scholarly journals Resolving the Complexity of Spatial Lipidomics Using MALDI TIMS Imaging Mass Spectrometry

2020 ◽  
Author(s):  
Katerina Djambazova ◽  
Dustin R. Klein ◽  
Lukasz Migas ◽  
Elizabeth Neumann ◽  
Emilio Rivera ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Acyl Chain ◽  
Imaging Mass Spectrometry ◽  
Structural Diversity ◽  
Data Interpretation ◽  
Whole Body ◽  
Tissue Sections ◽  
Mouse Pup

<p>Lipids are a structurally diverse class of molecules with important biological functions including cellular signaling and energy storage. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for direct map-ping of biomolecules in tissue. Fully characterizing the structural diversity of lipids remains a challenge due to the presence of isobaric and isomeric species, which greatly complicates data interpretation when only <i>m/z </i>information is available. Integrating ion mobility separations aids in deconvoluting these complex mixtures and addressing the challenges of lipid IMS. Here we demonstrate that a MALDI quadrupole time-of-flight (Q-TOF) mass spectrometer with trapped ion mobility spectrometry (TIMS) enables approximately a ~270% increase in the peak capacity during IMS experiments. MALDI TIMS-MS separation of lipid isomer standards, including sn-backbone isomers, acyl chain isomers, as well as double bond positional and geometric isomers are demonstrated. As a proof-of-concept, <i>in situ </i>separation and imaging of lipid isomers with distinct spatial distributions was performed using tissue sections from a whole-body mouse pup.</p>

scholarly journals Resolving the Complexity of Spatial Lipidomics Using MALDI TIMS Imaging Mass Spectrometry

2020 ◽  
Author(s):  
Katerina Djambazova ◽  
Dustin R. Klein ◽  
Lukasz Migas ◽  
Elizabeth Neumann ◽  
Emilio Rivera ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Acyl Chain ◽  
Imaging Mass Spectrometry ◽  
Structural Diversity ◽  
Data Interpretation ◽  
Whole Body ◽  
Tissue Sections ◽  
Mouse Pup

<p>Lipids are a structurally diverse class of molecules with important biological functions including cellular signaling and energy storage. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for direct map-ping of biomolecules in tissue. Fully characterizing the structural diversity of lipids remains a challenge due to the presence of isobaric and isomeric species, which greatly complicates data interpretation when only <i>m/z </i>information is available. Integrating ion mobility separations aids in deconvoluting these complex mixtures and addressing the challenges of lipid IMS. Here we demonstrate that a MALDI quadrupole time-of-flight (Q-TOF) mass spectrometer with trapped ion mobility spectrometry (TIMS) enables approximately a ~270% increase in the peak capacity during IMS experiments. MALDI TIMS-MS separation of lipid isomer standards, including sn-backbone isomers, acyl chain isomers, as well as double bond positional and geometric isomers are demonstrated. As a proof-of-concept, <i>in situ </i>separation and imaging of lipid isomers with distinct spatial distributions was performed using tissue sections from a whole-body mouse pup.</p>

scholarly journals Resolving the Complexity of Spatial Lipidomics Using MALDI TIMS Imaging Mass Spectrometry

2020 ◽  
Author(s):  
Katerina Djambazova ◽  
Dustin R. Klein ◽  
Lukasz Migas ◽  
Elizabeth Neumann ◽  
Emilio Rivera ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Acyl Chain ◽  
Imaging Mass Spectrometry ◽  
Structural Diversity ◽  
Data Interpretation ◽  
Whole Body ◽  
Tissue Sections ◽  
Mouse Pup

<p>Lipids are a structurally diverse class of molecules with important biological functions including cellular signaling and energy storage. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for direct map-ping of biomolecules in tissue. Fully characterizing the structural diversity of lipids remains a challenge due to the presence of isobaric and isomeric species, which greatly complicates data interpretation when only <i>m/z </i>information is available. Integrating ion mobility separations aids in deconvoluting these complex mixtures and addressing the challenges of lipid IMS. Here we demonstrate that a MALDI quadrupole time-of-flight (Q-TOF) mass spectrometer with trapped ion mobility spectrometry (TIMS) enables approximately a ~270% increase in the peak capacity during IMS experiments. MALDI TIMS-MS separation of lipid isomer standards, including sn-backbone isomers, acyl chain isomers, as well as double bond positional and geometric isomers are demonstrated. As a proof-of-concept, <i>in situ </i>separation and imaging of lipid isomers with distinct spatial distributions was performed using tissue sections from a whole-body mouse pup.</p>

scholarly journals Resolving the Complexity of Spatial Lipidomics with MALDI Trapped Ion Mobility Spectrometry

2020 ◽  
Author(s):  
Katerina Djambazova ◽  
Dustin R. Klein ◽  
Lukasz Migas ◽  
Elizabeth Neumann ◽  
Emilio Rivera ◽  
...  
Keyword(s):  
Ion Mobility Spectrometry ◽  
Ion Mobility ◽  
Acyl Chain ◽  
Imaging Mass Spectrometry ◽  
Structural Diversity ◽  
Whole Body ◽  
Mass Spectral ◽  
Trapped Ion ◽  
Trapped Ion Mobility Spectrometry ◽  
Mouse Pup

