Liquid extraction surface analysis field asymmetric waveform ion mobility spectrometry mass spectrometry for the analysis of dried blood spots

Griffiths, Rhonda; Dexter, Alex; Creese, Andrew J.; Cooper, Helen J.

doi:10.1039/c5an00933b

Cited by 53 publications

(55 citation statements)

References 40 publications

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“…The concern of a diminishing mass range as the device is shrunk down is another potential issue that, in contrast to mass spectrometry, does not affect FAIMS. There are many publications demonstrating the application of small FAIMS systems both to lowmass compounds, such as metabolites and lipids, 28 and high-mass compounds such as proteins. 29 …”

Section: Overview and Considerationsmentioning

confidence: 99%

Portable FAIMS: Applications and future perspectives

Costanzo¹,

Boock²,

Kemperman

et al. 2017

International Journal of Mass Spectrometry

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Miniaturized mass spectrometry (MMS) is optimal for a wide variety of applications that benefit from field-portable instrumentation. Like MMS, field asymmetric ion mobility spectrometry (FAIMS) has proven capable of providing in situ analysis, allowing researchers to bring the lab to the sample. FAIMS compliments MMS very well, but has the added benefit of operating at atmospheric pressure, unlike MS. This distinct advantage makes FAIMS uniquely suited for portability. Since its inception, FAIMS has been envisioned as a field-portable device, as it affords less expense and greater simplicity than many similar methods. Ideally, these are simple, robust devices that may be operated by non-professional personnel, yet still provide adequate data when in the field. While reducing the size and complexity tends to bring with it a loss of performance and accuracy, this is made up for by the incredibly high throughput and overall convenience of the instrument. Moreover, the FAIMS device used in the field can be brought back to the lab, and coupled to a conventional mass spectrometer to provide any necessary method development and compound validation. This work discusses the various considerations, uses, and applications for portable FAIMS instrumentation, and how the future of each applicable field may benefit from the development and acceptance of such a device.

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Section: Overview and Considerationsmentioning

confidence: 99%

Portable FAIMS: Applications and future perspectives

Costanzo¹,

Boock²,

Kemperman

et al. 2017

International Journal of Mass Spectrometry

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“…MALDI-MSI is ideally placed for in situ molecular mapping since lipids are directly ablated and ionized from tissue by a moving laser pulse, retaining critical spatial information (12)(13)(14)(15). In LESA-MS lipids are extracted directly from the surface of tissue with solvent, providing an orthogonal approach to the direct analysis of lipids from tissues (16)(17)(18). This allowed us to follow lipidome changes and to map these effects across the tissue.…”

Section: Introductionmentioning

confidence: 99%

Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer

et al. 2016

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MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven lung adenocarcinoma that affords reversible activation of MYC, used here as a tool for lipidomic profiling of MYC-dependent lung tumors formed in this model. Advanced mass spectrometric imaging and surface analysis techniques were used to characterize the spatial and temporal changes in lipid composition in lung tissue. We found that normal lung tissue was characterized predominantly by saturated phosphatidylcholines and phosphatidylglycerols, which are major lipid components of pulmonary surfactant. In contrast, tumor tissues displayed an increase in phosphatidylinositols and arachidonate-containing phospholipids that can serve as signaling precursors. Deactivating MYC resulted in a rapid and dramatic decrease in arachidonic acid and its eicosanoid metabolites. In tumors with high levels of MYC, we found an increase in cytosolic phospholipase A2 (cPLA2) activity with a preferential release of membrane-bound arachidonic acid, stimulating the lipoxygenase (LOX) and COX pathways also amplified by MYC at the level of gene expression. Deactivating MYC lowered cPLA2 activity along with COX2 and 5-LOX mRNA levels. Notably, inhibiting the COX/5-LOX pathways in vivo reduced tumor burden in a manner associated with reduced cell proliferation. Taken together, our results show how MYC drives the production of specific eicosanoids critical for lung cancer cell survival and proliferation, with possible implications for the use of COX and LOX pathway inhibitors for lung cancer therapy.

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“…High sensitivity is achieved by retaining all extracted analytes in a single droplet of solvent, offering a unique advantage over continuous flow systems. Furthermore, LESA allows great flexibility in experimental design as the sampling and ionisation steps are independent: for example, additional sample manipulation, such as digestion, separation (by ion mobility spectrometry or liquid chromatography), or implementation of multiple consecutive extraction steps (using the same solvent system or multiple solvent compositions) . These advantages, however, come at the price of the lowest spatial resolution among the ambient ionisation techniques described here.…”

Section: Ambient Surface Sampling Mass Spectrometry Techniquesmentioning

confidence: 99%

Ambient ionisation mass spectrometry for in situ analysis of intact proteins

2018

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Ambient surface mass spectrometry is an emerging field which shows great promise for the analysis of biomolecules directly from their biological substrate. In this article, we describe ambient ionisation mass spectrometry techniques for the in situ analysis of intact proteins. As a broad approach, the analysis of intact proteins offers unique advantages for the determination of primary sequence variations and posttranslational modifications, as well as interrogation of tertiary and quaternary structure and protein‐protein/ligand interactions. In situ analysis of intact proteins offers the potential to couple these advantages with information relating to their biological environment, for example, their spatial distributions within healthy and diseased tissues. Here, we describe the techniques most commonly applied to in situ protein analysis (liquid extraction surface analysis, continuous flow liquid microjunction surface sampling, nano desorption electrospray ionisation, and desorption electrospray ionisation), their advantages, and limitations and describe their applications to date. We also discuss the incorporation of ion mobility spectrometry techniques (high field asymmetric waveform ion mobility spectrometry and travelling wave ion mobility spectrometry) into ambient workflows. Finally, future directions for the field are discussed.

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Liquid extraction surface analysis field asymmetric waveform ion mobility spectrometry mass spectrometry for the analysis of dried blood spots

Cited by 53 publications

References 40 publications

Portable FAIMS: Applications and future perspectives

Portable FAIMS: Applications and future perspectives

Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer

Ambient ionisation mass spectrometry for in situ analysis of intact proteins

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