Compartmentalized perfusion for temporal control of the chemical microenvironment of iPSC-derived cardiac cells

Abstract

Organ-on-chip structures are predicted to have a significant influence in drug research. In these structures, perfusion can provide cells a more controllable environment to receive signaling molecules. In many current organ-on-chip applications, perfusion is used for shear stress stimulus for the cells, but it can also provide a more precise way of controlling the chemical microenvironment around the cells. In this paper, we propose an open-top organ-on-chip structure with compartment-specific perfusion to introduce stimulating molecules to cells with only minimal extra unspecific stimulus. Using numerical simulations, we show that shear stress sensed by the cells within the structure is low. We further validated the flow profile experimentally. We showed that the hiPSC-CMs accommodate to the flow environment where the shear stress is kept below 0.035 mPa. We also show that the beating rate of hiPSC-CMs increases due to the stimulation provided by chemical stimulant molecules introduced through the flow.