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Label-free detection of conformational changes in switchable DNA nanostructures with microwave microfluidics

Angela C. Stelson,Minghui Liu,Charles A. E. Little,Christian J. Long,N. Orloff,N. Stephanopoulos,J. Booth

Published 2019 in Nature Communications

ABSTRACT

Detection of conformational changes in biomolecular assemblies provides critical information into biological and self-assembly processes. State-of-the-art in situ biomolecular 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 with microwave microfluidics. We measure the electromagnetic properties of suspended DNA tweezer solutions from 50 kHz to 110 GHz and directly detect two distinct conformations of the structures. We develop a physical model to describe the electrical properties of the tweezers, and correlate model parameters to conformational changes. The strongest indicator for conformational changes in DNA tweezers are the ionic conductivity, while shifts in the magnitude of the cooperative water relaxation indicate the addition of fuel strands used to open the tweezer. Microwave microfluidic detection of conformational changes is a generalizable, non-destructive technique, making it attractive for high-throughput measurements. Methods to study conformational changes in biomolecules are limited in resolution and require labelling or other modifications of target analytes. Here the authors present a label-free, microwave microfluidic approach to detect conformational changes of DNA nanostructures based on ionic conductivity.

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