Multi-sensor continuous-flow bioreactor for dynamic and scalable cell culture

Abstract

Bioreactors are essential tools in tissue engineering and advanced cell culture because they provide dynamic environments that support cellular growth, organization and tissue maturation. However, most existing systems lack integrated real-time monitoring and feedback control, limiting their reproducibility, scalability and translational relevance. Here, we report the development of a modular, continuous-flow rotational (CFR) bioreactor system equipped with multi-sensor feedback to enable real-time monitoring and control of pH, temperature, dissolved oxygen, CO2 and rotation speed. A key design feature is a swivel connector architecture that enables uninterrupted media and gas exchange during chamber rotation while maintaining sterility and preventing tubing entanglement. Constructed from off-the-shelf components with custom firmware and a Python-based interface, the system maintains stable and physiologically relevant culture conditions. Its modular design supports both macro- and microscale formats and enables multiplexed experiments. The system's versatility was demonstrated by culturing U-87 MG glioblastoma cells on chitosan scaffolds and Jurkat T cells in suspension, resulting in improved cell viability and distribution compared with static controls. These results demonstrate that the CFR platform provides a scalable, sensor-integrated culture system for applications in tissue engineering, disease modelling, drug screening and regenerative medicine.