Imaging of Neurotransmitters and Small Molecules in Brain Tissues Using Laser Desorption/Ionization Mass Spectrometry Assisted with Zinc Oxide Nanoparticles

Abstract

Inorganic nanostructured materials such as silicon, carbon, metals, and metal oxides have been explored as matrices of low-background signals to assist the laser desorption/ionization (LDI) mass spectrometric (MS) analysis of small molecules, but their applications for imaging of small molecules in biological tissues remain limited in the literature. Titanium dioxide is one of the known nanoparticles (NP) that can effectively assist LDI MS imaging of low molecular weight molecules (LMWM). TiO2 NP is commercially available as dispersions, which can be applied using a chemical solution sprayer. However, aggregation of NP can occur in the dispersions, and the aggregated NP can slowly clog the sprayer nozzle. In this work, the use of zinc oxide (ZnO) NP for LDI MS imaging is investigated as a superior alternative due to its dissolution in acidic pH. ZnO NP was found to deliver similar or better results in the imaging of LMWM in comparison to TiO2 NP. The regular acid washes were effective in minimizing clogging and maintaining high reproducibility. High-quality images of mouse sagittal and rat coronal tissue sections were obtained. Ions were detected predominately as Na+ or K+ adducts in the positive ion mode. The number of LMWM detected with ZnO NP was similar to that obtained with TiO2 NP, and only a small degree of specificity was observed.

GABAB Receptor Agonist R-Baclofen Reverses Altered Auditory Reactivity and Filtering in the Cntnap2 Knock-Out Rat

“…Afterward, α-cyano-4-hydroxycinnamic acid standards were spotted onto the slides for internal mass calibration. ZnO matrix deposition using the TM Sprayer and MS data analysis of neurotransmitters were performed as previously described (Chen et al, 2021 ). MALDI-MS sample analyses were performed on a Sciex TOF/TOF 5800 MALDI mass spectrometer (Sciex, Framingham, MA, USA).…”

“…PnC and superior olivary complex (SOC) region of interest in the brainstem were manually selected to generate the average mass spectra. Mass peaks corresponding to neurotransmitters and metabolites ([GABA+K] + : 142m/z, [Glu+K] + : 186m/z, [Gln+K] + : 185m/z, [Choline+K] + : 143m/z, [Norepinephrine+K] + : 208m/z) were acquired from each mass spectra (Chen et al, 2021 ). Comparative analysis was performed based on the area under the curve (AUC) ratio (ratio between the peak of interest AUC to total AUC from 100 to 250m/z; Caughlin et al, 2017 ).…”

Plasmonic Gold Nanoshell-Assisted Laser Desorption/Ionization Mass Spectrometry for Small-Biomolecule Analysis and Tissue Imaging

“…Consequently, many of these nanomaterials represent a complementary strategy in the context of MSI analysis for a broad range of small biomolecules within various tissues. Alternatively, metal oxide NPs (e.g., Fe 3 O 4 , ZnO, porous Al 2 O 3 , and TiO 2 ) have been proposed as efficient matrices for mapping endogenous metabolites in plant and animal tissues. These NPs can benefit from relatively high melting and boiling points, which make them difficult to ionize, leading to a clean mass spectrum with highly reducing background signals .…”

Atropine-Phosphotungestate Polymeric-Based Metal Oxide Nanoparticles for Potentiometric Detection in Pharmaceutical Dosage Forms

“…Various studies are currently being conducted on zinc oxide nanoparticles (ZnONPs) and magnesium oxide nanoparticles (MgONPs). In addition, the application of both metal oxides in a variety of sectors including immunomodulatory agents [15,16], bactericidal agents [17,18], catalysis [19,20], tissue imaging [21,22], sensors [23,24], food packaging [25,26], and chemotherapeutics [27,28] has received more attention. In sensor construction, the thickness of the coating layer and chemical contents with respect to the loading ceria were examined using various microscopic and spectroscopic approaches including scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) [29,30].…”