Generating long material gradients by convection and alternating flow in a microchannel

Natural materials exhibit anisotropy with variations in soluble factors, cell distribution, and matrix properties. The ability to recreate the heterogeneity of the natural materials is a major challenge for investigating cell-material interactions and for developing biomimetic materials. Here we present a generic fluidic approach using convection and alternating flow to rapidly generate multi-centimeter gradients of biomolecules, polymers, beads and cells and cross-gradients of two species in a microchannel. A poly(ethylene-glycol) hydrogel gradient and a porous collagen gradient were generated with continuous variations in material properties. A composite material with a gelatin/hyaluronic acid cross-gradient was generated that exhibited a continuous gradient in cell attachment. This simple yet generic fluidic platform should prove useful for creating anisotropic biomimetic materials and high-throughput platforms for investigating cell-microenvironment interaction.