Harnessing effective molarity to design an electrochemical DNA-based platform for clinically relevant antibody detection

Rapid and easy-to-use platforms for antibody detection are likely to improve molecular diagnostics and immunotherapy monitoring. However, current technologies require multi-step, timeconsuming procedures that limit their applicability in these fields. Inspired by Nature, which often achieves regulation of reaction rates and binding affinity through nanoscale spatial confinement of biomolecules, here we demonstrate effective molarity-driven electrochemical DNA-based detection of target antibodies. We show a highly selective, signal-on DNA-based sensor that takes advantage of antibody-binding induced increase of local concentration to detect clinically relevant antibodies in blood serum. The sensing platform is modular, rapid, and versatile and allows the multiplex detection of both IgG and IgE antibodies. We also demonstrate the possible use of this strategy for the monitoring of therapeutic monoclonal antibodies in body fluids. Our approach highlights the potential of harnessing effective molarity for the design of electrochemical sensing strategies.