Detection of Neurofilament Light Chain with Label-Free Electrolyte-Gated Organic Field-Effect Transistors

Neurofilaments are structural scaffolding proteins of the neuronal cytoskeleton. Upon axonal injury, the neurofilament light chain (NF-L) is released into the interstitial fluid and eventually reaches the cerebrospinal fluid and blood. Therefore, NF-L is emerging as a biomarker of neurological disorders, including neurodegenerative dementia, Parkinson's disease, and multiple sclerosis. It is challenging to quantify NF-L in bodily fluids due to its low levels. This work reports the detection of NF-L in aqueous solutions with an organic electronic device. The biosensor is based on the electrolyte-gated organic field-effect transistor (EGOFET) architecture and can quantify NF-L down to sub-pM levels; thanks to modification of the device gate with anti-NF-L antibodies imparted with potentially controlled orientation. The response is fitted to the Guggenheim-Anderson-De Boer adsorption model to describe NF-L adsorption at the gate/electrolyte interface, to consider the formation of a strongly adsorbed protein layer bound to the antibody and the formation of weakly bound NF-L multilayers, an interpretation which is also backed up by morphological characterization via atomic force microscopy. The label-free, selective, and rapid response makes this EGOFET biosensor a promising tool for the diagnosis and monitoring of neuronal damages through the detection of NF-L in physio-pathological ranges.