Regulation of triazine-COF and CoAl-LDH substrates in composites for high-performance neurofilament-light chains electrochemical immunosensors

Early diagnosis of Alzheimer's disease (AD) can be achieved through the detection of neurofilament light chain (NfL) biomarker, which can slow down the progress of AD and improve quality of life for patients. In this paper, polyvalent Tb-metal organic frameworks (Tb-MOF) and CoAl-layered double hydroxides (CoAl-LDH) are directly acceded to the synthesis system of triazine-covalent organic frameworks (triazine-COF) using one-pot synthesis to obtain the COF-based composite (COF/MOF-LDH). Similarly, the composite of LDH-based (LDH/MOF-COF) is acquired by integrating Tb-MOF and triazine-COF into the synthesis system of CoAl-LDH via hydrothermal procedure. COF/MOF-LDH and LDH/MOF-COF are used as electrode modification materials to construct label-free electrochemical immunosensors for anchoring and detecting NfL. Under optimal conditions for detecting NfL, both modified sensors exhibit high degree of selectivity, stability and reproducibility. However, the COF/MOF-LDH sensor displays a wider linear concentration range (0.05 pg/mL - 100 ng/mL) with lower limit detection of 0.017 pg/mL (S/N=3), and high sensitivity of 130.8 μA·ng-1·mL·cm-2, attributing to large conjugation system of triazine-COF used for substrate modulation and the immobilisation of the anti-NfL through strong π-π affect and hydrogen bonding. Likely, the incorporation of polyvalent Tb-MOF and CoAl-LDH in COF/MOF-LDH considerably enhance sensitivity via improving active sites and response signals. Furthermore, the morphology, pore size and specific surface area differences of the composites are a reflection of the results of the substrate material control strategy. Especially, the N2 adsorption/desorption tests indicate the larger mesoporous structure of COF/MOF-LDH which facilitate the electron transfer and anti-NfL immobilization. Taken together, the immunosensor based on COF/MOF-LDH shows excellent detection performance which provides a pathway for early screening of AD.