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Electrochemical aptamer\u2010based biosensors offer a particularly promising and generalizable platform, as engineered aptamers can selectively bind diverse molecular targets and transduce binding\u2010induced conformational changes into robust electrochemical signals. Recent studies have demonstrated encouraging progress toward extended in vivo operation, including early examples of week\u2010scale functionality, highlighting the growing feasibility of this approach. Nevertheless, achieving robust and broadly applicable long\u2010term in vivo deployment remains an ongoing challenge due to factors such as sensor degradation and limitations in fully integrated device architectures. To address these challenges, multiple strategies have emerged, including drift\u2010canceling calibration, non\u2010natural nucleic acids, antifouling coatings, nanoengineered electrodes, advanced immobilization and ultralow\u2010power wireless systems, which are beginning to converge to enhance overall device performance. This review examines principles of aptamer\u2010based biosensing, delineates mechanisms of signal degradation, and surveys emerging strategies for stability enhancement and system\u2010level integration, outlining pathways toward longitudinal continuous molecular monitoring in personalized medicine.<\/jats:p>","DOI":"10.1002\/advs.77896","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Continuous Molecular Monitoring Using Electrochemical Aptamer\u2010Based Sensors: Remaining Challenges for Long\u2010Term In Vivo Deployment"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9282-3043","authenticated-orcid":false,"given":"Shibo","family":"Liu","sequence":"first","affiliation":[{"name":"Thayer School of Engineering Dartmouth College  Hanover NH 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