“RaMassays”: Synergistic Enhancement of Plasmon-Free Raman Scattering and Mass Spectrometry for Multimodal Analysis of Small Molecules

Abstract

SiO2/TiO2 core/shell (T-rex) beads were exploited as “all-in-one” building-block materials to create analytical assays that combine plasmon-free surface enhanced Raman scattering (SERS) and surface assisted laser desorption/ionization (SALDI) mass spectrometry (RaMassays). Such a multi-modal approach relies on the unique optical properties of T-rex beads, which are able to harvest and manage light in both UV and Vis range, making ionization and Raman scattering more efficient. RaMassays were successfully applied to the detection of small (molecular weight, M.W. <400 Da) molecules with a key relevance in biochemistry and pharmaceutical analysis. Caffeine and cocaine were utilized as molecular probes to test the combined SERS/SALDI response of RaMassays, showing excellent sensitivity and reproducibility. The differentiation between amphetamine/ephedrine and theophylline/theobromine couples demonstrated the synergistic reciprocal reinforcement of SERS and SALDI. Finally, the conversion of L-tyrosine in L-DOPA was utilized to probe RaMassays as analytical tools for characterizing reaction intermediates without introducing any spurious effects. RaMassays exhibit important advantages over plasmonic nanoparticles in terms of reproducibility, absence of interference and potential integration in multiplexed devices.

All‐dielectric core/shell resonators: From plasmon‐free SERS to multimodal analysis

“…The first example of multimodal analysis involving T‐rex beads is represented by the so‐called “Ramassays,” which are chemical assays resulting from the combination of Raman spectroscopy and mass spectrometry (Figure a) . The possibility to complement the information of a Raman experiment with mass spectrometry and vice versa can be a real breakthrough in analytical and bioanalytical chemistry.…”

A layer-by-layer assembled MoS2 thin film as an efficient platform for laser desorption/ionization mass spectrometry analysis of small molecules

“…From this point of view, the surface chemistry with thiol derivatives and high LDI-MS efficiency will play an important role for the development of a multi-modal analysis platform combining LDI-MS with other sensing technique such as SPR and SERS. 47–49 …”

Raman Plus X: Biomedical Applications of Multimodal Raman Spectroscopy

“…Another recent Raman/MS substrate is presented in a fascinating paper by Alessandri et al Using a special all dielectric nanoparticle substrate (SiO 2 /TiO 2 core/shell, AKA T-rex, nanoparticles), the authors demonstrate that the T-rex nanoparticles both provide plasmon-free SERS enhancement, while at the same time provide a background-free promotion of ionization via so-called Surface Laser Assisted Desorption/Ionization (SALDI). The multimodal SERS/SALDI platform (dubbed “RaMassay”) was used to identify two structurally related compounds difficult to discriminate by Raman, along with two regioisomers difficult to distinguish by MS [ 134 ]. These platforms have significant potential use in identification of illegal narcotics, small molecule drugs, reaction monitoring, and identification of explosive samples [ 135 ].…”