Molecularly imprinted polymers outperform lectin counterparts and enable more precise cancer diagnosis.

Accurately analysing the particular glycosylation status of protein biomarkers is of significant importance in the precise, early diagnosis of cancer. Existing methods mainly rely on the use of antibodies and lectins. However, due to the macroscopic and microscopic heterogeneity of glycans, precise analysis of glycosylation status still remains a challenge. Molecularly imprinted polymers (MIPs), as a synthetic alternative to antibodies or lectins, may provide new solutions but have not yet been explored. Herein, we report an appealing strategy called triple MIP-based plasmonic immunosandwich assay (triMIP-PISA) for precise cancer diagnosis in terms of the relative glycosylation expression of glycoprotein biomarkers. As proof of the principle, alpha fetoprotein (AFP), which has been used as a clinical biomarker for early detection of hepatocellular carcinoma (HCC), as well as its agglutinin (LCA)-reactive fraction (AFP-L3), which is mainly composed of core-fucosylated glycans, were used as two target proteoforms to test in this study. Using two MIPs that can specifically recognize the peptide sequence of AFP as well as a fucose-imprinted MIP that can specifically recognize the AFP-L3 fraction, facile simultaneous plasmon-enhanced Raman detection of AFP and AFP-L3 in serum was achieved, which allowed HCC patients to be distinguished from healthy individuals. Due to the excellent recognition properties of the MIPs that are comparable to those of antibodies and superior to those of lectins, our triMIP-PISA method exhibited improved precision as compared with an antibody plus lectin-based immunofluorescence assay. Thus, this strategy opened a new avenue towards the precise diagnosis of cancer.