Molecular histology analysis by matrix‐assisted laser desorption/ionization imaging mass spectrometry using gold nanoparticles as matrix

Abstract

Gold nanoparticles (AuNPs) were applied and optimized as matrix for matrix-assisted laser desorption/ionization mass spectrometry analysis of animal tissues, and enabled histological analysis of animal tissues at molecular level by imaging mass spectrometry (IMS). AuNPs were coated on animal tissue in a solvent-free manner via argon ion sputtering. Metabolites, including neurotransmitters, fatty acids and nucleobases, were directly detected from mouse brain tissue. Based on region-specific chemical profiles, fine histological features of mouse brain tissue and heterogeneous regions of tumor tissue were both revealed.

Current Status and Future Perspectives of Mass Spectrometry Imaging

“…Nanoparticles derived from metals, such as Au, Ag, Pt, Zn and Ti, have also been employed as matrix, which facilitates MALDI-MS detection of small molecules and metabolites [42,43]. Gold nanoparticles coated onto mouse brain tissue allowed detection of several metabolites, including neurotransmitters, fatty acids, nucleobases and glycosphingolipids (GSLs), such as minor molecular species of sulfatides and gangliosides [44,45]. Also, TiO 2 nanoparticles used in nanoparticle-assisted laser desorption/ionization imaging MS (Nano-PALDI-IMS) efficiently detected endogenous low molecular weight metabolites in mouse brain (80–500 Da) that were hardly detectable using DHB matrix [46].…”

Nanoparticles for Mass Spectrometry Applications

“…Direct application of SALDI-MS imaging using AuNP to life sciences was demonstrated through the molecular histology analysis of mouse brain tissue by Tang et al [76]. This approach relies on the coating of the target tissue with a layer of AuNPs with less than 10 nm by an ion sputtering technique suitable for ionization and subsequent identification of a wide range of metabolites, e.g., neurotransmitters, nucleobases, and fatty acids in different regions of mouse brain with great sensitivity, which enabled the distinction between tumor and unaffected brain areas.…”

“…Although many applications of the MSI technique have been reported, this section will focus on SALDI-MS imaging using NPs, namely, noble metal, TiO 2 , and SiO 2 NPs. The main advantage over conventional MALDI imaging is that specific mass signals for NP-based desorption become visible, which allows localization of a vast number of biomolecules in a sample [76,89].…”

Challenges and Recent Advances in Mass Spectrometric Imaging of Neurotransmitters

“…Using this technique, the analyte was fragmented and several of the unique fragment ions were monitored; thus, the matrix ions were no longer being detected and therefore did not interfere with the analyte signal. Recently, Tang et al used solvent-free argon ion sputtering to apply gold nanoparticles to mouse brain tissue and were able to directly detect neurotransmitters and other small molecules via MALDI-MSI [134]. Argon ion sputtering is a solvent-free matrix application method that has been reported to produce a thin, even layer of matrix coating onto the sample surface [134].…”

“…Recently, Tang et al used solvent-free argon ion sputtering to apply gold nanoparticles to mouse brain tissue and were able to directly detect neurotransmitters and other small molecules via MALDI-MSI [134]. Argon ion sputtering is a solvent-free matrix application method that has been reported to produce a thin, even layer of matrix coating onto the sample surface [134]. The chemical interference from the gold nanoparticles was very minimal, thus alleviating the common problem of matrix ions masking analyte ions in the lower molecular weight region.…”