Because of the tremendous information content, single-molecule detection with a vibrational spectroscopic technique is a goal well worth pursuing. The vibrational technique most suitable for single-molecule detection is surface-enhanced Raman spectroscopy (SERS). For example, Kneipp et al. recently demonstrated detection of 100 molecules of rhodamine 6G using surface-enhanced resonance Raman. Van Duyne and co-workers have recently detected just 10 molecules of pyridine using SERS and Raman microscopy. The key to sensitive detection using SERS lies in optimization of the enhancing surface. For excitation with easily accessible wavelengths, as well as ease of preparation and nearly ideal surface characteristics, Ag is often the metal of choice. SERS-active Ag has been prepared in a variety of ways, such as Ag colloids, vapor-deposited thin films, electrochemically roughened electrodes, nitric-acid-etched foils, thin films from the Tollens reaction, lithographically produced islands on Si posts, and, recently, vapor-deposition of Ag over a monolayer (or double layer) of nanospheres, followed by removal of the nanospheres. Each of the methods mentioned for the generation of SERS-active surfaces has advantages and limitations; i.e., there is still room for improvement and optimization of SERS-active surfaces.
Leo M. Sudnik, Karen L. Norrod, and Kathy L. Rowlen, "SERS-Active Ag Films from Photoreduction of Ag+ on TiO2," Appl. Spectrosc. 50, 422-424 (1996)