The cocaine E-AB sensor is a signal-on sensor that is sensitive to the probe packing density of aptamer probes on the electrode surface. (Left) Square wave voltammetry is used to measure the reduction of the appended methylene blue redox tag on the aptamer. In the absence of cocaine the methylene blue still undergoes collisions with the electrode surface producing a small voltammetric response. When cocaine is present, the aptamer folds to bind cocaine and consequently brings the redox tag in close proximity to the electrode surface causing an increase in measured current. (Right) A decrease in probe packing density results in both an increase in overall signal gain and a lowering of the cocaine binding affinity of the cocaine E-AB sensor. Sensors fabricated with 0.5, 0.1, and 0.025 μM DNA exhibit dissociation constants of 506 ± 13, 260 ± 50, and 164 ± 45 μM respectively.