Electrochemical, aptamer-based (E-AB) sensors provide a modular approach to the continuous, real-time measurement of specific molecules in the body. E-AB sensors consist of an aptamer “probe” modified, at one end, with a redox-active “reporter” and attached, at the other end, to an interrogating electrode. In the presence of target, the probe undergoes a binding-induced conformational change that alters the reporter’s rate of electron transfer, leading to an easily measurable electrochemical output. Because the signaling mechanism exploited in E-AB sensors relies on conformation-linked signal transduction, and not just target-binding, E-AB sensors are particularly insensitive to non-specific molecular interactions and easily support the continuous, real-time measurement of specific molecules in situ in the living body over the course of hours. Exploiting this ability to monitor molecules continuously, I describe here efforts to couple E-AB sensing with closed-loop control algorithms to achieve feedback-controlled delivery of therapeutic drugs directly in live animals. Specifically, I discuss how this approach to real-time drug dosing can be employed to hold drug plasma concentrations within therapeutic levels, minimize subject-to-subject variability in pharmacokinetic parameters, and use animal models to emulate human drug pharmacokinetics. As illustrated by these examples, E-AB sensing enables unprecedented subject-specific approaches to the treatment of disease that, in the long run, could dramatically improve patient outcomes.

Electrochemical, aptamer-based sensing supports real-time, closed-loop control of plasma drug levels directly in the body of live animals

255th National Meeting (2018)

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