Label-Free Detection of Conformational Changes in Switchable DNA Nanostructures with Microwave Microfluidics
Angela C. Stelson, Minghui Lu, Charles A. Little, Christian J. Long, Nathan D. Orloff, Nicolas Stephanopolous, James C. Booth
Detection of conformational changes in biomolecular assemblies provides critical information into biological and self-assembly processes. State-of-the-art in situ conformation detection techniques rely on fluorescent labels or protein-specific binding agents to signal conformational changes. Here, we present an on-chip, label-free technique to detect conformational changes in a DNA nanomechanical tweezer structure via microwave microfluidics. We measured the electromagnetic properties of suspended DNA tweezer solutions from 50 kHz to 110 GHzover six decades of frequency and directly detected the DNA tweezers. We developed a physical model to describe the electrical properties of the tweezers, and correlated model parameters to conformational changes. We found that the strongest indicators for conformational changes in DNA tweezers were the ionic conductivity and shifts in the magnitude of the cooperative water relaxation. Microwave microfluidics detection of conformational changes is a generalizable, non- destructive technique that and requires only nanoliter sample volumes, making it attractive for high-throughput measurements.