Imaging mass spectrometry: fundamentals and applications to drug discovery

Rubakhin, Stanislav S.; Jurchen, John C.; Monroe, Eric B.; Sweedler, Jonathan V.

doi:10.1016/s1359-6446(05)03458-6

Cited by 185 publications

(164 citation statements)

References 95 publications

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“…The sample is sprayed with a matrix, and the ions of interest are desorbed from the tissue by using a conventional MALDI source. The laser position over the target is gradually changed in steps over a predetermined x, y-grid, and the final ion image is plotted by using three-dimensional coordinates with x and y axes for positions and the z axis for the intensity of the particular ion (15). Diverse analytes have been characterized by MALDI-TOF imaging including drugs, peptides, and proteins in animal tissues (16), and herbicides (17) and peptides (18) in plants.…”

mentioning

confidence: 99%

Nonuniform distribution of glucosinolates in Arabidopsis thaliana leaves has important consequences for plant defense

Shroff

Vergara

Muck

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

261

236

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The spatial distribution of plant defenses within a leaf may be critical in explaining patterns of herbivory. The generalist lepidopteran larvae, Helicoverpa armigera (the cotton bollworm), avoided the midvein and periphery of Arabidopsis thaliana rosette leaves and fed almost exclusively on the inner lamina. This feeding pattern was attributed to glucosinolates because it was not evident in a myrosinase mutant that lacks the ability to activate glucosinolate defenses by hydrolysis. To measure the spatial distribution of glucosinolates in A. thaliana leaves at a fine scale, we constructed ion intensity maps from MALDI-TOF (matrix assisted laser desorption/ionization-time of flight) mass spectra. The major glucosinolates were found to be more abundant in tissues of the midvein and the periphery of the leaf than the inner lamina, patterns that were validated by HPLC analyses of dissected leaves. In addition, there were differences in the proportions of the three major glucosinolates in different leaf regions. Hence, the distribution of glucosinolates within the leaf appears to control the feeding preference of H. armigera larvae. The preferential allocation of glucosinolates to the periphery may play a key role in the defense of leaves by creating a barrier to the feeding of chewing herbivores that frequently approach leaves from the edge.antiherbivore defense ͉ MALDI-imaging ͉ plant natural products M any plant natural products appear to serve as defenses against herbivores because of their toxicity or deterrence in artificial diets or when added as a supplement to plant material (1, 2). However, to evaluate the actual defensive role of these substances in planta, it is necessary to estimate the amount that a potential herbivore would encounter during feeding. Although determining the amount of plant tissue ingested during a feeding bout is relatively straightforward, measuring the quantity of specific defense products in that tissue is not. Nearly all studies to date have quantified the levels of defensive metabolites at the level of the whole plant or organ (3). Little is known about the localization of antiherbivore defenses in individual tissues or parts of organs even though this may be critically important to the behavior of small herbivores and to the effectiveness of the defense.One of the most extensively studied classes of antiherbivore chemical defenses in plants is the glucosinolates, a group of sulfur-rich, amino acid-derived metabolites combining a ␤-Dglucopyranose residue linked via a sulfur atom to an Nhydroxyamino sulfate ester (4) (Fig. 1). Glucosinolates are widespread in the order Capparales, which includes vegetables (cabbage, cauliflower, and broccoli), spice plants supplying condiments (mustard, horseradish, and wasabi), and the model species, Arabidopsis thaliana (5, 6). Upon insect feeding or mechanical disruption, glucosinolates are hydrolyzed by an endogenous glucohydrolase activity known as myrosinase, and the released aglycone rearranges to form isothiocyanates, nitriles, and other pr...

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mentioning

confidence: 99%

Nonuniform distribution of glucosinolates in Arabidopsis thaliana leaves has important consequences for plant defense

Shroff

Vergara

Muck

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

261

236

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“…esorption electrospray ionization (DESI) [1,2] is a widely used ambient ionization technique [3][4][5][6][7][8], which is used for surface sampling [9,10], high throughput analysis [11,12], and chemical imaging [13][14][15][16][17], largely because of its applicability to in situ analyte detection from unmodified surfaces. In DESI, a nebulized electrospray of high-velocity charged microdroplets is directed at a surface from which the solvent extracts analyte and carries it to the mass spectrometer in the form of secondary microdroplets.…”

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confidence: 99%

Enhanced ion signals in desorption electrospray ionization using surfactant spray solutions

