SERS-based biosensor for detection of f-PSA%: Implications for the diagnosis of prostate cancer

In diagnosing prostate cancer and distinguishing it from other prostate diseases, the ratio of the concentration of free prostate-specific antigen (f-PSA) to total prostate-specific antigen (t-PSA), i.e., (f-PSA%) is more accurate than the concentration of t-PSA alone. Immunoassay based on surface-enhanced Raman scattering (SERS) frequency shift has been proven to be particularly suitable for detecting large biomolecules with high reproducibility. Along similar lines, the present study developed a SERS-based biosensor that simultaneously detects t-PSA and f-PSA. The 4-mercaptobenzoic acid (MBA) on the immunocapture substrate is coupled to the t-PSA antibody through the carboxyl group, and the combination of t-PSA induces the Raman frequency shifts of MBA. The immunocolloidal gold attached with f-PSA antibodies selectively capture the f-PSA that immobilized on the MBA-modified SERS substrates, allowing for f-PSA quantification according to the SERS intensities of the 5, 5'-Dithiobis (succinimidyl-2-nitrobenzoate) (DSNB) probe. The results show that f-PSA and t-PSA have good linear response in the concentration scale of 0.1-20 ng/mL, and 1-200 ng/mL, respectively. The biosensor combines Raman frequency shifts and intensities, which greatly simplifies traditional procedures for f-PSA% detection. All the results demonstrated the great potential of the proposed biosensor in highly reproducible and accurate diagnosis of prostate cancers.