Fig. 1: Protein binding can affect the signal of electrochemical, aptamer-based sensors (E-ABs).

a While E-ABs functionalized with off-the-shelf aptamers may present strong sensor signals in buffered solutions (keT,2 >> keT,1), this behavior may be significantly affected in plasma (keT,3 < keT,2) due to nonspecific protein binding if the original aptamer selection was not correctly carried out against protein counter selections. In plasma, proteins (shown as green and blue elements with various shapes) may interfere with electron transfer between the reporter methylene blue (MB) and the electrode, causing a smaller ΔkeT. b Square wave voltammograms illustrating a smaller ΔkeT in plasma (blue trace vs. black) relative to buffered saline (red trace vs. black). c Method proposed in this study to recover sensor sensitivity of buffered saline in plasma: in a first step, thrombin is added to the plasma to induce coagulation and clotting. Second, the protein clots are filtered out. Finally, the filtrate is used to measure target concentrations. d The use of this method leads to the recovery of the EC50 normally seen in buffered saline from plasma samples. Figure Fig 1a, c Created in BioRender. Demek, E. (2025) https://BioRender.com/uqgdnvw.