Cellular Dielectric Spectroscopy: A Label-Free Technology for Drug Discovery

Abstract

Cellular dielectric spectroscopy (CDS) provides realtime, label-free, universal measurements, enabling comprehensive pharmacological evaluation of cell surface receptors in living cells. The sensitivity of the measurement allows monitoring of ligand-mediated activation of endogenous receptors, therefore generating physiologically relevant data. Activation of receptors results in CDS response profiles that are characteristic of main subsets of G-protein coupled receptors (GPCRs) within a cell line. This allows cluster analysis of response profiles that may be used in several important applications, which include identification of the G-protein coupling of orphan GPCRs and the cataloging of active endogenous receptors in cells. In this study, CDS technology is used in the pharmacological evaluation of multiple receptors in many cell types, including primary cells. Specifically, data is presented demonstrating hit confirmation, receptor selectivity analysis, ligand potency, and Schild analysis of receptor-selective antagonists. CDS results compare favorably to other cell-based assays, and the robustness and reproducibility of CDS assays are reflected by low assay coefficient of variation (CVs) and reliable Z'-scores of the data. Because CDS requires no stable or transiently transfected cells or special reagents, assay development and data acquisition is simple and fast. The ease of use, universality, and label-free nature of the CDS-based platform make it well suited to secondary screening applications in drug discovery.