Aptamer-based immuno-SERS detection scheme. (A) Using unmodified metallic nanostructured surfaces, a strong SERS signal of the positively charged reporter crystal violet is detected. (B) When binding a monolayer of aptamers, the amount of crystal violet molecules on the metal surface is decreased due to electrostatic effects. This results in a lower SERS signal. (C) In the case of thrombin binding to the aptamer structure, more crystal violet molecules are bound to the surface (B). Thus, the SERS signal increases after the thrombin binding, albeit to a lower level than in case (A). Reprinted with permission from Hu et al. . Copyright 2009 American Chemical Society.