From understanding cellular function to novel drug discovery : the role of planar patch-clamp array chip technology

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DOIResolve DOI: http://doi.org/10.3389/fphar.2011.00051
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TypeArticle
Journal titleFrontiers in Pharmacology
Volume2
IssueOctober 51
Pages116; # of pages: 16
Subjectpatch-clamp whole-cell recordings; planar patch-clamp chip; giga-seal; synaptic transmission; cultured; cell placement; chemica lpatterning
AbstractAll excitable cell functions rely upon ion channels that are embedded in their plasma membrane. Perturbations of ion channel structure or function results in pathologies ranging from cardiac dysfunction to neurodegenerative disorders. Consequently, to understand the functions of excitable cells and to remedy their pathophysiology, it is important to understand the ion channel functions under various experimental conditions – including exposure to novel drug targets. Glass pipette patch-clamp is the state of the art technique to monitor the intrinsic and synaptic properties of neurons. However, this technique is labor intensive and has low data throughput. Planar patch-clamp chips, integrated into automated systems, offer high throughputs but are limited to isolated cells from suspensions, thus limiting their use in modeling physiologic function. These chips are therefore not most suitable for studies involving neuronal communication. Multielectrode arrays (MEAs), in contrast, have the ability to monitor network activity by measuring local field potentials from multiple extracellular sites, but specific ion channel activity is challenging to extract from these multiplexed signals. Here we describe a novel planar patch-clamp chip technology that enables the simultaneous high-resolution electrophysiological interrogation of individual neurons at multiple sites in synaptically connected neuronal networks, thereby combining the advantages of MEA and patch-clamp techniques. Each neuron can be probed through an aperture that connects to a dedicated subterranean microfluidic channel. Neurons growing in networks are aligned to the apertures by physisorbed or chemisorbed chemical cues. In this review, we describe the design and fabrication process of these chips, approaches to chemical patterning for cell placement, and present physiological data from cultured neuronal cells.
Publication date
LanguageEnglish
AffiliationNRC Institute for Microstructural Sciences; NRC Institute for Biological Sciences; NRC Steacie Institute for Molecular Sciences; National Research Council Canada
Peer reviewedYes
NPARC number18822648
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Record identifier17dc356d-9994-4804-8b97-437b9a169685
Record created2011-10-21
Record modified2016-05-09
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