Surface enhanced Raman scattering (SERS) at extremely high enhancement level turns the weak inelastic scattering effect of photons on vibrational quantum states into a structurally sensitive single-molecule and nanoscale probe. The effect opens up exciting opportunities for applications of vibrational spectroscopy in biology. The concept of SERS can be extended to two-photon excitation by exploiting surface enhanced hyper-Raman scattering (SEHRS). This critical review introduces the physics behind single-molecule SERS and discusses the capabilities of the effect in bioanalytics (100 references).

This Account discusses surface-enhanced Raman scattering at extremely high enhancement levels that can occur for molecules attached to silver and gold nanoclusters. Strongly enhanced and highly confined local optical fields enable surface-enhanced Stokes and anti-Stokes Raman spectroscopy of single molecules even under nonresonant excitation conditions as well as extremely large effective cross sections in two-photon excited Raman spectroscopy. The ability for very sensitive and spatially confined molecular structural probing makes gold and silver nanoclusters very promising tools for studies of small structures in biological materials, such as cellular compartments.