# Precision Channel Engineering of Nanotube-Embedded Organic Electrochemical Transistors for Ultrasensitive Neurofilament Light Chain Detection

## TL;DR

A new organic electrochemical transistor sensor was developed to detect neurofilament light chain at extremely low levels, aiding in early diagnosis of neurodegenerative diseases.

## Contribution

A novel nanotubular architecture in OECTs enables ultrasensitive detection of neurofilament light chain without labels or lithography.

## Key findings

- The sensor achieved a theoretical limit of detection of 0.062 fg/mL and a rigorous LOD of 32.77 fg/mL.
- The nanotubular design outperformed microstructured channels in antibody immobilization and signal transduction.
- The platform demonstrated exceptional selectivity and stability over 500 cycles.

## Abstract

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.