Mass spectrometry imaging as a tool for surgical decision‐making

Despite significant advances in image‐guided therapy, surgeons are still too often left with uncertainty when deciding to remove tissue. This binary decision between removing and leaving tissue during surgery implies that the surgeon should be able to distinguish tumor from healthy tissue. In neurosurgery, current image‐guidance approaches such as magnetic resonance imaging (MRI) combined with neuronavigation offer a map as to where the tumor should be, but the only definitive method to characterize the tissue at stake is histopathology. Although extremely valuable information is derived from this gold standard approach, it is limited to very few samples during surgery and is not practically used for the delineation of tumor margins. The development and implementation of faster, comprehensive, and complementary approaches for tissue characterization are required to support surgical decision‐making – an incremental and iterative process with tumor removed in multiple and often minute biopsies. The development of atmospheric pressure ionization sources makes it possible to analyze tissue specimens with little to no sample preparation. Here, we highlight the value of desorption electrospray ionization as one of many available approaches for the analysis of surgical tissue. Twelve surgical samples resected from a patient during surgery were analyzed and diagnosed as glioblastoma tumor or necrotic tissue by standard histopathology, and mass spectrometry results were further correlated to histopathology for critical validation of the approach. The use of a robust statistical approach reiterated results from the qualitative detection of potential biomarkers of these tissue types. The correlation of the mass spectrometry and histopathology results to MRI brings significant insight into tumor presentation that could not only serve to guide tumor resection, but that is also worthy of more detailed studies on our understanding of tumor presentation on MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Reaktionen auf der Spur

A new technique, desorption electrospray ionization coupled to mass spectrometry (DESI‐MS), has been used as a tool for reaction analysis. Charged droplets of a reagent are sprayed onto the catalyst, which has previously been deposited on a surface in front of a mass analyzer. The reaction starts as the droplets impact the catalyst on the surface and continues inside secondary microdroplets that are desorbed from the surface. These are directed toward the mass spec inlet. Using this technique, the very first milliseconds of a reaction can be observed. The first example describes the discovery of an extremely short‐lived intermediate in a C‐H amination reaction cycle. Another example describes how DESI‐MS has been used to identify catalyst arrest mechanisms in ruthenium catalyzed C‐H hydroxylation.     

Principal component analysis of urine metabolites detected by NMR and DESI–MS in patients with inborn errors of metabolism

Urine metabolic profiles of patients with inborn errors of metabolism were examined with nuclear magnetic resonance (NMR) and desorption electrospray ionization mass spectrometry (DESI-MS) methods. Spectra obtained from the study of urine samples from individual patients with argininosuccinic aciduria (ASA), classic homocystinuria (HCY), classic methylmalonic acidemia (MMA), maple syrup urine disease (MSUD), phenylketonuria (PKU) and type II tyrosinemia (TYRO) were compared with six control patient urine samples using principal component analysis (PCA). Target molecule spectra were identified from the loading plots of PCA output and compared with known metabolic profiles from the literature and metabolite databases. Results obtained from the two techniques were then correlated to obtain a common list of molecules associated with the different diseases and metabolic pathways. The combined approach discussed here may prove useful in the rapid screening of biological fluids from sick patients and may help to improve the understanding of these rare diseases.     

Imaging with mass spectrometry: Which ionization technique is best?

The use of mass spectrometry (MS) to acquire molecular images of biological tissues and other substrates has developed into an indispensable analytical tool over the past 25 years. Imaging mass spectrometry technologies are widely used today to study the in situ spatial distributions for a variety of analytes. Early MS images were acquired using secondary ion mass spectrometry and matrix-assisted laser desorption/ionization. Researchers have also designed and developed other ionization techniques in recent years to probe surfaces and generate MS images, including desorption electrospray ionization (DESI), nanoDESI, laser ablation electrospray ionization, and infrared matrix-assisted laser desorption electrospray ionization. Investigators now have a plethora of ionization techniques to select from when performing imaging mass spectrometry experiments. This brief perspective will highlight the utility and relative figures of merit of these techniques within the context of their use in imaging mass spectrometry.     

