Enzyme-DNA hybrids for ultrasensitive electrochemical detection of antibodies

Here we report a strategy 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 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. Using this strategy, we have demonstrated the sensitive (femtomolar limit of detection), specific and multiplexed detection of five different antibodies including three clinically relevant ones. The approach is also rapid (it only requires two reaction steps), works well in complex media (serum) and is cost-effective. A direct comparison with commercial ELISA kits demonstrates the promising features of this approach as a point-of-care platform for antibodies detection.