Comparing label-free biosensors for pharmacological screening with cell-based functional assays

Area of Science:

• Biotechnology
• Pharmacology
• Drug Discovery

Background:

• Label-free technologies are expanding in drug discovery for cellular target investigation.
• Electrical impedance-based and optical-based biosensors are two main classes of these instruments.
• G-protein coupled receptors (GPCRs) are a key target class, and their function studies are prominent in drug discovery.

Purpose of the Study:

• To compare the performance of impedance-based (CellKey) and optical-based (BIND, Epic) biosensors.
• To determine if these biosensors yield similar results for the same GPCR response.
• To assess differential sensitivities to G-protein signaling based on cell morphology changes.

Main Methods:

• Comparison of 1 impedance-based and 2 optical-based instruments.
• Testing with Gi-coupled (ACh M2), Gq-coupled (ACh M1), and Gs-coupled (CRF1) receptors.
• Evaluation in agonist and antagonist modes, including endogenous receptor and ligand-gated ion channel assays.

Main Results:

• All three instruments demonstrated robustness, yielding comparable potencies and assay variance.
• Both biosensor types showed high sensitivity for detecting receptor responses.
• The impedance-based biosensor uniquely distinguished G-protein coupling and revealed dual signaling for CRF1.

Conclusions:

• Impedance- and optical-based platforms provide robust live-cell, label-free assays suitable for drug discovery.
• These technologies typically yield similar pharmacological profiles for GPCR ligands.
• The impedance-based biosensor offers unique capabilities for G-protein coupling analysis.