Imaging with Mass Spectrometry

Pacholski, Michaeleen L.; Winograd, Nicholas

doi:10.1021/cr980137w

Cited by 288 publications

(217 citation statements)

References 192 publications

(379 reference statements)

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“…The quadrupole system suffers from loss of sensitivity at higher mass, but this is offset by the capability to perform MS/MS as needed. While time-of-flight mass spectrometers are more often employed for imaging tissue [12], performing simultaneous MS/MS and imaging with them is problematic.…”

Section: Secondary Ion Mass Spectrometermentioning

confidence: 99%

Secondary ion images of the developing rat brain

Todd

McMahon

McCandlish

2004

J. Am. Soc. Mass Spectrom.

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Secondary ion images were obtained from sections of rat brain over a 21 day postnatal period, using the intensity of m/z 184, phosphocholine. When compared with corresponding optical images of similar, but stained sections from the same animal, the secondary ion images appear to reflect less developed brains. During development, myelination occurs after axon extension. Apparently, myelination obscures the source of secondary m/z 184, phosphatidylcholine, from the analyzing ion probe; absenting myelination, secondary ion images show no physiological features. (J Am Soc Mass Spectrom 2004, 15, 1116 -1122) © 2004 American Society for Mass Spectrometry I mages obtained by a variety of methods-optical, secondary electron, nuclear magnetic resonance, etc., are integral to the philosophy of all branches of medicine. Among mass spectral methods, secondary ion mass spectrometry (SIMS) and imaging matrix assisted laser desorption (iMALDI) mass spectrometry are the major players in this arena [1]. These are both emerging methods, and as such, it is necessary to establish that not only are results consistent with known mass spectrometry, but also with known biomedicine.Secondary ions are emitted from tissue at virtually every m/z. We identify secondary ions by tandem mass spectrometry (MS/MS), and map the emission of ions whose structure we know. We then try to interpret the images in the context of known anatomy physiology. For example, the major peak in the secondary ion mass spectrum of almost any collection of animal cells is m/z 184, phosphocholine. Phosphocholine is unique among secondary ions emitted from tissue in that its structure has been verified by MS/MS [2], a method permitting distinction of phosphocholine from other sources of m/z 184 such as epinephrine. The secondary phosphocholine ion derives from the head group of phosphatidylcholine, (PC in the shorthand of biochemists) a major constituent of the animal cell membrane. Most of the outer layer of cell membranes in the brain is either phosphatidylcholine or sphingomyelin [3][4][5], and both compounds yield abundant m/z 184. Thus, detection of phosphocholine is consistent with the chemistry of low dose or static SIMS [6], a surface analytical method, and the fact that most of the surface of a tissue sample is comprised of compounds yielding phosphocholine secondary ions, m/z 184.The utility of SIMS for mapping phoshocholine is based on the observation that emission of phosphocholine secondary ions is heterogeneous across the tissue section surface [7]. Moreover, secondary m/z 184 images of adult rat brain show a direct correlation with optical images of stained tissue sections [8]. Regions of the brain containing a high density of cells such as cerebral cortex or the caudate/putamen yield an intense m/z 184 secondary ion signal, whereas acellular regions such as the corpus callosum or external capsule yield little or no m/z 184 secondary emission. In the adult, these acellular regions of the brain are very dense in cell projections (axons), many of which ar...

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Section: Secondary Ion Mass Spectrometermentioning

confidence: 99%

Secondary ion images of the developing rat brain

Todd

McMahon

McCandlish

2004

J. Am. Soc. Mass Spectrom.

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“…To make the sample preparation step easier, less time consuming, and reduce the risk of cross-contamination, we developed a simple version of the solvent-free sample preparation method, now called the vortex method [16]. Although the utility of solvent-free sample preparation for MALDI has been clearly demonstrated, the investigations into why it works and what impact these data have on our overall understanding of the MALDI process have only recently begun [17,18].To develop increased understanding of the utility of the solvent-free MALDI sample preparation method, we have investigated the morphology of these samples using different imaging experiments-optical imaging [19], scanning electron microscopy (SEM) [20], atomic force microscopy (AFM) [21], and time-of-flight secondary ion mass spectrometry (ToF-SIMS) [22]. Previous work has shown the utility of investigating MALDI sample morphology using imaging methods.…”

