Fig. 2: Influence of fluidics on cell status.

Influence of fluidics on cell status and its measurability: a static culture within a well is always constrained by diffusion processes that occur due to the cell model consuming nutrients and metabolizing molecules. In a flow-based culture, the concentration gradients due to diffusion are non-existent. An open system technically enables self-referencing sensors to control and monitor different parameters. This difference is qualitatively highlighted in the figure: left panel: cultures are either in a static well or in a flow-based setting; middle panel: cell metabolism leads to concentration gradients along the z-axis in wells, caused by diffusion processes; right panel: passaging abruptly resets the accumulation of metabolites/the concentration of nutrients. In a flow-based culture, the absolute concentrations of nutrients (cn) and metabolites (cm), respectively, can be measured at the inlet (cm/n_in) and outlet (cm/n out) of the cell model with respect to the bulk flow direction.