Simultaneous Chemical Separation and Surface-Enhanced Raman Spectral Detection Using Silver-Doped Sol-Gels

Over the past 30 years the combination of chemical separation and molecular analysis has proven invaluable to the analytical chemist in identifying chemicals at extremely low concentrations in complex matrices. For example, a drug and its metabolites can be effectively separated from blood plasma using gas chromatography and identified by the chemical fragments detected by mass spectrometry. More recently, the combination of liquid chromatography or flow injection analysis with surface-enhanced Raman spectroscopy (SERS) has been investigated for such applications. Advantages of this combination include minimal sample preparation, unrestricted use of water in the mobile phase, high chemical specificity through abundant molecular vibrational information, and extreme sensitivity as demonstrated by the detection of single molecules. Previous research has largely employed the three most common methods of generating SERS; roughened silver electrodes, silver coated substrates, and silver colloids for detecting separated analytes. The latter has gained the most attention, as colloids can be easily and inexpensively prepared, and mixing the colloids with the chromatographic column effluent using flow injection is highly reproducible. However, care must be taken to control aggregation of the colloids so that the amount of Raman signal enhancement is maintained. A range of experimental variables, such as analyte concentration and pH, can strongly influence aggregation and to some extent limit applications. Further, the choice of mobile phase is similarly limited by the need to maintain colloid integrity. Recently, we and others have been developing solgels to trap silver or gold particles as yet another method of generating SERS. Once the sol-gel has formed the metal particle size and aggregation are stabilized. Albeit changes in pH may still result in variable Raman signal intensities, such as the case of weak acids and bases, where the relative concentrations of the ionized and unionized forms may be influenced. In addition, we have shown that many of the common solvents, such as acetone, methanol and water can be used equally in generating SERS of analytes with these metal-