Cassie-Baxter Surfaces for Reversible, Barrier-Free Integration of Microfluidics and 3D Cell Culture.

3D cell culture and microfluidics both represent powerful tools for replicating critical components of the cell microenvironment; however, challenges involved in the integration of the two and compatibility with standard tissue culture protocols still represent a steep barrier to widespread adoption. Here we demonstrate the use of engineered surface roughness in the form of microfluidic channels to integrate 3D cell-laden hydrogels and microfluidic fluid delivery. When a liquid hydrogel precursor solution is pipetted onto a surface containing open microfluidic channels, the solid/liquid/air interface becomes pinned at sharp edges such that the hydrogel forms the "fourth wall" of the channels upon solidification. We designed Cassie-Baxter microfluidic surfaces that leverage this phenomenon, making it possible to have barrier-free diffusion between the channels and the hydrogel; in addition, sealing is robust enough to prevent leakage between the two components during fluid flow, but the sealing can also be reversed to facilitate recovery of the cell/hydrogel material after culture. This method was used to culture MDA-MB-231 cells in collagen, which remained viable and proliferated while receiving media exclusively through the microfluidic channels over the course of several days.