A cell-based bar code reader for high-throughput screening of ion channel-ligand interactions.
This paper presents a microfluidics-patch clamp platform for performing high-throughput screening and rapid characterization of weak-affinity ion channel-ligand interactions. This platform integrates a microfluidic chip consisting of multiple channels entering an open volume with standard patch clamp equipment. The microfluidic chip is placed on a motorized scanning stage and the method relies on the ability to scan rapidly, on the order of milliseconds, a patch-clamped cell across discrete zones of different solutions created in the open volume. Under ideal conditions, this method has the capacity to obtain kinetically resolved patch clamp measurements and dose-response curves of up to 10(3) ligand solutions in a single day.
Sinclair
Jon
J
Department of Physical Chemistry, and Microtechnology Centre, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
Pihl
Johan
J
Olofsson
Jessica
J
Karlsson
Mattias
M
Jardemark
Kent
K
Chiu
Daniel T
DT
Orwar
Owe
O
D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D001330:Electronic Data Processing; D007473:Ion Channels / Q000378:metabolism*; D008024:Ligands; D008832:Microchemistry / Q000295:instrumentation / Q000379:methods; D018408:Patch-Clamp Techniques / Q000295:instrumentation / Q000379:methods
D007473:Ion Channels; D008024:Ligands