Abstract
The objective of this research was to design a micro-bioreactor to sustain the CYP450 activity in the primary rat liver cells and to understand the related impact by the concentration of the applied medications. The study was divided into two parts. The first part involved a micro-tissue reactor (MTR) which primarily simulated the specific flow field structure of the liver lobule to provide a similar microenvironment to the liver cells outside the body. The purpose was to sustain and observe the effect of drug concentrations on the CYP450 activity in the primary rat liver cells under an in vitro environment that is comparable to the true physiological conditions. In the second part, the design of the acinus chip was to compensate for the inadequacies of the MTR such as cell adherence. The process of cell adherence usually ends with rapid degradation of the CYP450 activity. This new design would give the researchers the option of immediate perfusion after cell seeding without waiting for cell adherence. Also, the acinus chip could provide direct contact with the cell membrane which allows researchers to observe cell-to-cell interactions. In addition to providing the feature of dynamic control for observing the acinus-like gradient change, the acinus chip could also control and balance the shear stress and mass-transfer of the microenvironment. The end result is an in vitro microenvironment that closely resembled the true physiological state. The design allowed liver cells to maintain cytotoxic detoxification function even outside the body, and thus, made drug toxicity studies more convenient.