title: Patterning chemical stimulation of reconstructed neuronal networks.
abstract: A spatially resolved delivery of substances integrated with cell culture substrates shows promise for application in pharmacological assays, bioanalytical studies on cell signaling pathways and cell-based biosensors, where control over the extracellular biochemical environment with a cellular resolution is desirable. In this work, we studied a biohybrid system where rat embryonic cortical neuronal networks are reconstructed on microstructured silicon chips and interfaced to microfluidics. The design of cell-cell and cell-medium interactions in confined geometries is presented. We developed an aligned microcontact printing technique (AmicroCP) for poly(lysine)-extracellular matrix proteins on microstructured chips, which allows a high degree of geometrical control over the network architecture and alignment of the neuronal network with the microfluidic features of a substrate. Spatially resolved on-chip delivery of compounds with a cellular resolution is demonstrated by chemical stimulation of patterned rat cortical neurons within a network with a number of solutions of excitatory neurotransmitter glutamate delivered via microfluidics. The combination of the system described with a patch-clamp technique allowed both modulation of the biochemical environment on a cellular level and the monitoring of electrophysiological properties in the reconstructed rat embryonic cortical networks changed by this microenvironment.
authors.affiliation: Institute of Bio- and Nanosystems and Center of Nanoelectronic Systems for Information Technology, Research Center Jülich, 52425 Jülich, Germany. y.mourzina@fz-juelich.de
authors.forename: Yulia
authors.initials: Y
authors.lastname: Mourzina
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kaliaguine
authors.forename: Petra
authors.initials: P
authors.lastname: Schulte
authors.forename: Andreas
authors.initials: A
authors.lastname: Offenhäusser