Fluorinated Gold Nanoparticles for Nanostructure Imaging Mass Spectrometry

Abstract

Nanostructure imaging mass spectrometry (NIMS) with fluorinated gold nanoparticles (f-AuNPs) is a nanoparticle assisted laser desorption/ionization approach that requires low laser energy and has demonstrated high sensitivity. Here we describe NIMS with f-AuNPs for the comprehensive analysis of metabolites in biological tissues. F-AuNPs assist in desorption/ionization by laser-induced release of the fluorocarbon chains with minimal background noise. Since the energy barrier required to release the fluorocarbons from the AuNPs is minimal, the energy of the laser is maintained in the low μJ/pulse range, thus limiting metabolite in-source fragmentation. Electron microscopy analysis of tissue samples after f-AuNP NIMS shows a distinct "raising" of the surface as compared to matrix assisted laser desorption ionization ablation, indicative of a gentle desorption mechanism aiding in the generation of intact molecular ions. Moreover, the use of perfluorohexane to distribute the f-AuNPs on the tissue creates a hydrophobic environment minimizing metabolite solubilization and spatial dislocation. The transfer of the energy from the incident laser to the analytes through the release of the fluorocarbon chains similarly enhances the desorption/ionization of metabolites of different chemical nature, resulting in heterogeneous metabolome coverage. We performed the approach in a comparative study of the colon of mice exposed to three different diets. F-AuNP NIMS allows the direct detection of carbohydrates, lipids, bile acids, sulfur metabolites, amino acids, nucleotide precursors as well as other small molecules of varied biological origins. Ultimately, the diversified molecular coverage obtained provides a broad picture of a tissue's metabolic organization.

Influence of core size and capping ligand of gold nanoparticles on the desorption/ionization efficiency of small biomolecules in AP‐SALDI‐MS

“…We summed the ion currents of these two species and compared the four types of AuNP ligands. As shown in Figure 3A, the signal intensity for linoleic acid from AuNP[D‐1‐H] (= 1‐decanethiol) was significantly higher than those obtained for the other three ligands, which is consistent with previous findings, showing that signal intensities from hydrophobic nanomaterials are higher than from hydrophilic nanomaterials 28 . This is related to higher local temperatures obtained with the hydrophobic nanomaterials and thus slower energy dispersion.…”

“…Using gold nanorods (AuNR), Castellana et al demonstrated that infrared laser desorption/ionization-MS was capable of analyzing peptides very efficiently. 27 Furthermore, fluorinated AuNP were prepared for comprehensive analysis of metabolites in biological tissues using nanostructure imaging mass spectrometry (NIMS) with minimal background noise levels and high sensitivity as illustrated by Palermo et al 28 Only low laser energies were required during this process, which lead to very gentle desorption/ionization conditions with limited in-source fragmentation of the metabolites. Chiang et al 29 used mixed gold nanoparticles with diameters of 3 and 14 nm as probes for SALDI-MS to detect amino-thiol groups.…”

Nanostructured Substrates as Matrices for Surface Assisted Laser Desorption/Ionization Mass Spectrometry: A Progress Report from Material Research to Biomedical Applications

“…This fluorinated Au NP was further utilized for the comprehensive imaging of metabolites from the colon of mice exposed to three different diets by the same group. [158] Vachet et al developed a dual-mode MS imaging method to evaluate the stability of monolayer-functionalized Au NPs in vivo. [159] By using laser ablation inductively coupled plasma MS to monitor Au core and LDI-MS to monitor surface ligands, this approach revealed the site-specifically NP stability at the organ and suborgan level.…”

Mass Spectrometry Imaging of Neurotransmitters

“…Polyvinylpyrrolidone-capped AgNPs have been utilized for analysis of brain [69], and AuNPs with alkylamine surface modifications have been used for imaging of glycosphingolipids in the brain [70]. Fluorinated AuNPs have been shown to detect carbohydrates, lipids, bile acids, sulfur metabolites, amino acids, nucleotide precursors, and more in mouse colon [71].…”