Targeted molecular rapid SERS diagnosis in clinical human serum through aptamer origami-collapsed nanofingers chip

Surface-Enhanced Raman Scattering (SERS) offers great potential for label-free molecular diagnosis, especially in detecting disease biomarkers. However, the complexity of the biological environment in clinical human serum often significantly impairs detection accuracy. In this study, we present a highly effective SERS strategy utilizing aptamer origami-collapsed nanofingers for the precise qualitative and quantitative detection of specific targeted biomarkers in clinical serum. Here, the biomarker-specific aptamers are anchored to gold nanofingers, which then collapse during liquid evaporation, forming sub-nanometric gaps that enhance near-field strength. The serum is introduced directly into these stabilized nanofingers, where targeted biomarkers are selectively captured in aptamer hotspots, yielding pure Raman spectra of the biomarkers without interference from other serum molecules. The ratio of the biomarker's characteristic Raman peak to that of the aptamer allows for accurate quantification. This approach was validated with alpha-fetoprotein (AFP) for hepatocellular carcinoma and cardiac troponin I (cTnI) for acute myocardial infarction in clinical serum, achieving detection within 3 min. This strategy represents a significant advancement in SERS-based medical diagnostics, offering exceptional sensitivity and specificity in complex biological samples.