In situ sensors for blood-brain barrier (BBB) on a chip

The blood-brain barrier (BBB) is critical for the central nervous system, as its integrity protects neurons and other brain cells from harmful toxicants and disease-associated molecules, while it also blocks the delivery of therapeutic drugs to brain. Understanding the function and physiology of BBB have made slow progress due to the relative lack of effective models. Microfluidic BBB-on-a-chip models have gained attentions recently through recreating a more accessible, in vivo-like microenvironments. Although many fabrication and application methods have been demonstrated and improved for BBB-on-a-chip, the detection methods used in those systems seem to heavily reply on conventional analytical instruments, which are bulky, expensive, time-consuming, and not suitable for large-scale industrial operations. The TEER (transendothelial electrical resistance) measurement has become popular for identifying the integrity of BBB due to its compatibility, noninvasiveness, and rapid readings. While the TEER sensor has been a major success in BBB-on-a-chip, this may be the only major in situ sensor that have been successfully incorporated in BBB-on-a-chip models. In this review paper, we (1) compared the current BBB experimental models, (2) briefly summarized their fabrication considerations, (3) discussed the detection techniques used in such models, and (4) provided suggestions to incorporate various in situ biosensors/sensors into these models. The coming years will likely see the continued development of BBB-on-a-chip models, powerful detection techniques applied on these models will assist in improving our understanding of BBB function, providing new insights on neurological disease, as well as developing and screening novel therapeutic drugs.