title: High throughput electrophysiology using a fully automated, multiplexed recording system.
abstract: The drug discovery process centers around finding and optimizing novel compounds active at therapeutic targets. This process involves direct and indirect measures of how compounds affect the behavior of the target in question. The sheer number of compounds that must be tested poses problems for classes of ion channel targets for which direct functional measurements (e.g., traditional patch-clamping) are too cumbersome and indirect measurements (e.g., Ca(2+)-sensitive dyes) lack sufficient sensitivity or require unacceptable compromises. We present an optimized process for obtaining large numbers of direct electrophysiological measurements (two-electrode voltage-clamp) from Xenopus oocytes using a combination of automated oocyte handling, efficient and flexible liquid delivery, parallel operation, and powerful integrated data analysis. These improvements have had a marked impact, increasing the contribution electrophysiology makes in optimizing lead compound series and the discovery of new ones. The design of the system is detailed along with examples of data generated in support of lead optimization and discovery.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, IL 60064, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Trumbull
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Maslana
authors.forename: David G
authors.initials: DG
authors.lastname: McKenna
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Nemcek
authors.forename: Wende
authors.initials: W
authors.lastname: Niforatos
authors.forename: Jeffrey Y
authors.initials: JY
authors.lastname: Pan
authors.forename: Ashutosh S
authors.initials: AS
authors.lastname: Parihar
authors.forename: Char-Chang
authors.initials: CC
authors.lastname: Shieh
authors.forename: Julie A
authors.initials: JA
authors.lastname: Wilkins
authors.forename: Clark A
authors.initials: CA
authors.lastname: Briggs
authors.forename: Daniel
authors.initials: D
authors.lastname: Bertrand
mesh_terms: D000818:Animals; D001331:Automation; D001671:Biochemistry / Q000379:methods*; D004566:Electrodes; D004594:Electrophysiology / Q000295:instrumentation* / Q000379:methods*; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D007473:Ion Channels