Precision Channel Engineering of Nanotube-Embedded Organic Electrochemical Transistors for Ultrasensitive...

The quantitative monitoring of neurofilament light chain (Nf-L) is critical for the early diagnosis and prognosis of neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), yet achieving femtomolar sensitivity in a portable, label-free format remains a formidable challenge. Here, we report a high-performance organic electrochemical transistor (OECT) immunosensor engineered via the precise template-free electropolymerization of a dual-functional poly(EDOT-COOH-co-EDOT-EG3) copolymer. By systematically modulating the polymerization kinetics, we elucidated a decisive structure-function relationship governing biosensing efficacy: while microstructured channels formed at longer deposition times exhibited superior intrinsic transconductance due to maximized volumetric capacitance, the optimized nanotubular architecture provided the ideal balance of open porosity and accessible surface area. This specific nanotopography facilitated a significantly higher density of covalent antibody immobilization compared to its microstructured counterpart, thereby dominating the signal transduction mechanism through enhanced dielectric barrier formation upon antigen binding. Capitalizing on this morphology-governed sensitivity, the platform achieved a theoretical limit of detection (LOD) of 0.062 fg/mL (3σ criterion) and a rigorous LOD of 32.77 fg/mL (Hubaux-Vos method) across a broad dynamic range, along with exceptional selectivity and operational stability over 500 cycles. These findings underscore the critical role of precision channel engineering in bioelectronics, establishing a robust, lithography-free pathway for next-generation point-of-care diagnostics targeting diseases.