Recent advances in 3D cell culture models, including organoids, tumoroids, and spheroids, have improved the study of tissue interactions and treatment responses by mimicking in vivo environments. Electrochemical sensing provides label-free, real-time monitoring of analytes within these constructs, overcoming the limitations of destructive and optical methods. This review summarizes reports on electrochemical electrode array designs and applications for analyzing 3D cell constructs, focusing on the detection of reactive oxygen species, neurotransmitters, cancer biomarkers, and metabolites. Various electrode configurations enable spatial and volumetric analysis, and some combine electrochemical and optical techniques. Challenges remain, including limited chemical specificity, electrode fouling, signal variability from biological heterogeneity, difficulties in simultaneous multi-point measurements, and limited data analysis for interpreting complex signals. Future research should improve electrode architectures, scaffold designs, and long-term monitoring capabilities.
Organ-on-chip (OoC) platforms integrate living human cells into microfluidic devices for the purpose of replicating organ-level physiology in vitro; this approach offers advantages over conventional cell cultures and animal models in terms of physiological relevance and dynamic control. The incorporation of electrochemical sensors into these systems has emerged as a key strategy for enabling continuous, real time, non-invasive monitoring of cellular function, barrier integrity, and biomarker secretion. This review discusses recent advances in electrochemical sensing modalities applied across multiple OoC platforms, examines current limitations, including biofouling, fabrication complexity, and lack of standardization, and considers the prospects for translating these integrated systems into the spheres of drug development and personalized medicine.
Flexible electrochemical neuromorphic biosensors aim to combine biorecognition, soft mechanics, and history-dependent signal processing within the sensing interface. In these systems, biological inputs modulate electrochemical state variables such as ion distribution, redox state, interfacial charge, or channel conductance, allowing subsequent responses to be dependent on prior inputs. This review examines how various materials and complex architectures can achieve neural-like behavior in wearable biosensing, providing memory, plasticity and classification. However, analyte-driven plasticity is often demonstrated in static devices using pure buffers, whereas wearable validation is usually shown with conventional sensing. Future progress requires proof that recognized biomolecules or ions can write useful, reversible electrochemical changes in unprocessed biofluids under deformation, with clear analytical benefit beyond neuromorphic curve shape.
