Hybrid Microfluidic Chip Design with Two‐Photon Polymerized Protein‐Based Hydrogel Microstructures for Single Cell Experiments

Abstract Although hydrogels are among the most promising materials for a huge variety of biomimicking and tissue engineering applications, conventional materials such as polydimethylsiloxane (PDMS) still outweigh hydrogels in terms of processability for the production of microfluidic devices. Hence, incorporating hydrogel components inside conventional PDMS‐based microfluidic chips is a promising approach to take advantage of the many possibilities to utilize hydrogels, while maintaining standard properties of microfluidic devices in terms of mechanical stability. Microfluidic chips produced by standard soft lithography are combined with high‐resolution protein‐based hydrogel elements fabricated by two‐photon polymerization (2PP). Those hybrid chips are used to distinguish mechanical properties of different cell phenotypes by injecting pancreatic cancer cells inside the device and investigate mechanical interactions with the hydrogel microstructures. The Young's modulus of blocks printed at different experimental conditions is determined by atomic force microscopy measurements. To showcase the high 3D resolution of the presented fabrication method, fully 3D fibrous meshes are printed with different configurations inside microchannels. By measuring the velocity and circularity of pancreatic cancer cells that pass through meshes of varying densities, the impact on the cell flow is determined. Furthermore, the hydrogel precursor solution is successfully removed and the meshes are immersed in phosphate buffered saline.