Elucidating the Mechanisms Underlying the Signal Drift of Electrochemical Aptamer-Based Sensors in Whole Blood

• DOI: 10.1021/acssensors.1c01183
• Publication Date: 2021-09-07T15:24:03Z
• Authors: Kaylyn K. Leung; Alex M. Downs; Gabriel Ortega; Martin Kurnik; Kevin W. Plaxco
• Keywords: blood components; Chemical Sciences not elsewhere classified; electrochemically driven desorption; corrected sufficiently well; Information Systems not elsewhere classified; specific molecules irrespective; 610; much longer; developing electrochemical aptamer; Biochemistry; sensor signal decreases; 01 natural sciences; mechanisms underlying; Space Science; assembled monolayer; monitor drugs; likely require; electrochemical aptamer; perform real; enzymatic reactivity; challenging environments found; two primary sources; signal drift; Molecular Biology; thus improving; platform technology able; important obstacle; vivo monitoring; whole blood; results demonstrate; signal loss; systematically examined; vivo deployments; clinical practice; 0104 chemical sciences; biomedical research; 37 ° c; vivo measurement duration; like devices; Biological Sciences not elsewhere classified; suggesting targeted approaches

The ability to monitor drugs, metabolites, hormones, and other biomarkers in situ in the body would greatly advance both clinical practice and biomedical research. To this end, we are developing electrochemical aptamer-based (EAB) sensors, a platform technology able to perform real-time, in vivo monitoring of specific molecules irrespective of their chemical or enzymatic reactivity. An important obstacle to the deployment of EAB sensors in the challenging environments found in the living body is signal drift, whereby the sensor signal decreases over time. To date, we have demonstrated a number of approaches by which this drift can be corrected sufficiently well to achieve good measurement precision over multihour in vivo deployments. To achieve a much longer in vivo measurement duration, however, will likely require that we understand and address the sources of this effect. In response, here, we have systematically examined the mechanisms underlying the drift seen when EAB sensors and simpler, EAB-like devices are challenged in vitro at 37 °C in whole blood as a proxy for in vivo conditions. Our results demonstrate that electrochemically driven desorption of a self-assembled monolayer and fouling by blood components are the two primary sources of signal loss under these conditions, suggesting targeted approaches to remediating this degradation and thus improving the stability of EAB sensors and other, similar electrochemical biosensor technologies when deployed in the body.