Gold nanoshells improve LDI-MS tissue imaging

Plasmonic nanoshells have been accepted as efficient nanomaterials for LDI-MS recognition of many small molecules, although their uses in mass spectrometry imaging (MSI) are not well established. A study in the article Nanomaterials applied by ACS reported the development and optimization of [email protected] nanoshells with custom shell compositions and structures for high-sensitivity LDI-MS analysis and a variety of basic MSI applications.

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​​​​​​​Study: Plasmonic gold nanoshell-assisted laser desorption/ionization mass spectrometry for small biomolecule analysis and tissue imaging. Image credit: Carl Dupont/Shutterstock.com

Mass Spectrometry Imaging

Mass Spectrometric Imaging (MSI) has become a popular label-free method that enables spatial clarity of a wide range of analytes, including drugs, lipids, peptides, small biomolecules, and proteins found in various complex samples, such as single cells and biological tissues. .

Due to its upper limit of detection (LOD), high productivity, high salt tolerance and minimal sample consumption, matrix-assisted laser desorption/ionization (MALDI) has become one of the methods essential for MSI.

Disadvantages of MALDI

Although widely used, the approach has a number of inherent drawbacks of organic matrices, including poor point-to-point reproducibility, large background interference ions in low-mass areas and sometimes reduced ion yield to tiny molecules.

Due to the heterogeneous co-crystallization, it is still difficult to implant a coherent film of organic matrices on the tissue coating, which can lead to a decrease in the resolution of tissue imaging.

Recrystallization is essential to address the extraction of weak analytes to achieve good ionization yields, and much attention has been paid to minimizing this phenomenon. Therefore, the creation of a templateless LDI technique with the combined advantages of improved tissue imaging capabilities and recognition sensitivity is particularly desirable when it comes to mapping the spatial distribution of small molecules.

Inorganic ultraviolet absorbing nanomaterials

Inorganic nanomaterials that absorb ultraviolet (UV) light, such as those based on silicon, carbon, composite nanomaterials, metal nanoparticles (NPs), metal oxide NPs, and metal-organic structures (MOFs), have attracted a lot of attention. These newly developed nanomaterials have advantages such as low thermal conductivity, excellent light absorption, high electrical conductivity and high surface-to-volume ratio.

Although the fine architectures of nanomaterials vary, independent of sputtering or sputtering, their nanoscale characteristics often produce a homogeneous coating surface, making them suitable candidates for MSI testing and tissue imaging.

Metal-based nanoparticles

An effective alternative for tracking endogenous metabolites present in animal and plant tissues is to use metal oxide NPs. The high boiling and melting points of these NPs make them resistant to ionization, resulting in a clear mass spectrum with high limiting background signals.

Plasmonic nanomaterials

To meet the growing demand for rapid, targeted and sensitive detection of small biomolecules, composite nanomaterials with synergistic action have received great attention. Plasmonic nanomaterials have been extensively researched for LDIMS and tissue imaging of different metabolites due to characteristics of hot carriers and localized surface plasmon resonance (LSPR).

However, according to several studies, they have problems such as unavoidable aggregations and inadequate thermal conductivity. A continuous effort has been made to create plasmonic core-shell nanoparticles for the sensitive analysis of metabolites in a variety of biological samples to address these limitations.

Silicon-based nanomaterials

For efficient LDI-MS for metabolites present in human biofluid samples, a variety of silica core-based nanoshells have been presented. To provide a distinctive metabolic fingerprint, a number of plasmonic bimetallic/trimetallic alloys have also been produced. Despite significant efforts, the excellent performance of core-shell plasmonic nanoparticles and high potential for LDI-MS and tissue imaging in practical implementations are by no means optimal.

In this work, a number of [email protected] core-shell NPs with controllable nanoshell frameworks have been obtained through a multi-cycle reduction reaction of Au3+ ions with SiO film2 spheres. The production procedure is simple, reproducible and not very reactive.

SiO2@Au nanoshells show improved performance in evaluating many small compounds with significantly less background interference, compared to typical organic matrices, due to enhanced photoelectric effects, hot carrier generation and local heating.

Important Findings

Three things could explain why these plasmonic gold nanobeads have better tissue imaging characteristics than currently present nanomaterials with a single composition. First, SiO2@Au nanoshells have significantly high light-heat conversion efficiency. Second, nanoscale roughness provides a particular crevice zone for the specific trapping of cations and small molecules from complex biological mixtures. Finally, the negatively charged layer promotes the creation of a layer of cations during the ionization procedure. All of these factors contribute to a high ion yield.

Small molecule lipid species and metabolites can be spatially observed in strawberry tissues, brain tissues of mice, and whole body tissues of bees and zebrafish due to nanoscale size and homogeneous stratification of SiO2@At nanoshells. This concrete evidence shows that the capabilities of plasmonic-based nano-shell materials can be enhanced for use in practical MSI applications.

Reference

Du, M., Chen, D. et al. (2022). Plasmonic gold nanoshell-assisted laser desorption/ionization mass spectrometry (LDI-MS) for small biomolecule analysis and tissue imaging. Available at: https://doi.org/10.1021/acsanm.2c01850

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