Recent advances in sensor-integrated brain-on-a-chip devices for real-time brain monitoring.

Brain science has remained in the global spotlight as an important field of scientific and technological discovery. Numerous in vitro and in vivo animal studies have been performed to understand the pathological processes involved in brain diseases and develop strategies for their diagnosis and treatment. However, owing to species differences between animals and humans, several drugs have shown high rates of treatment failure in clinical settings, hindering the development of diagnostic and treatment modalities for brain diseases. In this scenario, microfluidic brain-on-a-chip (BOC) devices, which allow the direct use of human tissues for experiments, have emerged as novel tools for effectively avoiding species differences and performing screening for new drugs. Although microfluidic BOC technology has achieved significant progress in recent years, monitoring slight changes in neurochemicals, neurotransmitters, and environmental states in the brain has remained challenging owing to the brain's complex environment. Hence, the integration of BOC with new sensors that have high sensitivity and high selectivity is urgently required for the real-time dynamic monitoring of BOC parameters. As sensor-based technologies for BOC have not been summarized, here, we review the principle, fabrication process, and application-based classification of sensor-integrated BOC, and then summarize the opportunities and challenges for their development. Generally, sensor-integrated BOC enables real-time monitoring and dynamic analysis, accurately measuring minute changes in the brain and thus enabling the realization of in vivo brain analysis and drug development.