AbstractThe rapid detection of lung cancer in early stages using the antigen cytokeratin-19 fragment (CYFRA 21-1) as a tumor marker in human serum plays an important role in the survival of patients and taking a fast surgical reaction. This study aimed to employ the green synthesized carbon quantum dots conjugated zinc oxide nanocomposite as a highly sensitive fluorescence immunosensing solution for fast determination of CYFRA 21-1 antigen in human serum. The suggested method was conducted by applying a hydrothermal method to prepare carbon quantum dots using Citrus lemon pericarp. The formed carbon quantum dots were used in the reduction and stabilization of zinc acetate to synthesize carbon quantum dots-zinc oxide nanocomposite. To form a sandwich capping antibody-antigen-antibody immunosensing system, a CYFRA 21-1 antigen was trapped by immobilizing a non-conjugated monoclonal antibody BM 19.21 on the surface of carbon quantum dots-zinc oxide nanocomposite and another monoclonal antibody KS 19.1, which was coated on the microtiter well surface. This system has a tunable fluorescence feature recorded at excitation and emission of λ_ex = 470 and λ_em = 520 nm, respectively. The suggested nanocomposite fluorescence immunosensing system displayed a linear relationship of 0.01–100 ng mL⁻¹ with a limit of detection of 0.008 ng mL⁻¹. The suggested immunosensing system based on carbon quantum dots-zinc oxide nanocomposite provides a promising approach for rapid diagnoses of lung cancer by detecting CYFRA 21-1 in human serum.