Label-free and real-time impedance sensor integrated liver chip for toxicity assessment: Mechanism and application

The toxicity assessment of environmental pollutants to people accurately will improve public safety and enhance environmental governance. Here, a microfluidic electrical biosensor was designed to monitor the toxicity of pollutants to 3D human hepatoma cell clusters (HepG2) and assess some effects of environmental pollutants. Interdigital microelectrodes were integrated into several channels at the bottom of each reactor in the chip to perform in-situ, label-free, electrical impedance measurements. The pattern of change in the cell impedance during the growth of the cell clusters was explored and found to be closely related to cell proliferation and apoptosis. We describe cell cluster impedance changes by a parameter identified as the cell cluster index (CI) and demonstrate its relevance as a measure of overall cell viability. The optimal detection frequency of the biosensor was determined to yield the highest detection sensitivity at a frequency of 10 kHz. The change in the toxicity of azo dye Reactive Black 5 (RB5) was evaluated by the biosensor after exposure to toxins generated by natural functional flora DDMZ1 as degradation by-products of this dye. The microfluidic impedance sensor provides a non-invasive, label-free, in-situ, real-time, and high-throughput method to monitor and assess the toxicity of environmental pollutants.