Dr. Ralf Strasser, PhD, Dynamic Biosensors GmbH, Munich, Germany

heliX®: The Modular Biosensor for Measuring Interactions from small molecules to cells
switchSENSE^® is an automated fluorescence-based biosensor chip technology that employs electrically actuated DNA nanolevers for the real-time measurement of binding kinetics (k_a, k_d) but also affinity vs. avidity with a high sensitivity (K_D values down to the fM range).

Fluorescent dyes located on the biosensor surface detect the interaction of ligand and analyte molecules in two different ways. The fluorescence proximity sensing mode detects the binding of molecules in real-time through changes in the dye’s local environment. On the other hand, the high frequency dynamic switching mode probes the hydrodynamic friction of the ligand molecule and allows to determine conformational changes and kinetic analysis at the same time. These measurement features are valuable for drug development and hit validation.

The DNA-encoded anchor sequences present on the biochip surface allow the immobilization of a wide range of different molecules or even a combination of different molecules in varying ratios and densities for mimicking the cell surface. Furthermore, the use of two different fluorophores on the same sensor spot allows to monitor two independent signals from two interactions at the same time and determine between affinity and avidity for multi-specific binders.

Thanks to our unique novel Y-structure DNA format, competition assays or ternary complex formation characterization can be addressed using Fluorescence Resonance Energy Transfer (FRET) experiments.

In this talk, we demonstrate how to characterize binary and/or ternary complex formation in a single measurement with a Targeted Protein Degradation example such PROTACs.

Finally, one new application– the Realtime Interaction Cytometry technology – allowing kinetics directly on cells, will be presented. Association and dissociation kinetics of fluorescently labeled proteins/antibodies are measured directly from the cell surface. For that, new chips with polymer cages were designed to capture single cells.