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Real-time, continuous in vivo molecular monitoring is crucial for advancing biomedical research and clinical healthcare, yet traditional methods face significant limitations. Electrochemical DNA-based (eDNA) biosensors are emerging as a powerful and highly versatile platform to address these needs. This review highlights key advancements within the last three years in eDNA biosensors tailored for in vivo continuous monitoring, emphasizing strategies to overcome challenges in stability, selectivity, and reversibility. Specifically, we delve into core eDNA biosensor designs and their in vivo applications, such as therapeutic drug monitoring, pharmacokinetic studies, real-time tracking of disease and neurochemical biomarkers, and feedback-controlled drug delivery. Furthermore, we critically examine significant progress in developing calibration-free operational strategies and ongoing efforts to tackle challenges related to long-term stability, receptor responsiveness, and target selectivity. The continued evolution of these platforms and their integration with artificial intelligence, positions eDNA biosensors as transformative tools for future biomedical breakthroughs and precision healthcare. Highlights • eDNA sensors enable versatile real-time in vivo molecular monitoring. • Key eDNA platforms: EAB, DNA pendulum, and aptamer-FET biosensors. • In vivo eDNA sensors advance TDM and personalized drug therapy. • Calibration-free strategies simplify in vivo eDNA sensor operation. • Overcoming stability and selectivity is key for eDNA sensor translation.
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Chamorro-García et al. (2025) studied this question.
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