Manipulation of cells and cell spheroids using collagen hydrogel microbeads prepared by microfluidic devices

We present a manipulation technique of cells and cell spheroids by utilizing cell-size collagen hydrogel microbeads. Collagen hydrogel beads were prepared by using non-equilibrium microfluidic W/O droplets containing hydrogel molecules, formed in a continuous phase of a water-soluble organic solvent. Monodisperse collagen hydrogel beads with sizes smaller than 20 μm were produced, and their morphologies were controlled by changing the flow rates and the types of collagen molecules, and by adding cross-linking reagents. As applications to cell and cell spheroid manipulation, hydrogel beads containing magnetic nanoparticles were produced and then utilized to form cell-bead complexes and heterogeneous cell spheroids. The presented micrometer-size collagen hydrogel beads would be highly useful as new types of cell handling tools, cell cultivation matrices, and building blocks for tissue engineering.