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While blood remains the clinical gold standard, interstitial fluid (ISF) presents a minimally invasive alternative that reflects local tissue physiology, although its biomarker kinetics often differ from blood. It is currently impossible to achieve simultaneous, continuous monitoring of both compartments, limiting insight into their dynamic relationship. To address this, we present BICEP (blood-ISF continuous-sensing electrochemical probe), a wireless electrochemical platform for continuous dual-compartment monitoring of analytes in blood and ISF. The BICEP system incorporates microfabricated soft sensors with biofouling-resistant aptamer interfaces, paired with a wearable potentiostat for remote configuration and readout. Using this system, we continuously tracked kanamycin signal in both anesthetized and freely moving rats, revealing distinct kinetic profiles and individualized temporal delays between blood and ISF signals. These findings confirm that ISF is not merely a proxy for blood but exhibits unique molecular kinetics influenced by individual variability and physiological state. This platform advances personalized health monitoring by providing integrated, dynamic correlation of blood and ISF biomarkers, deepening understanding of their physiological interplay under real-life conditions and paving the way for broader use of wearable ISF-based biosensors.<\/jats:p>","DOI":"10.1126\/sciadv.aed1895","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:00:40Z","timestamp":1779300040000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Continuous monitoring of blood\u2013interstitial fluid intercompartmental molecular kinetics in freely moving animals"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7080-5927","authenticated-orcid":true,"given":"Yihang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, 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