Wearable and implantable aptamer sensors for physiological monitoring

The transition from reactive healthcare to proactive precision medicine necessitates technologies capable of real-time, continuous monitoring of physiological biomarkers. While enzymatic sensors have paved the way for metabolic tracking, they are intrinsically restricted to a narrow spectrum of redox-active analytes and often suffer from limited stability in complex biological environments. In contrast, electrochemical aptamer-based (E-AB) sensors have emerged as a revolutionary platform, offering a universal, reagent-free sensing mechanism driven by binding-induced conformational changes, independent of the target’s chemical reactivity. This review provides a comprehensive analysis of the technological trajectory of E-AB sensors across the physiological continuum of biofluids: blood, interstitial fluid (ISF), and sweat. We critically examine distinct applications ranging from implantable wires for intravascular therapeutic drug monitoring and microneedle arrays for minimally invasive ISF analysis to wearable devices for non-invasive sweat sensing. A central theme of this work is the pivotal role of “soft material” strategies in facilitating the seamless integration of rigid electronics with soft biological tissues. We highlight how functional materials - including anti-fouling coatings, hydrogel interfaces, and flexible porous nanocomposites - bridge mechanical and chemical mismatches to mitigate biofouling and ensure stable, long-term bio-interfaces. Finally, we outline the remaining hurdles for clinical translation, discussing strategies to achieve ultra-sensitivity, establish calibration-free methodologies, and integrate artificial intelligence (AI) for intelligent data processing, ultimately aiming for ubiquitous personalized healthcare.