Ultrasensitive electrochemical aptasensor for lipopolysaccharide detection based on target-mediated ring-opening metathesis polymerization amplification

Lipopolysaccharide (LPS), a critical biomarker for Gram-negative bacterial infections, holds essential application value in clinical diagnosis, precision therapeutics, and public health surveillance through its ultrasensitive detection. This study successfully developed a novel electrochemical aptasensing platform by ring-opening metathesis polymerization (ROMP) - mediated signal amplification. The biosensor fabrication involves: (i) LPS aptamer-mediated target recognition; (ii) the modification of LPS glycan chains with the ROMP initiator (4-vinylbenzeneboronic acid) through boronate affinity; (iii) AquaMet-catalyzed ROMP of norbornene dicarboxylic anhydride to generate polymer chains on the electrode surface; (iv) 2,2,6,6-tetramethylpiperidin-4-ylamine (TEMPO) reporter immobilization through aminolysis between polymer terminal anhydride groups and TEMPO-NH 2 under mild conditions. This architecture enables remarkable signal amplification through a cascade mechanism: each LPS molecule can be functionalized with many ROMP initiation sites, and subsequent ROMP generates polymer chains incorporating thousands of TEMPO reporter molecules. The biosensor demonstrated exceptional performance, achieving an ultra-low detection limit of 0.338 fg/mL with a wide linear dynamic range spanning six orders of magnitude (1.0 fg/mL to 1.0 ng/mL). The study confirmed the biosensor's operational simplicity, superior sensitivity, excellent selectivity, cost-effectiveness, and robust anti-interference capability in complex clinical matrices. The modular design not only facilitates low-abundance LPS detection but also establishes a universal platform for ultrasensitive analysis of other glycosylated biomarkers, highlighting broad application potential in early disease diagnosis and therapeutic monitoring.