<p><b>Lipids are a structurally diverse class of molecules, with</b> <b>important biological functions including cellular signaling and energy storage. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for visualization of molecules directly from tissue, but has difficulty addressing the structural diversity of the lipidome, owing to the presence of many isobaric and isomeric species that overlap in <i>m/z</i> space. Integrating ion mobility separations aids in mass spectral deconvolution and address lipid complexity. Here we demonstrate that a MALDI quadrupole time-of-flight (QTOF) mass spectrometer with trapped ion mobility spectrometry (TIMS) enables a significant increase in the peak capacity (~207%) during </b>lipid<b> IMS experiment</b>s<b>. MALDI-TIMS was also used for separation of lipid isomer standards, including sn-backbone isomers, acyl chain isomers, as well as double bond positional and geometric isomers was also demonstrated. Proof of concept, <i>in situ</i> separation and imaging of lipid isomers with distinct spatial distributions was demonstrated using whole-body mouse pup tissue. </b></p>

scholarly journals Postembedding Decalcification of Mineralized Tissue Sections Preserves the Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Thaqif El Khassawna ◽  
Diaa Eldin S. Daghma ◽  
Sabine Stoetzel ◽  
Seemun Ray ◽  
Stefanie Kern ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
In Situ Hybridization ◽  
Research Question ◽  
Imaging Mass Spectrometry ◽  
Protein Signaling ◽  
Experimental Animals ◽  
Correlative Analysis ◽  
Tissue Sections ◽  
Novel Approach

Bone histology of decalcified or undecalcified samples depends on the investigation. However, in research each method provides different information to answer the scientific question. Decalcification is the first step after sample fixation and governs what analysis is later feasible on the sections. Besides, decalcification is favored for immunostaining and in situ hybridization. Otherwise, sample decalcification can be damaging to bone biomaterials implants that contains calcium or strontium. On the other hand, after decalcification mineralization cannot be assessed using histology or imaging mass spectrometry. The current study provides a solution to the hardship caused by material presence within the bone tissue. The protocol presents a possibility of gaining sequential and alternating decalcified and undecalcified sections from the same bone sample. In this manner, investigations using histology, protein signaling, in situ hybridization, and mass spectrometry on the same sample can better answer the intended research question. Indeed, decalcification of sections and grindings resulted in well-preserved sample and biomaterials integrity. Immunostaining was comparable to that of classically decalcified samples. The study offers a novel approach that incites correlative analysis on the same sample and reduces the number of processed samples whether clinical biopsies or experimental animals.

Spatial Metabolomics of the Human Kidney Using MALDI Trapped Ion Mobility Imaging Mass Spectrometry

2020 ◽  
Author(s):  
Elizabeth Neumann ◽  
Lukasz Migas ◽  
Jamie L. Allen ◽  
Richard Caprioli ◽  
Raf Van de Plas ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Imaging Mass Spectrometry ◽  
Structural Complexity ◽  
Human Kidney ◽  
Resolving Power ◽  
Mobility Separation ◽  
Trapped Ion ◽  
Mobility Data ◽  
Ion Mobility Separation

<div> <div> <p>Small metabolites are essential for normal and diseased biological function but are difficult to study because of their inherent structural complexity. MALDI imaging mass spectrometry (IMS) of small metabolites is particularly challenging as MALDI matrix clusters are often isobaric with metabolite ions, requiring high resolving power instrumentation or derivatization to circumvent this issue. An alternative to this is to perform ion mobility separation before ion detection, enabling the visualization of metabolites without the interference of matrix ions. Here, we use MALDI timsTOF IMS to image small metabolites at high spatial resolution within the human kidney. Through this, we have found metabolites, such as arginic acid, acetylcarnitine, and choline that localize to the cortex, medulla, and renal pelvis, respectively. We have also demonstrated that trapped ion mobility spectrometry (TIMS) can resolve matrix peaks from metabolite signal and separate both isobaric and isomeric metabolites with different localizations within the kidney. The added ion mobility data dimension dramatically increased the peak capacity for molecular imaging experiments. Future work will involve further exploring the small metabolite profiles of human kidneys as a function of age, gender, and ethnicity.</p></div></div>

scholarly journals Exemplifying the Screening Power of Mass Spectrometry Imaging over Label-Based Technologies for Simultaneous Monitoring of Drug and Metabolite Distributions in Tissue Sections

2015 ◽  
Vol 21 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Richard J. A. Goodwin ◽  
Anna Nilsson ◽  
C. Logan Mackay ◽  
John G. Swales ◽  
Maria K. Johansson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Cyclic Peptide ◽  
Analysis Data ◽  
Resolving Power ◽  
High Mass ◽  
Whole Body ◽  
Ion Cyclotron Resonance ◽  
Label Free ◽  
Tissue Sections

Mass spectrometry imaging (MSI) provides pharmaceutical researchers with a suite of technologies to screen and assess compound distributions and relative abundances directly from tissue sections and offer insight into drug discovery–applicable queries such as blood-brain barrier access, tumor penetration/retention, and compound toxicity related to drug retention in specific organs/cell types. Label-free MSI offers advantages over label-based assays, such as quantitative whole-body autoradiography (QWBA), in the ability to simultaneously differentiate and monitor both drug and drug metabolites. Such discrimination is not possible by label-based assays if a drug metabolite still contains the radiolabel. Here, we present data exemplifying the advantages of MSI analysis. Data of the distribution of AZD2820, a therapeutic cyclic peptide, are related to corresponding QWBA data. Distribution of AZD2820 and two metabolites is achieved by MSI, which [14C]AZD2820 QWBA fails to differentiate. Furthermore, the high mass-resolving power of Fourier transform ion cyclotron resonance MS is used to separate closely associated ions.

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