An approach for optimizing gold nanoparticles for possible medical applications, using correlative electron energy loss and Raman spectroscopies on electron beam lithographically fabricated arrays

Surface-enhanced Raman spectroscopy (SERS), as induced by noble metal nanoparticles, is used for medical applications. In this study, gold nanoparticle parameters such as size, shape, separation, substrate etc. are varied systematically using electron beam lithographic fabrication methods. The resultant Raman spectra intensities are correlated with the nanoparticle surface plasmon energies as determined by electron energy loss spectroscopy (EELS) in a scanning transmission electron microscope (STEM) at nanometer-scale resolution. It is found that the largest enhancement is achieved when the illuminating laser energy closely matches, or is slightly higher than, the surface plasmon energies. In general, nanoparticle size is a strong determinant factor, and higher intensities are generated by sharply defined features. This approach allows a procedure to identify the optimum combination of nanoparticle parameters and laser energy to generate the largest Raman signals, thus enabling detection, for instance, of smaller, early-stage cancer tumors.