The most common ‘Liver-on-a-chip’ models for drug testing are for testing acute drug toxicity 3– 5. Liver chip models utilize minimal cells and reagents, allowing more tests to be performed using human cells of limited quantity. These models permit the study of drug interactions in vitro and could be alternatives to animal experimentation 1, 2. ‘Liver-on-a-chip’ models have attracted much attention since they recapitulate some in vivo tissue structures and functions, biochemical cues and mechanical microenvironment. The chronic drug response to repeated dosing of Diclofenac and Acetaminophen evaluated in PIC were more sensitive than the static culture control.

It operates in a biosafety cabinet, thus minimizing risk of contamination. The chip act as an incubator, having 5% CO 2 pressure-driven culture-media flow, on-chip heater and active debubbler. Hepatocyte functions were significantly improved and maintained at constant values (urea, albumin synthesis, and CYP450 enzyme activities) for 14 days.

Rat hepatocyte spheroids constrained between a cover glass and a porous-ultrathin Parylene C membrane experienced optimal mass transfer and limited shear stress from the flowing culture media maintained cell viability over 24 days. We have designed a perfusion-incubator-liver-chip (PIC) for 3D cell culture, that assures a tangential flow of the media over the spheroids culture.

To develop liver chips that can assess repeated dosing chronic hepatotoxicity, we need to ensure that hepatocyte functions be maintained at constant values over two weeks in stable culture conditions of sterility, temperature, pH, fluidic-flow of culture media and drugs. Liver chips have been developed to recapitulate in vivo physiological conditions to enhance hepatocyte functions for assessing acute responses to drugs.

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