Exploring microfluidics-based organoid interactions through analysis of albumin secretion.

Abstract

Organoids-on-a-chip exhibit significant potential for advancing disease modeling, drug screening, and precision medicine, largely due to their capacity to facilitate interactions among organoids. However, the influence of chip design on these interactions remains poorly understood, primarily due to our limited knowledge of the mediators of communication and the complexity of interaction dynamics. This study demonstrates that analyzing albumin secretion from liver organoids within an organoids-on-a-chip system can provide a measure of the interaction intensity among organoids, offering valuable insights into how chip design influences these interactions. Our findings reveal that the interaction dynamics of target organoids is primarily affected by the types of neighboring organoids positioned upstream. For instance, adipose organoids located upstream and adjacent to liver organoids considerably stimulate functional improvements in the liver organoids, whereas adipose organoids in other arrangements do not produce similar effects. Importantly, both theoretical and experimental evidence indicate that the interaction dynamics is independent of the physical distance between organoids. Instead, it can be adjusted by flow rate, well depth, introducing a vascular barrier, or the media volume within the system. However, it is crucial to note that the influence of these factors is not linear. Finally, the exosome was identified as one of key mediators of communication within the organoids-on-a-chip system.