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Heart-on-a-Chip Model with Integrated Extra- and Intracellular Bioelectronics for Monitoring Cardiac Electrophysiology under Acute Hypoxia
journal contribution
posted on 2020-03-08, 12:03 authored by Haitao Liu, Olurotimi A. Bolonduro, Ning Hu, Jie Ju, Akshita A. Rao, Breanna M. Duffy, Zhaohui Huang, Lauren D. Black, Brian P. TimkoWe demonstrated a
bioelectronic heart-on-a-chip model for studying
the effects of acute hypoxia on cardiac function. A microfluidic channel
enabled rapid modulation of medium oxygenation, which mimicked the
regimes induced by a temporary coronary occlusion and reversibly activated
hypoxia-related transduction pathways in HL-1 cardiac model cells.
Extracellular bioelectronics provided continuous readouts demonstrating
that hypoxic cells experienced an initial period of tachycardia followed
by a reduction in beat rate and eventually arrhythmia. Intracellular
bioelectronics consisting of Pt nanopillars temporarily entered the
cytosol following electroporation, yielding action potential (AP)-like
readouts. We found that APs narrowed during hypoxia, consistent with
proposed mechanisms by which oxygen deficits activate ATP-dependent
K+ channels that promote membrane repolarization. Significantly,
both extra- and intracellular devices could be multiplexed, enabling
mapping capabilities unachievable by other electrophysiological tools.
Our platform represents a significant advance toward understanding
electrophysiological responses to hypoxia and could be applicable
to disease modeling and drug development.
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Keywords
Acute Hypoxiadisease modelingmicrofluidic channelExtracellular bioelectronicsPt nanopillarsunderstanding electrophysiological responsesdrug developmentmembrane repolarizationHLintracellular devicesbioelectronic heart-on-a-chip modelMonitoring Cardiac Electrophysiologymapping capabilitiesATP-dependent Khypoxic cellsIntegrated ExtraIntracellular bioelectronicsmodel cellselectrophysiological toolsmedium oxygenationAPreadoutIntracellular Bioelectronicshypoxia-related transduction pathwaysHeart-on-a-Chip Modeloxygen deficits
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