Gravitational sedimentation-based approach for ultra-simple and flexible cell patterning coculture on microfluidic device

Combining patterning coculture technique with microfluidics enables the reconstruction of complex in-vivo system to facilitate in-vitro studies on cell-cell and cell-environment interactions. However, simple and versatile approaches for patterning coculture of cells on microfluidic platforms remain lacking. In this study, a novel gravitational sedimentation-based approach is presented to achieve ultra-simple and flexible cell patterning coculture on a microfluidic platform, where multiple cell types can be patterned simultaneously to form a well-organized cell coculture. In contrast to other approaches, the proposed approach allows the rapid patterning of multiple cell types in microfluidic channels without the use of sheath flow and a prepatterned functional surface. This feature greatly simplifies the experimental setup, operation, and chip fabrication. Moreover, cell patterning can be adjusted by simply modifying the cell-loading tubing direction, thereby enabling great flexibility for the construction of different cell patterns without complicating the chip design and flow control. A series of physical and biological experiments are conducted to validate the proposed approach. This research paves a new way for building physiologically realistic in-vitro coculture models on microfluidic platforms for various applications, such as cell-cell interaction and drug screening.