Long-duration, real-time molecular measurements in the living body

The National Institute of Biomedical Imaging and Bioengineering awarded the University of California, Santa Barbara $582,137 on September 1, 2026, under the Discovery and Applied Research for Technological Innovations to Improve Human Health program (CFDA 93.286) to develop electrochemical aptamer-based sensors for long-duration, real-time molecular measurements in living tissue.

The research aims to extend the in vivo operational lifespan of electrochemical aptamer-based sensors beyond their current limitation of less than 24 hours to enable continuous monitoring of drug and biomarker concentrations. Previous work demonstrated week-long operation spanning over 47,000 high-precision measurements. The project will address sensor degradation through nuclease-resistant nucleic acid backbones, high-surface-area electrodes, improved antifouling surfaces, more stable monolayers, and protective size-selective coatings. Success could enable real-time physiological monitoring, disease diagnosis and surveillance, and personalized drug dosing.

Performance occurs at the University of California, Santa Barbara in Santa Barbara, California. The period of performance runs from September 1, 2026, through May 31, 2030. The award is classified as a Project Grant.

Abstract

The ability to monitor drug and biomarker concentrations in the body continuously and in real time could transform our understanding of physiology, enhance the diagnosis and monitoring of disease, and enable high-precision, truly personalized drug dosing. Towards this goal, we are developing electrochemical aptamer- based (EAB) sensors, the only real-time monitoring technology currently available that can measure molecules as diverse as urea (molecular weight 60 DA) and C-reactive protein (molecular weight 125 KDA) in situ in the veins, brains, and peripheral tissues of live subjects. These powerful advantages notwithstanding, a challenge nevertheless remains: degradation has previously limited the in vivo run time of EAB sensors to less than 24 H, reducing their clinical and scientific utility. (the continuous glucose monitor, for example, did not come into widespread clinical use until IT reached 5 day duration, and current models achieve 2 weeks.) in preliminary studies, we have shown that the failure of in vivo EAB sensors is caused primarily by nuclease-mediated cleavage of their target-recognizing aptamers, with fouling by high-molecular-weight blood components and the loss of electrode-protecting monolayers playing smaller, but still measurable roles. Fortunately, these same findings point to actionable solutions, such as the use of (I) nuclease-resistant, non-natural nucleic acid backbones, (II) high-signal, high-surface-area electrodes, (III) improved antifouling surfaces, (IV) more stable monolayers, and (V) protective, size-selective coatings. As preliminary results, we have used the first of these approaches to achieve a major, hitherto unprecedented breakthrough: demonstration of a platform molecular sensing approach achieving week-long, in vivo operation spanning more than 47,000 high-precision drug measurements. Building on this foundation, here we propose: (1) the further development of strategies to mitigate in vivo EAB sensor degradation, (2) systematic characterization and, if need be, mitigation of host responses to long-duration sensor implantation, and (3) preclinical validation of multiweek sensors targeting a number of clinically-important drugs and biomarkers. Ultimately, our goal is to extend the in vivo duration of this generalizable molecular measurement approach to >2 weeks under the argument that, by analogy to the clinical impact of the continuous glucose monitor, this would unlock such important applications as outpatient surveillance. More generally, by enabling convenient, real-time, long-duration tracking of molecular dynamics, success in the proposed efforts would dramatically expand the utility of EAB sensors in both biomedical research and clinical care.