title: CMOS nanoelectrode array for all-electrical intracellular electrophysiological imaging.
abstract: Developing a new tool capable of high-precision electrophysiological recording of a large network of electrogenic cells has long been an outstanding challenge in neurobiology and cardiology. Here, we combine nanoscale intracellular electrodes with complementary metal-oxide-semiconductor (CMOS) integrated circuits to realize a high-fidelity all-electrical electrophysiological imager for parallel intracellular recording at the network level. Our CMOS nanoelectrode array has 1,024 recording/stimulation 'pixels' equipped with vertical nanoelectrodes, and can simultaneously record intracellular membrane potentials from hundreds of connected in vitro neonatal rat ventricular cardiomyocytes. We demonstrate that this network-level intracellular recording capability can be used to examine the effect of pharmaceuticals on the delicate dynamics of a cardiomyocyte network, thus opening up new opportunities in tissue-based pharmacological screening for cardiac and neuronal diseases as well as fundamental studies of electrogenic cells and their networks.
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Jeffrey
authors.identifier: 0000-0001-6317-2641
authors.initials: J
authors.lastname: Abbott
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Tianyang
authors.initials: T
authors.lastname: Ye
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Marsela
authors.initials: M
authors.lastname: Jorgolli
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Rona S
authors.initials: RS
authors.lastname: Gertner
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Donhee
authors.initials: D
authors.lastname: Ham
authors.affiliation: Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.|Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Hongkun
authors.initials: H
authors.lastname: Park
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging; D004566:Electrodes; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats