Label-free MIP-SERS biosensor for sensitive detection of colorectal cancer biomarker

Early diagnosis of colorectal cancer can significantly improve the overall survival rate of patients, thus selective and sensitive detection of biomarkers in serum samples is vital for early detection and dynamic monitoring of cancer. Nucleoside diphosphate kinase NM23-H2 (NDKB) is an important biomarker and therapeutic target for the diagnosis of colorectal cancer (CRC). Here, a label-free and ultrasensitive biosensor for NDKB protein markers is presented for the first time, combining the characteristic capture selectivity of molecularly imprinted polymers (MIPs) and the ultrasensitivity of surface-enhanced Raman Spectroscopy (SERS) technique. The imprinted cavity serves as the only channel for Raman reporter to approach the SERS substrate, providing highly complementary non-covalent binding sites that selectively capture the target protein based on ionic, hydrogen bonding or hy-drophobic interactions. Specific recognition of the NDKB protein will perfectly fill the imprinted cavity, which makes it difficult for the Raman reporter to get close to the SERS substrate, and the Raman signal decreases significantly, while the proteins of other structural sizes can not match the imprinted cavity. Through the change of the Raman signal, the proposed biosensor can realize the ultra-sensitive detection of NDKB, and the limit of detection (LOD) is 0.82 pg/mL. Compared with the traditional immunoassay technology, this combined approach with the advantages of low cost, fast response, high sensitivity and selectivity, provides clinical application potential for the early diagnosis of CRC.