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Screening


Figure 1: Trending of label-free instrument usage


10% 20% 30% 40% 50% 60%


0% Using Now © HighTech Business Decisions Not Using, But Considering Not Using, Not Considering


2007 2010


lines up, I think this is useful.” A High Throughput Screening lab


Advances in label-free technology Both biomolecular interactions and whole cells can be assayed using a variety of label-free instruments available today. Recent advances in label-free instruments offer improved cost, throughput, increased sensitivity and more sophisticated data analysis. Some examples of these advances made by label-free instrument suppliers are described below.


Molecular Devices


“Presently, we are using label-free technologies in collaboration with another company. We’re look- ing at and thinking about purchasing a surface plasmon resonance instrument, however, the limi- tation is the throughput. We’ve also looked at a number of the impedance-based technologies. The cost and applicability is more for secondary screen- ing not primary.”


A medium throughput screening lab


“For binding assays the current format limits the size of the protein, above ~65,000 you won’t detect the change in molecular weight. On the cell-based side, I am seeing label-free technologies as pretty promising. It is kind of a black box, but as long as we characterise the hits and the pharmacology


Table 1: Limitations of label-free technology LIMITATIONS


Cost of instruments and plates Low throughput


Less useful for primary screening, used more in other areas


Unclear biological result, no functional meaning, black box


Low sensitivity or limited detection Not applicable for all assays


Technology needs specialised plates and linkers


© HighTech Business Decisions 42 16 11 10 8 5 1 1 NUMBER OF MENTIONS


In late 2008, Molecular Devices (www.molecu- lardevices.com) launched the CellKey® 384 System; the only 384-well impedance-based label- free system for cell-based assays. With fully inte- grated fluidics and thermal control, the system delivers robust and sensitive universal assays for measuring a wide range of targets important to the drug discovery community. The system has well proven abilities to measure G-protein coupled receptor (GPCR) and Tyrosine Kinase Receptor (TKR) activation and also demonstrated capabili- ties in the measurement of ligand-gated ion chan- nels and adhesion molecules, among other targets. Debra Gallant, Product Manager at Molecular Devices, comments: “Two growing trends in recep- tor biology can be hugely benefitted by the adop- tion of label-free cell-based assays. The first is the study of more biorelevant systems. The nature of the non-invasive label-free measurement provides the sensitivity to measure endogenous receptor tar- gets in native cell types, including primary cells. Therefore, one is able to study receptors in their natural environment, not the artificial environment that is imposed when using a recombinant expres- sion system or artificial dyes and tags which may disrupt native signalling cascades. The second trend is an ever growing understanding that signal trans- duction pathways, particularly those of 7 trans- membrane receptors, are far more complex than previously understood and that current technolo- gies don’t do enough to address this complexity. The lack of high quality assay data frequently leads drug discovery researchers down false paths during hit identification and characterisation. The ability to study multiple signalling cascades and deliver high information kinetic data makes the CellKey® System an ideal tool for addressing this need.”


GE Healthcare Life Sciences


GE Healthcare Life Sciences (www.gelifesci- ences.com) has launched two new systems for label-free interaction analysis in 2010, according


Drug Discovery World Winter 2010/11


Percent of Respondents


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