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Ion channels are transm embrane proteins, found in virtually all cell types
throughout the human body. Ion channels underlie neural communication,
memory, behavior, every movement and heartbeat, and are as such prone to
cause disease if malfunctioning. Therefore ion channels are very important
targets in drug discovery. The gold standard technique for obtaining information
on ion channel function with high information content and temporal resolution is
patch-clamp. The technique measures the minute currents originating from the
movement of ions across the cellular membrane, and enables determination of
the potency and efficacy of a drug. However, patch-clamp suffers from serious
throughput restrictions due to its laborious nature. To address the throughput
problems we have developed a microfluidic chip containing 48 microchannels
for an extremely rapid, sequential delivery of a large number of completely
controlled solution environments to a lifted, patch-clamped cell. In this way,
throughput is increased drastically compared to classical patch-clamp perfusion
set-ups, with uncompromised data quality. The 48-microchannel chip has been
used for the characterization of drugs affecting ligand-gated ion channels
including agonists, antagonists and positive modulators with positive effects on
both throughput and data quality.
throughout the human body. Ion channels underlie neural communication,
memory, behavior, every movement and heartbeat, and are as such prone to
cause disease if malfunctioning. Therefore ion channels are very important
targets in drug discovery. The gold standard technique for obtaining information
on ion channel function with high information content and temporal resolution is
patch-clamp. The technique measures the minute currents originating from the
movement of ions across the cellular membrane, and enables determination of
the potency and efficacy of a drug. However, patch-clamp suffers from serious
throughput restrictions due to its laborious nature. To address the throughput
problems we have developed a microfluidic chip containing 48 microchannels
for an extremely rapid, sequential delivery of a large number of completely
controlled solution environments to a lifted, patch-clamped cell. In this way,
throughput is increased drastically compared to classical patch-clamp perfusion
set-ups, with uncompromised data quality. The 48-microchannel chip has been
used for the characterization of drugs affecting ligand-gated ion channels
including agonists, antagonists and positive modulators with positive effects on
both throughput and data quality.
Publisher
Year
Volume
Physical description
Dates
published
2006
Contributors
author
author
author
author
author
References
Document Type
Publication order reference
Identifiers
URI
http://hdl.handle.net/11089/12207
YADDA identifier
bwmeta1.element.hdl_11089_12207
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