Programmable, multiplexed DNA circuits supporting clinically relevant, electrochemical antibody detection

Current health emergencies have highlighted the need to have rapid, sensitive and convenient platforms for the detection of specific antibodies. In response we report here the design of an electrochemical DNA circuit that responds quantitatively to multiple specific antibodies. The approach employs synthetic antigenconjugated nucleic acid strands that are rationally designed to induce a strand displacement reaction and release a redox-reporter modified strand upon the recognition of a specific target antibody. The approach is sensitive (low nanomolar detection limit), specific (no signal is observed in the presence of non-targeted antibodies) and selective (the platform can be employed in complex media, including 90% serum). The programmable nature of the strand displacement circuit makes it also versatile and we demonstrate here the detection of five different antibodies, including three of which are clinically relevant. By using different redox reporters, we also show that the antibody-responsive circuit can be multiplexed and responds to different antibodies in the same solution without cross-talk.