A “turn-off” SERS assay of heparin with high selectivity based on heparin–peptide complex and Raman labelled gold nanoparticles

• Highly selective and sensitive “turn-off” SERS assay for heparin.
• Heparin–peptide complex and Raman labelled gold nanoparticles.
• A rapid, separation-free detection of heparin in human blood serum samples.

Stable SERS response originating from gold nanoparticles (Au NPs) is demonstrated for the first time to be suitable for detection of heparin with high selectivity. Herein we report a novel “turn-off” SERS assay for heparin based on Raman labelled Au NPs and competitive bonding between heparin and two specialized peptides, such as RKGSGRRLVKC (11-peptide) and CALNN (5-peptide). By means of coordination interactions and other non-electrostatic forces, these 5-peptide capped Au NPs are induced to undergo controllable aggregation upon the additive of 11-peptide and heparin with a concentration range (0–2.4 U/mL), which correspondingly cause quantitative changes of SERS intensity of 4-MBA conjugated on Au NPs. The decreased Raman intensity obtained by subtracting two cases of additives which contain only 11-peptide and the mixture of 11-peptide and heparin, is proportional to the concentration of heparin over a range of 0.2–2.4 U/mL (R2=0.99157), with a limit of detection (LOD) of 0.042 U/mL (S/N=3:1). Moreover, the proposed highly selective method has potential application for rapid, separation-free detection of heparin in human blood serum samples.