Liver-On-A-Chip Model: an Alternative to Animal Models-Development Challenges and Future Perspectives

Abstract

Purpose: To create a fast, affordable, reproducible a liver-on-a chip platform as an alternative to animal models of liver diseases. Methods: The platform was fabricated out of fused silica by using femtosecond laser microprocessing. A channel with integrated filters of micropillars was produced by Selective Laser Etching (SLE) technique. Nano gratings were inscribed inside the glass by using focused femtosecond laser radiation. Subsequently, liver cells were etched in 35% Potassium Hydroxide (KOH) at 90 ° C or Hydrofluoric acid. The contact between both plates was achieved by intense light radiation with an integrated filter. There were 700 fs duration pulses used for SLE and 200 fs for laser welding. The light was focused with a 20 x 0.45 NA objective for SLE and a 0.5 NA aspherical lens for laser welding. The human liver HCC cell line HepG2(GS) was employed for biocompatibility testing. Results: The platform consists of one channel divided into three sub channels by micropillars: the central channel for cells and two side channels for cell medium. All channels have inlet and outlet reservoirs with the depth up to 200 μm, and width of central and side channels up to 200 and 400 μm, respectively. Additionally, the final size of micropillars was 55 x 36 μm with a gap of 14 μm in between. Conclusion: Based on our previously published work, this study provides a step-by-step design and validates the concept of testing human liver cancer cells. In addition, it provides developmental advancements and drawbacks of liver-on-a-chip designs.