Fig. 2

Structural differences between organoids and tumor-on-a-chip—nanocarriers are represented as spheres within the models. Organoids are 3D cell culture systems derived from one or more patient-derived cells or stem cells, including, for example, goblet, paneth, enterocytes, neural, basal, luminal, and tumor cells (illustrated in various shapes and colors in the figure). Organoids replicate specific structural and functional features of tumors, including cellular heterogeneity, spatial organization, and self-organization capacity, within a supportive extracellular matrix. However, organoids lack the dynamic fluid flow, mechanical forces, and controlled environmental conditions provided by tumor-on-a-chip systems. In contrast, the tumor-on-a-chip is a microfluidic platform that integrates mechanical, biochemical, and fluidic cues to more accurately mimic the tumor microenvironment. This system features interconnected channels and compartments that enable the co-culture of multiple cell types, real-time monitoring of cellular responses, and precise manipulation of factors such as nutrient gradients and oxygen levels. The schematic design of the chip in the figure is representative and serves as an example of a 3-channel ToC organized to allow communication between the channels; in practice, these systems can be fabricated in various designs with many different cells, such as endothelial cells, fibroblasts, mesenchymal stem cells, immune cells and tumor cells, to meet specific experimental needs