In response to the above considerations, we propose here a two-step assay, termed Enzyme-Linked DNA Displacement (ELIDIS) assay, that combines the programmability and versatility of antibody-responsive DNA-based systems with the sensitivity of enzyme amplification (Figure ). In the first step (antibodyresponsive reaction) we use antigen-conjugated DNA strands that induce the release of an enzyme-DNA hybrid strand from a preformed duplex complex upon the recognition of a specific target antibody (Figure , top). In the second step (amplification reaction), the reaction solution is transferred to an electrode surface so that the enzyme-DNA hybrid output strand can hybridize with a complementary strand immobilized on the electrode surface and provide a measurable current signal in the presence of the enzymatic substrate (Figure , bottom). We demonstrate here that this approach enables ultrasensitive detection of multiple antibodies in a rapid and specific manner.