NEURO-connect: Prof Netz Arroyo, Monitoring the Movement of Molecules From Blood to the Brain via Real-time Aptamer-based Sensors

Electrochemical, aptamer-based sensors (E-ABs) enable specific, continuous, and real-time molecular measurements in vivo. Their selectivity and modularity stem from the use of nucleic acid aptamers—single-stranded DNA oligos selected in vitro for their ability to bind specific molecular targets. To create E-ABs, redox-reporter-modified aptamers are attached to gold electrodes via thiol-based self-assembly. These modified aptamers are engineered to exhibit two thermodynamic states: an unbound, slow electron-transferring state in the absence of the target, and a bound, fast electron-transferring state in the presence of the target. The two states exist in dynamic equilibrium, with the aptamers reversibly binding to and dissociating from their targets within milliseconds; thus, their fractional populations depend on target concentration. This sensor architecture facilitates continuous molecular sensing in vivo through serial electrochemical interrogation. Leveraging this unique capability, the Netz Lab is using E-ABs to study molecular transport from blood to the brain across the blood-brain barrier, and within the brain to understand the real-time kinetics of drug distribution. This presentation will discuss our achievements to date, as well as the many open questions that remain.