The flow limiting operator: a new approach to environmental control in flow bioreactors

Bioreactors have become a critical step for the testing of new biomaterials and pharmaceuticals. They need to be controllable, ideally high-throughput, and produce a biologically relevant environment. For example, in the brain, it is essential to recreate multiple flow–pressure profiles daily and mimic brain fluid movement for a bioreactor to be more physiologic. In this study, we demonstrate a scalable system that regulates flow rate, pressure, and pulsation amplitude. We also show that with new microcontroller technology, up to 15 chambers running in parallel is theoretically possible. Our system, the Flow Limiting Operator (FLO), achieves these goals by multiplexing a series of valves and pumps to control pressure and volumetric flow rate instead of relying on head gas pressure. With the ability to control multiple parameters and its ease of use, both scientists and clinicians can use FLO to study the effects of pulsation amplitude of the fluid flow, flow rate, and pressure on intercellular interactions for both biomaterials and pharmaceuticals.