scholarly journals Unravel the Local Complexity of Biological Environments by MALDI Mass Spectrometry Imaging

2021 ◽  
Vol 22 (22) ◽  
pp. 12393
Author(s):  
Elvira Sgobba ◽  
Yohann Daguerre ◽  
Marco Giampà

Classic metabolomic methods have proven to be very useful to study functional biology and variation in the chemical composition of different tissues. However, they do not provide any information in terms of spatial localization within fine structures. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) does and reaches at best a spatial resolution of 0.25 μm depending on the laser setup, making it a very powerful tool to analyze the local complexity of biological samples at the cellular level. Here, we intend to give an overview of the diversity of the molecules and localizations analyzed using this method as well as to update on the latest adaptations made to circumvent the complexity of samples. MALDI MSI has been widely used in medical sciences and is now developing in research areas as diverse as entomology, microbiology, plant biology, and plant–microbe interactions, the rhizobia symbiosis being the most exhaustively described so far. Those are the fields of interest on which we will focus to demonstrate MALDI MSI strengths in characterizing the spatial distributions of metabolites, lipids, and peptides in relation to biological questions.

Author(s):  
Riccardo Zecchi ◽  
Pietro Franceschi ◽  
Laura Tigli ◽  
Davide Amidani ◽  
Chiara Catozzi ◽  
...  

AbstractCorticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard’s reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples. Graphical abstract


2020 ◽  
Vol 58 (6) ◽  
pp. 914-929 ◽  
Author(s):  
Klára Ščupáková ◽  
Benjamin Balluff ◽  
Caitlin Tressler ◽  
Tobi Adelaja ◽  
Ron M.A. Heeren ◽  
...  

AbstractMass spectrometry (MS) is the workhorse of metabolomics, proteomics and lipidomics. Mass spectrometry imaging (MSI), its extension to spatially resolved analysis of tissues, is a powerful tool for visualizing molecular information within the histological context of tissue. This review summarizes recent developments in MSI and highlights current challenges that remain to achieve molecular imaging at the cellular level of clinical specimens. We focus on matrix-assisted laser desorption/ionization (MALDI)-MSI. We discuss the current status of each of the analysis steps and remaining challenges to reach the desired level of cellular imaging. Currently, analyte delocalization and degradation, matrix crystal size, laser focus restrictions and detector sensitivity are factors that are limiting spatial resolution. New sample preparation devices and laser optic systems are being developed to push the boundaries of these limitations. Furthermore, we review the processing of cellular MSI data and images, and the systematic integration of these data in the light of available algorithms and databases. We discuss roadblocks in the data analysis pipeline and show how technology from other fields can be used to overcome these. Finally, we conclude with curative and community efforts that are needed to enable contextualization of the information obtained.


2021 ◽  
Author(s):  
Christoph Bookmeyer ◽  
Ulrich Röhling ◽  
Klaus Dreisewerd ◽  
Jens Soltwisch

Abstract Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a rapidly growing method in many fields of the life sciences. For many analyte classes, however, its sensitivity is limited due to poor ionization efficiencies. To mitigate this problem, we here introduce a novel and cost-effective postionization scheme at high repetition rates based on the interplay of single-photon photoionization and subsequent charge transfer reactions. Importantly, the fine vacuum conditions of a dual ion-funnel ion source effectively thermalize the evolving MALDI plume and enable ample gas-phase reactions as well as the addition of chemical dopants that crucially support chemical ionization. Supported by acetone dopant, [M + H]+/[M-H]− signals of numerous glycerophospho-, sphingo-, and further lipids, registered from mammal brain and kidney sections, were boosted by up to three orders of magnitude, similar to results obtained with laser-based postionization (MALDI-2). Experiments utilizing deuterated matrix and dopant, however, indicate complex ionization pathways different from MALDI2.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 610
Author(s):  
Mariann Inga Van Meter ◽  
Salah M. Khan ◽  
Brynne V. Taulbee-Cotton ◽  
Nathan H. Dimmitt ◽  
Nathan D. Hubbard ◽  
...  

Agglomeration of active pharmaceutical ingredients (API) in tablets can lead to decreased bioavailability in some enabling formulations. In a previous study, we determined that crystalline APIs can be detected as agglomeration in tablets formulated with amorphous acetaminophen tablets. Multiple method advancements are presented to better resolve agglomeration caused by crystallinity in standard tablets. In this study, we also evaluate three “budget” over-the-counter headache medications (subsequently labeled as brands A, B, and C) for agglomeration of the three APIs in the formulation: Acetaminophen, aspirin, and caffeine. Electrospray laser desorption ionization mass spectrometry imaging (ELDI-MSI) was used to diagnose agglomeration in the tablets by creating molecular images and observing the spatial distributions of the APIs. Brand A had virtually no agglomeration or clustering of the active ingredients. Brand B had extensive clustering of aspirin and caffeine, but acetaminophen was observed in near equal abundance across the tablet. Brand C also had extensive clustering of aspirin and caffeine, and minor clustering of acetaminophen. These results show that agglomeration with active ingredients in over-the-counter tablets can be simultaneously detected using ELDI-MS imaging.


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