A Neurofilament-Light Chains Electrochemical Immunosensor Expected to Reveal the Early Stage of Neurodegenerative Diseases

Abstract

The increasing aged-associated neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, are perplexing the world due to the incurability of these diseases in the advanced stage. It is crucial to develop an early diagnosis, which can be realized by detecting an effective biomarker like neurofilament-light chains (NfL). In this research, zirconium-based MOF with lanthanum doping (La/UiO-66-NH₂) is synthesized easily and economically, followed by pyrolysis to obtain MOF derivative material (ZrO₂@La₂O₃). Furthermore, the composite membrane of ZrO₂@La₂O₃ and ionic liquid (IL) is served as an immobilization matrix of neurofilament protein antibody (anti-NfL) to construct a label-free electrochemical immunosensor. The experimental results show that above composite improves  immobilization of anti-NfL and the electrochemical properties of the electrode. Under optimal incubation conditions, the immunosensor responds to NfL in a range of 0.05~200 ng·mL^-1 with a detection limit of 0.012 ng·mL^-1 (S/N=3). All of them are attributed to the electronic structure with more lattice defects in form of oxygen vacancies by doping lanthanum (La), the specific spatial structure of bimetallic oxide and carbon matrix by calcination and excellent conductivity and good viscosity of ionic liquid. The fabricated immunosensor is featured with low cost, simple fabrication and rapid detection, which might be a efficient platform satisfying demand for determination of NfL in the future, and significantly assist the clinical diagnosis and treatment of neurodegenerative diseases.

Keywords: MOF derivative material, ZrO2@La2O3, electrochemical immunosensor, neurofilament light protein.