Thyroid biomarker biosensing: Nanomaterial-enabled electrochemical platforms, clinical translation, point-of-care technologies, and intelligent diagnostics

Thyroid disorders represent a substantial clinical burden, requiring reliable biomarker measurement for diagnosis, monitoring, and disease assessment. Thyroid-stimulating hormone (TSH), triiodothyronine (T₃), thyroxine (T₄), thyroglobulin (T_g), calcitonin (CT), and thyroid-associated nucleic acid biomarkers are important analytical targets. Although established immunoassays, ELISA, imaging, and cytological methods remain integral to clinical practice, limitations related to laboratory infrastructure, sample requirements, and workflow complexity have driven the development of alternative analytical platforms. This review focuses primarily on nanomaterial-assisted electrochemical biosensors for thyroid biomarker analysis, examining how nanomaterial properties, biorecognition strategies, and electrochemical transduction influence analytical performance. Metal and metal oxide nanoparticles, carbon nanomaterials, metal-organic frameworks, metal chalcogenides, MXenes, quantum dots, and molecularly imprinted polymers are discussed for their roles in signal amplification, interfacial charge transfer, selectivity, and sensor stability. Complementary approaches, including chemiluminescent, photoelectrochemical, optical, and other emerging sensing strategies, are also considered to contextualize the broader analytical landscape, particularly in relation to their implementation in commercial laboratory and point-of-care platforms for thyroid analysis. Seventy representative analytical and diagnostic systems are comparatively evaluated according to sensing technology, detection range, sample type, and assay time, together with their progression toward portable point-of-care devices, commercial analyzers, rapid diagnostic formats, and wearable platforms. Emerging artificial intelligence and machine learning approaches for signal interpretation, disease classification, and risk assessment are discussed. Challenges in nanomaterial reproducibility, bioreceptor stability, biofouling, matrix effects, fabrication, analytical standardization, external validation, and clinical translation are critically examined. The review identifies key analytical and technological priorities for translating thyroid biosensors from sensitive experimental platforms into robust, reproducible, and clinically relevant diagnostic tools.