Development of bimetallic nanoparticles for Surface-Assisted Laser Desorption/Ionisation Mass Spectrometry imaging of small molecules

Mass Spectrometry Imaging (MSI) allows the simultaneous visualisation of hundreds to thousands of molecules in biological tissue slides enabling the comprehension of complex biochemical processes. Additionally, the analysis of untargeted MSI data with advanced statistical tools has the potential to reveal pertinent features of the sample such as the progression or outcome of a disease or the response to a treatment. Recently, metallic nanoparticles (NPs) have received increasing attention as desorption/ionization substrate for Surface-Assisted Laser Desorption/Ionization-MS (SALDI-MS). Metallic NPs provide several advantages over organic MALDI matrices for the analysis of small molecules: high absorption coefficients of the ionization laser (in the UV-Visible range), the ability to load small molecules on their surface by physical or chemical adsorption, little interferences in the low m/z range and a simple sample preparation (no crystallization required). SALDI-MSI is adapted to study the variations of the molecular composition associated with various diseases and to visualize the localization of pertinent small molecules in complex biological tissues. Innovative Au@Ag (core@shell) bimetallic NPs are interesting for SALDI applications, especially because controlling the thickness of the Ag shell around the Au core allows the tuning of the absorption in near-UV. These Au@Ag NPs permits to maximize the energy absorption for an efficient ionization and desorption of analytes adsorbed to the NPs. Moreover Au@Ag NPs can also be used for Surface-Enhanced Raman Spectroscopy (SERS) imaging which is a highly complementary technique. We report here a study of ovarian cancer tissue using Au@Ag NPs to characterize the overexpression of membrane receptor in the tumor by SERS imaging and to gain molecular insights by SALDI-MSI.