Integration of electrochemical sensors in organ-on-a-chip microfluidic platforms: Advances and perspectives

Electrochemical sensors integrated into organ-on-a-chip (OoC) - single-organ systems and more complex multi-organ (body-on-a-chip) - microfluidic platforms constitute a rapidly advancing interface between biosensing, microfluidics, and microphysiological systems (MPS), with major implications for biomedical research, drug discovery, toxicology, and personalized medicine. By transducing biochemical and biophysical events at the tissue-device interface into quantifiable electrical signals, these sensors enable real-time, label-free, and highly sensitive monitoring of metabolites, ions, barrier integrity, and cellular activity under physiologically relevant conditions. Within OoC and MPS platforms, electrochemical sensing can be implemented through different integration strategies, including on-chip configurations such as in-line and on-line sensing directly embedded within microfluidic channels, as well as off-chip approaches. The integration of miniaturized and multiplexed electrochemical sensors into MPS enables continuous and high-throughput functional monitoring of key physiological parameters, including metabolic activity variation, biomolecules gradients, barrier function, and responses to drugs and toxic compounds. Multi-OoC configurations benefit from electrochemical readouts to interrogate dynamic inter-organ communication and systemic responses, supporting more predictive human-relevant models. This is mostly relevant for new approach methodologies (NAMs), which aim to reduce animal experimentation while improving human relevance and predictive accuracy. Overall, electrochemical sensor-integrated OoC/MPS platforms represent powerful NAMs aligned with 3Rs (replacement, reduction, and refinement) principles, enabling high-throughput screening, improved physiological relevance, and enhanced predictive modeling for drug development and regulatory applications. In this review, we address recent advances in electrochemical sensor integration within OoC and MPS platforms, discussing fabrication strategies, sensing modalities, and system-level architectures, as well as current challenges and future perspectives.