Survey of oligoethylene glycol-based self-assembled monolayers on electrochemical aptamer-based sensor in biological fluids

The ability to monitor levels of endogenous markers and clearance profiles of drugs and their metabolites can improve the quality of biomedical research and precision with which therapies are individualized. Towards this end, electrochemical aptamer-based (EAB) sensors have been developed that support the real-time monitoring of specific analytes in vivo with clinically relevant specificity and sensitivity. A challenge associated with the in vivo deployment of EAB sensors, however, is how to manage the signal drift which, although correctable, ultimately leads to unacceptably low signal-to-noise ratios, limiting the measurement duration. Motivated by the correction of signal drift, in this paper, we have explored the use of oligoethylene glycol (OEG), a widely employed antifouling coating, to reduce the signal drift in EAB sensors. Counter to expectations, however, when challenged in 37 °C whole blood in vitro, EAB sensors employing OEG-modified self-assembled monolayers exhibit both greater drift and reduced signal gain, compared with those employ a simple, hydroxyl-terminated monolayer. On the other hand, when EAB sensor was prepared with a mix monolayer using MCH and lipoamido OEG 2 alcohol, reduced signal noise was observed compared to the same sensor prepared with MCH presumably due to improved SAM construction. These results suggest broader exploration of antifouling materials will be required to improve the signal drift of EAB sensors. •Signal drift limits EAB sensor's measurement duration in vivo.•Oligoethylene glycol was employed as SAM to reduce the signal drift in EAB sensors.•In blood, EAB sensors with OEG SAM exhibit greater drift and reduced signal gain.•EAB sensor prepared with MCH and OEG mix monolayer reduced signal noise.•In vivo, drift data of mix monolayer showed similar trends.