Circulating microRNA electrochemical assays in thyroid cancer

Thyroid cancer is the most prevalent endocrine malignancy; however, it is difficult to preoperatively distinguish between benign and malignant nodules and to ensure reliable surveillance after therapy. Circulating microRNAs (miRNAs) provide a minimally invasive molecular signal for testing, although conventional qPCR and sequencing pipeline technologies have cost, labor, and standardization challenges. This review summarizes the progress in the electrochemical biosensing of thyroid-relevant miRNAs along sample-to-clinic continuum. Signal recovery is strongly determined by preanalytical variables such as matrix selection (serum, plasma, whole blood, or extracellular vesicles), hemolysis control, storage conditions, extraction chemistry, spike-in controls, and normalization strategy using exogenous and endogenous controls. Yield can be further stabilized by the enrichment of extracellular vesicles, low-input protocols, and the reduction of batch effects. Analytically, voltammetric, impedimetric, electrochemiluminescent, and photoelectrochemical formats use rational probe design with nanostructured interfaces, such as gold nanoparticles, graphene derivatives, and MXenes, along with catalytic amplification duplex-specific nuclease (DSN), hybridization chain reaction (HCR), catalytic hairpin assembly (CHA), or CRISPR modules. While many platforms report ultra-low analytical limits of detection (femtomolar to attomolar) and wide linear ranges in buffer or spiked matrices, fewer studies have established functional sensitivity and clinical detection rates in unprocessed patient serum/plasma, where endogenous inhibitors and biological heterogeneity can dominate performance. Recurring signatures, such as miR-146b, miR-221, miR-222, and miR-21, have been shown to aid in early diagnosis, risk stratification, and postoperative follow-ups, whereas multiplex panels and cartridge-based platforms have been shown to be resilient to biological heterogeneity and complement cytology, mutation panels, and thyroglobulin, particularly in indeterminate Bethesda III or IV nodules and antibody-interfered follow-ups. The remaining limitations are inter-study method variation, poor inter-center validation, and unclear regulatory mechanisms of these miRNAs. An effective roadmap will focus on balanced collection and processing, preset thresholds with external calibration and commutable references, and blind prospective trials integrated into clinical practice with decision curve and health-economic analyses to speed up translation.