Electrochemical Aptamer-Based Sensors Supporting Real-Time, Seconds-Resolved, Molecular Measurements in Awake, Behaving Rats

Abstract The real-time, in vivo measurement of drugs, metabolites, and biomarkers in awake animals could enable unprecedented insights into metabolic regulation, pharmacokinetics, pharmacodynamics, and behavioral response. In pursuit of this vision, here we demonstrate a subcutaneous electrochemical aptamer-based (EAB) sensor architecture that (i) supports the seconds-resolved, real-time measurement of specific molecular analytes over extended periods in freely moving, normally behaving rats and (ii) we believe is easily transferrable to other researchers. The approach also enables concurrent behavioral tracking captured ambulation metrics, which can reveal correlations between the in vivo concentrations of psychoactive drugs and locomotor behavior. The results of this multimodal approach validate EAB sensors for multianalyte detection in dynamic physiological contexts and highlights the physiological and psychobiological relevance of interstitial fluid drug concentrations, with implications for precision dosing, real-time molecular diagnostics, and behavioral pharmacology.