Microfluidic Multielectrode Arrays for Spatially Localized Drug Delivery and Electrical Recordings of Primary Neuronal Cultures

Neuropathological models and neurological disease progression and treatments have always been of great interest in biomedical research because of their impact on society. The application of in vitro microfluidic devices to neuroscience-related disciplines provided several advancements in therapeutics or neuronal modeling thanks to the ability to control the cellular microenvironment at spatiotemporal level. Recently, the introduction of three-dimensional nanostructures has allowed high performance in both in vitro recording of electrogenic cells and drug delivery using minimally invasive devices. Independently, both delivery and recording have let to pioneering solutions in neurobiology. However, their combination on a single chip would provide further fundamental improvements in drug screening systems and would offer comprehensive insights into pathologies and diseases progression. Therefore, it is crucial to develop platforms able to monitor progressive changes in electrophysiological behavior in the electrogenic cellular network, induced by spatially localized injection of biochemical agents. In this work, we show the application of a microfluidic multielectrode array (MEA) platform to record spontaneous and chemically stimulated activity in primary neuronal networks. By means of spatially localized caffeine injection via microfluidic nanochannels, the device demonstrated its capability of combined localized drug delivery and cell signaling recording. The platform could detect activity of the neural network at multiple sites while delivering molecules into just a few selected cells, thereby examining the effect of biochemical agents on the desired portion of cell culture.