Abstract
In recent years, liver-related diseases such as chronic liver disease, cirrhosis and liver cancer, are leading cause of disease related deaths Related drug development and testing have always been the goal of medical research. Drug development is expensive due to the several steps involved before the pre-clinical and clinical trials making it expensive and yet the success rate is very low. With the development of biological micro-electromechanical technology, we were able to construct a liver-lobule-mimetic tissue for effective drug testing. Although there are differences in the in vitro testing of drug and it’s in vivo practical application, the in vitro platform provides preliminary and easy observation which can be useful for researchers towards the development of in vitro liver reconstruction model. This research presents an integrated drug testing lab chip where in the liver-lobule-mimetic electrode pattern is used to generate in vitro liver cell pattern. Based on polarity difference of cells, positive and negative DEP force is utilized to manipulate and pattern heterogeneous cells for mimicking the inherent hepatic morphology, increasing the cell-cell interaction. The concentration gradient generator design and acoustic micromixer generates five different concentrations of acetaldehyde, which is used to induce in vitro liver inflammation and observe neutrophil migration in Alcoholic Liver Inflammation In the design of chip test platform, there are upper channel and bottom channel. Moreover, the intermediate bonding layer of a porous PDMS thin film has a hole which has a diameter of 5μm. When neutrophil injected into upper channel, it would attach to the PDMS thin film. Then bottom channel of chip established in vitro reconstruction of the biological model of liver inflammation to generate chemotactic response. The cell were treated by using acetaldehyde in the concentration of 175μM after the cell were arranged in liver lobule-mimetic. Experimental results indicate that the secretion of IL-8 is 3-fold higher compared with the liver lobule-mimetic without cell arrangement. Furthermore, neutrophil would produce different number of migration by the influence of liver inflammation. The ultimate goal of this research is to construct an in vitro liver tissue, mimicking the in vivo liver in its functioning and prove its usefulness in drug testing