Antibody-Free Discrimination of Protein Biomarkers in Human Serum Based on Surface-Enhanced Raman Spectroscopy

Protein biomarkers are very important indicators of diseases and have great potential in cancer early diagnosis. The majority of detection methods for protein biomarkers currently rely on specific capture antibodies or aptamers with chemiluminescent and fluorescent labels. Here, an antibody-free strategy for discrimination of versatile proteins is proposed based on surface-enhanced Raman spectroscopy. The SERS spectral variation of a linker molecule, perylenetetra carboxylic acid (PTCA), is found to directly correlate with the protein types, according to which protein biomarkers even homologous proteins with very similar molecular structures can be discriminated with the aid of hierarchical cluster analysis. Furthermore, the feasibility of the proposed approach has been proved in early liver cancer diagnosis with clinical samples. All the results indicate that PTCA as a universal SERS probe has great potential in rapid, accurate, and direct protein biomarker discrimination in cancer diagnosis.