Badu‐Tawiah

Cooks

2010

J. Am. Soc. Mass Spectrom.

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Solvent optimization is an important procedure in desorption electrospray ionization (DESI) and in this study the effects of solvent surface tension are explored. Data are presented for methanol/water/surfactant solvent systems, which show increases in ion signals of more than an order of magnitude when low concentrations of surfactants are added to the standard methanol/water (1:1) spray solvent. Examples of analytes tested include food chemicals, peptides, pharmaceuticals, and drugs of abuse. The improvement in ion intensity is mainly attributed to the effect of surface tension in producing smaller spray droplets, which are shown to cover a larger surface area. Surfactant-containing spray solutions allowed extension of DESI-MS analysis to previously intractable analytes like melamine and highly hydrophobic compounds like the sudan dyes. ( [3][4][5][6][7][8], which is used for surface sampling [9,10], high throughput analysis [11,12], and chemical imaging [13][14][15][16][17], largely because of its applicability to in situ analyte detection from unmodified surfaces. In DESI, a nebulized electrospray of high-velocity charged microdroplets is directed at a surface from which the solvent extracts analyte and carries it to the mass spectrometer in the form of secondary microdroplets. This methodology has been applied in a variety of disciplines including forensics [18,19], environmental science [20], food science [12,21], and pharmaceutical science [22]. With increased interest in ambient desorption mass spectrometry, the need has arisen to develop more versatile solvent systems that are applicable to a wider range of samples than is currently the case. One aspect of this effort is the use of non-aqueous spray solutions [23] and another is the addition of reagents to the spray solvent chosen to react and give ionic derivatives of the analytes of interest [24]. Both are discussed further below. In this work, we explore the special properties of spray solutions containing surfactants, in an attempt to increase the ion intensity and to learn more about the mechanisms of DESI.Three mechanisms have been identified in DESI, all falling under the rubric of droplet pick-up. The first and best established is the droplet micro-extraction mechanism [25,26]. In this mechanism, initial droplets arriving at the surface form a localized and probably discontinuous liquid thin film, which dissolves analyte present on the surface. Subsequent droplet-liquid-thin-film collisions produce secondary microdroplets containing the analyte, which are then sucked into the mass spectrometer for mass/charge analysis. A second mechanism is believed to involve gas-phase ion/molecule reactions [2]. In this case, vaporization of the analyte from the surface is followed by fast charge-transfer reactions with protonated (or other) solvent molecules or droplets to produce charged analytes, which are then transferred into the mass spectrometer for mass analysis. A third mechanism, which also seems to make a limited contribution to ion production in ...

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“…For the past century, the ability to image the distribution of a compound within a tissue or single cell has been a powerful tool for scientists, and has often necessitated the development of antibodies or other selective probes. Several MS-based approaches, including secondary ion mass spectrometry (SIMS), have been used for (107)(108)(109)(110), that allowed the study of larger peptides and proteins in biological materials. As described by Caprioli et al (see Reference 11, in this volume), one creates images with MALDI MS by coating the sample with a thin, homogenous layer of matrix prior to the collection of a series of mass spectra from an ordered array of locations across the sample.…”

Section: Imaging Peptide Distributionsmentioning

confidence: 99%

Peptides in the Brain: Mass Spectrometry–Based Measurement Approaches and Challenges

Li¹,

Sweedler

2008

Annual Rev. Anal. Chem.

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131

172

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The function and activity of almost every circuit in the human brain are modified by the signaling peptides (SPs) surrounding the neurons. As the complement of peptides can vary even in adjacent neurons and their physiological actions can occur over a broad range of concentrations, the required figures of merit for techniques to characterize SPs are surprisingly stringent. In this review, we describe the formation and catabolism of SPs and highlight a range of mass spectrometric techniques used to characterize SPs. Approaches that supply high chemical information content, direct tissue profiling, spatially resolved data, and temporal information on peptide release are also described. Because of advances in measurement technologies, our knowledge of SPs has greatly increased over the last decade, and SP discoveries will continue as the capabilities of modern measurement approaches improve. 451

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Imaging mass spectrometry: fundamentals and applications to drug discovery

Cited by 185 publications

References 95 publications

Nonuniform distribution of glucosinolates in Arabidopsis thaliana leaves has important consequences for plant defense

Nonuniform distribution of glucosinolates in Arabidopsis thaliana leaves has important consequences for plant defense

Enhanced ion signals in desorption electrospray ionization using surfactant spray solutions

Peptides in the Brain: Mass Spectrometry–Based Measurement Approaches and Challenges

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