Relative Quantification of Lipid Isomers in Imaging Mass Spectrometry Using Gas-Phase Charge Inversion Ion/Ion Reactions and Infrared Multiphoton Dissociation

Structural Elucidation of Ubiquitin via Gas-Phase Ion/Ion Cross-Linking Reactions Using Sodium-Cationized Reagents Coupled with Infrared Multiphoton Dissociation

“…However, IRMPD in the ICR cell is better suited to produce sufficient, modified internal fragment peptide ions relative to sustained off-resonance irradiation (SORI) CID due to higher fragmentation efficiency . To enable this, a Synrad Duo Lase 50 W continuous wave CO 2 laser (J48-5W; Synrad, Mukilteo, WA, USA) was interfaced to the rear of the ICR magnet bore, as described previously . Briefly, the laser beam (10.6 μm wavelength) was introduced into the ICR cell through a barium fluoride (BaF 2 ) window.…”

Seeing is Believing: Developing Multimodal Metabolic Insights at the Molecular Level

“…While a few studies have explored the combination of Raman microscopy and MSI, ,− to the best of our knowledge, there is a scarcity of literature on the combined use of SRS microscopy and MALDI-MSI for multimodal imaging. In this section, we envision various practical scenarios in which the complementarity of both modalities can be employed within a multimodal workflow to inform researchers on metabolic discoveries: Cancer: For cancer tissues, SRS imaging can noninvasively and rapidly provide information on lipid phenotyping, distribution, desaturation levels, and cellular morphology. , This information can be leveraged for MSI by guiding researchers to specific regions of interest for data acquisition such that high mass resolution experiments with ion pairing, MS/MS, or ion mobility can be utilized to further characterize the lipids to identify the lipid chains, double bond positions, and detect additional classes such as sphingolipids, phospholipids, and glycerolipids that may not be easily detected with SRS imaging, enabling a more comprehensive understanding of tumor heterogeneity and progression in such tissues . This multimodal approach would save time while also leading to direct identification of lipid species. Clinical (tissue biopsy) samples: This versatile approach can be extrapolated to clinical scenarios involving tissue biopsy samples.…”

“…Cancer: For cancer tissues, SRS imaging can noninvasively and rapidly provide information on lipid phenotyping, distribution, desaturation levels, and cellular morphology. , This information can be leveraged for MSI by guiding researchers to specific regions of interest for data acquisition such that high mass resolution experiments with ion pairing, MS/MS, or ion mobility can be utilized to further characterize the lipids to identify the lipid chains, double bond positions, and detect additional classes such as sphingolipids, phospholipids, and glycerolipids that may not be easily detected with SRS imaging, enabling a more comprehensive understanding of tumor heterogeneity and progression in such tissues . This multimodal approach would save time while also leading to direct identification of lipid species.…”

“…This information can be leveraged for MSI by guiding researchers to specific regions of interest for data acquisition such that high mass resolution experiments with ion pairing, MS/MS, or ion mobility can be utilized to further characterize the lipids to identify the lipid chains, double bond positions, and detect additional classes such as sphingolipids, phospholipids, and glycerolipids that may not be easily detected with SRS imaging, enabling a more comprehensive understanding of tumor heterogeneity and progression in such tissues 172. …”

MS3 Imaging Enables the Simultaneous Analysis of Phospholipid C═C and sn-Position Isomers in Tissues

“…It has been revealed that lipid structure features such as headgroup, unsaturation degree, CC locations, and fatty acyl sn -positions are closely associated with lipid functions. − Tandem mass spectrometry (MS/MS) has been widely used in lipidomics for the identification of molecular species information on complex lipids. − However, it still remains challenging to unambiguously identify lipid CC location isomers or sn -position isomers in biological samples. In recent years, the development of novel dissociation methods such as ozone-induced dissociation (OzID), , electron impact excitation of ions from organics (EIEIO), − and ultraviolet photodissociation (UVPD) , enabled identification of detailed structural information on intact lipids by MS. To avoid modification on mass spectrometers, some chemical modification strategies have been developed to identify detailed structures of lipids by collision-induced dissociation (CID) MS 2 , such as the Paternò–Büchi (PB) reaction, − epoxidation, , ion/ion reactions, − and singlet-oxygen ene reaction. , On being coupled with ESI-MS/MS, these methods were able to identify sn - or CC location isomers of several classes of lipids in tissue and biofluid extracts. , …”