An AC electrothermal self-circulating system with a minimalist process to construct a biomimetic liver lobule model for drug testing

摘要

Liver-on-chip, due to its precision and low cost for constructing in vitro models, has tremendous potential for drug toxicity testing and pathological studies. By applying APAP (acetaminophen) treatment of different concentrations, a dynamic self-circulating liver lobule model for drug testing was proven useful for emulating the human physiological system. However, the demand for a dynamic system of on-chip organs is difficult to fulfil due to the relatively cumbersome fabrication processes. In this paper, the design and fabrication of an AC electrothermal self-circulating system combined with a 3D biomimetic liver lobule is described. The system was fabricated using a low-cost ITO laser etching process within a few seconds. A large number of interdigital electrodes were arranged in a limited space to increase the fluid flow-driven efficiency. The liver lobule consists of two parts, a hepatocyte cell-laden layer and an endothelial layer, which exhibit a sandwich radial shaped pattern that is more bionic in structure and function. By evaluating the velocity and temperature in the self-circulating system at various voltages and frequencies, we obtained a set of reliable input parameters to provide an adequate supply of culture fluid without cell damage. The metabolism of the liver lobule in dynamic culture and static culture was compared based on cell viability, albumin secretion and urea synthesis.