Large-Scale, High-Resolution Microelectrode Arrays for Interrogation of Neurons and Networks

High-density microelectrode arrays (HD-MEAs) are increasingly being used for the observation and manipulation of neurons and networks in vitro. Large-scale electrode arrays allow for long-term extracellular recording of the electrical activity from thousands of neurons simultaneously. Beyond population activity, it has also become possible to extract information of single neurons at subcellular level (e.g., the propagation of action potentials along axons). In effect, HD-MEAs have become an electrical imaging platform for label-free extraction of the structure and activation of cells in cultures and tissues. The quality of HD-MEA data depends on the resolution of the electrode array and the signal-to-noise ratio. In this chapter, we begin with an introduction to HD-MEA signals. We provide an overview of the developments on complementary metal-oxide-semiconductor or CMOS-based HD-MEA technology. We also discuss the factors affecting the performance of HD-MEAs and the trending application requirements that drive the efforts for future devices. We conclude with an outlook on the potential of HD-MEAs for advancing basic neuroscience and drug discovery.