Metallic nanoparticles in a cellular environment have a tendency to aggregate which poses a major obstacle in extending in vivo surface enhanced Raman spectroscopy (SERS) applications beyond the qualification and into quanti. cation domain. We introduce and demonstrate a novel SERS technique that will enable precise quanti. cation of exogenous chemicals in living human cells. Effective quanti. cation of the local concentrations of a dinitrophenol derivative (DAMP) based on a normalizing technique is shown by utilizing gold nanoparticle entrapment in the lysosomal compartments in human cells. We believe that the quanti. cation technique developed here is general and can be extended to different environments utilizing different types of nanoparticles beyond the intracellular scheme proposed. (c) 2008 Elsevier B. V. All rights reserved.