mentioning

confidence: 99%

“…To develop increased understanding of the utility of the solvent-free MALDI sample preparation method, we have investigated the morphology of these samples using different imaging experiments-optical imaging [19], scanning electron microscopy (SEM) [20], atomic force microscopy (AFM) [21], and time-of-flight secondary ion mass spectrometry (ToF-SIMS) [22]. Previous work has shown the utility of investigating MALDI sample morphology using imaging methods.…”

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confidence: 99%

Imaging the morphology of solvent-free prepared MALDI samples

Hanton

McEvoy

Stets

2008

J. Am. Soc. Mass Spectrom.

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Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is an important technique to characterize many different materials, including synthetic polymers. MALDI mass spectral data can be used to determine the polymer average molecular weights, repeat units, and end groups. The development of solvent-free sample preparation methods has enabled MALDI to analyze insoluble materials and, interestingly, can provide higher-quality mass spectral data. Although the utility of solvent-free sample preparation for MALDI has been demonstrated, the reasons for its success are only now being discovered. In this study, we use microscopy tools to image samples prepared using solvent-free methods to examine the morphology of these samples. The samples are prepared using a simple vortex method. Our results show that the average particle size of typical MALDI matrices is reduced from their original tens to hundreds of micrometers to hundreds of nanometers. This size reduction of the matrix occurs in one minute using the vortex method. We also observe remarkably smooth and homogeneous sample morphologies for the laser to interrogate, especially considering the relatively crude methods used to prepare our samples. [5][6][7][8][9][10]. MALDI can generate important data on the telomer repeat units, end groups, and average molecular weights of these materials. MALDI methods have been developed to address a broad variety of different polymer materials containing different chemistries. One of the key issues in traditional MALDI sample preparation is making true solutions of the analyte and the matrix [9]. Many interesting polymeric analytes are either completely insoluble or present significant challenges in making analytically useful solutions. To address these issues, solvent-free sample preparation methods have been developed. While several groups investigated solventfree sample preparation methods at nearly the same time, the methods developed by Trimpin, Räder, and coworkers have gained widespread use [11][12][13][14][15]. To make the sample preparation step easier, less time consuming, and reduce the risk of cross-contamination, we developed a simple version of the solvent-free sample preparation method, now called the vortex method [16]. Although the utility of solvent-free sample preparation for MALDI has been clearly demonstrated, the investigations into why it works and what impact these data have on our overall understanding of the MALDI process have only recently begun [17,18].To develop increased understanding of the utility of the solvent-free MALDI sample preparation method, we have investigated the morphology of these samples using different imaging experiments-optical imaging [19], scanning electron microscopy (SEM) [20], atomic force microscopy (AFM) [21], and time-of-flight secondary ion mass spectrometry (ToF-SIMS) [22]. Previous work has shown the utility of investigating MALDI sample morphology using imaging methods. We have used SEM to investigate the morphology of electrospray deposited samples [23] ...

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“…This results in higher secondary ion yields and yield enhancements on silicon than aluminum substrates. S econdary ion mass spectrometry (SIMS) is widely used to study the chemical composition of surfaces in areas from biological systems to materials chemistry [1,2]. One of the problems with the SIMS analysis of surfaces is that low secondary molecular ion yields are often observed for atomic primary ion impacts.…”

mentioning

confidence: 99%

“…Examples of polyatomic ions that exhibit this behavior include Au n ϩ [3][4][5][6][7][8], (CsI) n Cs ϩ [3,9,10], C 60 ϩ [8,9,[11][12][13][14][15], SF 5 ϩ [16 -21], and Au n Ϫ [22,23]. Thus, using polyatomic projectiles can potentially improve secondary ion yields, which may lead to an increase in the maximum useful spatial resolution that can be achieved, currently ϳ200 nm [1]. To improve spatial resolution, we require both high secondary ion yields and primary ion beams with a small beam diameter.…”

mentioning

confidence: 99%