Screening
Figure 12
Cellectricon’s Dynaflow®HT system is now for driving medicinal chemistry optimisation of ion channel compound activity at BioFocus
mation regarding compound mechanism of action; and 2) enable automated electrophysiology screens of up to 120,000 compounds. The use of these instruments has led to the delivery of validated hits to its clients for multiple programmes. Dyna- flow®HT is a new electrophysiology technology available at BioFocus that provides 96 individual recording channels grouped in clusters of six. The Dynaflow system is built around a consumable containing microfluidic flow channels and pro- vides excellent data suitable for driving medicinal chemistry optimisation of compound activity. PatchXpress® 16 channel giga-seal quality record- ing and conventional electrophysiology techniques are also used for detailed follow-up/mechanistic studies. Combining the BioFocus diverse collection of 900,000 compounds with the available in-house expertise and APC technologies provides client programmes with a wealth of strategic options for hit finding and hit expansion and provides a rapid route into medicinal chemistry optimisation (Figure 12).
‘leak’ ion channel programmes. Clients can access custom cell line generation – BioFocus has access to Millipore PrecisION™ cell lines and MaxCyte STX bulk transient transfected cell lines. FLIPR and radiometric screening technologies are avail- able as alternative diversity screening technologies for rapid prioritisation of compound activity in fol- low-up studies. BioFocus’ two IonWorks® Quattro™ assay systems combined with custom voltage protocols are designed to: 1) Reveal infor-
Figure 13: Sweep plot of Nav1.5 currents done using automated patch clamp as part of B’SYS routine testing (IC50 Lidocaine: 1.53 mM; Hill 1.243)
50
B’SYS (
www.bsys.ch) is a GLP-accredited CRO focusing on functional ion channel screening using automated and manual patch-clamp, fluorescence techniques and assay development including cell line design. Quality control systems apply to all assays in both GLP and non-GLP studies. B’SYS operates a single facility which houses scientists, technical platforms and administration under a single roof, resulting in short ways and fast and qualified responses. Expansion over the past few years has served mainly to satisfy the quality requirement of clients that left academia-related testing labs and to clients that rely on fast turn- around of studies in an auditable CRO. During the past few years B’SYS observed an increasing need of high quality ion channel screenings. For the clas- sical cardiac screening, automated patch clamp systems such as QPatch are available that provide data quality almost comparable with manual patch-clamping. Screening of validated CNS tar- gets requires sophisticated assays: voltage-gated channels often have to be tested on use dependence or in different voltage dependent states. Strict con- trol of high seal resistance and low serial resistance are crucial to record reliable data. Testing ligand- gated channels like GABA, Gluamate or Acetylcholine receptors requires precise, fast and reproducible drug application systems to avoid desensitisation and to provide robust data. Finally, critical data analysis is essential. Following these requirements, B’SYS broadened its library of ion targets, including validated mammalian and
Drug Discovery World Fall 2011
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