Highly catalytic CoFe-prussian blue analogue/ZIF-67 yolk-shell nanocube-decorated MBene nanosheets for ultrasensitive electrochemical cancer-specific neoantigen biosensor

[Display omitted] Neoantigens exclusively presented by human leukocyte antigens (HLAs) on cancer cell surfaces are newly discovered and highly cancer-specific biomarkers for cancer diagnosis. The current available method for detecting neoantigens is predominantly based on Mass spectrometry with inevitable limitations of high cost, complexity and isotope labels. In this work, we describe the development of an innovative catalytic electrochemical biosensor for ultrasensitive detection of neoantigen in cell lysates. Such biosensor design involves the synthesis of new and highly catalytic CoFe-prussian blue analogue/ZIF-67 yolk-shell nanocube-decorated MBene nanosheets (CoFe-PBA/ZIF-67/MBene) and the derivatization of electrochemically inert neoantigen to electroactive molecule. The as synthesized CoFe-PBA/ZIF-67/MBene nanocomposite exhibits large specific surface area, excellent conductivity and abundant active sites for electrochemical oxidation of the derivatized neoantigens for the yield of considerably amplified currents for sensitive detection of target neoantigen with low to 0.047 nM detection limit. The biosensor can also be applied for monitoring low levels of HLA-presented neoantigen complexes in cell lysates, offering new insights into methodological advancements in neoantigen analyses for cancer research.