自建电喷雾解吸电离源（DESI）在大分子分析中的应用及离子化机理探索

自建了简易的电喷雾解吸电离源(DESI),优化了DESI源喷口的位置和角度,并将其用于常见多肽和蛋白质的分析。多肽和小质量蛋白质(<20 kDa)可以容易地从表面解吸电离,生成清晰的质谱。而牛血清白蛋白(66.4 kDa)不能产生清晰的多电荷分布的质谱,说明当前DESI源的设计可能存在一个电离的分子量上限。通过比较不同的实验条件并对比ESI-MS,发现溶剂分子的挥发过程对电荷分布以及峰宽均有显著影响,可能是由于ESI更软引起。载样表面的性质对DESI-MS的信号强度有较大影响。金表面的自组装单分子膜(SAM)相对于纯金表面有较好的绝缘性,并有助于产生较强信号,说明来自表面的电子转移(电中和)是电喷雾解吸电离过程中的一个重要因素。该文的研究有助于对DESI-MS的实验条件和载样表面的选择,同时增进了对电喷雾解吸电离机理的了解。     

Analysis of questioned documents: A review

During the last years (2000–2014), many publications concerning the forensic analysis of questioned documents have been published, and new techniques and methodologies are nowadays employed to overcome forensic caseworks. This article reviews a comprehensive collection of the works focused on this issue, including dating studies, the analysis of inks from pens and printers, the analysis of paper, the analysis of other samples related to questioned documents and studies on intersecting lines. These sections highlight the most relevant analytical studies by a wide range of analytical techniques. Separation and spectrometric techniques are critically discussed and compared, emphasizing the advantages and disadvantages of each one. Finally, concluding remarks on the research published are included.     

Effects of dopants in the imaging of mouse brain by desorption electrospray ionization/post-photoionization mass spectrometry

Desorption electrospray ionization/post-photoionization (DESI/PI) is a newly developed ionization method by the combination of DESI and post-photoionization for the simultaneous imaging of polar and nonpolar compounds in biological tissues. Dopants are of great importance in DESI/PI for the enhancement of signal intensities through ion–molecule reactions. In this work, to evaluate the performance of dopants in DESI/PI, an efficient homogenate model was developed, and four kinds of dopants (toluene, chlorobenzene, bromobenzene, and anisole) were tested using homogenate of mouse brain tissue as target sample. The influences of the dopants on the signal enhancements of different compounds were explained reasonably by the ionization mechanism. Then, the dopants with their optimum volume contents were applied to the mass spectrometry imaging (MSI). For a comprehensive imaging of various compounds with different polarities, methanol/toluene/formic acid (7:3:0.1) was chosen as the best choice. Finally, the stronger quantitative ability of DESI/PI with toluene as dopant for a few compounds in mouse brain tissue was demonstrated.     

Ambient mass spectrometry: Direct analysis of dimethoate,tebuconazole, and trifloxystrobin on olive and vine leaves by desorption electrospray ionization interface

A new field of application for a relatively new mass‐spectrometric interface such as desorption electrospray ionization was evaluated. For this purpose, its behavior was tested versus quantitative analysis of dimethoate, trifloxystrobin, and tebuconazole directly on olive and vine leaves surface. The goal was workers exposure assessment during field re‐entry operations since evidence suggests an association between chronic occupational exposure to some agrochemicals and severe adverse effects. Desorption electrospray ionization gave good response working in positive ionization mode, while numerous test were necessary for the choice of a unique blend of spray solvents suitable for all 3 substances. The best compromise, in terms of signal to noise ratios, was obtained with the CH₃OH/H₂O (80:20) mixture. The obvious difficulties related to the impossibility to use the internal standard were overcome through an accurate validation. Limits of detection and quantitation, dynamic ranges, matrix effects, and intraday precisions were calculated, and a small monitoring campaign was arranged to test method applicability and to evaluate potential dermal exposure. This protocol was developed in work safety field, but after a brief investigation, it was find to be suitable also for food residue evaluation.     

Ambient ionisation mass spectrometry for in situ analysis of intact proteins

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.     

Analysis of sexual assault evidence by desorption electrospray ionization mass spectrometry

Desorption electrospray ionization mass spectrometry (DESI‐MS) is employed in the forensic analysis of chemical components present in condoms and imaging of latent fingerprints as circumstantial evidence of sexual assault. Polymers such as nonoxynol‐9, polyethylene glycol, and polydimethylsiloxane, as well as small molecules additives such as N‐methylmorpholine, N‐octylamine, N,N‐dibutyl formamide, and isonox 132, commonly used in lubricated condom formulations, were successfully characterized by DESI. The results suggest that DESI‐MS is useful for identification of this type of evidence, and it has advantages over conventional extractive techniques, in terms of speed of analysis and ease of use. Copyright © 2013 John Wiley & Sons, Ltd.