Paper-based immunosensor integrated with bioinspired Cu-polydopamine nanozyme for voltammetric detection of CA-15-3 tumor marker

This manuscript describes the fabrication and characterization of a highly conductive paper-based nanoplatform for immobliztion of anti-CA 15-3 antibodies. For this purpose, cellulosic filter paper (FP) was first coated with Cu nanosponges (CuNSs) through ion beam sputtering deposition (IBSD) method and then covered with Cu-doped polydopamine nanospheres (Cu-PDA). Polydopamine doped with copper exhibited laccase (multi-copper oxidase)-mimicking properties. Bioinspired by the structure of the active site and the electron transfer mechanism of laccase, Cu-PDA nanozyme catalyzed the oxidation of hydroquinone (HQ) signal probe. In this design, CA-15-3, a prognostic biomarker in the breast cancer, was chosen as a model target. To the best of our knowledge, this is the only paper on the design of an electrochemical biosensor based on dense and uniform CuNSs produced by IBSD. More importantly, Cu-PDA is biocompatible and biodegradable, which makes it a potential competitor in the point-of-care (POC) biosensing applications. Thus, this paper-based sensing strategy can be used in designing cost-effective flexible chips consisting of electrodes printed on paper for in-situ and real-time monitoring biomarkers under clinical conditions. In addition to these outstanding features, the LOD (1.3 mU mL 1) and LOQ (4.3 mU mL 1) of the Ab/HQ/Cu-PDA/CuNSs/FP-based immunosensor was significantly lower than the clinically relevant cut-off level (30 U mL 1). In the practical applications, one of the key superiorities of this immuosensor is the wide DLR (5 mU mL 1–280 U mL 1) which covers the ultimate value of healthy and patient individuals.