Real-time sensing technologies are an important component of the MAINSTREAM programme, supporting the development of advanced approaches for monitoring stem cell culture and manufacturing processes. A major challenge in mesenchymal stem cell (MSC) manufacturing is maintaining healthy, high-quality cell populations during large-scale expansion while avoiding unwanted differentiation and cellular senescence. Conventional tissue culture systems often provide limited information about the changing biological environment during cell growth, making it difficult to identify early signs of stress or loss of stem cell phenotype.

Within MAINSTREAM, sensor development focuses on creating non-invasive, label-free, and real-time monitoring tools capable of continuously tracking changes within the cell culture environment throughout the manufacturing process. Unlike traditional analytical approaches, which are often offline, destructive, and limited to endpoint measurements, real-time sensing technologies can provide continuous information without disrupting the culture system. This may help researchers better understand dynamic changes within the culture environment and improve control over long-term MSC expansion and scale-up.

Research within the programme includes the development of miniaturised electrochemical sensing platforms based on microelectrode and interdigitated electrode technologies. These systems are designed to detect subtle biological and environmental changes associated with cell activity, proliferation, metabolism, viability, and differentiation during long-term culture. By measuring electrical and impedance responses within the culture environment, the sensors can provide continuous insight into cell behaviour and overall culture health.

The sensing platforms are being developed for integration directly into cell culture systems, enabling continuous monitoring throughout expansion and scale-up processes. A key aim of this work is to use real-time monitoring technologies to better understand and control factors linked to MSC health and senescence. Changes in cellular metabolism, respiration, and microenvironmental conditions can occur before visible loss of cell quality, and electrochemical sensing may help identify these early indicators during expansion.

By correlating sensor readouts with biological and mechanobiological measurements, these technologies may support improved optimisation of culture conditions, enhanced reproducibility and more reliable quality control strategies for stem cell manufacturing. Although electrode and sensor development represent one component of the broader MAINSTREAM programme, they contribute to the wider goal of enabling scalable, reliable, and translational stem cell technologies for regenerative medicine, immunotherapy and disease modelling.