Monitoring the Movement of Molecules in the Body via Real-time Aptamer-based Sensors

Electrochemical, aptamer-based sensors (E-ABs) enable highly specific, continuous, real-time molecular measurements in vivo. Their remarkable selectivity and versatility arise from nucleic acid aptamers—single-stranded DNA molecules carefully selected in vitro for their strong affinity to specific molecular targets. To construct E-ABs, these aptamers are modified with redox reporters and immobilized onto gold electrodes via thiol-based self-assembly. The modified aptamers are designed to adopt one of two thermodynamic states: an unbound, slower electron-transferring state in the absence of the target, and a bound, faster electron-transferring state when the target is present. These states exist in dynamic equilibrium, allowing the aptamers to reversibly bind and release their targets within milliseconds, so that their fractional populations continuously reflect the target’s concentration. This sensor architecture enables uninterrupted molecular monitoring in vivo through repeated electrochemical measurements. Leveraging this capability, the Netz Lab uses E-ABs to investigate molecular transport across biological membranes, specifically examining two pathways: the movement of therapeutic agents from blood to the brain and from blood to dermal interstitial fluid. This presentation will cover our progress to date and the many intriguing questions that remain.