Hyper Alginate Gel Microbead Formation by Molecular Diffusion at the Hydrogel/Droplet Interface

Abstract

We report a simple method for forming monodispersed, uniformly shaped gel microbeads with precisely controlled sizes. The basis of our method is the placement of monodispersed sodium alginate droplets, formed by a microfluidic device, on an agarose slab gel containing a high-osmotic-pressure gelation agent (CaCl(2) aq.): (1) the droplets are cross-linked (gelated) due to the diffusion of the gelation agent from the agarose slab gel to the sodium alginate droplets and (2) the droplets simultaneously shrink to a fraction of their original size (<100 μm in diameter) due to the diffusion of water molecules from the sodium alginate droplets to the agarose slab gel. We verified the mass transfer mechanism between the droplet and the agarose slab gel. This method circumvents the limitations of gel microbead formation, such as the need to prepare microchannels of various sizes, microchannel clogging, and the deformation of the produced gel microbeads.

pH‐Switchable Macroscopic Assembly through Host–Guest Inclusion

“…Sodium alginate is a natural polysaccharide having carboxylic groups and has been widely used in biomedical applications due to its biocompatibility and biodegrability 29–31. In this study, Alg was selected as matrix.…”

Engineered microscale hydrogels for drug delivery, cell therapy, and sequencing

“…Successful microfluidic-directed gelation of PEG-based macromers specifically, PEG-maleimide (Headen et al 2014, 2018a, 2018b; Foster et al 2017), PEG-vinylsulfone (Allazetta et al 2013; Lienemann et al 2017), PEG-acrylates (Choi et al 2016), alginate (Tan and Takeuchi 2007; Hirama et al 2012; Kim et al 2014; Chen et al 2016a; Mao et al 2017; Zhang et al 2018), and methacrylated gelatin (Rossow et al 2012; Lee and Cha 2018) have been established to date. These biomaterial systems vary in crosslinking chemistry, pH requirements, and number of precursor solutions required before gelation, all of which drive design requirements of the microfluidic device for the microgel on-chip gelation process.…”

Microfluidic preparation, shrinkage, and surface modification of monodispersed alginate microbeads for 3D cell culture

“…21 So far, a few efforts have been devoted to making small alginate MB from microuidic devices. [21][22][23][24] In one study, ALG droplets were generated in a regular microuidic device and collected on an agarose slab, where ALG droplets shrank and were crosslinked by Ca 2+ to achieve designed sizes. 22 However, the addition of the agarose slab raises the complexity of fabrication process.…”