Enzyme‐Linked DNA Displacement (ELIDIS) Assay for Ultrasensitive Electrochemical Detection of Antibodies**

Abstract Here we report the development of a method for the electrochemical ultrasensitive detection of antibodies that couples the programmability and versatility of DNA‐based systems with the sensitivity provided by enzymatic amplification. The platform, termed Enzyme‐Linked DNA Displacement (ELIDIS), is based on the use of antigen‐DNA conjugates that, upon the bivalent binding of a specific target antibody, induce the release of an enzyme‐DNA hybrid strand from a preformed duplex. Such enzyme‐DNA hybrid strand can then be electrochemically detected with a disposable electrode with high sensitivity. We applied ELIDIS to demonstrate the sensitive (limit of detection in the picomolar range), specific and multiplexed detection of five different antibodies including three clinically relevant ones. ELIDIS is also rapid (it only requires two reaction steps), works well in complex media (serum) and is cost‐effective. A direct comparison with a commercial ELISA kit for the detection of Cetuximab demonstrates the promising features of ELIDIS as a point‐of‐care platform for antibodies detection.