Highly Sensitive Surface-Enhanced Raman Scattering Sensing of Heparin Based on Antiaggregation of Functionalized Silver Nanoparticles

We report a simple and sensitive surface-enhanced Raman scattering (SERS) platform for the detection of heparin, based on antiaggregation of 4-mercaptopyridine (4-MPY) functionalized silver nanoparticles (Ag NPs). Here, protamine was employed as a medium for inducing the aggregation of negatively charged 4-MPY functionalized Ag NPs through surface electrostatic interaction, which resulted in significantly enhanced Raman signal of the Raman reporter. However, in the presence of heparin, the interaction between heparin and protamine decreased the concentration of free protamine, which dissipated the aggregated 4-MPY functionalized Ag NPs and thus decreased Raman enhancement effect. The degree of aggregation and Raman enhancement effect was proportional to the concentration of added heparin. Under optimized assay conditions, good linear relationship was obtained over the range of 0.5-150 ng/mL (R(2) = 0.998) with a minimum detectable concentration of 0.5 ng/mL in standard aqueous solution. Furthermore, the developed method was also successfully applied for detecting heparin in fetal bovine serum samples with a linear range of 1-400 ng/mL.