An ultrasensitive “turn-off” SERS sensor for quantitatively detecting heparin based on 4-mercaptobenzoic acid functionalized gold nanoparticles

An ultrasensitive “turn off” Surface Enhanced Raman Spectroscopy (SERS) sensor was developed for the detection of heparin based on the anti-aggregation of 4-mercaptobenzoic acid stabilized gold nanoparticles. In this paper, protamine, a small protein molecule with positive charges, could induce the aggregation of 4-MBA functionalized gold nanoparticles via surface electrostatic interaction. However, in the presence of heparin, the aggregation of 4-MBA functionalized gold nanoparticles decreased due to the fact that heparin has a strong affinity toward protamine, further causing the loss of the Raman enhanced effect. The normalized SERS intensity of the Raman reporter was proportional to the concentration of added heparin and a good linear detection range was obtained from 0.05 to 20 ng mL−1 (R2 = 0.999) with a calculated detection limit of 0.03 ng mL−1. Moreover, the developed highly selective method is also successfully demonstrated in fetal bovine serum. Our method is specific, simple and cheap, which could be applied to other further research studies of heparin.