title: Perfused drop microfluidic device for brain slice culture-based drug discovery.
abstract: Living slices of brain tissue are widely used to model brain processes in vitro. In addition to basic neurophysiology studies, brain slices are also extensively used for pharmacology, toxicology, and drug discovery research. In these experiments, high parallelism and throughput are critical. Capability to conduct long-term electrical recording experiments may also be necessary to address disease processes that require protein synthesis and neural circuit rewiring. We developed a novel perfused drop microfluidic device for use with long term cultures of brain slices (organotypic cultures). Slices of hippocampus were placed into wells cut in polydimethylsiloxane (PDMS) film. Fluid level in the wells was hydrostatically controlled such that a drop was formed around each slice. The drops were continuously perfused with culture medium through microchannels. We found that viable organotypic hippocampal slice cultures could be maintained for at least 9 days in vitro. PDMS microfluidic network could be readily integrated with substrate-printed microelectrodes for parallel electrical recordings of multiple perfused organotypic cultures on a single MEA chip. We expect that this highly scalable perfused drop microfluidic device will facilitate high-throughput drug discovery and toxicology.
authors.affiliation: Department of Electrical and Computer Engineering, Lehigh University, 111 Research Dr. D-320, Bethlehem, PA, 18015, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Materials Science and Engineering Department, Lehigh University, Bethlehem, PA, 18015, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Pan
authors.affiliation: Materials Science and Engineering Department, Lehigh University, Bethlehem, PA, 18015, USA.|Bioengineering Program, Lehigh University, Bethlehem, PA, 18015, USA.
authors.forename: Xuanhong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Electrical and Computer Engineering, Lehigh University, 111 Research Dr. D-320, Bethlehem, PA, 18015, USA. berdichevsky@lehigh.edu.|Bioengineering Program, Lehigh University, Bethlehem, PA, 18015, USA. berdichevsky@lehigh.edu.
authors.forename: Yevgeny
authors.initials: Y
authors.lastname: Berdichevsky
mesh_terms: D000818:Animals; D001921:Brain / Q000648:ultrastructure*; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D055808:Drug Discovery; D004867:Equipment Design; D006624:Hippocampus / Q000648:ultrastructure; D008839:Microelectrodes; D044085:Microfluidics / Q000295:instrumentation*; D008962:Models, Theoretical; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004129:Dimethylpolysiloxanes; C013830:baysilon
keywords: High-throughput; Hippocampus; MEA; Microfluidic; Organotypic; Perfusion