Body-on-a-chip (BOC), a microfluidic cell culture device that mimics in vivo organ network systems on a chip, has been increasingly attracting attention as a new drug development tool, which has already demonstrated its potential for an alternative to animal experiments. Unlike conventional in vitro drug testing that simply expose drugs to cells on petri dishes, one major advantage of BOC is that it can be used to simulate pharmacokinetics such as absorption and metabolism of chemical substances on a more concise and extensive level. However, regarding to researches of previous BOC, one drawback is that the design of BOC is typically very complicated and difficult to handle in practice without special skills. In this study, we developed a simple-to-use BOC by combining a unique spheroid microarray and a seesaw-like stage.

　Our BOC device was fabricated using a silicone rubber with microwell structures on both ends of a microchannel. In the chip device, different cell types such as liver (HepG2), heart (HMC) and breast cancer tissue (MCF-7) form spheroid organ models. In addition, this chip device was designed to hold the cell culture insert on the microchannel so that a cell layer model such as skin and small intestine for drug absorption or exposure can be integrated. A two-organ system, composed of HepG2 and MCF-7, was used to demonstrate that anti-cancer prodrug cyclophosphamide (CPA) was metabolized by HepG2 to phosphamides mustard and inhibited the proliferation of MCF-7 cells on the seesaw-like bioreactor. The system was designed to evaluate a number of samples simultaneously and can be utilized in a large scale as an in vitro platform for comprehensive systemic toxicity evaluations.