Screening
References 1 Comley, J (2003). Patchers vs Screeners – divergent opinion on high throughput electro- physiology! DDW 4(4): 47-57. 2 Owen, D and Silverthorne, A (2002). Channelling Drug Discovery: current trends in ion channel drug discovery research. DDW 3(2): 48-61. 3 Ion Channel Screening Trends 2011 Report, published by HTStec Limited, Cambridge, UK, March 2011. 4 Fleming, MR and Kaczmarek, LK (2009). Use of optical biosensors to detect
modulation of Slack potassium channels by G protein-coupled receptors. Journal of Receptors and Signal Transduction 29(3): 173-181. 5 Scheel, O et al (2011). Introduction of a Modular Automated-Voltage-Clamp Platform and Its Correlation with Manual Human Ether-a- go-go Related Gene Voltage- Clamp Data. Assay Drug Dev. Technol. 2011 Jun 15. 6 Librede ref. 7 Xu, SZ et al (2008). TRPC channel activation by extracellular thioredoxin. Nature 451(7174): 69-72. 8 Milligan, CJ et al (2009). Robotic multiwell planar patch-clamp for native and primary mammalian cells. Nature Protocols 4(2): 244-255.
Table 2. Ion Channel Products Or Services Offered By Vendors Reported ION CHANNEL PRODUCTS OR SERVICES
Other
VENDOR/ PROVIDER BioFocus B'SYS
Cellectricon ChanTest Corning
Cytocentrics EMD Millipore
Essen Biosciences Fluxion Biosciences Flyion
Hamamatsu Librede
Molecular Devices Nanion Technologies Sophion Biosciences
Fluorescent Imaging
Instruments Manual
Patch Clamp Instruments
Automated Patch Clamp Instruments
Instruments For Ion Channel Testing
Contract Screening Services
Cells and Cell Line
Development
Table 2: Ion channel products or services offered by vendors reported
read is parallel (Nanion); or in other flexible new platforms supporting ligand-gated testing at gigaohm seal resistance (Cytocentrics, Fluxion, Flyion).
Microfluidics and rapid solution exchange: The inclusion of microfluidic technology into APC devices has enabled continuous compound perfu- sion and continuous recording during the entire protocol (Fluxion). Microfluidic technology also makes it possible to apply and remove compound very rapidly (low ms range) while not exposing the cells to strong forces that would disrupt the cell and terminate the recording (Cellectricon, Sophion). Other instruments achieve extremely rapid solution exchange (<10ms) by using a permanent perfusion and sophisticated liquid-handling systems enabling ultra-rapid and precisely triggered agonist applica- tion (Cytocentrics); or use a fine quartz capillary inside the micropipette to deliver the compound solution directly on to the cell surface (flyion).
Other technologies and approaches: Response pro- files focused on the translocation of large cellular molecules associated with ion channel activity mon- itored by label-free can provide additional informa- tion about the functionality of ion channels and their activity modulators (Corning). Cell-free elec- trophysiological screening of ion channels in mem-
62
branes derived directly from cells of interest have also been described (Librede). New methods enabling 100% R-series compensation make exper- iments on fast voltage-gated ion channels more accurate and add to the quality focus (Sophion).
In conclusion, the availability of a rapidly evolving range of APC systems over the past decade and their widespread global adoption by pharmaceutical com- panies, CROs and academic research centres has rev- olutionised ion channel screening. Although for the present fluorescence imaging assays is still preferred in primary screening, it seems only a matter of time before APC is fully adopted as an alternative to man- ual patch clamp for compliant hERG.
DDW
Dr John Comley is Managing Director of HTStec Limited an independent market research consultan- cy whose focus is on assisting clients delivering novel enabling platform technologies (liquid han- dling, laboratory automation, detection instrumen- tation and assay reagent technologies) to drug dis- covery and the life sciences. Since its formation eight years ago, HTStec has published more than 70 mar- ket reports on enabling technologies and Dr Comley has authored more than 35 review articles in Drug Discovery World. Please contact
info@htstec.com for more information about HTStec reports.
Drug Discovery World Fall 2011
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