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Small (Weinheim an der Bergstrasse, Germany)
Published

Ultrasensitive Detection of Neurofilament Light in Plasma Using F(Ab')<sub>2</sub>-Modified Graphene Field-Effect Biosensor

Authors

Selvinaz Burcu Kizilates, Rica Asrosa, Lenart Senicar, Anuja Sharma, Seda Gungordu Er, Nisha Naeem, Ahmad Nizamuddin Bin Muhammad Mustafa, Yang Wu, Neil Graham, Amanda Heslegrave, Mohan Edirisinghe, Antonio Lombardo, Elias Torres, Henrik Zetterberg, Sami Ramadan, David J Sharp, Bing Li

Abstract

Small. 2026 May 26:e73928. doi: 10.1002/smll.73928. Online ahead of print.

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.

PMID:42187004 | DOI:10.1002/smll.73928

UK DRI Authors

Amanda Heslegrave

Dr Amanda Heslegrave

Principal Research Fellow

Co-leading the UK DRI Biomarker Factory platform based at UK DRI at UCL

Dr Amanda Heslegrave

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg
Headshot of Bing Li, man with short dark hair and glasses

Dr Bing Li

UK DRI Affiliate Member - CR&T

Dr Bing Li