Tissue Imaging at Atmospheric Pressure Using Desorption Electrospray Ionization (DESI) Mass Spectrometry

Wiseman, Justin M.; Ifa, Demian R.; Song, Qingyu; Cooks, R. Graham

doi:10.1002/anie.200602449

Cited by 549 publications

(437 citation statements)

References 23 publications

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“…In the alternative serial sectioning approach, serial sections of the object are obtained through mechanical sectioning and individually analyzed. Matrix assisted laser desorption ionization (MALDI-MS) [8] is the only technique that have been used to serial sectioning analysis for 3D imaging.SIMS and MALDI are well established techniques that have been widely used for molecular imaging under vacuum but newer ambient ionization methods such as DESI [9,10], LAESI, AP-IR-MALDI and LA-FAPA allow the direct analysis of samples in the open atmosphere. In particular, DESI-MS is an ambient desorption ionization method with the advantages of little or no sample preparation, ease of implementation and simplified analysis [11].…”

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confidence: 99%

“…SIMS and MALDI are well established techniques that have been widely used for molecular imaging under vacuum but newer ambient ionization methods such as DESI [9,10], LAESI, AP-IR-MALDI and LA-FAPA allow the direct analysis of samples in the open atmosphere. In particular, DESI-MS is an ambient desorption ionization method with the advantages of little or no sample preparation, ease of implementation and simplified analysis [11].…”

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Three‐Dimensional Vizualization of Mouse Brain by Lipid Analysis Using Ambient Ionization Mass Spectrometry

Eberlin

Ifa

et al. 2010

Angewandte Chemie

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Keywords ambient ionization; molecular imaging; mass spectrometry; mouse brain model; phospholipids; tissue analysis Two-dimensional (2D) imaging mass spectrometry (MS) [1] has emerged as a powerful technique in the biological sciences. It allows direct investigation of the distribution of a variety of lipids, drugs, biological defensive agents, pigments and proteins in plant and animal tissues with high specificity and without the need of fluorescent or radioactive labelling normally used in histochemical protocols. [2,3] In imaging MS, the chemical identity of molecules present on a surface is investigated as a function of their 2D spatial distribution (x and y coordinates).Three-dimensional (3D) images can be constructed from a suitable set of 2D data and they illustrate the spatial distributions of specific biomolecules in substructures of tissues including pathological features [4]. Two basic approaches, depth profiling and serial sectioning, have been described for recording the information needed to create 3D MS-based images. In depth profiling experiments, the desorbing agent is used to remove shallow layers of material from the surface of the object in between recording surface analysis data. Secondary ion mass spectrometry (SIMS) [5], laser ablation electrospray ionization (LAESI) [2,6] and laser ablation flowing atmospheric-pressure afterglow (LA-FAPA) [7] are ionization techniques that have been used to create 3D MS models by depth profiling. In the alternative serial sectioning approach, serial sections of the object are obtained through mechanical sectioning and individually analyzed. Matrix assisted laser desorption ionization (MALDI-MS) [8] is the only technique that have been used to serial sectioning analysis for 3D imaging.SIMS and MALDI are well established techniques that have been widely used for molecular imaging under vacuum but newer ambient ionization methods such as DESI [9,10], LAESI, AP-IR-MALDI and LA-FAPA allow the direct analysis of samples in the open atmosphere. In particular, DESI-MS is an ambient desorption ionization method with the advantages of little or no sample preparation, ease of implementation and simplified analysis [11]. Most importantly, the problem of endogenous compounds dislocation during sample preparation procedures of traditional histochemical analysis can be overcome, because tissue sections are analyzed directly outside the mass spectrometer without any treatments after sectioning. It has been shown that DESI-MS imaging can be used to distinguish between cancerous and non-cancerous tissue samples using multiple marker lipids [12]. DESI-MS imaging has also In order to obtain high quality 2D images, essential to building reliable 3D images, experimental conditions were optimized to maximize the signal intensity and increase image quality (see Supporting Information for Experimental Section). Indeed, it has been shown that several experimental parameters can be optimized to improve the quality of DESI data. [9,15] Two distinctive mass spectral patterns were ob...

