Ratiometric surface-enhanced Raman spectroscopy detection of 5-hydroxyindole-3-acetic acid based on Au@MIL-125@MIPs...

5-Hydroxyindole-3-acetic acid (5-HIAA) is a molecular marker that can be used in the early diagnosis of carcinoid tumors, and the development of sophisticated 5-HIAA assays is therefore of great importance. Surface-enhanced Raman spectroscopy (SERS) has been widely used for the rapid and sensitive detection of disease biomarkers. Insufficient specificity for tumor markers and poor spectral reproducibility are the bottlenecks in the practical use of SERS technology. In this study, based on MIL-125 surface-loaded gold nanoparticles (Au@MIL-125), a novel strategy was proposed to obtain Au@MIL-125@molecularly imprinted polymers (MIPs) as functional SERS substrates by wrapping a thin MIP shell around the Au@MIL-125 surface for selective separation followed by a 5-HIAA assay. The Raman peak intensity ratio (I₈₆₅/I₁₀₇₈) was used to quantify 5-HIAA after a SERS spectral calibration with an embedded internal standard (i.e., 4-aminobenzenethiol) to improve the quantitative accuracy. The linear range was from 10^-11 to 10^-7 M, and the limit of detection (LOD) was 5.45 × 10^-13 M. The method of integrating the MIPs with the metal MOF-based nanocomposites was shown to be useful in the analysis of real samples using SERS. The application of SERS for the selective and quantitative detection of analytes in real sample analysis, therefore, has great potential.