An FT-Raman and FT-SERS microprobe with the spatial resolution on the micrometer scale has been developed. The main interfacing components are discussed and the whole setup is validated with the use of different SERS-active substrates: silver and gold colloids and gold island films. Micro-FT-SERS spectra of crocetin, mitoxantrone, and mitoxantrone/DNA complexes have been obtained, and the mass detection limits are found to be on the order of 5 × 10<sup>2</sup> molecules. Adsorption on the SERS-active substrates does not induce any detectable changes in the all-trans configuration of the crocetin. Adsorption of the mitoxantrone/DNA complex does not induce detectable perturbations of the molecular interactions within the complex. Moreover, interactions between the drug and DNA induces very similar effects in both the resonance Raman and FT-SERS spectra of the drugs. These effects were found to be consistent with the model of mitoxantrone/DNA intercalation proposed from nuclear magnetic resonance and resonance Raman data. The signal-to-noise ratios found indicate that submonolayer amounts of intracellularly localized drugs totaling less than 10<sup>-18</sup> mole can be detected by means of the FT-SERS microprobe. Hence, both the extralow mass detection limit of the technique and its sensitivity to interactions within the supramolecular complexes will in the future allow the drug to be followed within the living cell.
A. Beljebbar, G. D. Sockalingum, J. F. Angiboust, and M. Manfait, "Near-Infrared FT-SERS Microspectroscopy on Silver and Gold Surfaces: Technical Development, Mass Sensitivity, and Biological Applications," Appl. Spectrosc. 50, 148-153 (1996)