ABSTRACT Neurofilament light (NfL) is a discriminative blood biomarker for many neurological diseases. Current accurate analysis relating to NfL relies on state‐of‐the‐art technologies such as the single‐molecule array (Simoa) and immunoprecipitation‐mass spectrometry (IP‐MS), which require complicated machinery, skilled operational personnel, and well‐equipped laboratories. Herein, we demonstrate a robust on‐chip graphene field‐effect transistor (GFET) biosensing platform for the ultrasensitive detection of NfL. This work utilizes smaller antibody fragments F(ab’) 2 to mitigate Debye screening and enhance sensing performance, alongside quantitative characterization of 1‐pyrenebutyric acid N‐hydroxysuccinimide ester (PBASE) surface density to support controlled antibody immobilization. Compared with whole antibody‐based GFETs, this F(ab’) 2 ‐modified GFET platform is shown to achieve a 114% increase in sensitivity, a fivefold improvement in the limit‐of‐detection (LoD) down to 0.18 pg/mL, and a wide dynamic detection range from 0.18 to 1500 pg/mL, together with good selectivity, stability, and reproducibility. This biosensing platform is validated against Simoa technology for the detection of NfL in clinical plasma samples, yielding a high correlation coefficient of 0.99. These results demonstrate the potential of GFETs for point‐of‐care diagnosis and the monitoring of neurological diseases in frontline clinical settings, outperforming conventional immunoassays and approaching Simoa sensitivity.
Kizilates et al. (Tue,) studied this question.