On the Blood Components Contributing to the Drift of Electrochemical Aptamer-Based Biosensors

Electrochemical aptamer-based (EAB) sensors support the high-frequency, real-time measurement of specific molecules, including metabolites, pharmacological agents, and biomarkers, in situ in the living body. A challenge that complicates their long-term, in vivo deployment, however, is signal drift, which causes a reduction in their signal output over time that is unrelated to the presence of target. Previously, we and others have shown that, when placed in undiluted whole blood at body temperature, EAB sensor drift arises predominantly due to fouling and enzymatic degradation of the DNA aptamer, with the former dominating in vitro in days-old bovine blood, and the latter dominating in vivo in blood flowing through the rat jugular. Building on this background, here we explore the specific blood components that prompt the EAB sensor drift in vitro. Comparison of the drift produced by whole blood, washed blood cells, and plasma demonstrates that this drift is caused by blood proteins rather than blood cells. And studies employing size-fractionated serum and plasma indicate that the proteins causing drift are approximately of molecular weight >100 kDa. The latter observation explains past successes in mitigating drift via the use of molecular-weight-selective films.