Application of GLA-on-chip in drug experiments and disease models. (a) A microfluidic approach for in vitro assessment of inter-organ interactions in drug metabolism using GLA-on-chip. Top: Schematic illustration and photograph of the PDMS biochip. Bottom: Morphological evaluation of liver and intestinal slices directly after slicing, after 3 h of incubation in well plates, and in the biochip. (Magnification: 100×) [88] ©Copyright 2010, Royal Soc Chemistry. (b) Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines. Top: Principle, design of GLA-on-chip. Bottom: Microscopic analysis of HepG2 C3A integrity in the microchips [89] ©Copyright 2014, Elsevier. (c) A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin, and kidney equivalents. Top: The microfluidic four-organ-chip device at a glance. Bottom: Performance of human tissues in the 4 °C after 28 days of co-culture [58] ©Copyright 2015, Royal Soc Chemistry. (d) Body-on-a-chip simulation with gastrointestinal (GI) tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Top: Schematic of the silicon chip and GI tract module of the body-on-a-chip system. Middle: Representative confocal images taken of nanoparticle accumulations at different focal planes of Caco-2/HT29-MTX co-cultures. Bottom: Mean concentrations of aspartate aminotransferase (AST) and the percent area of on-chip liver chambers that was covered with viable HepG2/C3A cells after 24 h of exposure to 50 nm carboxylate polystyrene nanoparticles at varying concentrations [97] ©Copyright 2014, Royal Soc Chemistry. (e) GLA-on-chip for multiple drugs absorption and metabolism behavior simulations. Top: Schematic illustration of the double-layer microchip. Bottom: Influence of genistein and dacarbazine combination influence on HepG2 cell viability and apoptosis in the intestine–liver model [94] ©Copyright 2018, Science Press. (f) GLA-on-chip reveals the intestinal protective role on hepatic damage by emulating ethanol first-pass metabolism. Top: Schematic representation of the InLiver-OC and CFD study. Bottom: Protective role of 3D-HIM on Et-OH-induced liver cytotoxicity [98] ©Copyright 2020, Frontiers. * represents significance analysis, * p < 0.05.