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High throughput label-free analysis of endogenous cell-surface receptor activity， in a single comprehensive assay methodology， independent of the signaling pathway.

The CellKey® 384 System is a universal， high throughput label-free platform for real-time cell-based functional analysis of endogenous and recombinant receptors. The system enables the measurement of a wide range of targets in a single-assay， including all families of G-protein coupled receptors (GPCRs)， as well as tyrosine kinase receptors (TKRs)， adhesion molecules， and indirect measurement of ion channel activation. In particular， the system is a major breakthrough for accurate monitoring of G_αi- and G_αs-coupled GPCR receptors， as it overcomes many of the challenges and limitations found with the traditionally available assay formats.

The underlying technology of the system is cellular dielectric spectroscopy (CDS)， an impedance based measurement that eliminates the need for labels， such as tags， dyes， or specialized reagents. By eliminating the requirement for labels， the CellKey System streamlines assay development by reducing the number of steps to be optimized， and allows users to develop one standard assay solution for multiple target classes， regardless of pathway.

The 384-well format increases throughput and enables up to 25，000 samples to be acquired per 8 hour day. The higher density microplate format reduces the per well assay costs by reducing the cells/well and reagents requirements. Additionally， the CellKey 384 System includes a tip wash system， which extends unattended operation.

The system was designed to meet the needs of drug discovery scientists-- from target identification and validation through lead optimization. It is sensitive enough to monitor ligand-mediated activation of endogenous receptors expressed in adherent or non-adherent cell lines， including primary cells. The benefit of this is the ability to generate more physiologically relevant data than obtained when using genetically and chemically manipulated cells.

While traditional technologies measure only discrete intracellular events， such as Ca²⁺ flux or cAMP fluctuation， the CellKey System measures the integrated response of the whole cell to receptor activation. By presenting a more complete picture of the complex pathways activated， scientists gain a better understanding of the cellular response. For example， upon detecting GPCR activation， the CellKey System generates robust and reproducible response profiles that are characteristic of G_αs-， G_αi- or G_αq- GPCRs. This qualitative data can be used to identify and deconvolute the pathway(s) through which receptors transduce their signals， and enables detailed interpretation of the mechanism of action (MOA) of lead compounds.

The CellKey 384 System is a fully integrated solution consisting of the instrument with on-board temperature control and internally integrated fluidics， a custom microplate for detection， and an extensive software suite. The integrated pipettor head allows the system to add ligand while simultaneously capturing the immediate cellular response. This feature contributes to the robustness and reproducibility of the CellKey System response profiles. The system software manages both data acquisition and the information-rich， real-time kinetic data analysis. Additionally， the system has been designed to integrate with most available automation options.