Microphysiological immune-on-chip systems: engineering human immunity for precision immunotherapy, vaccine...

Microphysiological immune-on-chip systems have emerged as transformative biomedical microdevices capable of recreating the structural, biochemical, and mechanical complexity of the human immune microenvironment under physiologically relevant conditions. By integrating microfluidics, biomaterials, tissue engineering, biosensing, and microelectromechanical systems technologies, these platforms enable dynamic investigation of immune cell behavior, intercellular communication, and host-pathogen interactions with unprecedented spatial and temporal precision. Compared with conventional two-dimensional cultures and animal models, immune-on-chip platforms provide superior physiological relevance, real-time monitoring, and enhanced predictive capability for evaluating immune responses. Recent advances have enabled the development of lymph node-, bone marrow-, thymus-, spleen-, and tumor immune microenvironment-on-chip models that support applications in immunotherapy screening, vaccine evaluation, autoimmune disease modelling, infectious disease research, and personalized medicine. Furthermore, the integration of embedded biosensors, high-content imaging, artificial intelligence-assisted analytics, and multi-organ microphysiological systems is accelerating the transition of these devices toward clinically relevant and patient-specific applications. Despite remarkable progress, challenges including standardization, immune system complexity, long-term cellular stability, manufacturing scalability, regulatory acceptance, and clinical validation continue to limit widespread adoption. This review provides a comprehensive overview of the engineering principles, fabrication strategies, and biological design of immune-on-chip systems, critically examines their current biomedical applications, discusses emerging technological innovations, and highlights the key translational challenges that must be addressed to realize next-generation precision immunology. By bridging advances in biomedical microdevices with immunological research, this review outlines future directions for developing robust, clinically translatable immune-on-chip platforms for precision diagnostics, therapeutic development, and personalized healthcare.