Integration of secreted signaling molecule sensing on cell monitoring platforms: a critical review

Monitoring cell secretion in complex microenvironments is crucial for understanding cellular behavior and advancing physiological and pathological research. While traditional cell culture methods, including organoids and spheroids, provide valuable models, real-time monitoring of cell secretion of signaling molecules remains challenging. Integrating advanced monitoring technologies into these systems often disrupts the delicate balance of the microenvironment, making it difficult to achieve sensitivity and specificity. This review explored recent strategies for integrating the monitoring of cell secretion of signaling molecules, crucial for understanding and replicating cell microenvironments, within cell culture platforms, addressing challenges such as non-adherent cell models and the focus on single-cell methodologies. We highlight advancements in biosensors, microfluidics, and three-dimensional culture methods, and discuss their potential to enhance real-time, multiplexed cell monitoring. By examining the advantages, limitations, and future prospects of these technologies, we aim to contribute to the development of integrated systems that facilitate comprehensive cell monitoring, ultimately advancing biological research and pharmaceutical development.