Fig. 2. (A) The parent aptamer (CA40) is predicted to fold into a G-quadruplex, which is thought to be the target-binding site,14,15 flanked by a 12-base-pair stem. (B) Exploiting the intrinsic fluorescence of irinotecan (Fig. S1†) we find that, when free in solution, the aptamer exhibits a dissociation constant of 475 nM. (C) When redox-reporter-modified and anchored to the sensor's interrogating electrode, however, its affinity and signal gain are reduced significantly, particularly when deployed in undiluted whole blood. (D) The E-AB sensor nevertheless rapidly responds to when challenged (here in buffer) with irinotecan. Binding curves in panel C employed a square-wave frequency of 120 Hz. The kinetic experiments in panel D employed a square-wave frequency of 500 Hz and a repetition rate of 0.2 Hz.