Investigation of permeability and flow dynamics in liver on a chip: An integrated experimental and computational study

In recent years, organ-on-a-chip (OoC) systems have emerged as innovative tools for in vitro simulation of the complex human organ function. Fluid dynamics, encompassing shear stress, velocity, and pressure, have a significant impact on cell behavior, particularly within liver sinusoids, affecting essential processes such as albumin synthesis and hepatocyte polarization. Therefore, it is very important to accurately mimic these physiological conditions in liver-on-a-chip (LoC) platforms to precisely replicate the liver functions. For this purpose, we investigated in this work the effect of two key design factors of our sinusoidal LoC model on fluid flow and the resultant mass transport of biospecies. These factors are the channel width and the semipermeable membrane properties (polyethylene terephthalate (PET) vs. polycarbonate (PC). This study was conducted using a dual-channel microfluidic chip infused with a food dye, acetaminophen (APAP), and cell culture medium. The membrane permeability across each configuration was determined using UV-Vis spectrophotometry, a reliable technique for determining the flow of materials across the membrane. Additionally, live/dead staining analysis and the enzyme-linked immunosorbent assay (ELISA) were employed as analytical methods to gain insights into cell viability and biological responses under different flow regimes.