Meeting review: a summary of the Label-Free Summit.

'All our knowledge has its origins in our perceptions.' Leonardo da Vinci Scientific progress is often enabled by the development of new tools and technologies that have given us new ways of perceiving the world. In the early days of our science, optical microscopy gave us the ability to observe cells for the first time and opened the new world of cell biology. More recently, advances in cloning and labeling technologies have permitted us to study the interactions of individual proteins. Now, label-free detection technology provides another promising advance--the means to generically study signal transduction in living cells through the dynamic mass redistribution (DMR) of intracellular contents. On October 6-7, 2008 a group of researchers gathered in Corning, NY to share recent advances in the field of label-free detection. Attendees came from nearby Ithaca, NY and as far away as Tokyo, Japan, representing a diverse set of institutions engaged in drug discovery research. Topics ranged from seven transmembrane receptor (7TMR) signaling, to high throughput screening and profiling, and to new applications such as ion channels and viral infection assays. Overall, the Label-Free Summit has given us additional perspective on the potential of this promising technology.

Evaluation of dynamic mass redistribution technology for pharmacological studies of recombinant and endogenously expressed g protein-coupled receptors.

The Epic cell assay technology (Corning Inc., Corning, NY) uses a resonant waveguide grating optical biosensor to measure cellular response to ligands manifested through dynamic mass redistribution (DMR) of cellular contents. The DMR measurement is a noninvasive, label-free assay that can be used to assess the pharmacological properties of compounds. In this study, a panel of 12 compounds was evaluated against two G protein-coupled receptor (GPCR) targets in recombinant expressed cell lines using the Corning Epic system in 384-well microplates. The evaluation was performed in a double-blinded fashion such that the identity and properties of both the GPCR targets and compounds were unknown to the researchers at the time of the study. Analysis of the DMR response from cell stimulation was used to identify compounds that functioned as agonists or antagonists and to evaluate the associated efficacy and potency. DMR results were shown to have good agreement with data obtained from cyclic AMP and calcium flux assays for compounds evaluated. A further analysis was performed and successfully identified the signaling pathways that the two GPCRs activated. In addition, the DMR measurement was able to detect responses from an endogenous receptor in these cells. The Epic DMR technology provides a generic platform amenable to pharmacological evaluation of cellular responses to GPCR activation in a label-free live cell assay format.