A Glycoform‐Resolved Dual‐Modal Ratiometric Immunoassay Improves the Diagnostic Precision for Hepatocellular Carcinoma

The glycosylation pattern of alpha fetoprotein (AFP) paves the basis for precise early diagnosis of hepatocellular carcinoma (HCC). However, existing analytical methods ignore the contribution of terminal sialic acid, which has been reported to be highly connected with HCC. Besides, the development of diagnostic assays is severely hindered by the preparation of anti-glycans antibodies. Molecularly imprinted polymers (MIPs), as synthetic antibody mimics, provide unique strengths to address these issues. Herein, we report a MIPs-based dual-modal ratiometric immunoassay for precise HCC diagnosis. Using a "pit one against ten" MIP to recognize a subset of glycans containing sialic acid and/or core fucose, we demonstrated our assay exhibited improved precision as compared with ELISA. This assay provided not only a glycoform-resolved method for precise HCC diagnosis, but also a new paradigm for developing antibody mimics via molecular imprinting towards challenging biomedical applications.