A soft metal-polyphenol capsule-based ultrasensitive immunoassay for electrochemical detection of Epstein-Barr (EB) virus infection

Herein, we have proposed a soft metal-phenolic capsule (sMPC)-based electrochemical immunoassay for ultrasensitive detection of Epstein-Barr virus capsid antigen IgA (EBVCA-IgA), a biomarker of nasopharyngeal carcinoma. Metal probes with large size contain a number of metal ions, which are very beneficial to signal amplification for anodic stripping voltammetry; however, these probes easily precipitate due to their heavy weight, leading to low recognition efficiency and compromised performance. In this study, we demonstrate sMPCs fabricated by metal-coordination interactions exhibit unique surface behavior compared with their solid counterparts, which significantly enhance recognition efficiency and thus improve sensitivity despite of their micrometer size. Taking advantage of the sMPCs, the involved electrochemical immunoassay shows a much-improved sensitivity with an ultralow detection limit of 0.46 fM for EBVCA-IgA and can also be used in real sample analysis. So far as we know, this is the first report on a sMPC-based electrochemical strategy. Furthermore, it clarifies the potential effect of the rigidness of probes on the performance of an involved biosensor, which is meaningful to guide the design of other functional probes. The advantages of this method, including easy to fabrication, ultrasensitivity and good selectivity, ensure a promising potential in the point-of-care diagnostics of critical diseases.