagen microparticles for preparing microengineered composite spheroids of primary hepatocytes

“…We recently developed a process to produce monodisperse, single micrometer-sized particles made of natural/synthetic polymers by using droplets in a nonequilibrium state formed in microfluidic devices 35,36 . This process begins by forming droplets of an aqueous solution of precursor molecules in a continuous phase of water-soluble polar organic solvent, such as methyl acetate.…”

Multiphase Microfluidic Processes to Produce Alginate-Based Microparticles and Fibers

“…As an efficient strategy to produce general microparticles with small sizes, a solvent extraction method was developed and utilized to produce various types of particles (Freitas , 2005). Several studies have been reported on the microfluidic production of alginate particles by employing this concept (Rondeau and Cooper-White, 2008;Sugaya et al, 2013), wherein a polar organic solvent (e.g., dimethyl carbonate and methyl acetate) that is miscible with water was used as the continuous phase. Sugaya et al (2013) prepared single micrometer-sized alginate microparticles via the rapid dissolution of microdroplets in a non-equilibrium state (Figure 6).…”

“…Several studies have been reported on the microfluidic production of alginate particles by employing this concept (Rondeau and Cooper-White, 2008;Sugaya et al, 2013), wherein a polar organic solvent (e.g., dimethyl carbonate and methyl acetate) that is miscible with water was used as the continuous phase. Sugaya et al (2013) prepared single micrometer-sized alginate microparticles via the rapid dissolution of microdroplets in a non-equilibrium state (Figure 6). Droplets of a diluted solution of Na-alg were generated in the continuous phase of methyl acetate.…”

Formation of Monodisperse Hierarchical Lipid Particles Utilizing Microfluidic Droplets in a Nonequilibrium State

“…We recently reported strategies for producing monodisperse microparticles by using microfluidic droplets in a non-equilibrium state (i.e., non-equilibrium droplets) 29,30 . Oil-in-water (O/W) or water-in-oil (W/O) droplets were generated by using water and a polar organic solvent (e.g., ethyl acetate) as either the continuous or dispersed phase.…”