The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted
in improved models of human organs compared to static culture insert-based ones. These
chip devices provide controlled cell culture environments to mimic physiological functions
and properties. Models of the blood-brain barrier (BBB) especially profited from this
advanced technological approach. The BBB represents the tightest endothelial barrier
within the vasculature with high electric resistance and low passive permeability,
providing a controlled interface between the circulation and the brain. The multi-cell
type dynamic BBB-on-chip models are in demand in several fields as alternatives to
expensive animal studies or static culture inserts methods. Their combination with
integrated biosensors provides real-time and noninvasive monitoring of the integrity
of the BBB and of the presence and concentration of agents contributing to the physiological
and metabolic functions and pathologies. In this review, we describe built-in sensors
to characterize BBB models via quasi-direct current and electrical impedance measurements,
as well as the different types of biosensors for the detection of metabolites, drugs,
or toxic agents. We also give an outlook on the future of the field, with potential
combinations of existing methods and possible improvements of current techniques.
