Construction of a sensitive and selective plasmonic biosensor for prostate specific antigen by combining magnetic molecularly-imprinted polymer and surface-enhanced Raman spectroscopy

Selective and sensitive detection of cancer biomarkers in serum samples is critical for early diagnosis of cancer. Prostate specific antigen is an important biomarker of prostate cancer, which ranks high among cancer-related deaths of men over 50 years old. Herein, a novel analytical method was introduced for detection of PSA by combining high selectivity of molecularly-imprinted polymers and high sensitivity of surface-enhanced Raman spectroscopy (SERS). Firstly, magnetic nanoparticles were grafted with an imprinted layer by using tannic acid as a functional monomer, diethylenetriamine as a cross-linker and prostate specific antigen as a template molecule. Detailed surface characterization and re-binding experiment results indicated that the imprinting of the antigen was successful with an imprinting factor of 5.58. The prepared magnetic molecularly imprinted polymers (MMIPs) were used as an antibody-free capture probe and labeled with gold nanoparticles that were modified with anti-PSA and a Raman reporter, namely 5,5'-dithiobis-(2-nitrobenzoic acid). Thus, a plasmonic structure (sandwich complex) was formed between MMIP and the SERS label. The limit of detection and limit of quantification of the designed sensor were 0.9 pg/mL and 3.2 pg/mL, respectively. The sensor also showed high recovery rates (98.0-100.1% for healthy person and 99.0-101.3% for patient) with low standard deviations (less than 4.3% for healthy person and less than 3.3% for patient) for PSA in serum samples. Compared with the traditional immunoassays, the proposed method has several advantages like low cost, reduced detection procedure, fast response, high sensitivity and selectivity. It is believed that the proposed method can be potentially used for selective and sensitive determination of tumor marker of prostate cancer in clinical applications.