AP-MALDI Mass Spectrometry Imaging of Gangliosides Using 2,6-Dihydroxyacetophenone

Jackson, Shelley N.; Muller, Ludovic; Roux, Aurélie; Öktem, Berk; Moskovets, Eugene; Doroshenko, Vladimir M.; Woods, Amina S.

doi:10.1007/s13361-018-1928-8

Cited by 53 publications

(52 citation statements)

References 49 publications

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“…In order to characterize the ISE in MALDI analysis with the feasibility of source pressure control, we utilized a high spatial resolution SubAP-MALDI source with improved source pressure adjusting capability compared to the regular AP-MALDI source. Similar to the previous AP-MALDI setup developed by MassTech, 41–42 SubAP-MALDI was interfaced with a QE-HF Orbitrap instrument (Scheme 1a). A representative mass spectrum of a peptide standard mixture recorded from the SubAP-MALDI-Orbitrap is shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Characterizing and alleviating ion suppression effects in atmospheric pressure matrix‐assisted laser desorption/ionization

Cao

Liu

et al. 2019

Rapid Comm Mass Spectrometry

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RATIONALE: As a powerful ambient ion source, atmospheric pressure (AP)-MALDI enables direct analysis at atmospheric pressure/temperature and minimal sample preparation. With the increasing usage of AP-MALDI sources with Orbitrap instruments, systematic characterization of the extent of ion suppression effect (ISE) in AP-MALDI-Orbitrap mass spectrometry imaging (MSI) is desirable. Recently, a new low-pressure MALDI platform has been introduced that reportedly provided better sensitivity. While extensive research efforts have been devoted to improving spatial resolution, fewer studies focused on the characterization and sensitivity improvement of these MALDI platforms that, coupled with high-resolution Orbitraps, provide powerful strategy for MS imaging. METHODS: Here, we compared the analytical performance of AP and low-pressure (subatmospheric) MALDI sources to study the effect of pressure control in the ion source. Using a model peptide/protein mixture, we systematically evaluated the factors influencing ISE. Furthermore, the effect of laser spot size was evaluated through tissue imaging analysis of lipids and neuropeptides. The effects of ion suppression and laser spot size have also been examined by comparing the number of identified molecular species during MSI analysis. RESULTS: Several key operating parameters including source pressure, laser energy, laser repetition rate, and microscopic slide coating materials were optimized to minimize the ISE. Under the optimal conditions, the subatmospheric AP-MALDI-Orbitrap platform with high spatial and mass spectral resolution enabled significantly improved coverage of several lipid and neuropeptide families in the MS analysis of mouse brain tissue sections. CONCLUSIONS: The new SubAP-MALDI source coupled with an Orbitrap mass spectrometer was established as a viable platform for in situ endogenous biomolecular analysis with increased sensitivity compared to conventional AP-MALDI sources as evidenced by the confident identification of neuropeptides from mouse brain imaging analyses. The alleviated ISE was key to substantial performance improvement due to optimized intermediate pressure conditions and better ion collection by the ion funnel.

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Section: Resultsmentioning

confidence: 99%

Characterizing and alleviating ion suppression effects in atmospheric pressure matrix‐assisted laser desorption/ionization

Cao

Liu

et al. 2019

Rapid Comm Mass Spectrometry

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“…However, the enhancement seen in negative ion mode is possibly more akin to a global intensity increase whereby similar ionic species are comparatively prominent both with and without plasma. Despite the substantial influence of the plasma in these data the influence of the matrix in dictating the identity of the species ionised is not to be overlooked [38].…”

Section: Analysis Of Murine Brainmentioning

confidence: 99%

Construction and testing of an atmospheric-pressure transmission-mode matrix assisted laser desorption ionisation mass spectrometry imaging ion source with plasma ionisation enhancement

Steven

Shaw

Murta

et al. 2019

Analytica Chimica Acta

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Matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) at atmospheric pressure (AP) is, with a few notable exceptions, overshadowed by its vacuum based forms and AP transmission mode (TM) MALDI-MS lacks the uptake its potential benefits might suggest. The reasons for this are not fully understood and it is clear further development is required to realise the flexibility and power of this ionisation method and geometry. Here we report the build of a new AP-TM-MALDI-MSI ion source with plasma ionisation enhancement. This novel ion source is used to analyse a selection of increasingly complex systems from molecular standards to murine brain tissue sections. Significant enhancement of detected ion intensity is observed in both positive and negative ion mode in all systems, with up to 2000 fold increases observed for a range of tissue endogenous species. The substantial improvements conferred by the plasma enhancement are then employed to demonstrate the acquisition of proof of concept tissue images, with high quality spectra obtained down to 10 × 10 µm pixel size.

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“…High-beam millisecond synchrotron X-rays 43 and nanosecond laser (3–5 ns, 266 nm, 30 Hz) 44,45 have been previously used for residue oxidation-based solution protein surface mapping. Herein, we first adapted a nanosecond solid-state Nd:YAG laser with a relatively gentle nature (2 ns, 355 nm) 46,47 , to initiate photochemical reactions of NBA in a sub-atmospheric pressure (Sub)AP-MALDI source coupled to an Orbitrap instrument. A similar laser system in vacuum MALDI platform in a time-of-flight (ToF) instrument (Bruker RapifleX, more details in Online Methods) was then employed specifically for large protein structural probing.…”

Section: Resultsmentioning

confidence: 99%

Nanosecond photochemically promoted click chemistry for enhanced neuropeptide visualization and rapid protein labeling

Cao

et al. 2019

Nat Commun

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Comprehensive protein identification and concomitant structural probing of proteins are of great biological significance. However, this is challenging to accomplish simultaneously in one confined space. Here, we develop a nanosecond photochemical reaction (nsPCR)-based click chemistry, capable of structural probing of proteins and enhancing their identifications through on-demand removal of surrounding matrices within nanoseconds. The nsPCR is initiated using a photoactive compound, 2-nitrobenzaldehyde (NBA), and is examined by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). Benefiting from the on-demand matrix-removal effect, this nsPCR strategy enables enhanced neuropeptide identification and visualization from complex tissue samples such as mouse brain tissue. The design shows great promise for structural probing of proteins up to 155 kDa due to the exclusive accessibility of nsPCR to primary amine groups, as demonstrated by its general applicability using a series of proteins with various lysine residues from multiple sample sources, with accumulated labeling efficiencies greater than 90%.

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AP-MALDI Mass Spectrometry Imaging of Gangliosides Using 2,6-Dihydroxyacetophenone

Cited by 53 publications

References 49 publications

Characterizing and alleviating ion suppression effects in atmospheric pressure matrix‐assisted laser desorption/ionization

Characterizing and alleviating ion suppression effects in atmospheric pressure matrix‐assisted laser desorption/ionization

Construction and testing of an atmospheric-pressure transmission-mode matrix assisted laser desorption ionisation mass spectrometry imaging ion source with plasma ionisation enhancement

Nanosecond photochemically promoted click chemistry for enhanced neuropeptide visualization and rapid protein labeling

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