Magnetron-Sputtered Niobium Nanoparticles for Molecular Imaging of Brain Tissues through Surface-Assisted Laser Desorption/Ionization Mass Spectrometry

Precise molecular identification of specific biomarkers in biological tissues is essential for accurate diagnostics of various diseases, injuries, and other clinically relevant issues. Surface-assisted laser desorption/ionization mass spectrometry imaging (SALDI MSI) has emerged as a powerful tool for biochemical analysis, particularly using noble-metal nanoparticle (NP) matrices. These are often, but not always, synthesized using wet chemistry approaches. Here, we report on NPs of naturally monoisotopic niobium (Nb) as an alternative to more expensive NPs of noble metals in SALDI MSI. The Nb NPs are synthesized by a magnetron sputtering inert gas aggregation technique, which avoids the use of wet chemical pathways and allows the direct deposition of the NPs onto biological specimens. The NPs are partially oxidized and consist of a body-centered cubic (bcc) polycrystalline metal Nb core enclosed by an amorphous Nb2O5 shell. The mean size of the NPs is 25 nm, and the shell thickness is 4 nm. When seeded onto slices of the mouse brain, the Nb NPs form an effective matrix for high-resolution SALDI MSI of complex biological samples in both negative and positive ionization modes. The use of ultrahigh-resolution mass spectrometry allowed the identification of different Nb adducts and multiple phospholipid ion classes at m/z < 1000, including phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, phosphatidic acids, and galactoceramides, some of which are not easily accessible from biological tissues with conventional matrix-assisted laser desorption/ionization (MALDI) matrices. This work qualifies Nb NPs as an efficient, accessible, and easy-to-handle matrix for SALDI MSI for the first time. In addition, it highlights the potential utilization of other, yet unexplored transition-metal NPs, motivating their future research.