Biosensing empowered by molecular identification: Advances in surface plasmon resonance techniques coupled with mass spectrometry and Raman spectroscopy

Surface plasmon resonance (SPR) has been utilized extensively in bioanalysis since the early 90s due to its unique combination of label-free, highly sensitive, and robust detection. In recent years, SPR has been coupled with and complimented by several other techniques that provide the qualitative and molecular information that SPR lacks. In this paper, advances in studies that present molecular identification to quantitative measurements by SPR are reviewed. In particular, coupling of SPR measurements and MALDI mass spectrometry (MALDI-MS) has been broadly explored where plasmon-assisted ionization upon gold substrates appears to demonstrate many added benefits. Imaging SPR analysis, upon coupling, has contributed to new analytical capability that proves to be powerful with elevated throughput. The combination of SPR and Raman spectroscopy has also found a wide range of applications in providing molecular information that promotes quantitative analysis. Similar to MALDI, the plasmonic thin-film metal substrates provide a desired surface structure and property for Raman enhancement, improving subsequent molecular recognition. Instrumentation advancements and improvements in coupling efficiency has facilitated a series of SPR sensor developments where the plasmonic properties of the surface contribute uniquely to the performance of the coupled technique.