Electrochemical aptamer-based (E-AB) sensors are a technology that enables precise measurements of specific molecular targets in the body. E-AB sensors have been demonstrated to support real-time therapeutic drug monitoring and feedback-controlled drug dosing in living animals. However, one drawback of E-AB sensors is the rapid degradation of their sensing interface upon continuous interrogation by, for example, voltammetry. Over time, the faradaic current from their aptamer-attached redox reporter decreases, and the currents from charging the electrical double-layer increase beyond the faradaic current, thus preventing signaling. The latter effect is due to progressive desorption of the electrode-passivating alkyl thiol monolayers employed in these sensors. This progressive degradation limits their in-vivo operational life to hours, a period too short for monitoring the vast majority of drugs in humans, which generally have half-lives in the order of days. In response, our laboratory is investigating novel monolayer chemistries that extend the operational life of E-AB sensors without compromising their sensing performance or biocompatibility. In this presentation, I will discuss the effects that different monolayer chemistries have on E-AB sensing performance and how they extend the in-vitro operational life of E-AB sensors from hours to days in undiluted biological fluids. I will also discuss other strategies we are pursuing to prevent the progressive degradation of the reporter's signal.

Strategies to extend the operational stability of electrochemical, aptamer-based sensors in vivo

ACS Fall 2020 Virtual Meeting

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