Variable gain DNA nanostructure charge amplifiers for biosensing

Electronic measurements of engineered nanostructures comprised solely of DNA (DNA origami) enable new signal conditioning modalities for use in biosensing. DNA origami, designed to take on arbitrary shapes and allow programmable motion triggered by conjugated biomolecules, have sufficient mass and charge to generate a large electrochemical signal. Here, we demonstrate the ability to electrostatically control the DNA origami conformation, and thereby the resulting signal amplification, when the structure binds a nucleic acid analyte. Critically, unlike previous studies that employ DNA origami to amplify an electrical signal, we show that the conformation changes under an applied field are reversible. This applied field also simultaneously accelerates structural transitions above the rate determined by thermal motion. We tuned this property of the structures to achieve a response that was ≈2 × 10⁴ times greater (i.e., a gain or amplification) than the value from DNA hybridization under similar conditions. Because this signal amplification is independent of DNA origami-analyte interactions, our approach is agnostic of the end application. Furthermore, since large signal changes are only triggered in response to desirable interactions, we minimize the deleterious effects of non-specific binding. The above benefits of self-assembled DNA origami make them ideally suited for multiplexed biosensing when paired with highly parallel electronic readout.