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confidence: 99%

Three‐Dimensional Vizualization of Mouse Brain by Lipid Analysis Using Ambient Ionization Mass Spectrometry

Eberlin

Ifa

et al. 2010

Angewandte Chemie

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“…Examining tissue for disease includes finding tumor margins by analyzing the lipid distributions in tissue sections sent to pathology during surgery, 23 noninvasive examination of skin lesions, and examination of needle biopsies in the doctor's office. The measurements made on biological fluids could include metabolomics studies, characterization of inborn errors of metabolism, and self-monitoring of biological fluids, an application for which regulatory permissions will have to develop along with the technology.…”

Section: A Personal Mass Specmentioning

confidence: 99%

Handheld Miniature Ion Trap Mass Spectrometers

2009

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For field applications, "miniature" and "rapid" have become almost synonymous, yet these small mass spectrometers are not useful if performance is too severely compromised. (To listen to a podcast about this feature, please go to the Analytical Chemistry website at pubs. acs.org/journal/ancham.)MS is widely regarded as the gold standard for chemical analysis with respect to selectivity, detection limits, and broad applicability. However, mass spectrometers are comparatively delicate instruments, partly a consequence of the need for a vacuum system into which the sample is introduced. There have long been efforts at direct MS analysis of complex mixtures, 1 but extensive sample cleanup and increasingly sophisticated multianalyzers have been involved. These considerations have limited the applications of MS outside the laboratory. It is striking that although progress in many areas of technology is strongly associated with miniaturization, this correlation is barely evident in MS.Nevertheless, for many applications of MS, in situ experiments would have significant advantages over laboratory measurements, even if there are significant losses in analytical performance. Some applications of immediate interest include environmental monitoring (especially surveys that require large numbers of samples), quality control, food safety, forensics, security and public safety, and clinical diagnostics. The objective of this article is to summarize recent progress in developing handheld miniature mass spectrometers. Note that the focus is on complete systems, not particular components, even important ones like the mass analyzer. ON THE SMALL SIDEInterest in small mass analyzers stretches back several decades. For example, a hyperbolic ion trap analyzer the size of a quarter with a 2.5-mm radius and an m/z range of 70,000 was reported in 1991.2 A Mattauch-Herzog-type, nonscanning, double-focusing sector mass analyzer was reported in 1991, and a very small, double-focusing, crossed electric-and magnetic-field sector analyzer was described in 2001.3,4 Recent work by Ramsey, Austin, Short, and others has advanced small analyzers further, and the emphasis is increasingly turning to microelectromechanical systems (MEMS)-fabricated mass analyzers. [5][6][7][8] However, only in the past decadesand especially in the past 5 yearsshas significant progress been made in the development of small, low-power, portable, autonomous mass spectrometer systems; some have progressed to the point of commercialization. A review in 2000 summarized the mass analyzers used in miniature instruments, showing examples of virtually all the common types, including quadrupole mass filters, quadrupole ion traps, magnetic sector fields, TOF, and FT ion cyclotron resonance instruments. 9 More recent work has seen the commercialization of a novel toroidal ion trap system. 10 A website devoted to small instruments and a conference series on MS in harsh environments prominently features handheld mass spectrometers (www.gcms.

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“…8 electrospray 11 ionization mass spectrometry, this method has some advantages: specifically lower sensitivity to contaminants, lower detection limits, and the ability to store samples and analyze them minutes (or days) later. Compared to MALDI, SIMS is suitable for studying elements and small molecules usually not exceeding 500 Da, while providing spatial resolution on a sub-micron level.…”

Section: Introductionmentioning

confidence: 99%

Vacuum compatible sample positioning device for matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry imaging

Aizikov

Smith

Chargin

et al. 2011

Review of Scientific Instruments

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The high mass accuracy and resolving power of Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS) make them ideal mass detectors for mass spectrometry imaging (MSI), promising to provide unmatched molecular resolution capabilities. The intrinsic low tolerance of FT-ICR MS to RF interference, however, along with typically vertical positioning of the sample, and MSI acquisition speed requirements present numerous engineering challenges in creating robotics capable of achieving the spatial resolution to match. This work discusses a two-dimensional positioning stage designed to address these issues. The stage is capable of operating in ∼1 × 10 -8 mbar vacuum. The range of motion is set to 100 mm × 100 mm to accommodate large samples, while the positioning accuracy is demonstrated to be less than 0.4 micron in both directions under vertical load over the entire range. This device was integrated into three different matrix assisted laser desorption/ionization (MALDI) FT-ICR instruments and showed no detectable RF noise. The "oversampling" MALDI-MSI experiments, under which the sample is completely ablated at each position, followed by the target movement of the distance smaller than the laser beam, conducted on the custom-built 7T FT-ICR MS demonstrate the stability and positional accuracy of the stage robotics which delivers high spatial resolution mass spectral images at a fraction of the laser spot diameter.

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Tissue Imaging at Atmospheric Pressure Using Desorption Electrospray Ionization (DESI) Mass Spectrometry

Cited by 549 publications

References 23 publications

Three‐Dimensional Vizualization of Mouse Brain by Lipid Analysis Using Ambient Ionization Mass Spectrometry

Three‐Dimensional Vizualization of Mouse Brain by Lipid Analysis Using Ambient Ionization Mass Spectrometry

Handheld Miniature Ion Trap Mass Spectrometers

Vacuum compatible sample positioning device for matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry imaging

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