Combination of liquid-based column separations with surface-enhanced Raman spectroscopy

Surface-enhanced Raman spectroscopy is a constantly developing analytical method providing not only high-sensitive quantitative but also qualitative information on an analyte. Thus, it is reasonable that it has been tested as a promising detection method in column separations. Although its implementation in analytical separations is not widespread, some surprising results, like enormous signal enhancement and demonstrations of single-molecule identifications, proved in only a few special examples, indicate the potential of the method. The high detection sensitivity and selectivity would be of paramount importance in trace analyses of biologically relevant molecules in complex matrices. However, the combination of surface-enhanced Raman spectroscopy with column separation methods brings two principal issues. Interactions of analytes with metal substrates can cause deteriorations of separations and the detection can be affected by background electrolytes or elution agents. Thus, in principle, this review is on the experimental and methodological solutions to these problems. First, theoretical and practical aspects of Raman scattering, and excitation of surface plasmon in colloid suspensions of nanoparticles and on planar nanostructured substrates are briefly explained. Advances in experimental arrangements of online and at-line couplings with column liquid phase separation methods, including microfluidic devices, are described together with chosen analytical applications.