Interconnected multi-well device with three-dimensional shaker–driven culture medium circulation for use as a multi-organ microphysiological system

Multi-organ microphysiological systems (multi-organ MPSs) are in vitro platforms that simulate interactions between multiple organs in the body. However, most of existing multi-organ MPSs often suffer from high complexity and low-throughput due to their reliance on pumps for medium circulation. We have developed a simple multi-organ MPS device, namely interconnected multi-well device, that utilizes a three-dimensional shaker for medium circulation, eliminating the need for pumps. The device consists of two components: a set of four connected cell-culture cups and a series of four interconnected wells. Up to six devices can fit in a standard 24-well plate. The device supports various culture methodologies, including conventional two-dimensional culture and spheroid culture, and can accommodate cell culture inserts. Here, we demonstrate medium and immune cell circulation through the entirety of the device. Then, as a representative use-case scenario, we demonstrate using the device to evaluate the anticancer effects of the prodrug capecitabine, whose metabolite exhibit anticancer effect, in a two-organ system composed of liver and cancer. In short, our interconnected multi-well device is user-friendly, adaptable to various culture methods, and multi-throughput, and it shows promise for becoming a valuable tool for in vitro organ interaction research.