Clinically Feasible Approaches to the Real-Time Measurement of Drugs, Metabolites, and Biomarkers in the Living Body

The continuous, real-time measurement of specific molecules in situ in the body promises to revolutionize the precision of drug dosing, the reach of physiological research, and the accuracy and timeliness of clinical diagnostics. Motivated by these prospects, here we critically review the set of molecular sensing technologies that ( a ) have been demonstrated to support seconds-resolved measurements in mammalian subjects and ( b ) appear translatable to the clinic. The relevant technologies employ four readout modalities: ( a ) direct or enzymatic electrochemical detection, ( b ) indirect electrochemical detection, ( c ) optical strategies, and ( d ) photoacoustic sensing. For each, we analyze the engineering requirements to support real-time, in vivo operation—which include reversibility, reagentless interrogation, and selectivity—and the remaining barriers to clinical adoption, including sensitivity and long-term in vivo stability and biocompatibility. Collectively, the advances surveyed here suggest that seconds-resolved molecular monitoring in humans is within reach and will herald a new era of precision diagnostics and closed-loop therapeutics.