Ultrasensitive Detection of Aesculetin Using a Ruthenium Nanoparticle-Modified Carbon Fiber Microelectrode and Mechanistic Investigation of Its Interaction with DNA

• A ruthenium nanoparticle-modified carbon fiber microelectrode (RuNPs/CFME) was developed for ultrasensitive detection of aesculetin. • The RuNPs/CFME exhibited a 2.2-fold decrease in charge transfer resistance and significantly enhanced electrocatalytic activity. • The sensor demonstrated a wide linear range (0.01-1 μM), with a low detection limit of 1.62 nM and excellent reproducibility (RSD < 2%). • The platform successfully investigated the interaction between aesculetin and DNA, revealing a dominant electrostatic binding mode. • Practical applicability was confirmed through high recovery rates (95.7-102.6%) in human serum samples. This study presents the development of an ultrasensitive electrochemical sensor based on a ruthenium nanoparticle-modified carbon fiber microelectrode (RuNPs/CFME) for the detection of aesculetin and investigation of its interaction with DNA. The RuNPs/CFME exhibited significantly enhanced electrocatalytic activity, attributed to the large specific surface area and excellent conductivity of RuNPs, resulting in 54.6% decrease in charge transfer resistance compared to the bare electrode. The sensor demonstrated a linear response to aesculetin in the concentration range of 0.01-1 μM, with a detection limit (LOD) of 1.62 nM and a quantification limit (LOQ) of 5.44 nM. The electrode process was adsorption-controlled and involved a two-electron transfer. The modified sensor displayed high selectivity against common interferents, excellent reproducibility (RSD < 2%), and stability (>95% signal retention after 10 days). Furthermore, the platform was applied to study the interaction between aesculetin and calf thymus dsDNA, revealing a binding mechanism dominated by electrostatic interactions, as evidenced by a negative shift in oxidation potential and current attenuation. The sensor was successfully employed for aesculetin detection in human serum samples, achieving recoveries of 95.7-102.6%, demonstrating its potential for pharmacological applications and drug-DNA interaction studies.