A multi-throughput multi-organ-on-a-chip system on a plate formatted pneumatic pressure-driven medium circulation platform

摘要

This paper reports a multi-throughput multi-organ-on-a-chip system formed on a pneumatic pressure- driven medium circulation platform with a microplate-sized format as a novel type of microphysiological system. The pneumatic pressure-driven platform enabled parallelized multi-organ experiments (i.e. simultaneous operation of multiple multi-organ culture units) and pipette-friendly liquid handling for various conventional cell culture experiments, including cell seeding, medium change, live/dead staining, cell growth analysis, gene expression analysis of collected cells, and liquid chromatography-mass spectrometry analysis of chemical compounds in the culture medium. An eight-throughput two-organ system and a four- throughput four-organ system were constructed on a common platform, with different microfluidic plates. The two-organ system, composed of liver and cancer models, was used to demonstrate the effect of an anticancer prodrug, capecitabine (CAP), whose metabolite 5-fluorouracil (5-FU) after metabolism by HepaRG hepatic cells inhibited the proliferation of HCT-116 cancer cells. The four-organ system, composed of intestine, liver, cancer, and connective tissue models, was used to demonstrate evaluation of the effects of 5-FU and two prodrugs of 5-FU (CAP and tegafur) on multiple organ models, including cancer and connective tissue.