A Programmable Electrochemical Y‐Shaped DNA Scaffold Sensor for the Single‐Step Detection of Antibodies and Proteins in Untreated Biological Fluids

Abstract Proteins and antibodies are key biomarkers for diagnosing and monitoring specific medical conditions. Currently, gold standard techniques used for their quantification require laborious multi‐step procedures, involving high costs and slow response times. It is possible to overcome these limitations by exploiting the chemistry and programmability of DNA to design a reagentless electrochemical sensing platform. Specifically, three DNA single strands are engineered that can self‐assemble into a Y‐shaped DNA nanostructure that resembles one of the IgGs. In order to convert this DNA nanostructure into a responsive DNA‐scaffold bioreceptor, it is modified including two recognition elements, two redox tag molecules, and a thiol group. In the absence of the target, the scaffold receptor can efficiently collide with the electrode surface and generate a strong electrochemical signal. The presence of the target induces its bivalent binding, which produces steric hindrance interactions that limit the receptor's collisional activity. In its bound state, the redox tags can therefore approach the surface at a slower rate, leading to a signal decrease that is quantitatively related to the target concentration. The Y‐shape DNA scaffold sensor can detect nanomolar concentrations of antibodies and proteins in <15 min with a single‐step procedure directly in untreated biological fluids.