(Left) E-DNA sensors consist of a stem-loop DNA modified with a redox reporter (here methylene blue) and attached to an interrogating gold electrode via an introduced thiol group.[7b] This probe undergoes a large-scale conformational switch upon hybridization with a DNA complementary to the loop, leading to large change in Faradaic current from the redox reporter. The affinity of such “switch-based” probes can be rationally tuned by many orders of magnitude, without affecting their specificity, by simply altering the stability of their nonbinding, non-signalling state (e.g., by varying the stability of the E-DNA probe’s stem with the change of the GC base pairs content).[9] (Right) Here we have employed a set of three E-DNA probes sharing a common recognition element but spanning almost three orders of magnitude of target affinity. Error bars in this figure and in the following figures represent the average and standard deviations of measurements performed on at least three independently sensors.