A Novel Signal‐On Electrochemiluminescence Immunosensor for the Detection of NSCLC Antigen Biomarker Based on New Co‐Reaction Accelerators

Abstract Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer with substantial morbidity and mortality. Herein, a new signal‐on electrochemiluminescence (ECL) immunosensor based on multiple amplification strategies is constructed for ultrasensitive detection of cytokeratin 19 fragment antigen 21‐1 (CYFRA21‐1) biomarker related to NSCLC. Polyethyleneimine (PEI) functionalized MXene is decorated with NiMn layer double hydroxide (NiMn LDH) to form MXene‐PEI‐NiMn LDH composite. Specially, the La‐MOF@ZIF‐67 bimetallic organic framework (named as LZBM) and MXene‐PEI‐NiMn LDH both served as coreaction accelerators to improve the ECL emission of the luminol‐H 2 O 2 system. To be specific, Au nanoparticles (AuNPs) coated MXene‐PEI‐NiMn LDH is applied to immobilize primary CYFRA21‐1 antibody (Ab 1 ), while AuNPs decorated LZBM was used for the loading of luminol and secondary CYFRA21‐1 antibody (Ab 2 ) to form tracer label. Therefore, the ECL signal of the sandwich‐type immunosensor is significantly enhanced due to the high loading capability for luminol and the synergistic catalytic ability for the decomposition of H 2 O 2 into reactive oxygen species (ROS). Under the optimal experimental conditions, the ECL immunosensor exhibited good analytical performances for CYFRA21‐1 detection with a wide linear range (100 fg mL −1 −100 ng mL −1 ) and a low limit of detection (85.20 fg mL −1 ), providing a promising method for early diagnosis of NSCLC.